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Uremia

Uremia refers to the pathological manifestations that occur with severe azotemia or kidney failure. Symptoms of uremia develop as kidney function declines and waste products accumulate in the blood. Chronic kidney disease is defined as kidney damage or decreased kidney function lasting at least 3 months. It is staged based on glomerular filtration rate. Common complications in later stages include fluid and electrolyte abnormalities like hyperkalemia and metabolic acidosis, endocrine disorders like mineral bone disease, and neurological and cardiovascular issues. Dialysis can improve some manifestations of uremia but others may persist or progress despite treatment.

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UREMIA DR SAMIR SALLY,MD COSULTANT NEPHROLOGY MANSOURA UROLOGY & NEPHROLOGY CENTRE, MANSOURA UNIVERSITY
UREMIA Azotemia refers to high levels of urea but is used primarily when the abnormality can be measured chemically but is not yet so severe as to produce symptoms. Uremia is the pathological manifestations of severe azotemia. There is no specific time for the onset of uremia for people with progressive loss of kidney function. Both uremia and the uremic syndrome have been used interchangeably to define a very high plasma urea concentration that is the result of renal failure
INTRODUCTION All patients with renal disease should undergo an assessment of renal function by estimating (GFR) from ser creatinine. This measurement is used clinically to evaluate the degree of renal impairment, to follow the course of the disease, and to assess the response to therapy. An attempt must also be made to obtain a specific diagnosis. careful urinalysis, kidney ultrasound, referral to a nephrologist, and a kidney biopsy.
IDENTIFICATION OF RISK FACTORS AND STAGING OF CKD Risk factors: 1. hypertension, 2. diabetes mellitus, 3. autoimmune disease, 4. older age, 5. a family history of renal disease, 6. a previous episode of acute kidney injury, 7. Kidney donors and transplant recipients 8. and the presence of a. proteinuria, b. abnormal urinary sediment, or c. structural abnormalities of the urinary tract
CALCULATION OF GFR Methods of calculation Cockcroft-Gault formula MDRD formula/modified MDRD CKD-EPI when eGFR values above 60 ml/min/1.7 sq meter is desired This CKD-EPI equation calculator should be used when Scr  reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2  are desired This CKD-EPI equation calculator should be used when Scr  reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2  are desired This CKD-EPI equation calculator should be used when Scr  reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2  are desired This CKD-EPI equation calculator should be used when Scr  reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2  are desire
THE COCKCROFT-GAULT CALCULATION GFR ml/min/1.73m2 = (140-age) x Lean BW Kg 72 x S creatinine mg% ( x 0.85 for Females )
84 F 22 M 66 M 66 F • Wt (kg) 45.5 104.5 77.2 71.8 • Screat 1.2 1.2 1.2 1.2 • eGFR 26.9 142.7 66.1 52.3 (Calculated with Cockcroft-Gault)
• MDRD GFR Formula* 170 x [SCr]-0.999 x [Age]-0.176 x [0.762 if female] x [1.180 if black] x [Alb]+0.318 • Modified MDRD Formula 186.338 x [SCr]-1.154 x [Age]-0.203 x [1.212 if black] x [0.742 if female] MDRD GFR *From Levey et al, 1999 Ann Intern Med 130: 461-470 (A calculator may be found at www.hdcn.org)
RELATIONSHIP OF SERUM CREATININE TO GFR
HOW THE KIDNEY RESPONDS TO INJURY? The kidney is able to adapt to damage by increasing the filtration rate in the remaining normal nephrons, a process called adaptive hyperfiltration. As a result, the patient with mild RI often has a normal or near- normal ser creatinine. Additional homeostatic mechanisms (most frequently occurring within the renal tubules) permit the serum concentrations of sodium, potassium, calcium, and phosphorous and the total body water to also remain within the normal range.
PHYSIOLOGIC CHANGES IN CHRONIC KIDNEY DISEASE Increased single nephron GFR Afferent arteriolar vasodilation Intraglomerular hypertension Loss of glomerular permselectivity Inabilty to appropriately dilute or concentrate the urine in the face of volume challenge
PHYSIOLOGIC CHANGES IN CHRONIC KIDNEY DISEASE Intraglomerular hypertension and glomerular hypertrophy leading to glomerular scarring (glomerulosclerosis). Additional causes may include systemic hypertension, hyperlipidemia, metabolic acidosis, and tubulointerstitial disease. Thus, proteinuria typically is present in patients with progressive CKD, even in primary tubulointerstitial diseases such as reflux nephropathy. Principal targets for renal protection —the blood pressure goal and, the proteinuria goal
PHYSIOLOGIC CHANGES IN CKD - ACE inhibitors or ARBs agents in patients with proteinuric CKD if begun before irreversible scarring - ARBs do not appear to be more beneficial than other antihypertensive agents in patients with nonproteinuric CKD. - When used in patients with CKD, common side effects of ARBs include a mild to moderate reduction in GFR and hyperkalemia, which occurs soon after the initiation of therapy or an increase in dose
PATHOGENESIS OF SECONDARY GLOMERULOSCLEROSIS Nephron Mass Glomerular Volume and Glomerular Hypertension Epithelial Cell Density and Foot Process Fusion Glomerular Sclerosis and Hyalinosis Primary Insult Proteinuria
LEFT: SCHEMA OF THE NORMAL GLOMERULAR ARCHITECTURE. RIGHT: SECONDARY GLOMERULAR CHANGES
PHYSIOLOGIC CHANGES IN CKD The gradual decline in function in patients with (CKD) is initially asymptomatic. However, different signs and symptoms may be observed with advanced RF, including volume overload, hyperkalemia, metabolic acidosis, hypertension, anemia, and (MBDs). The onset of (ESRD) results in a constellation of signs and symptoms referred to as uremia.
WHAT IS CKD? Chronic kidney disease is defined based on the presence of either kidney damage or decreased kidney function for three or more months, irrespective of cause. • Criteria: Duration ≥3 months, based on documentation or inference Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
CHRONIC KIDNEY DISEASE A) Pathologic abnormalities (examples). Cause is based on underlying illness and pathology. Markers of kidney damage may reflect pathology. 1.Glomerular diseases (diabetes, autoimmune diseases, systemic infections, drugs, neoplasia) 2.Vascular diseases (atherosclerosis, hypertension, ischemia, vasculitis, thrombotic microangiopathy) 3.Tubulointerstitial diseases (urinary tract infections, stones, obstruction, drug toxicity) 4.Cystic disease (polycystic kidney disease) Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
CHRONIC KIDNEY DISEASE B) History of kidney transplantation. In addition to pathologic abnormalities observed in native kidneys, common pathologic abnormalities include the following: 1.Chronic allograft nephropathy (non-specific findings of tubular atrophy, interstitial fibrosis, vascular and glomerular sclerosis) 2.Rejection 3.Drug toxicity (calcineurin inhibitors) 4.BK virus nephropathy 5.Recurrent disease (glomerular disease, oxalosis, Fabry disease) Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
CHRONIC KIDNEY DISEASE C) Albuminuria as a marker of kidney damage (increased glomerular permeability, urine albumin-to-creatinine ratio [ACR] >30 mg/g).* 1.The normal urine ACR in young adults is <10 mg/g. Urine ACR categories 10-29, 30-300 and >300 mg are termed "high normal, high, and very high" respectively. Urine ACR >2200 mg/g is accompanied by signs and symptoms of nephrotic syndrome 2.Threshold value corresponds approximately to urine dipstick values of trace or 1+ 3.High urine ACR can be confirmed by urine albumin excretion in a timed urine collection Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
CHRONIC KIDNEY DISEASE D) Urinary sediment abnormalities as markers of kidney damage 1.RBC casts in proliferative glomerulonephritis 2.WBC casts in pyelonephritis or interstitial nephritis 3.Oval fat bodies or fatty casts in diseases with proteinuria 4.Granular casts and renal tubular epithelial cells in many parenchymal diseases (non-specific) Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
CHRONIC KIDNEY DISEASE E) Imaging abnormalities as markers of kidney damage (ultrasound, computed tomography and magnetic resonance imaging with or without contrast, isotope scans, angiography). 1.Polycystic kidneys 2.Hydronephrosis due to obstruction 3.Cortical scarring due to infarcts, pyelonephritis or vesicoureteral reflux 4.Renal masses or enlarged kidneys due to infiltrative diseases 5.Renal artery stenosis 6.Small and echogenic kidneys (common in later stages of CKD due to many parenchymal diseases) Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
ETIOLOGY OF CHRONIC KIDNEY DISEASE Diabetes 43% HTN 25% GN 12% Other 20% Diabetes HTN GN Other
CHRONIC KIDNEY DISEASE No direct correlation exists between the absolute serum levels of (BUN) or creatinine and the development of uremic symptoms. Some patients have relatively low levels (eg, a BUN of 60 mg/dL in an older patient) but are markedly symptomatic, while others have marked elevations (eg, a BUN of 140 mg/dL]) but remain asymptomatic.
CHRONIC KIDNEY DISEASE Certain drugs also interfere with either creatinine secretion or the assay used to measure the serum creatinine. These include cimetidine, trimethoprim, cefoxitin, and flucytosine. In these settings, There will be no change in the true GFR; Absence of a concurrent elevation in the (BUN)
3 SPHERES OF DYSFUNCTION OF UREMIC SYNDROME
MANIFESTATIONS OF CHRONIC UREMIA Fig. 47-5
CLINICAL ABNORMALITIES IN UREMIA 1. Fluid and electrolyte disturbances 2. Endocrine-metabolic disturbances 3. Neuromuscular disturbances 4. Cardiovascular and pulmonary disturbances 5. Dermatologic disturbances 6. Gastrointestinal disturbances 7. Hematologic and immunologic disturbances (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy.
