Chronic Renal Failure

1,969 views
1,800 views

Published on

Definition, Diagnosis, Clinical Manifestations, management.

Published in: Health & Medicine
0 Comments
10 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,969
On SlideShare
0
From Embeds
0
Number of Embeds
3
Actions
Shares
0
Downloads
219
Comments
0
Likes
10
Embeds 0
No embeds

No notes for slide

Chronic Renal Failure

  1. 1. CHRONIC RENAL FAILURE YOUAN BI BENIET MARIUS. PHARM D, MASTER OF CLINICAL PHARMACY. UNIVERSITY OF NAIROBI
  2. 2. OUTLINES DEFINITION ETIOLOGY and PATHOGENESIS PATHOPHYSIOLOGY and CLINICAL MANIFESTATIONS DIAGNOSIS TREATMENT
  3. 3. DEFINITION Progressive and irreversible loss of renal function over time; based on a gradual decline in the GFR and creatinine clearance ,frequently leading to end stage renal disease (ESRD).
  4. 4. CRF=CRI=CRD= CKD  Multiple terms have been applied to chronic renal failure  the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (NKF KDOQI) has replaced all of these terms with CKD  It encompasses the continuum of kidney dysfunction from mild kidney damage to kidney failure, and includes end-stage renal disease (ESRD).
  5. 5. END STAGE RENAL DISEASE A clinical state or condition in which there has been an irreversible loss of renal function, and these patients usually need to accept renal replacement therapy in order to avoid life-threatening uremia.
  6. 6. UREMIA Uremia is the clinical and laboratory syndrome, reflecting dysfunction of all organ systems as a result of untreated or undertreated acute or chronic renal failure.
  7. 7. ESTABLISHED CHRONIC KIDNEY DISEASE 1 Decline of kidney function for 3 months or more 2 Evidence of kidney damage or GFR <60 mL/min/1.73 m2
  8. 8. 5 DIFFERENT STAGES Each patient is classified into one of the 5 following stages of CRF because management and prognosis varies according to the progression of damage.
  9. 9. Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m2) Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m2) Stage 3: Moderate reduction in GFR (30-59 mL/min/1.73 m2) Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m2) Stage 5: Kidney failure (GFR <15
  10. 10. ETIOLOGY: COMMON CAUSES OF CRF Diabetes mellitus hypertension glomerulonephritis polycystic kidney
  11. 11. PATHOGENESIS OF CRF
  12. 12. 1-ALTERATIONS IN FLUIDS AND 2- METABOLIC ACIDOSIS 3- ANEMIA 4 -RENAL OSTEODYSTROPHY 5-COMPLICATIONS OF UREMIA ELECTROLYTES
  13. 13. 1-Alterations in Fluids and Electrolytes →Sodium & Water retention → Fluid movement into the extravascular space → pitting edema in the lower extremity Swelling 1. Generalized edema →Fluid accumulation → Pulmonary edema and loss of air space → Ventilation-perfusion mismatch. Shortness of breath 2.Pulmonary crackles
  14. 14. Kidney damage : Inability to secrete potassium Malaise, palpitations, arrhythmias 5. Hyperkalemia in the urine 1-Water and Electrolytes disorders
  15. 15. 4.Impaired H+ secretion from the body. Protein-energy malnutrition due to metabolic acidosis Loss of lean body mass 4. Weight lost 2- METABOLIC ACIDOSIS
  16. 16. 3.Loss of Erythropoietin Fatigue, reduced exercise capacity, and pallor 3. Anemia release 3- ANEMIA
  17. 17. Firstly: kidney fail to excrete phosphate. Hyperphosphatemia 4 -RENAL OSTEODYSTROPHY Secondary : high parathyroid hormone levels.
  18. 18. Early stages (1-2-3) hyperphosphatemia Hypocalcaemia Later stages( 4-5) decreased synthesis of 1α-hydroxylase 4 -RENAL OSTEODYSTROPHY by negative feedback.
