Chronic Kidney Disease Internal Medicine August 2011
Definition Structural or functional abnormalities of the kidneys for ≥3months, as manifested by either: 1. Kidney damage, with or without decreased GFR, as defined by pathologic abnormalities markers of kidney damage, including abnormalities in the composition of the blood or urine or abnormalities in imaging tests Kidney transplantation 2. GFR <60 ml/min/1.73 m2, with or without kidney damage
Definition Kidney Failure is defined as either (1) a level of GFR to <15 mL/min/1.73 m2, which is accompanied in most cases by uremia, or (2) a need for initiation of kidney replacement therapy (dialysis or transplantation) for complications of decreased GFR. End-Stage Renal Disease (ESRD) administrative term for disbursement by Medicare, specifically the level of GFR (creatinine of 8mg/dl) and occurrence of kidney failure symptoms necessitating replacement therapy. ESRD includes patients treated by dialysis or transplantation.
Causes and Incidence Chronic renal failure occurs in approximately 1 out of 1,000 people. Causative diseases include any type: 1. Diabetes mellitus - most common cause 2. Hypertension 3. Glomerulonephritis 4. Others chronic pyelonephritis, PKD /polycystic kidney disease, obstructive uropathy (stones, BPH, cancer, etc), Alport syndrome, and drug-induced nephropathy
Estimation of GFR Cockcroft- Gault Formula ( 140 – age ) x Weight in Kg CrCl (ml/min)= x ( 0.85 if female ) 72 x Serum Creat (mg/dl) MDRD Study Equation GFR (mil/min/1.73 m2) = 186 x (SCr) -1.154 x (age) -.203 x (0.724 if female) x (1.210 if African American)
Stages of Chronic Kidney Disease
Symptoms INITIAL (non-specific) LATER unintentional weight increase or decrease urine loss output need to urinate at night nausea, vomiting anasarca general ill feeling easy bruising or bleeding fatigue blood in the vomit or stools headache breath odor (uremic fetor) frequent hiccups muscle twitching or cramps generalized itching restless legs syndrome (pruritus) increased skin pigmentation uremic frost decreased sensation decreased alertness/ lethargy
Uremic Syndrome attributed to a variety of toxic substances, mainly nitrogenous (protein and amino acid byproducts urea (when >50 mmol/l) and cyanate (CNO-) guanidino compounds (eg guanidinosuccinic acid) middle molecules (mw 300-3,500) - mainly polypeptides urates and other metabolites of nucleic acids aliphatic amines and metabolites of aromatic amino acids hormones (eg PTH) advanced glycation end-products other factors already considered – bone disease, acidosis, and fluid and electrolyte disturbances – also contribute to the picture of full-blown uremia.
Signs and Tests Blood pressure may be high Urinalysis may show protein, blood, pus or other abnormalities Creatinine and BUN levels progressively increase Creatinine clearance progressively decreases Potassium elevated Calcium low and Phosphorus high Arterial blood gas show metabolic acidosis Xray of bones may show osteodystrophy
Signs and Tests Changes that indicate chronic renal failure, including both kidneys being smaller than normal, may be seen on: abdominal ultrasound plain KUB X-ray abdominal CT scan or MRI However, CKD with normal sized or enlarged kidneys: amyloidosis, diabetes multiple myeloma polycystic kidneys accelerated hypertension
Determinants of Rate of Progression Type of Renal Disease rate of decline in PCKD and interstitial nephritis slower than in CGN membranous Nephropathy may spontaneously remit with or without treatment Hypertension Proteinuria Race – blacks fare worse Sex – women with PCKD fare better Pregnancy – GFR falls faster Diabetics – high sugar accelerates Smokers
Importance of Proteinuria Interpretation Explanation Spot urine albumin-to-creatinine ratio >30 mg/g or Marker of kidney spot urine total protein-to-creatinine ratio >200 mg/g damage for >3 months defines CKD Spot urine total protein-to-creatinine ratio >500-1000 Clue to the type mg/g suggests diabetic kidney disease, glomerular (diagnosis) of CKD diseases, or transplant glomerulopathy. Risk factor for adverse Higher proteinuria predicts faster progression of outcomes kidney disease and increased risk of CVD. Strict blood pressure control and ACE inhibitors are Effect modifier for more effective in slowing kidney disease interventions progression in patients with higher baseline proteinuria. Hypothesized surrogate If validated, then lowering proteinuria would be a outcomes and target for goal of therapy. interventions