CLINICAL ABNORMALITIES IN UREMIA 1. Fluid and electrolyte disturbances a. Volume expansion (I) b. Hyponatremia (I) c. Hyperkalemia (I) d. Hyperphosphatemia (I) (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy.
FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS Hyponatremia – water restriction ECFV expansion – salt restriction Thiazides – limited utility in stages 3-5 CKD - loop diuretics needed Loop Diuretics resistance – Higher doses Metolazone – combined with loop diuretics, which inhibits the sodium chloride co-transporter of the distal convoluted tubule, can help effect renal salt excretion
FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS • HYPERKALEMIA • Precipitated by • increased dietary potassium intake, • protein catabolism, • hemolysis, • hemorrhage, • transfusion of stored red blood cells, • and metabolic acidosis • Medications .
FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS Hyperkalemia A common reason for initiation of RRT There is limited K excretion as GFR falls Diabetics may have a type IV RTA (hyporeninemic hypoaldosteronism) Use of ACE-I can exacerbate hyperkalemia
FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS Hyperkalemia - Potassium balance usually remains intact until GFR < 10-20 mL/min - Tx of acute hyperkalemia involves cardiac monitoring, IV calcium chloride or gluconate, insulin with glucose, bicarbonate, and potassium-binding resins - Chronic hyperkalemia tx’d with dietary k restriction, and Ca resonium PRN
FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS Hypokalemia: • Not common in CKD • reduced dietary potassium intake • GI losses • Diuretic therapy • Fanconi’s syndrome • RTA • Hereditary or acquired Tubulointerstitial disease
FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS Metabolic acidosis • common disturbance in advanced CKD • combination of hyperkalemia and hyperchloremic metabolic acidosis is often present, even at earlier stages of CKD (stages 1–3) • Treat hyperkalemia • the pH is rarely <7.35 • usually be corrected with oral sodium bicarbonate supplementation
CLINICAL ABNORMALITIES IN UREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 2. Endocrine-metabolic disturbances
CLINICAL ABNORMALITIES IN UREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 2. Endocrine-metabolic disturbances
PTH Pi Ca2+ Renal Mass 25(OH)D3 1,25(OH)2D3 1-alpha-hydroxylase1-alpha-hydroxylase + Acidosis + Hyperparathyroid Related Bone Disease Impaired Absorption Osteitis Fibrosa Cystica
RENAL OSTEODYSTROPHY
DISORDERS OF CALCIUM AND PHOSPHATE METABOLISM Other complications of abnormal mineral metabolism: • Calciphylaxis (calcific uremic arteriolopathy) • Other etiologies • use of oral calcium as a phosphate binder • Warfarin
CLINICAL ABNORMALITIES IN UREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 2. Endocrine-metabolic disturbances
CKD patients have a nutritional deficiency of 25-OH Vitamin D which itself leads to an increase in PTH secretion Levels of 25-OH D should be measured when PTH-Intact >70pg/ml Treatment <5ng/ml 50,000U Ergocalciferol/wk x12, then q mo x6 5-15ng/ml 50,000/wk x 4, then q mo x 6 16-30ng/ml 50,000/month x 6 Measure 25(OH)-D at 6 months Maintenance 800-1200 IU qd Calcium and Phosphorus Balance: Recommendations (KDOQI)
DISORDERS OF CALCIUM AND PHOSPHATE METABOLISM The principal complications of abnormalities of calcium and phosphate metabolism in CKD 1. occur in the skeleton and 2. the vascular bed, 3. with occasional severe involvement of extraosseous soft tissues Bone manifestations of CKD, classified as: • associated with high bone turnover with increased PTH levels • low bone turnover with low or normal PTH levels
DISORDERS OF CALCIUM AND PHOSPHATE METABOLISM The principal complications of abnormalities of calcium and phosphate metabolism in CKD 1. occur in the skeleton and 2. the vascular bed, 3. with occasional severe involvement of extraosseous soft tissues Bone manifestations of CKD, classified as: • associated with high bone turnover with increased PTH levels • low bone turnover with low or normal PTH levels
COMPLICATIONS OF LONGTERM CALCIUM AND PHOSPHORUS IMBALANCE Tertiary hyperparathyroidism Renal osteodystrophy Demineralization Bone pain Fractures Systemic toxicity Cutaneous - Calciphylaxis Cardiovascular, accelerated vascular calcification
How are these goals achieved ? Control of dietary phosphorus intake to 0.8-1g/d May need initiation of “Phosphate binders” with meals When 25(OH)-D < 30pg/ml and PTH-I > target, initiate treatment with exogenous “Active Vitamin D” A few patients with very elevated PTH-I values may benefit from Calcimimetics Calcium and Phosphorus Balance KDOQI Recommendations
The use of calcium based binders is now falling out of favor because of the recognition of accelerated vascular calcification proposed to be associated with them. Although controversial, this is thought by some to be associated with the development of coronary atherosclerosis and is related to the presence and/or consequences of elevated serum phosphorus, calcium, and (PTH) Calcium and Phosphorus Balance
Treatment of Secondary Hyperparathyroidism Calcimimetic agents • Rapid onset (hours) • Inhibit PTH secretion • Inhibit PTH synthesis • Inhibit parathyroid cellular proliferation • Decrease serum calcium Vitamin D Sterols • Act on genomic receptor • Slow onset (days to weeks) • Inhibit PTH synthesis • Increase serum calcium
Phosphorus Ca2+ 1,25(OH)2D3 (Use Cautiously) New Paradigm in Treatment of Secondary Hyperparathyroidism Non-calcium Based Binders Cinacalcet PTH
13C.1 Adynamic bone disease in stage 5 CKD (as determined either by bone biopsy or intact PTH <100 pg/ml [11.0 pmol/L]) should be treated by allowing plasma levels of intact PTH to rise in order to increase bone turnover. (OPINION) 13C.1a This can be accomplished by decreasing doses of calcium-based phosphate binders and vitamin D or eliminating such therapy. (OPINION) Adynamic bone disease
Indication Bio-Intact PTH > 800 pg/mL refractory to medical therapy Severe hypercalcemia Progressive high turnover bone disease Complications May result in excessive low PTH levels Symptomatic hypocalcemia Risk for injury to recurrent laryngeal nerve Parathyroidectomy
CLINICAL ABNORMALITIES IN UREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 3. Neuromuscular disturbances
CLINICAL ABNORMALITIES IN UREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
CLINICAL ABNORMALITIES IN UREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
CLINICAL ABNORMALITIES IN UREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
CLINICAL ABNORMALITIES IN UREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
CLINICAL ABNORMALITIES IN UREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
CLINICAL ABNORMALITIES IN UREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
CARDIOVASCULAR ABNORMALITIES Ischemic vascular disease The CKD-related risk factors comprise 1. anemia, 2. hyperphosphatemia, 3. hyperparathyroidism, 4. sleep apnea, and 5. generalized inflammation Cardiac troponin levels are frequently elevated in CKD without evidence of acute ischemia.
CLINICAL ABNORMALITIES IN UREMIA 1.Pallor (I)b 2.Hyperpigmentation (I, P, or D) 3.Pruritus (P) 4.Ecchymoses (I) 5.Nephrogenic fibrosing dermopathy (D) 6.Uremic frost (I) (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 5. Dermatologic disturbances
CLINICAL ABNORMALITIES IN UREMIA 1.Anorexia (I) 2.Nausea and vomiting (I) 3.Gastroenteritis (I) 4.Peptic ulcer (I or P) 5.Gastrointestinal bleeding (I, P, or D) 6.Idiopathic ascites (D) 7.Peritonitis (D) (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 6. Gastrointestinal disturbances
IDIOPATHIC ASCITES Ascites in ESKD patients is predominantly of the low SAAG and high protein variety which is a manifestation of the combined effect of altered peritoneal membrane permeability, fluid overload and under-dialysis. The severity of ascites is affected by the presence of concomitant cardiac failure and hypoalbuminemia. Investigations to rule out tuberculosis, if the clinical and laboratory based suspicion is strongly in favour of this diagnosis.
IDIOPATHIC ASCITES
CLINICAL ABNORMALITIES IN UREMIA 1.Anemia (I)b 2.Lymphocytopenia (P) 3.Bleeding diathesis (I or D)b 4.Increased susceptibility to infection 5.(I or P) 6.Leukopenia (D) 7.Thrombocytopenia (D) (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 7. Hematologic and immunologic disturbances
HEMATOLOGIC ABNORMALITIES Anemia A normocytic, normochromic anemia develops when the GFR decreases to < 30-35 ml/min : decreasing production of erythropoietin Reduced renal mass Uremic inhibition of bone marrow Decreased RBC life-span PTH induced marrow fibrosis Iron deficiency Folate or vitamin B12 deficiency Aluminum related bone disease
The 2012 KDIGO guidelines, Patients who do not have anemia, Hgb should be checked when it is clinically indicated and at least yearly Patients with stage 3 CKD at least every six months Patients with stage 4 to 5 CKD, at least every three months Patients with stage 5D should be monitored monthly.
Investigations Nonrenal causes of anemia. Red blood cell indices, Absolute reticulocyte count, Serum iron, total iron-binding capacity, percent Transferrin saturation, serum ferritin, White blood cell count and differential, platelet count, B12 and folate if (MCV) is increased, Ocult blood in stool. This work-up should be performed prior to administering ESA therapy.