  19. 19. To compensate low calcium →Increases parathyroid hormone secretion Secondary and tertiary hyperparathyroidism High bone turnover 4 -RENAL OSTEODYSTROPHY
  20. 20. osteoporosis Osteomalacia High bone turnover Calcium deposition in soft tissue. high blood calcium levels 4 -RENAL OSTEODYSTROPHY
  21. 21. Uremia-induced platelet dysfunction Uremic pericarditis Urea and other toxins accumulate in the blood and cause life threatening issues Uremic encephalopathy 5-COMPLICATIONS OF UREMIA
  22. 22. COMPLICATIONS OF UREMIA Uremia-induced platelet dysfunction Uremic pericarditis Uremic encephalopathy Increased tendency to bleed and ecchymosis Ecchymosis, GI bleeding Chest pain, malaise Headaches, confusion, coma Pericardial friction rub
  23. 23. CHRONIC KIDNEY CLINICAL MANIFESTATIONS COMPLICATIONS OF UREMIA And
  24. 24. AIM OF TREATMENT
  25. 25. 1. PREVENTION OF FURTHER DETERIORATION 2. TREAT COMPLICATION 3. ESTABLISHMENT OF TREATMENT STRATEGY FOR ESRD AIM OF TREATMENT
  26. 26. 1.PREVENTION OF FURTHER DETERIORATION
  27. 27. 1.PREVENTION OF FURTHER DETERIORATION
  28. 28.  GLOMERULAR PERMEABILITY : PROTEINURIA IN CHRONIC KIDNEY DISEASE  HYPERGLYCEMIA : DIABETIC KIDNEY DISEASE (DKD)  RAAS : HYPERTENSION IN CHRONIC KIDNEY DISEASE 1.PREVENTION OF FURTHER DETERIORATION
  29. 29. DIABETIC KIDNEY DISEASE (DKD) *Albumin-to-Creatinine Ratio (UACR) Early Identification of Diabetic Nephropathy UACR >30 mg albumin/g Cr (on ≥2 occasions 3–6 mo apart) GFR <60 mL/min/1.73 m2 separated by 3 mo Therapeutic Targets Blood Pressure control : BP 120–130/75–80 mmHg Glycemic control : Hb A1c <7.0% Cholesterol control : LDL-C <70–100 mg/dL Proteinuria control : UACR* <30 mg/g
  30. 30. 4- Incretin mimetic or GLP-1 agonist Exenatide (Byetta) in GFR 30 mL/min/1.73 m2 Liraglutide(Victoza) in GFR 60 mL/min/1.73 m2 1.GLYCEMIC CONTROL • For all patients • Some drugs are C.I. or require dose adjustments 2. BLOOD PRESSURE & PROTEINURIA CONTROL :ACE inhibitor and ARB •ACEI or ARB for type I and type II diabetes with UACR 30-300 mg/g(micro albuminuria) •ACEI (captopril) preferred for type I diabetes with UACR>300 (macro albuminuria). •ARB (losartan or irbesartan) preferred for type II diabetes with UACR > 300 (macro albuminuria).