Dietary Requirements1. Protein 0.6-0.8 gm/k/day supplements of essential amino acids at 0.3 gm/k/day may allow lower protein intake to 0.4 gm/k/day intake for uremic patient not yet dialysed: 0.4 - 0.6gm/k/day for dialysed patients: increase to 1.0 - 1.2 gm/k/day2. Energy 35 kcal/k/day for sedentary, stable, non-obese HD patients higher with strenuous labor, underweight or hypercatabolic
Dietary Requirements3. Fat limit cholesterol <300 mg/day more proportion of mono- or polyunsaturated than saturated4. Na+ 7-10 gm/day (table salt) if with adequate urine <6 gm/day or <100 mmol/day if with fluid retention/edema5. K+ HD: restrict to 2-3 gm/day (50-75 meq/day) PD: 3-4 gm/day or 75-100 meq/day
Dietary Requirements6. Ca++ restrict milk products so supplemental Ca++ is needed (1-1.5 gm/day) + Vitamin D to keep serum Ca++ >2.5 mg/dl7. Phosphorus restrict to 0.6 - 1.2 gm/day to maintain s.Phos <4.5 to 5.5 mg/dl phosphate binders as needed such as calcium carbonate and calcium acetate8. Vitamins/ Minerals ascorbic acid < 150-200 mg maximum to avoid oxalosis folic acid 1000 mcg; vit.B1 30 or > mg/day; B6 20 or more mg/day; Other water soluble vitamins based on RDA provide selenium and zinc vitamin A preparations must be avoided
Management withProgressive Renal Disease1. early recognition2. monitoring the progression3. detection and correction of reversible causes4. institution of interventions to delay progression, eg diet, ACEinhibitors, BP, and sugar control5. avoidance of additional renal injury, eg smoking, NSAIDs, radiocontrast, aminoglycosides6. treatment of complications, eg acid- base, mineral, and fluid-electrolyte abnormalities7. planning ahead for renal replacement therapy (dialysis or transplantation)
Prevention to ESRD ACEI/ ARBs established renoprotection with proteinuria reduction higher doses recommended Blood Pressure BP target of <130/85mmHg and when proteinuria >1gm/day or GFR <55ml/min; aim for ≤125/75 Cholesterol ideal LDL-C <100mg/dl and HDL-C >50mg/dl statins have the most benefit Fasting Sugar intensive sugar control with target HbA1c of <7%
Prevention to ESRD Diet Modified protein intake with 1.0gm/k/day for normal GFR 0.8gm/k/day for CRI; and 0.4-0.6gm/k/day for severe CRF Very low protein diet 0.3-0.4gm/k/day with ketoAA supplements Educate Exercise/ weight reduction, smoking cessation, alcohol avoidance, early nephro referral Gases Acid-base control with giving of alkali such as NaHCO3 tablets to achieve HCO3 level ≥20mmol/L Hemoglobin Hgb target 11-12g/L beneficial in CKD Erythropoietin replacement – best treatment
Clinical Practice Guideline forDetection, Evaluation, and Management ofCKDSTAGE DESCRIPTION GFR EVALUATION MANAGEMENT At increased risk Test for CKD Risk factor management Diagnosis Kidney damage Specific therapy, based on diagnosis Comorbid conditions 1 with normal or >90 Management of comorbid conditions CVD and CVD risk GFR Treatment of CVD and CVD risk factors factors Kidney damage 2 60-89 Rate of progression Slowing rate of loss of kidney function 1 with mild GFR Prevention and treatment of 3 Moderate GFR 30-59 Complications complications Preparation for kidney replacement 4 Severe GFR 15-29 therapy Referral to Nephrologist 5 Kidney Failure <15 Kidney replacement therapy 1Target blood pressure less than 130/80 mm Hg. Angiotension converting enzyme inhibitors (ACEI) or angiotensionreceptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200mg/g.
Prognosis There is no cure for chronic renal failure. Untreated, usually progresses to end-stage renal disease. Lifelong treatment may control the symptoms of chronic renal failure. Dialysis or kidney transplant required eventually. Otherwise, condition is terminal.Support Groups The stress of illness can often be helped by joining a support group where members share common experiences and problems.