HEMATOLOGIC ABNORMALITIES Abnormal hemostasis 1. prolonged bleeding time, 2. decreased activity of platelet factor III, 3. abnormal platelet aggregation and adhesiveness, 4. and impaired prothrombin consumption. Clinical manifestations include 1. an increased tendency to bleeding and bruising, 2. prolonged bleeding from surgical incisions, 3. menorrhagia, 4. and spontaneous GI bleeding
Balancing the impact of decreased protein intake on the rate of progression of renal disease, against hypoalbuminemia and malnutrition Can we restrict protein intake sufficiently, without leading to malnutrition, especially important in patients with eGFR < 25 ml/min Nutrition
common in patients with advanced CKD because of a lower food intake (principally due to anorexia), decreased intestinal absorption and digestion, and metabolic acidosis Many additional studies have shown a strong correlation between malnutrition and death in maintenance dialysis patients. To best assess nutritional status, the serum albumin and BW should be measured serially; these should be measured approximately every one to three months and more frequently, if necessary Malnutrition
Patients with CKD are at increased risk for infection The risk of bacterial infection (particularly pulmonary and genitourinary) increases with the decline in kidney function . Preventive measures such as influenza and pneumococcal immunization Infection and vaccination
2012 KDIGO guidelines : ●Adults with all stages of CKD should be offered annual vaccination with influenza virus unless contraindicated. Adults with stage 4 and 5 CKD who are at high risk of progression of● CKD should be immunized against hepatitis B and the response confirmed by immunologic testing. Adults with CKD stages 4 and 5 should be vaccinated with polyvalent● pneumococcal vaccine unless contraindicated. Patients who have received pneumococcal vaccination should be offered revaccination within five years. US has recommended two forms of pneumococcal vaccine, including (PPSV23 [Pneumovax or Pnu-Immune]) and the (PCV13 [Prevnar for individuals aged ≥19 years with an immunocompromising condition, including CKD Vaccination
The primary finding in CKD is hypertriglyceridemia, with the total cholesterol concentration usually being normal (perhaps due in part to malnutrition in some patients). 2013 KDIGO guidelines that recommend an initial evaluation with lipid profile, including total cholesterol, (LDL-C), (HDL-C), and triglycerides As per the KDIGO guidelines, follow-up evaluation of lipid profiles is generally not necessary for patients age ≥50 years since statin therapy is not titrated to the lipid profile. Dyslipidemia
Follow-up testing may be performed among patients who are age <50 years who are not already on a statin Follow-up evaluation may also be performed to assess adherence to statin treatment, if there is a change in the modality of renal replacement therapy, or if there is concern about new secondary causes of dyslipidemia. Dyslipidemia
Dyslipidemia
Patients with (CKD) should be referred to a nephrologist when (eGFR) is <30 mL/min/1.73 m2 in order to discuss and potentially plan for renal replacement therapy. There is less consensus about referral for patients with higher eGFRs. Lower costs and/or decreased morbidity and mortality may be associated with early referral and care by nephrologists REFERRAL TO NEPHROLOGISTS
 Poorly controlled HTNPoorly controlled HTN  Diabetes mellitus with atypical renal manifestationsDiabetes mellitus with atypical renal manifestations  Proteinuria or nephrotic syndrome without retinopathyProteinuria or nephrotic syndrome without retinopathy  Renal insufficiency without proteinuria or retinopathyRenal insufficiency without proteinuria or retinopathy  Sudden onset of nephrotic syndrome or rapidly changing serumSudden onset of nephrotic syndrome or rapidly changing serum creatininecreatinine  Systemic disease associated with renal involvementSystemic disease associated with renal involvement  Heavy proteinuriaHeavy proteinuria  Urine-sediment abnormalitiesUrine-sediment abnormalities  PriorPrior to onset of uremic symptomsto onset of uremic symptoms REFERRAL TO NEPHROLOGISTS
In most studies, referral to the nephrologist is considered late if it is within one to six months of the requirement for renal replacement therapy . 25 to 50 percent of patients beginning chronic renal replacement therapy in US required dialysis within one month of their first nephrology visit , 22 to 49 percent of patients were first seen by a nephrologist less than four months prior to the initiation of dialysis REFERRAL TO NEPHROLOGISTS
One retrospective study has suggested that a multidisciplinary approach may improve survival . The 2012 (KDIGO) CKD guidelines suggest management of CKD patients in a multidisciplinary setting, with access to dietary counseling, renal replacement therapies, transplant options, vascular access surgery, and ethical, psychological and social care . REFERRAL TO NEPHROLOGISTS
●Pericarditis or pleuritis (urgent indication). Progressive uremic encephalopathy or neuropathy, (urgent indication).● A clinically significant bleeding diathesis attributable to uremia (urgent● indication). Fluid overload refractory to diuretics.● ●Hypertension poorly responsive to antihypertensive medications. Persistent metabolic disturbances that are refractory to medical● therapy. ●Persistent nausea and vomiting. Evidence of malnutrition.● Indications for renal replacement therapy
The timing of initiation of dialysis is unclear To help avoid the onset of possible life-threatening complications of uremia, the initiation of dialysis should be considered in the asymptomatic patient with an extremely low eGFR. However, some clinicians may choose to closely monitor (weekly) even when the eGFR is less than 8 to 10 mL/min/1.73 m2, with the initiation of dialysis upon the onset of uremic signs/symptoms. Asymptomatic patients with progressive CKD
Dialysis provided evidence for the validity of the intoxication : Visual Evidence: uremic frost disappeared Comatose patients were waking up Survival was increased What we see today is a different life-threatening condition that is known as the “residual uremic syndrome” The “Residual” Syndrome
A. Accumulation of: 1. large molecular weight solutes that are difficult to remove by dialysis 2. protein-bound small molecular weight solutes that are difficult to remove by dialysis 3. dialyzable solutes that are incompletely removed B. Indirect phenomena: 1. Accelerated protein “aging” 2. Inflammation 3. Tissue calcification 4. Toxic effect of hormone imbalance C. A toxic effect of the dialysis itself Possible Causes of the “Residual” Syndrome
Subtle signs of malnutrition Increased susceptibility to infection Increased susceptibility to cardiovascular complications Low-grade serositis Impaired vascular reactivity Hypothermia Reduced exercise capacity and O2 utilization Fatigue Subtle psychological disturbances such as loss of focus and ambition (or is it depression?) Sleep disturbances Restless Legs Clinical Manifestations of the “Residual” Syndrome
Uremia is the pathological manifestations of severe azotemia. All patients with renal disease should undergo an assessment of renal function Chronic kidney disease is defined based on the presence of either kidney damage or decreased kidney function for three or more months, irrespective of cause. No direct correlation exists between the absolute serum levels of (BUN) or creatinine and the development of uremic symptoms. Lower costs and/or decreased morbidity and mortality may be associated with early referral and care by nephrologists   Conclusion
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Uremia

  • 1.
    UREMIA DR SAMIR SALLY,MD COSULTANTNEPHROLOGY MANSOURA UROLOGY & NEPHROLOGY CENTRE, MANSOURA UNIVERSITY
  • 2.
    UREMIA Azotemia refers to highlevels of urea but is used primarily when the abnormality can be measured chemically but is not yet so severe as to produce symptoms. Uremia is the pathological manifestations of severe azotemia. There is no specific time for the onset of uremia for people with progressive loss of kidney function. Both uremia and the uremic syndrome have been used interchangeably to define a very high plasma urea concentration that is the result of renal failure
  • 3.
    INTRODUCTION All patients withrenal disease should undergo an assessment of renal function by estimating (GFR) from ser creatinine. This measurement is used clinically to evaluate the degree of renal impairment, to follow the course of the disease, and to assess the response to therapy. An attempt must also be made to obtain a specific diagnosis. careful urinalysis, kidney ultrasound, referral to a nephrologist, and a kidney biopsy.
  • 4.
    IDENTIFICATION OF RISKFACTORS AND STAGING OF CKD Risk factors: 1. hypertension, 2. diabetes mellitus, 3. autoimmune disease, 4. older age, 5. a family history of renal disease, 6. a previous episode of acute kidney injury, 7. Kidney donors and transplant recipients 8. and the presence of a. proteinuria, b. abnormal urinary sediment, or c. structural abnormalities of the urinary tract
  • 5.
    CALCULATION OF GFR Methodsof calculation Cockcroft-Gault formula MDRD formula/modified MDRD CKD-EPI when eGFR values above 60 ml/min/1.7 sq meter is desired This CKD-EPI equation calculator should be used when Scr  reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2  are desired This CKD-EPI equation calculator should be used when Scr  reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2  are desired This CKD-EPI equation calculator should be used when Scr  reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2  are desired This CKD-EPI equation calculator should be used when Scr  reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2  are desire
  • 6.
    THE COCKCROFT-GAULT CALCULATION GFRml/min/1.73m2 = (140-age) x Lean BW Kg 72 x S creatinine mg% ( x 0.85 for Females )
  • 7.
    84 F 22M 66 M 66 F • Wt (kg) 45.5 104.5 77.2 71.8 • Screat 1.2 1.2 1.2 1.2 • eGFR 26.9 142.7 66.1 52.3 (Calculated with Cockcroft-Gault)
  • 8.
    • MDRD GFRFormula* 170 x [SCr]-0.999 x [Age]-0.176 x [0.762 if female] x [1.180 if black] x [Alb]+0.318 • Modified MDRD Formula 186.338 x [SCr]-1.154 x [Age]-0.203 x [1.212 if black] x [0.742 if female] MDRD GFR *From Levey et al, 1999 Ann Intern Med 130: 461-470 (A calculator may be found at www.hdcn.org)
  • 9.
    RELATIONSHIP OF SERUMCREATININE TO GFR
  • 10.