  31. 31. 3.For a SBP goal < 130 • Add diuretic first • Then add CCB or Beta blockers • Avoid DHPCCB without ACEI or ARB 4.For patients UACR> 500-1000 •Consider a low SPB goal •Consider measure to reduce proteinuria • - Increase dose of ACEI or ARB •- Use ACEI and ARB in combination •- Add others agent that lowers proteinuria ARA (spironolactone,epleronone) because of ‘’aldosterone escape” phenomenon. GFR >30 ml/min/1.73m2
  32. 32. 4- Incretin mimetic or GLP-1 agonist Exenatide (Byetta) in GFR 30 mL/min/1.73 m2 Liraglutide(Victoza) in GFR 60 mL/min/1.73 m2 5.Monitor serum potassium •ACE and ARB also ARA may cause k •Avoid others mdct that causes k (NSAID,COX2 inhibitors, K sparing diuretics Diuretics) •Treat hyperkalemia with diuretics .caution 6. CHOLESTEROL CONTROL •Patients with diabetes mellitus are at high risk for cardiovascular disease •Evidence of relationship between albuminuria and the rate of LDL production •Use LDL cholesterol-lowering medicines, such as statins or a statin/ezetimibe combination
  33. 33. 7. Monitor GFR •If GFR decline is > 30% from baseline within 4 weeks, evaluate the cause. •Continue ACEI and ARB if GFR decline is < 30% over 4 mouths FINALY
  34. 34. Drugs dosage in DKD • ACEi : Captopril recommended dose for long- term use is 25 mg orally 3 times a day • ARB : Losartan Initial dose:50 mg orally once d. Maintenance dose: 25 to 100 mg orally in 1 to 2 divided doses. • ARA : Spironolactone :25 to 200 mg/day orally in 1 or 2 divided doses. •Statins : Gemfibrozil : 300 mg twice daily for GFR <50 mL/min/1.73 m2
  35. 35. GLUCOSE LOWERING DRUGS CONTRE INDICATED IN CKD 1- Biguanide : Metformin if SCr 1.5 mg/dL in men, 1.4 mg/dL in women” or GFR 30 mL/min/1.73 m2 2- sulfonylureas Tolazamide ,Tolbutamide, Acetohexamide and Glyburide. Chlorpropamide if GFR 50 mL/min/1.73 m2. 3- Alpha-glucosidase inhibitors Acarbose if GFR 30 mL/min/1.73 m2 Miglitol if GFR 25 mL/min/1.73 m2
  36. 36. GLUCOSE LOWERING DOSE ADJUSTMENT 2. Second-generation sulfonylureas Glimepiride : Start conservatively at 1 mg daily 1. First-generation sulfonylureas Chlorpropamide : reduce dose 50% if GFR 50-80 mL/min/1.73 m2 3. DPP-4 inhibitor Sitagliptin GFR > 50 mL/min/1.73 m2 : 100 mg daily GFR 30-50 mL/min/1.73 m2 : 50 mg daily GFR 30 mL/min/1.73 m2: 25 mg daily Saxagliptin GFR > 50 mL/min/1.73 m2: 5 mg daily GFR < 50 mL/min/1.73 m2: 2.5 mg daily
  37. 37.  GLOMERULAR PERMEABILITY : PROTEINURIA IN CHRONIC KIDNEY DISEASE  HYPERGLYCEMIA : DIABETIC KIDNEY DISEASE (DKD)  RAAS : HYPERTENSION IN CHRONIC KIDNEY DISEASE PREVENTION OF FURTHER DETERIORATION
  38. 38. HYPERTENSION IN CHRONIC RENALE FAILURE More patients develop hypertension from CRF than develop CRF from hypertension ( hypertensive nephrosclerosis ). Therapeutic Targets 120–130/75–80 mmHg CVD risk increases at SBP ≤120 mmHg
  39. 39. 1.First-line Agents •GFR >20 mL/min/1.73 m2 give ACEI or ARB 2. Second-line Agents •GFR ≥40 mL/min/1.73 m2 : Add thiazide if anti- RAAS agent is first-line • Thiazide diuretics are generally ineffective if the GFR <40 mL/min/1.73 •GFR <40 mL/min/1.73 m2 Add loop agent, furosemide (twice daily dosing) or metolazone, if anti-RAAS agent started as first line
  40. 40. 3. Third-line Agents • HR >84 bpm NDHPCCB( dihydropyridine calcium channel blockers) (diltiazem, verapamil),BB or α/β blocker (labetalol ) • HR ≤84 bpm CCB ( amlodipine, diltiazem) • Avoid DHPCCBs in proteinuric CRF(Amlodipine ,Nicardipine) 4. Initial BP: if SBP ≥150 mmHg • Initiate a 2-drug regimen, ACEI/thiazide ,ARB/thiazide or ACEI/CCB, in a patient taking no antihypertensive . 5. Caution . • Sodium intake Should be low than 100 mEq/d • Sympathomimetic (pseudephedrine, “diet” pills, cocaine) drugs and NSAIDs must be avoid .