    HOW THE KIDNEYRESPONDS TO INJURY? The kidney is able to adapt to damage by increasing the filtration rate in the remaining normal nephrons, a process called adaptive hyperfiltration. As a result, the patient with mild RI often has a normal or near- normal ser creatinine. Additional homeostatic mechanisms (most frequently occurring within the renal tubules) permit the serum concentrations of sodium, potassium, calcium, and phosphorous and the total body water to also remain within the normal range.
  • 11.
    PHYSIOLOGIC CHANGES INCHRONIC KIDNEY DISEASE Increased single nephron GFR Afferent arteriolar vasodilation Intraglomerular hypertension Loss of glomerular permselectivity Inabilty to appropriately dilute or concentrate the urine in the face of volume challenge
  • 12.
    PHYSIOLOGIC CHANGES INCHRONIC KIDNEY DISEASE Intraglomerular hypertension and glomerular hypertrophy leading to glomerular scarring (glomerulosclerosis). Additional causes may include systemic hypertension, hyperlipidemia, metabolic acidosis, and tubulointerstitial disease. Thus, proteinuria typically is present in patients with progressive CKD, even in primary tubulointerstitial diseases such as reflux nephropathy. Principal targets for renal protection —the blood pressure goal and, the proteinuria goal
  • 13.
    PHYSIOLOGIC CHANGES INCKD - ACE inhibitors or ARBs agents in patients with proteinuric CKD if begun before irreversible scarring - ARBs do not appear to be more beneficial than other antihypertensive agents in patients with nonproteinuric CKD. - When used in patients with CKD, common side effects of ARBs include a mild to moderate reduction in GFR and hyperkalemia, which occurs soon after the initiation of therapy or an increase in dose
  • 14.
    PATHOGENESIS OF SECONDARY GLOMERULOSCLEROSIS NephronMass Glomerular Volume and Glomerular Hypertension Epithelial Cell Density and Foot Process Fusion Glomerular Sclerosis and Hyalinosis Primary Insult Proteinuria
  • 15.
    LEFT: SCHEMA OFTHE NORMAL GLOMERULAR ARCHITECTURE. RIGHT: SECONDARY GLOMERULAR CHANGES
  • 16.
    PHYSIOLOGIC CHANGES INCKD The gradual decline in function in patients with (CKD) is initially asymptomatic. However, different signs and symptoms may be observed with advanced RF, including volume overload, hyperkalemia, metabolic acidosis, hypertension, anemia, and (MBDs). The onset of (ESRD) results in a constellation of signs and symptoms referred to as uremia.
  • 17.
    WHAT IS CKD? Chronickidney disease is defined based on the presence of either kidney damage or decreased kidney function for three or more months, irrespective of cause. • Criteria: Duration ≥3 months, based on documentation or inference Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
  • 18.
    CHRONIC KIDNEY DISEASE A)Pathologic abnormalities (examples). Cause is based on underlying illness and pathology. Markers of kidney damage may reflect pathology. 1.Glomerular diseases (diabetes, autoimmune diseases, systemic infections, drugs, neoplasia) 2.Vascular diseases (atherosclerosis, hypertension, ischemia, vasculitis, thrombotic microangiopathy) 3.Tubulointerstitial diseases (urinary tract infections, stones, obstruction, drug toxicity) 4.Cystic disease (polycystic kidney disease) Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
  • 19.
    CHRONIC KIDNEY DISEASE B)History of kidney transplantation. In addition to pathologic abnormalities observed in native kidneys, common pathologic abnormalities include the following: 1.Chronic allograft nephropathy (non-specific findings of tubular atrophy, interstitial fibrosis, vascular and glomerular sclerosis) 2.Rejection 3.Drug toxicity (calcineurin inhibitors) 4.BK virus nephropathy 5.Recurrent disease (glomerular disease, oxalosis, Fabry disease) Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
  • 20.
    CHRONIC KIDNEY DISEASE C)Albuminuria as a marker of kidney damage (increased glomerular permeability, urine albumin-to-creatinine ratio [ACR] >30 mg/g).* 1.The normal urine ACR in young adults is <10 mg/g. Urine ACR categories 10-29, 30-300 and >300 mg are termed "high normal, high, and very high" respectively. Urine ACR >2200 mg/g is accompanied by signs and symptoms of nephrotic syndrome 2.Threshold value corresponds approximately to urine dipstick values of trace or 1+ 3.High urine ACR can be confirmed by urine albumin excretion in a timed urine collection Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
  • 21.
    CHRONIC KIDNEY DISEASE D)Urinary sediment abnormalities as markers of kidney damage 1.RBC casts in proliferative glomerulonephritis 2.WBC casts in pyelonephritis or interstitial nephritis 3.Oval fat bodies or fatty casts in diseases with proteinuria 4.Granular casts and renal tubular epithelial cells in many parenchymal diseases (non-specific) Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
  • 22.
    CHRONIC KIDNEY DISEASE E)Imaging abnormalities as markers of kidney damage (ultrasound, computed tomography and magnetic resonance imaging with or without contrast, isotope scans, angiography). 1.Polycystic kidneys 2.Hydronephrosis due to obstruction 3.Cortical scarring due to infarcts, pyelonephritis or vesicoureteral reflux 4.Renal masses or enlarged kidneys due to infiltrative diseases 5.Renal artery stenosis 6.Small and echogenic kidneys (common in later stages of CKD due to many parenchymal diseases) Kidney damage, as defined by structural abnormalities or functional abnormalities other than decreased GFR
  • 24.
    ETIOLOGY OF CHRONICKIDNEY DISEASE Diabetes 43% HTN 25% GN 12% Other 20% Diabetes HTN GN Other
  • 25.
    CHRONIC KIDNEY DISEASE Nodirect correlation exists between the absolute serum levels of (BUN) or creatinine and the development of uremic symptoms. Some patients have relatively low levels (eg, a BUN of 60 mg/dL in an older patient) but are markedly symptomatic, while others have marked elevations (eg, a BUN of 140 mg/dL]) but remain asymptomatic.
  • 26.
    CHRONIC KIDNEY DISEASE Certaindrugs also interfere with either creatinine secretion or the assay used to measure the serum creatinine. These include cimetidine, trimethoprim, cefoxitin, and flucytosine. In these settings, There will be no change in the true GFR; Absence of a concurrent elevation in the (BUN)
  • 27.
    3 SPHERES OFDYSFUNCTION OF UREMIC SYNDROME
  • 28.
  • 29.
    CLINICAL ABNORMALITIES INUREMIA 1. Fluid and electrolyte disturbances 2. Endocrine-metabolic disturbances 3. Neuromuscular disturbances 4. Cardiovascular and pulmonary disturbances 5. Dermatologic disturbances 6. Gastrointestinal disturbances 7. Hematologic and immunologic disturbances (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy.
  • 30.
    CLINICAL ABNORMALITIES INUREMIA 1. Fluid and electrolyte disturbances a. Volume expansion (I) b. Hyponatremia (I) c. Hyperkalemia (I) d. Hyperphosphatemia (I) (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy.
  • 31.
    FLUID, ELECTROLYTE,AND ACID-BASEDISORDERS Hyponatremia – water restriction ECFV expansion – salt restriction Thiazides – limited utility in stages 3-5 CKD - loop diuretics needed Loop Diuretics resistance – Higher doses Metolazone – combined with loop diuretics, which inhibits the sodium chloride co-transporter of the distal convoluted tubule, can help effect renal salt excretion
  • 32.
    FLUID, ELECTROLYTE,AND ACID-BASEDISORDERS • HYPERKALEMIA • Precipitated by • increased dietary potassium intake, • protein catabolism, • hemolysis, • hemorrhage, • transfusion of stored red blood cells, • and metabolic acidosis • Medications .
  • 33.
    FLUID, ELECTROLYTE,AND ACID-BASEDISORDERS Hyperkalemia A common reason for initiation of RRT There is limited K excretion as GFR falls Diabetics may have a type IV RTA (hyporeninemic hypoaldosteronism) Use of ACE-I can exacerbate hyperkalemia
  • 34.
    FLUID, ELECTROLYTE,AND ACID-BASEDISORDERS Hyperkalemia - Potassium balance usually remains intact until GFR < 10-20 mL/min - Tx of acute hyperkalemia involves cardiac monitoring, IV calcium chloride or gluconate, insulin with glucose, bicarbonate, and potassium-binding resins - Chronic hyperkalemia tx’d with dietary k restriction, and Ca resonium PRN
  • 35.
    FLUID, ELECTROLYTE,AND ACID-BASEDISORDERS Hypokalemia: • Not common in CKD • reduced dietary potassium intake • GI losses • Diuretic therapy • Fanconi’s syndrome • RTA • Hereditary or acquired Tubulointerstitial disease
  • 36.
    FLUID, ELECTROLYTE,AND ACID-BASEDISORDERS Metabolic acidosis • common disturbance in advanced CKD • combination of hyperkalemia and hyperchloremic metabolic acidosis is often present, even at earlier stages of CKD (stages 1–3) • Treat hyperkalemia • the pH is rarely <7.35 • usually be corrected with oral sodium bicarbonate supplementation
  • 37.
    CLINICAL ABNORMALITIES INUREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 2. Endocrine-metabolic disturbances
  • 38.
    CLINICAL ABNORMALITIES INUREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 2. Endocrine-metabolic disturbances
  • 39.
    PTH Pi Ca2+ Renal Mass 25(OH)D31,25(OH)2D3 1-alpha-hydroxylase1-alpha-hydroxylase + Acidosis + Hyperparathyroid Related Bone Disease Impaired Absorption Osteitis Fibrosa Cystica
  • 40.
  • 41.