  41. 41. Drugs dosage in HKD • Anti RAAS: same dosage with DKD • Thiazide : Hydrochlorothiazide : ID:12.5 mg orally once a day. M dose: 12.5 to 50 mg orally as a single or 2 divided doses • Thiazide -like: Metolazone : 5 to 20 mg once daily. • Loop D : Furosemide Oral: ID: 20 to 80 mg per dose. M D: Increase in increments of 20 to 40 mg/dose every 6 to 8 hours to desired effect. with a maximum daily dose of 600 mg. • NDHPCCB: Diltiazem ID: 30 to 60 mg orally 3 to 4 times a day Maintenance dose: 180 to 360 mg orally/day in divided doses. • DHPCCB: Amlodipine Initial dose: 5 mg orally once a day Maintenance dose: 5 to 10 mg orally once a day
  42. 42.  GLOMERULAR PERMEABILITY : PROTEINURIA IN CHRONIC KIDNEY DISEASE  HYPERGLYCEMIA : DIABETIC KIDNEY DISEASE (DKD)  RAAS : HYPERTENSION IN CHRONIC KIDNEY DISEASE PREVENTION OF FURTHER DETERIORATION
  43. 43. PROTEINURIA IN CRF Therapeutic Targets UPC <200 mg/g (protein as mg/dL; creatinine as g/dL) UACR <30 mg/g TREATMENT 2 different types : Diabetes proteinuria and non diabetes proteinuria
  44. 44. First-line Agents for Proteinuria Reduction •Non-diabetic proteinuria ACEI •Diabetes, type 1 ACEI •Diabetes, type 2 ARB or ACEI Second-line Agents for Proteinuria Reduction •Diabetes, types 1 or 2 Anti-RAAS + Non-DHPCCB if HR >60 bpm Third-line Agents for Proteinuria Reduction Diabetes, type I et II : ACEI + ARB or ARB + ACEI
  45. 45. 1. PREVENTION OF FURTHER DETERIORATION 2. TREATMENT OF COMPLICATIONS 3. ESTABLISHMENT OF TREATMENT STRATEGY FOR ESRD AIM OF TREATMENT
  46. 46. COMPLICATIONS OF CRF
  47. 47. TREATMENT OF CRF COMPLICATIONS
  48. 48. Metabolic Acidosis • NaHCO3 0.5–1.0 mEq/kg daily • Target HCO3 22–26 mEq/L
  49. 49. Iron Replacement (%TSAT, SF) •1. 50-100 mg IV twice per week for 5 weeks; if iron are still low, repeat the same course.) •2. If iron indices are normal yet Hb is still inadequate, administer IV iron as outlined above; monitor Hb, Tsat, and ferritin. •3. Withhold iron therapy when TSat >50% and/or ferritin >800 ng/mL(>800 ug/L).
  50. 50. IRON DOSES REGIMENS
  51. 51. (ESAs) Therapy : Epoetin alfa only if Hb <10 g/dl •Starting dosage 50-150 units/kg per week IV or SC (once, twice, or three times per w •Target hemoglobin(Hb): 11-12 g/dL •Optimal rate of correction: Increase Hb by 1-2 g/dL over 4-week (ESAs) Therapy Darbepoetin alfa only if Hb< 10 g/dl •Starting dosage: 0.45 ug/kg administered as a single IV or SC injection once weekly or 0.75 ug/kg ad as a single IV or SC inj once every 2W •Target Hb: ≤12 g/dL •Optimal rate of correction : Increase Hb by 1-2 g/dL over 4-week period
  52. 52. IMPORTANT FACTORS FOR TREATMENT  2 Goals -HPTH suppression - hyperphosphatemia suppression  Corrected Ca = Serum Ca + [ 0.8 × (4.0 − Albumin)]  Corrected Ca × P = Ca × P product (CPP)  iPTH .
  53. 53. Therapeutic PTH suppression: Vitamin D •Sterols Ergocalciferol (D2) •25(OH)D is <15 ng/mL: 50,000 IU q1 wk × 4, thenq1 mo × 4, unless corrected Ca >9.5 g/dL and/orP >4.6 mg/dL •25(OH)D is 15–30 ng/mL: 50,000 IU q1 mo × 6, same condition. •Cholecalciferol (D3) •25(OH)D is <30 ng/mL: 1,750 IU once daily
  54. 54. Therapeutic PTH suppression: Active Vitamin D sterols •Calcitriol 0.25–0.50 mcg once daily in CKD Stages 3 and 4 •Doxercalciferol •iPTH is <600 pg/mL: 1.0–1.5 mcg once daily •iPTH is 600–1200 pg/mL: 1.0–3.0 mcg once daily
  55. 55. Phosphorus Binders •Calcium acetate 1.0–1.5 g elemental Ca daily for P >4.6 mg/dL and Ca 8.8–10.2 mg/dL •Sevelamer HCl 800–2400 mg 3 times daily for P >4.6 mg/dL and ifCa >10.2 mg/dL (Ca- based P-binder contraindicated)
  56. 56. 1. PREVENTION OF FURTHER DETERIORATION 2. TREATMENT OF COMPLICATIONS 3. ESTABLISHMENT OF TREATMENT STRATEGY FOR ESRD AIM OF TREATMENT
  57. 57. TREATMENT STRATEGY FOR ESRD Renal Replacement Therapy (RRT) required when the kidneys are functioning at less than 10–15%. RRT is accomplished in one of the following ways: •1- Dialysis • Hemodialysis • Peritoneal dialysis •2- Kidney transplant
  58. 58. 1 - DIALYSIS (DIA-THROUGH , LYSIS –LOOSENING) *When the access should be created??? Serum creatinine> 4.0g/dL GFR falls to <20 mL/min *Close monitoring of nutritional status is important
  59. 59. Chronic indications for dialysis: 1.Symptomatic renal failure 2.Difficulty in medically controlling fluid overload, serum potassium, and/or serum phosphorus when the GFR is very low INDICATIONS:
  60. 60. Dialysis (a)Haemodialysis (b)Peritoneal dialysis (a)Haemodialysis is the removal of nitrogenous and toxic products of metabolism from the blood by means of a haemodialyzer system NOT provides the same degree of health as renal function provides because there is no resorptive capability in the dialysis membrane. Exchange occurs between the patient’s plasma and dialysate across a semi permeable membrane that allows uremic toxins to diffuse out of the plasma while retaining the formed components and protein composition of blood
  61. 61. COMPONENTS of dialysis unit 1.Dialyzer 2.Dialysate production unit 3.Roller blood pump 4.Heparin infusion pump 5.Devices to monitor the conductivity,temperature,flow rate and pressure of dialysate
  62. 62. The frequency and duration of dialysis treatment are related to 1. Body size 2. residual renal function 3.Protein intake 4.Tolerance to fluid removal #The typical patient undergoes haemodialysis 3 times/week with each treatment lasting approximately 3-4 hours on standard dialysis units and slightly less time on high efficiency/high flux dialysis units NEWER FORMS :Nocturnal and daily dialysis with improved control of 1.Biochemical abnormalities 2.Blood pressure and volume status
  63. 63. Types of vascular access foe maintenance haemodialysis **Classic construction is side to side anastomosis b/w the radial artery and cephalic vein at the forearm 1.Primary arteriovenous(AV) fistula/shunt/external cannula system: Preferred for long term treatment. 2. Synthetic AV graft: Fistulae are created by means of autografts,PTFE grafts ,Dacron etc. A fistula is an enlarged vein (usually in your arm), created by connecting an artery directly to a vein. 4.Cuffed tunneled catheters: indwelling central venous catheters used
  64. 64. (B) Peritoneal dialysis(accounts for10% of dialysis t/t) 1. access is achieved via a catheter through the abdominal wall into the peritoneum 2. 1-2 liters of dialysate is placed in the peritoneal cavity and is allowed to remain for varying intervals of time 3. Substances diffuse across the semipermeable peritoneal membrane to dialysate