    DISORDERS OF CALCIUMAND PHOSPHATE METABOLISM Other complications of abnormal mineral metabolism: • Calciphylaxis (calcific uremic arteriolopathy) • Other etiologies • use of oral calcium as a phosphate binder • Warfarin
  • 42.
    CLINICAL ABNORMALITIES INUREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 2. Endocrine-metabolic disturbances
  • 43.
    CKD patients havea nutritional deficiency of 25-OH Vitamin D which itself leads to an increase in PTH secretion Levels of 25-OH D should be measured when PTH-Intact >70pg/ml Treatment <5ng/ml 50,000U Ergocalciferol/wk x12, then q mo x6 5-15ng/ml 50,000/wk x 4, then q mo x 6 16-30ng/ml 50,000/month x 6 Measure 25(OH)-D at 6 months Maintenance 800-1200 IU qd Calcium and Phosphorus Balance: Recommendations (KDOQI)
  • 44.
    DISORDERS OF CALCIUMAND PHOSPHATE METABOLISM The principal complications of abnormalities of calcium and phosphate metabolism in CKD 1. occur in the skeleton and 2. the vascular bed, 3. with occasional severe involvement of extraosseous soft tissues Bone manifestations of CKD, classified as: • associated with high bone turnover with increased PTH levels • low bone turnover with low or normal PTH levels
  • 45.
    DISORDERS OF CALCIUMAND PHOSPHATE METABOLISM The principal complications of abnormalities of calcium and phosphate metabolism in CKD 1. occur in the skeleton and 2. the vascular bed, 3. with occasional severe involvement of extraosseous soft tissues Bone manifestations of CKD, classified as: • associated with high bone turnover with increased PTH levels • low bone turnover with low or normal PTH levels
  • 46.
    COMPLICATIONS OF LONGTERMCALCIUM AND PHOSPHORUS IMBALANCE Tertiary hyperparathyroidism Renal osteodystrophy Demineralization Bone pain Fractures Systemic toxicity Cutaneous - Calciphylaxis Cardiovascular, accelerated vascular calcification
  • 47.
    How are thesegoals achieved ? Control of dietary phosphorus intake to 0.8-1g/d May need initiation of “Phosphate binders” with meals When 25(OH)-D < 30pg/ml and PTH-I > target, initiate treatment with exogenous “Active Vitamin D” A few patients with very elevated PTH-I values may benefit from Calcimimetics Calcium and Phosphorus Balance KDOQI Recommendations
  • 48.
    The use ofcalcium based binders is now falling out of favor because of the recognition of accelerated vascular calcification proposed to be associated with them. Although controversial, this is thought by some to be associated with the development of coronary atherosclerosis and is related to the presence and/or consequences of elevated serum phosphorus, calcium, and (PTH) Calcium and Phosphorus Balance
  • 49.
    Treatment of SecondaryHyperparathyroidism Calcimimetic agents • Rapid onset (hours) • Inhibit PTH secretion • Inhibit PTH synthesis • Inhibit parathyroid cellular proliferation • Decrease serum calcium Vitamin D Sterols • Act on genomic receptor • Slow onset (days to weeks) • Inhibit PTH synthesis • Increase serum calcium
  • 50.
    Phosphorus Ca2+ 1,25(OH)2D3 (Use Cautiously) New Paradigmin Treatment of Secondary Hyperparathyroidism Non-calcium Based Binders Cinacalcet PTH
  • 51.
    13C.1 Adynamic bonedisease in stage 5 CKD (as determined either by bone biopsy or intact PTH <100 pg/ml [11.0 pmol/L]) should be treated by allowing plasma levels of intact PTH to rise in order to increase bone turnover. (OPINION) 13C.1a This can be accomplished by decreasing doses of calcium-based phosphate binders and vitamin D or eliminating such therapy. (OPINION) Adynamic bone disease
  • 52.
    Indication Bio-Intact PTH >800 pg/mL refractory to medical therapy Severe hypercalcemia Progressive high turnover bone disease Complications May result in excessive low PTH levels Symptomatic hypocalcemia Risk for injury to recurrent laryngeal nerve Parathyroidectomy
  • 53.
    CLINICAL ABNORMALITIES INUREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 3. Neuromuscular disturbances
  • 54.
    CLINICAL ABNORMALITIES INUREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
  • 55.
    CLINICAL ABNORMALITIES INUREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
  • 56.
    CLINICAL ABNORMALITIES INUREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
  • 57.
    CLINICAL ABNORMALITIES INUREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
  • 58.
    CLINICAL ABNORMALITIES INUREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
  • 59.
    CLINICAL ABNORMALITIES INUREMIA (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 4. Cardiovascular and pulmonary disturbances
  • 60.
    CARDIOVASCULAR ABNORMALITIES Ischemic vasculardisease The CKD-related risk factors comprise 1. anemia, 2. hyperphosphatemia, 3. hyperparathyroidism, 4. sleep apnea, and 5. generalized inflammation Cardiac troponin levels are frequently elevated in CKD without evidence of acute ischemia.
  • 61.
    CLINICAL ABNORMALITIES INUREMIA 1.Pallor (I)b 2.Hyperpigmentation (I, P, or D) 3.Pruritus (P) 4.Ecchymoses (I) 5.Nephrogenic fibrosing dermopathy (D) 6.Uremic frost (I) (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 5. Dermatologic disturbances
  • 62.
    CLINICAL ABNORMALITIES INUREMIA 1.Anorexia (I) 2.Nausea and vomiting (I) 3.Gastroenteritis (I) 4.Peptic ulcer (I or P) 5.Gastrointestinal bleeding (I, P, or D) 6.Idiopathic ascites (D) 7.Peritonitis (D) (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 6. Gastrointestinal disturbances
  • 63.
    IDIOPATHIC ASCITES Ascites inESKD patients is predominantly of the low SAAG and high protein variety which is a manifestation of the combined effect of altered peritoneal membrane permeability, fluid overload and under-dialysis. The severity of ascites is affected by the presence of concomitant cardiac failure and hypoalbuminemia. Investigations to rule out tuberculosis, if the clinical and laboratory based suspicion is strongly in favour of this diagnosis.
  • 64.
  • 65.
    CLINICAL ABNORMALITIES INUREMIA 1.Anemia (I)b 2.Lymphocytopenia (P) 3.Bleeding diathesis (I or D)b 4.Increased susceptibility to infection 5.(I or P) 6.Leukopenia (D) 7.Thrombocytopenia (D) (I) improves with an optimal program of dialysis and related therapy; (P) persist or even progress, despite an optimal program; (D) develops only after initiation of dialysis therapy. 7. Hematologic and immunologic disturbances
  • 66.
    HEMATOLOGIC ABNORMALITIES Anemia A normocytic,normochromic anemia develops when the GFR decreases to < 30-35 ml/min : decreasing production of erythropoietin Reduced renal mass Uremic inhibition of bone marrow Decreased RBC life-span PTH induced marrow fibrosis Iron deficiency Folate or vitamin B12 deficiency Aluminum related bone disease
  • 67.
    The 2012 KDIGOguidelines, Patients who do not have anemia, Hgb should be checked when it is clinically indicated and at least yearly Patients with stage 3 CKD at least every six months Patients with stage 4 to 5 CKD, at least every three months Patients with stage 5D should be monitored monthly.
  • 68.
    Investigations Nonrenal causes ofanemia. Red blood cell indices, Absolute reticulocyte count, Serum iron, total iron-binding capacity, percent Transferrin saturation, serum ferritin, White blood cell count and differential, platelet count, B12 and folate if (MCV) is increased, Ocult blood in stool. This work-up should be performed prior to administering ESA therapy.
  • 69.
    HEMATOLOGIC ABNORMALITIES Abnormal hemostasis 1.prolonged bleeding time, 2. decreased activity of platelet factor III, 3. abnormal platelet aggregation and adhesiveness, 4. and impaired prothrombin consumption. Clinical manifestations include 1. an increased tendency to bleeding and bruising, 2. prolonged bleeding from surgical incisions, 3. menorrhagia, 4. and spontaneous GI bleeding
  • 70.
    Balancing the impactof decreased protein intake on the rate of progression of renal disease, against hypoalbuminemia and malnutrition Can we restrict protein intake sufficiently, without leading to malnutrition, especially important in patients with eGFR < 25 ml/min Nutrition
  • 71.
    common in patientswith advanced CKD because of a lower food intake (principally due to anorexia), decreased intestinal absorption and digestion, and metabolic acidosis Many additional studies have shown a strong correlation between malnutrition and death in maintenance dialysis patients. To best assess nutritional status, the serum albumin and BW should be measured serially; these should be measured approximately every one to three months and more frequently, if necessary Malnutrition
  • 72.
    Patients with CKDare at increased risk for infection The risk of bacterial infection (particularly pulmonary and genitourinary) increases with the decline in kidney function . Preventive measures such as influenza and pneumococcal immunization Infection and vaccination
  • 73.
    2012 KDIGO guidelines: ●Adults with all stages of CKD should be offered annual vaccination with influenza virus unless contraindicated. Adults with stage 4 and 5 CKD who are at high risk of progression of● CKD should be immunized against hepatitis B and the response confirmed by immunologic testing. Adults with CKD stages 4 and 5 should be vaccinated with polyvalent● pneumococcal vaccine unless contraindicated. Patients who have received pneumococcal vaccination should be offered revaccination within five years. US has recommended two forms of pneumococcal vaccine, including (PPSV23 [Pneumovax or Pnu-Immune]) and the (PCV13 [Prevnar for individuals aged ≥19 years with an immunocompromising condition, including CKD Vaccination
  • 74.