  65. 65. Hookup Infusion Diffusion (fresh) Diffusion (waste) Drainage
  66. 66. Various Regimens for peritoneal dialysis: 1.Chronic ambulatory patients..:2 L of dialysis fluid instilled in the peritoneal cavity, allowed to remain for 30 mins and drained out 2.Continuous cyclic peritoneal dialysis, in which 2-3 L of dialysate is exchanged every hour over a 6-8 hour period overnight,7days /week as it allows (a)great deal of personal freedom (b)No risk of air embolism and blood leaks (c) Hepariniztion unnecessary SO used as PRIMARY therapy/as a TEMPORARY MEASURE
  67. 67. 2.RENAL TRANSPLANTATION Treatment of choice for patients with irreversible kidney failure However the use of transplantation is limited by organ availability INDICATIONS:1. ESRD 2. Glomerulonephritis 3.Pyelonephritis 4.Congenital abnormalities 5.Nephrotic syndrome
  68. 68. DEFINITION OF DDS The dialysis disequilibrium syndrome is defined as a clinical syndrome of neurologic deterioration that is seen in patients who undergo hemodialysis. It is more likely to occur in patients during or immediately after their first treatment, but can occur in any patient who receives hemodialysis.
  69. 69. PATHOPHYSIOLOGY the principle factor leading to the disequilibrium syndrome is the development of an osmotic gradient due to the rate of removal of urea causing water to move into the brain
  70. 70. CLINICAL MANIFESTATION The symptoms involve the neurologic system and are similar to symptoms that occur with increased intracranial pressure or acute hyponatremia, such as  restlessness,  headache,  mental confusion  coma
  71. 71. DIFFERENTIAL DIAGNOSIS FOR SIGNS AND SYMPTOMS OF DD  1. Subdural hematoma  2. Uremia  3.Non ketotic hyperosmolar coma  4. Acute cerebrovascular event  5. Dialysis dementia  6. Excessive ultrafiltration and seizure  7. Hypoglycemia  8. Malignant hypertension  9. Hyponatremia
  72. 72. PREVENTION OF THE DIALYSIS DISEQUILIBRIUM SYNDROME Goal is to prevent the development of an osmotic gradient causing water to move into the brain.
  73. 73. FIRST METHOD : HEMOFILTRATION perform hemofiltration on the patient instead of dialysis . convective removal of solute from the patient in place of diffusive removal. Thus, the osmolalities of the body fluid compartments will not change as rapidly as they do during standard hemodialysis
  74. 74. SECOND METHOD :USING STANDARD HEMODIALYSIS The approach that is widely recommended is to slowly lower the blood urea concentration. A goal of reducing the urea concentration by 40 % over 2 h for the first treatment is reasonable This would be a urea reduction ratio [URR0(pre-dialysis BUN − post-dialysis BUN)/ predialysis BUN] of 0.4
  75. 75. THIRD METHOD : ADD AN OSMOTIC AGENT TO THE BLOOD STREAM In addition to the slow removal of urea, another way to prevent the syndrome is to add an osmotic agent to the blood stream, as this will help prevent the development of a blood–brain osmotic gradient and consequently help prevent cerebral edema.
  76. 76. OSMOTIC AGENT  Mannitol and glucose  The easiest agent to add to the blood stream is sodium  Glycerol  urea itself
  77. 77. TREATMENT OF THE DIALYSIS DISEQUILIBRIUM SYNDROME The treatment of disequilibrium after it has developed is aimed at reducing the intracranial pressure of the patient. Standard maneuvers are to give mannitol or hypertonic saline to raise the blood osmolality and to hyperventilate the patient
  78. 78. BMY

×