    The primary findingin CKD is hypertriglyceridemia, with the total cholesterol concentration usually being normal (perhaps due in part to malnutrition in some patients). 2013 KDIGO guidelines that recommend an initial evaluation with lipid profile, including total cholesterol, (LDL-C), (HDL-C), and triglycerides As per the KDIGO guidelines, follow-up evaluation of lipid profiles is generally not necessary for patients age ≥50 years since statin therapy is not titrated to the lipid profile. Dyslipidemia
  • 75.
    Follow-up testing maybe performed among patients who are age <50 years who are not already on a statin Follow-up evaluation may also be performed to assess adherence to statin treatment, if there is a change in the modality of renal replacement therapy, or if there is concern about new secondary causes of dyslipidemia. Dyslipidemia
  • 76.
  • 77.
    Patients with (CKD)should be referred to a nephrologist when (eGFR) is <30 mL/min/1.73 m2 in order to discuss and potentially plan for renal replacement therapy. There is less consensus about referral for patients with higher eGFRs. Lower costs and/or decreased morbidity and mortality may be associated with early referral and care by nephrologists REFERRAL TO NEPHROLOGISTS
  • 78.
     Poorly controlledHTNPoorly controlled HTN  Diabetes mellitus with atypical renal manifestationsDiabetes mellitus with atypical renal manifestations  Proteinuria or nephrotic syndrome without retinopathyProteinuria or nephrotic syndrome without retinopathy  Renal insufficiency without proteinuria or retinopathyRenal insufficiency without proteinuria or retinopathy  Sudden onset of nephrotic syndrome or rapidly changing serumSudden onset of nephrotic syndrome or rapidly changing serum creatininecreatinine  Systemic disease associated with renal involvementSystemic disease associated with renal involvement  Heavy proteinuriaHeavy proteinuria  Urine-sediment abnormalitiesUrine-sediment abnormalities  PriorPrior to onset of uremic symptomsto onset of uremic symptoms REFERRAL TO NEPHROLOGISTS
  • 79.
    In most studies,referral to the nephrologist is considered late if it is within one to six months of the requirement for renal replacement therapy . 25 to 50 percent of patients beginning chronic renal replacement therapy in US required dialysis within one month of their first nephrology visit , 22 to 49 percent of patients were first seen by a nephrologist less than four months prior to the initiation of dialysis REFERRAL TO NEPHROLOGISTS
  • 80.
    One retrospective studyhas suggested that a multidisciplinary approach may improve survival . The 2012 (KDIGO) CKD guidelines suggest management of CKD patients in a multidisciplinary setting, with access to dietary counseling, renal replacement therapies, transplant options, vascular access surgery, and ethical, psychological and social care . REFERRAL TO NEPHROLOGISTS
  • 81.
    ●Pericarditis or pleuritis(urgent indication). Progressive uremic encephalopathy or neuropathy, (urgent indication).● A clinically significant bleeding diathesis attributable to uremia (urgent● indication). Fluid overload refractory to diuretics.● ●Hypertension poorly responsive to antihypertensive medications. Persistent metabolic disturbances that are refractory to medical● therapy. ●Persistent nausea and vomiting. Evidence of malnutrition.● Indications for renal replacement therapy
  • 82.
    The timing ofinitiation of dialysis is unclear To help avoid the onset of possible life-threatening complications of uremia, the initiation of dialysis should be considered in the asymptomatic patient with an extremely low eGFR. However, some clinicians may choose to closely monitor (weekly) even when the eGFR is less than 8 to 10 mL/min/1.73 m2, with the initiation of dialysis upon the onset of uremic signs/symptoms. Asymptomatic patients with progressive CKD
  • 83.
    Dialysis provided evidencefor the validity of the intoxication : Visual Evidence: uremic frost disappeared Comatose patients were waking up Survival was increased What we see today is a different life-threatening condition that is known as the “residual uremic syndrome” The “Residual” Syndrome
  • 84.
    A. Accumulation of: 1.large molecular weight solutes that are difficult to remove by dialysis 2. protein-bound small molecular weight solutes that are difficult to remove by dialysis 3. dialyzable solutes that are incompletely removed B. Indirect phenomena: 1. Accelerated protein “aging” 2. Inflammation 3. Tissue calcification 4. Toxic effect of hormone imbalance C. A toxic effect of the dialysis itself Possible Causes of the “Residual” Syndrome
  • 85.
    Subtle signs ofmalnutrition Increased susceptibility to infection Increased susceptibility to cardiovascular complications Low-grade serositis Impaired vascular reactivity Hypothermia Reduced exercise capacity and O2 utilization Fatigue Subtle psychological disturbances such as loss of focus and ambition (or is it depression?) Sleep disturbances Restless Legs Clinical Manifestations of the “Residual” Syndrome
  • 86.
    Uremia is thepathological manifestations of severe azotemia. All patients with renal disease should undergo an assessment of renal function Chronic kidney disease is defined based on the presence of either kidney damage or decreased kidney function for three or more months, irrespective of cause. No direct correlation exists between the absolute serum levels of (BUN) or creatinine and the development of uremic symptoms. Lower costs and/or decreased morbidity and mortality may be associated with early referral and care by nephrologists   Conclusion
  • 88.

Editor's Notes

  • #3 People with [GFR] between 50 and 60 mL and 30 years of age may have uremia to a degree. This means an estimated 8 million people in the United States with a GFR of less than 60 mL have uremic symptoms. The symptoms, such as fatigue, can be very vague, making the diagnosis of impaired renal function difficult. It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR. Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
  • #4 It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR. Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
  • #5 It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR. Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
  • #6 GFR can be assessed by the renal clearance of a substance Clearance of substance X (Cx) = UxVx/Sx Recall GFR * Sx = UxVx (amount filtered = amount excreted) Cx = UxV/Sx Cx = GFR Two important assumptions: Marker neither secreted or absorbed Steady state Examples of markers: inulin, iothalamate, iohexol, serum creatinine, cystatin-C
  • #7 It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR. Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
  • #11 It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR. Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
  • #12 Glomerular hypertrophy Focal segmental glomerulosclerosis with hyalinosis Interstitial fibrosis Vascular sclerosis Epithelial foot process fusion
  • #13 Glomerular hypertrophy Focal segmental glomerulosclerosis with hyalinosis Interstitial fibrosis Vascular sclerosis Epithelial foot process fusion
  • #14 It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR. Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
  • #16 Figure 280-1 Left: Schema of the normal glomerular architecture. Right: Secondary glomerular changes associated with a reduction in nephron number, including enlargement of capillary lumens and focal adhesions, which are thought to occur consequent to compensatory hyperfiltration and hypertrophy in the remaining nephrons.
  • #17 It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR. Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
  • #18 The persistence of the damage or decreased function for at least three months is necessary to distinguish CKD from acute kidney disease. Kidney damage refers to pathologic abnormalities, whether established via renal biopsy or imaging studies, or inferred from markers such as urinary sediment abnormalities or increased rates of urinary albumin excretion. Decreased kidney function refers to a decreased glomerular filtration rate (GFR), which is usually estimated (eGFR) using serum creatinine and one of several available equations.
  • #19 Pathologic abnormalities (examples). Cause is based on underlying illness and pathology. Markers of kidney damage may reflect pathology. Glomerular diseases (diabetes, autoimmune diseases, systemic infections, drugs, neoplasia) Vascular diseases (atherosclerosis, hypertension, ischemia, vasculitis, thrombotic microangiopathy) Tubulointerstitial diseases (urinary tract infections, stones, obstruction, drug toxicity) Cystic disease (polycystic kidney disease)
  • #20 B) History of kidney transplantation. In addition to pathologic abnormalities observed in native kidneys, common pathologic abnormalities include the following: Chronic allograft nephropathy (non-specific findings of tubular atrophy, interstitial fibrosis, vascular and glomerular sclerosis) Rejection Drug toxicity (calcineurin inhibitors) BK virus nephropathy Recurrent disease (glomerular disease, oxalosis, Fabry disease)
  • #21 C) Albuminuria as a marker of kidney damage (increased glomerular permeability, urine albumin-to-creatinine ratio [ACR] &amp;gt;30 mg/g).* The normal urine ACR in young adults is &amp;lt;10 mg/g. Urine ACR categories 10-29, 30-300 and &amp;gt;300 mg are termed &amp;quot;high normal, high, and very high&amp;quot; respectively. Urine ACR &amp;gt;2200 mg/g is accompanied by signs and symptoms of nephrotic syndrome (low serum albumin, edema and high serum cholesterol). Threshold value corresponds approximately to urine dipstick values of trace or 1+, depending on urine concentration High urine ACR can be confirmed by urine albumin excretion in a timed urine collection
  • #22 D) Urinary sediment abnormalities as markers of kidney damage RBC casts in proliferative glomerulonephritis WBC casts in pyelonephritis or interstitial nephritis Oval fat bodies or fatty casts in diseases with proteinuria Granular casts and renal tubular epithelial cells in many parenchymal diseases (non-specific)
  • #23 E) Imaging abnormalities as markers of kidney damage (ultrasound, computed tomography and magnetic resonance imaging with or without contrast, isotope scans, angiography). Polycystic kidneys Hydronephrosis due to obstruction Cortical scarring due to infarcts, pyelonephritis or vesicoureteral reflux Renal masses or enlarged kidneys due to infiltrative diseases Renal artery stenosis Small and echogenic kidneys (common in later stages of CKD due to many parenchymal diseases)
  • #24 GFR and albuminuria grid to reflect the risk of progression by intensity of coloring (green, yellow, orange, red, deep red). The numbers in the boxes are a guide to the frequency of monitoring (number of times per year). Reprinted by permission from: Macmillan Publishers Ltd: Kidney International. KDIGO. Summary of recommendation statements. Kidney Int 2013; 3(Suppl):5. Copyright © 2013.http://www.nature.com/ki/index.html. Graphic 59716 Version 6.0
  • #28 In summary, the pathophysiology of the uremic syndrome can be divided into manifestations in three spheres of dysfunction: (1) those consequent to the accumulation of toxins that normally undergo renal excretion, including products of protein metabolism; (2) those consequent to the loss of other renal functions, such as fluid and electrolyte homeostasis and hormone regulation; and (3) progressive systemic inflammation and its vascular and nutritional consequences.
  • #30 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A.
  • #31 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A.
  • #32 Hyponatremia is not commonly seen in CKD patients but, when present, can respond to water restriction. If the patient has evidence of ECFV expansion (peripheral edema, sometimes hypertension poorly responsive to therapy), he or she should be counseled regarding salt restriction. Thiazide diuretics have limited utility in stages 3–5 CKD, such that administration of loop diuretics, including furosemide, bumetanide, or torsemide, may also be needed. Resistance to loop diuretics in renal failure often mandates use of higher doses than those used in patients with near-normal kidney function. The combination of loop diuretics with metolazone, which inhibits the sodium chloride co-transporter of the distal convoluted tubule, can help effect renal salt excretion. Ongoing diuretic resistance with intractable edema and hypertension in advanced CKD may serve as an indication to initiate dialysis.
  • #33 These include increased dietary potassium intake, protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells, and metabolic acidosis. In addition, a host of medications can inhibit renal potassium excretion. The most important medications in this respect include the angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and spironolactone and other potassium-sparing diuretics such as amiloride, eplerenone, and triamterene. Nonselective beta blockers may result in a postprandial rise in the serum potassium but do not cause persistent hyperkalemia. These include increased dietary potassium intake, protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells, and metabolic acidosis. In addition, a host of medications can inhibit renal potassium excretion. The most important medications in this respect include the angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and spironolactone and other potassium-sparing diuretics such as amiloride, eplerenone, and triamterene.
  • #34 These include increased dietary potassium intake, protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells, and metabolic acidosis. In addition, a host of medications can inhibit renal potassium excretion. The most important medications in this respect include the angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and spironolactone and other potassium-sparing diuretics such as amiloride, eplerenone, and triamterene.
  • #35 These include increased dietary potassium intake, protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells, and metabolic acidosis. In addition, a host of medications can inhibit renal potassium excretion. The most important medications in this respect include the angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and spironolactone and other potassium-sparing diuretics such as amiloride, eplerenone, and triamterene.
  • #36 Hypokalemia is not common in CKD and usually reflects markedly reduced dietary potassium intake, especially in association with excessive diuretic therapy or concurrent GI losses. Hypokalemia can also occur as a result of primary renal potassium wasting in association with other solute transport abnormalities, such as Fanconi’s syndrome, renal tubular acidosis, or other forms of hereditary or acquired tubulointerstitial disease. However, even with these conditions, as the GFR declines, the tendency to hypokalemia diminishes and hyperkalemia may supervene. Therefore, the use of potassium supplements and potassium-sparing diuretics should be constantly reevaluated as GFR declines. Fanconi syndrome (also known as Fanconi&amp;apos;s syndrome) is a disease of the proximal renal tubules[1] of the kidney in which glucose, amino acids, uric acid, phosphateand bicarbonate are passed into the urine, instead of being reabsorbed. Fanconi syndrome affects the proximal tubule, which is the first part of the tubule to process fluid after it is filtered through the glomerulus. It may be inherited, or caused by drugs or heavy metals.
  • #37 Hyperkalemia, if present, further depresses ammonia production. The combination of hyperkalemia and hyperchloremic metabolic acidosis is often present, even at earlier stages of CKD (stages 1–3), in patients with diabetic nephropathy or in those with predominant tubulointerstitial disease or obstructive uropathy; this is a non-anion-gap metabolic acidosis. Treatment of hyperkalemia may increase renal ammonia production, improve renal generation of bicarbonate, and improve the metabolic acidosis. Alkali supplementation may attenuate the catabolic state and possibly slow CKD progression and accordingly is recommended when the serum bicarbonate concentration falls below 20–23 mmol/L. The concomitant sodium load mandates careful attention to volume status and the potential need for diuretic agents.
  • #39 Water restriction is indicated only if there is a problem with hyponatremia. Otherwise, patients with CKD and an intact thirst mechanism may be instructed to drink fluids in a quantity that keeps them just ahead of their thirst. Hyperkalemia often responds to dietary restriction of potassium, avoidance of potassium supplements (including occult sources, such as dietary salt substitutes) as well as potassium-retaining medications (especially ACE inhibitors or ARBs), or the use of kaliuretic diuretics. Kaliuretic diuretics promote urinary potassium excretion, while potassium-binding resins, such as calcium resonium or sodium polystyrene, can promote potassium loss through the GI tract and may reduce the incidence of hyperkalemia in CKD patients. Intractable hyperkalemia is an indication (although uncommon) to consider institution of dialysis in a CKD patient.
  • #40 In most patients with stable CKD, the total-body content of sodium and water is modestly increased, although this may not be apparent on clinical examination. Normal renal function guarantees that the tubular reabsorption of filtered sodium and water is adjusted so that urinary excretion matches intake. Many forms of renal disease (e.g., glomerulonephritis) disrupt this glomerulotubular balance such that dietary intake of sodium exceeds its urinary excretion, leading to sodium retention and attendant extracellular fluid volume (ECFV) expansion. This expansion may contribute to hypertension, which itself can accelerate the nephron injury. As long as water intake does not exceed the capacity for water clearance, the ECFV expansion will be isotonic and the patient will have a normal plasma sodium concentration and effective osmolality
  • #41 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A. renal osteodystrophy CKD-MBD, thus defined, is characterized by the following: ●Abnormalities of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D metabolism ●Abnormalities in bone turnover, mineralization, volume linear growth, or strength ●Vascular or other soft-tissue calcification Sexual dysfunction — Significant abnormalities in sexual and reproductive function are frequently observed in patients with advanced renal disease. As an example, &amp;gt;50 percent of uremic men complain of symptoms that include erectile dysfunction, decreased libido, and marked declines in the frequency of intercourse ; in addition, disturbances in menstruation and fertility are commonly encountered in women with CKD, usually leading to amenorrhea by the time the patient reaches ESRD. An important clinical implication of these abnormalities is that pregnancy that is carried to term is uncommon in women with a plasma creatinine concentration of ≥3 mg/dL (265 micromol/L)
  • #42 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A. renal osteodystrophy CKD-MBD, thus defined, is characterized by the following: ●Abnormalities of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D metabolism ●Abnormalities in bone turnover, mineralization, volume linear growth, or strength ●Vascular or other soft-tissue calcification
  • #45 Calciphylaxis (calcific uremic arteriolopathy) is a devastating condition seen almost exclusively in patients with advanced CKD. It is heralded by livedo reticularis and advances to patches of ischemic necrosis, especially on the legs, thighs, abdomen, and breasts However, more recently, calciphylaxis has been seen with increasing frequency in the absence of severe hyperparathyroidism. one of the effects of warfarin therapy is to decrease the vitamin K–dependent regeneration of matrix GLA protein. This latter protein is important in preventing vascular calcification. Thus, warfarin treatment is considered a risk factor for calciphylaxis, and if a patient develops this syndrome, this medication should be discontinued and replaced with alternative forms of anticoagulation.
  • #46 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A. renal osteodystrophy CKD-MBD, thus defined, is characterized by the following: ●Abnormalities of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D metabolism ●Abnormalities in bone turnover, mineralization, volume linear growth, or strength ●Vascular or other soft-tissue calcification
  • #47 .
  • #48 The principal complications of abnormalities of calcium and phosphate metabolism in CKD occur in the skeleton and the vascular bed, with occasional severe involvement of extraosseous soft tissues. The major disorders of bone disease can be classified into those associated with high bone turnover with increased PTH levels (including osteitis fibrosa cystica, the classic lesion of secondary hyperparathyroidism) and low bone turnover with low or normal PTH levels (adynamic bone disease and osteomalacia).
  • #49 The principal complications of abnormalities of calcium and phosphate metabolism in CKD occur in the skeleton and the vascular bed, with occasional severe involvement of extraosseous soft tissues. The major disorders of bone disease can be classified into those associated with high bone turnover with increased PTH levels (including osteitis fibrosa cystica, the classic lesion of secondary hyperparathyroidism) and low bone turnover with low or normal PTH levels (adynamic bone disease and osteomalacia).
  • #50 Recent epidemiologic evidence has shown a strong association between hyperphosphatemia and increased cardiovascular mortality rate in patients with stage 5 CKD and even in patients with earlier stages of CKD. The magnitude of the calcification is proportional to age and hyperphosphatemia and is also associated with low PTH levels and low bone turnover. It is possible that in patients with advanced kidney disease, ingested calcium cannot be deposited in bones with low turnover and, therefore, is deposited at extraosseous sites, such as the vascular bed and soft tissues. It is interesting in this regard that there is also an association between osteoporosis and vascular calcification in the general population. Finally, there is recent evidence indicating that hyperphosphatemia can induce a change in gene expression in vascular cells to an osteoblast-like profile, leading to vascular calcification and even ossification.
  • #57 The dialysis disequilibrium syndrome (DDS) is an increasingly rare syndrome characterized by neurologic symptoms of varying severity that affect dialysis patients, particularly when they are first started on hemodialysis [1,2]. It is thought to be due primarily to cerebral edema. Risk factors for DDS include the following [2-6]: ●First dialysis treatment ●Markedly elevated blood urea concentration predialysis (ie, &amp;gt;175 mg/dL or 60 mmol/L) ●Chronic kidney disease (CKD, as compared with acute kidney injury [AKI]) ●Severe metabolic acidosis ●Older age ●Pediatric patients ●Pre-existing neurologic disease (head trauma, stroke, seizure disorder) ●Other conditions characterized by cerebral edema (hyponatremia, hepatic encephalopathy, malignant hypertension) ●Any condition that increases permeability of the blood brain barrier (such as sepsis, vasculitis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome [TTP/HUS], encephalitis, or meningitis) Reverse osmotic shift — Hemodialysis rapidly removes small solutes such as urea, particularly in patients who have marked azotemia. The reduction in blood urea nitrogen (BUN) lowers the plasma osmolality, thereby creating a transient osmotic gradient that promotes water movement into the cells. In the brain, this water shift produces cerebral edema and a variable degree of acute neurologic dysfunction. The pathogenetic importance of urea in DDS has been demonstrated by experiments in uremic rats [10-12]. In one report, for example, rapid dialysis lowered the BUN from 200 to 95 mg/dL (72 to 34 mmol/L) in 90 minutes [10]. This change was associated with a 6 percent increase in brain water. Neither undialyzed rats nor those rats dialyzed against a bath to which urea was added to prevent a fall in BUN developed cerebral edema. Furthermore, the retention of brain urea appears to account for most of the increase in brain water [11]. Urea is generally considered an &amp;quot;ineffective&amp;quot; osmole because of its ability to permeate cell membranes. However, this effect may take several hours to reach completion. Thus, there is insufficient time for urea equilibration when hemodialysis rapidly reduces the BUN; as a result, urea transiently acts as an effective osmole, promoting water movement into the brain. In the above experiments, for example, the 53 percent acute reduction in BUN was only associated with a 13 percent reduction in brain urea nitrogen [10]. In addition, animal studies have suggested that there may be a decrease in urea transporters and an increase in water channels in uremia, which would increase the reflection coefficient (or ability to elicit an osmotic force) of urea [13]. Intracerebral acidosis and idiogenic osmoles — Some investigators have suggested that the reverse osmotic shift cannot account for the development of cerebral edema in DDS, since urea movement out of the brain is sufficiently rapid to prevent a large osmotic gradient between the brain and extracellular fluid [2]. They have proposed that a decrease in cerebral intracellular pH, occurring via an uncertain mechanism, is of primary importance [2,12]. Both displacement of bound sodium and potassium by the excess hydrogen ions and enhanced production of organic acids can increase intracellular osmolality and promote water movement into the brain [14]. PREVENTION — Measures to prevent DDS should be used among patients at high risk, particularly including new dialysis patients, patients who have extremely high blood urea nitrogen (BUN) concentrations, or patients who have other active neurologic conditions at the time of dialysis. The most important preventive measure is to limit the reduction in BUN per treatment so that there is a gradual reduction that is distributed over several days. Slow urea removal can be achieved by one of the following methods: ●With hemodialysis, therapy can be initiated with two hours of dialysis at a relatively low blood flow rate of 150 to 250 mL/min with a small surface area dialyzer (0.9 to 1.2 m2). ●The patient should have a repeat dialysis session daily for three to four days, with modifications in the prescription depending upon clinical response. If the patient shows no signs of DDS, the blood flow rate can be increased by 50 mL/min per treatment (up to 300 to 400 mL/min), and the duration of dialysis can be increased in 30-minute increments (up to four or more hours, as necessary for adequate solute removal). ●Patients who also have marked fluid overload can be treated with ultrafiltration (which removes less urea per unit time and does not change plasma osmolarity), followed by a short period of hemodialysis [15]. (See &amp;quot;Renal replacement therapy (dialysis) in acute kidney injury (acute renal failure): Metabolic and hemodynamic considerations&amp;quot;.) ●Among patients with extremely elevated BUN or neurologic symptoms, dialysis should be initiated as an inpatient, although there are no data that have demonstrated better outcomes with this approach
  • #58 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A.
  • #59 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A.
  • #60 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A.
  • #61 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A.
  • #62 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A.
  • #63 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A.
  • #64 The CKD-related risk factors comprise anemia, hyperphosphatemia, hyperparathyroidism, sleep apnea, and generalized inflammation.
  • #65 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A.
  • #66 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A.
  • #69 Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation. The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable. (I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy; (P) denotes an abnormality that tends to persist or even progress, despite an optimal program; (D) denotes an abnormality that develops only after initiation of dialysis therapy. bImproves with dialysis and erythropoietin therapy. Abbreviation: Lp(a), lipoprotein A.
  • #70 A normocytic, normochromic anemia is observed as early as stage 3 CKD and is almost universal by stage 4. The primary cause in patients with CKD is insufficient production of erythropoietin (EPO) by the diseased kidneys.
  • #71 A normocytic, normochromic anemia is observed as early as stage 3 CKD and is almost universal by stage 4. The primary cause in patients with CKD is insufficient production of erythropoietin (EPO) by the diseased kidneys.
  • #72 A normocytic, normochromic anemia is observed as early as stage 3 CKD and is almost universal by stage 4. The primary cause in patients with CKD is insufficient production of erythropoietin (EPO) by the diseased kidneys. Goal Hgb 11-12 Recombinant erythropoeitin Epogen/Procrit 50-150 U/kg/wk SQ Darbopoetin alfa (ARANESP) Start 0.45mcg/kg SQ once every 2 weeks, usually dosed every three to four weeks when patient is stable in the therapeutic range Recent concerns re increased risk of cardiovascular events associated with an elevated Hgb in association with use of high doses of these products Iron Goal Ferritin &amp;gt;200, TSAT &amp;gt;20% Oral agents Chromagen: 33% iron Ferrous sulfate: 20% iron Niferex (Polysaccharide with Vit C): 150mg elemental iron Ferrous fumurate: 33% iron Ferrous gluconate (Fergon): 12% iron Oral agents do not work well, primarily b/o ill tolerated GI side effects
  • #73 A normocytic, normochromic anemia is observed as early as stage 3 CKD and is almost universal by stage 4. The primary cause in patients with CKD is insufficient production of erythropoietin (EPO) by the diseased kidneys. A number of different modalities can be used in this setting, including the correction of anemia, the administration of desmopressin (dDAVP), cryoprecipitate, estrogen, and the initiation of dialysis.
  • #74 Abnormal bleeding time and coagulopathy in patients with renal failure may be reversed temporarily with desmopressin (DDAVP), cryoprecipitate, IV conjugated estrogens, blood transfusions, and EPO therapy. Optimal dialysis will usually correct a prolonged bleeding time.
  • #75 A normocytic, normochromic anemia is observed as early as stage 3 CKD and is almost universal by stage 4. The primary cause in patients with CKD is insufficient production of erythropoietin (EPO) by the diseased kidneys.
  • #83 Limited data suggest that lipid lowering may have an additional benefit in patients with CKD, which is slowing the rate of progression of the underlying renal disease.
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  • #86 . Similar patterns relating to late referral have been reported from other parts of the world [69-71]. The proportion of dialysis patients who required dialysis within one month of the first visit to a nephrologist ranged from 25 percent in Paris, France [69] to 58 percent in Sao Paulo, Brazil [70]. The prevalence of late referral can also have significant regional variation within a country; in the larger cities of Australia, the proportion of patients referred within three months of needing to start dialysis ranged from 14 to 44 percent [72]. Causes of late referral — Late referral to the nephrologist can be due to unavoidable causes, the referral biases of physicians, patient factors, socioeconomic status of the patient, and/or the structure of the healthcare system(s) within a certain country . Unavoidable causes — Unavoidable causes of late referral include end-stage renal disease (ESRD) that follows acute kidney injury (AKI), &amp;quot;asymptomatic&amp;quot; kidney failure only presenting at an advanced stage, or a patient&amp;apos;s refusal to seek help until symptoms occur. The majority of patients referred to the nephrologist in a timely manner tend to have a functioning permanent access at the start of dialysis compared with only a small minority of late referrals The late referral of patients has therefore resulted in a large number of dialysis patients without permanent vascular access at the time of initiation of dialysis
  • #87 . Multidisciplinary chronic kidney disease clinic — The optimal medical care of CKD patients may be best provided by a team of healthcare professionals who practice at a single site (ie, a CKD clinic), following the principles of the chronic disease model of care [100]. Such CKD clinics focus on guideline-driven nephrology care, management of comorbidities, lifestyle modification, and patient education in order to optimize patient outcomes. Observational and nonrandomized prospective studies have suggested that, compared with standard nephrology care, patients who attend a multidisciplinary CKD clinic have fewer hospitalizations, are more likely to have an arterial-venous fistula rather than graft or catheter, are more likely to start dialysis as an outpatient, and are more likely to adhere to established CKD anemia or mineral and bone disease (MBD) goals
  • #88 . Multidisciplinary chronic kidney disease clinic — The optimal medical care of CKD patients may be best provided by a team of healthcare professionals who practice at a single site (ie, a CKD clinic), following the principles of the chronic disease model of care [100]. Such CKD clinics focus on guideline-driven nephrology care, management of comorbidities, lifestyle modification, and patient education in order to optimize patient outcomes. Observational and nonrandomized prospective studies have suggested that, compared with standard nephrology care, patients who attend a multidisciplinary CKD clinic have fewer hospitalizations, are more likely to have an arterial-venous fistula rather than graft or catheter, are more likely to start dialysis as an outpatient, and are more likely to adhere to established CKD anemia or mineral and bone disease (MBD) goals
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