In the name of God Chronic Renal Failure

2. In the name of GodChronic Renal Failure By: Dr. Shahram Ala (PharmD, BCPS)

3. Kidney • Each kidney has about 1 million nephrons • Receives 25% 0f GFR (1200 ml/min, > 1700 lit/d) • 1-1.5 lit urine (waste products & excess water) • Reabsorption of sodium, glucose, water • Secretion of urea, Cr, K+, H+, phosphate

4. Other functions of kidneys • Renin secretion • Erythropoietin secretion • Activation of vit D3 (Calcitriol)

5. ARF: Rapid onset, usually reversible, rapid reduction in urine volume CRF: Slow onset, progressive, is not reversible Renal Failureup to 75% of function can be lost before it is noticeable

6. Treatment Modalities • Hemodialysis • Peritoneal Dialysis • Renal Transplant • In 1950s, Life expectancy of ESRD patients was just a few days to weeks

7. Classification

8. Worldwide ESRD

9. CRF & ESRD • CRF and ESRD are significant causes of morbidity & mortality

10. Analgesic Nephropathy • Tubulointerstitial renal disease (Papillary necrosis and interstitial nephritis) due to ingestion of a mixture of 2 analgesics usually with codeine or caffeine • More prevalent in females (5-7.1 times) with peak incidence between 4th and 5th decade • Salt-wasting nephropathy, ↓urine concentrating & acidifying capacity • Symptoms: flank pain, pyuria, hematuria, urethral obstruction

11. Analgesic Nephropathy (cont.) • Mechanism: oxidative metabolite of acetaminophen beside reduced glutathione capacity (due to ASA) • Management: abstinence from NSAIDs & combination analgesics, high fluid intake (if possible), management of ESRD is similar to other causes

12. Medication Use • Both HD & PD patients receive a median of 8 different drugs including: • Antihypertensives (CCBs, ACEIs) • Antidiabetic agents • Erythropoietin • Phosphate-binding agents • Multivitamins • Vit D supplements • ASA • Analgesics • GI agents • Warfarin • Nonadherence & drug-related problems

13. General feature in CRF • Most patients are symptom free until renal function is <25% normal • At renal function <10% normal, uremic symptoms occurs • At renal function<5%, dialysis or transplant is required • Intact nephron hypothesis

14. Pathogenesis • Glomerular capillary hypertension • Microalbuminuria or proteinuria • Increased renal plasma flow (with high Pr Intake) • Dyslipoproteinemia (esp. TG-rich apo-B-lipoproteins)

15. Clinical assessment • Evaluation of renal function • BUN, SrCr • Clcr= (140-Age)BW/72*SrCr (*%85 for Females) • Clcr based on urine collection and measurement of UCr • Due to TS of creatinine in renal dysfunction, Clcr overestimates the GFR • Proteinuria (Alb, Alb/Cr Ratio) • Microalbuminuria: 30-300 mg/24h • Overt proteinuria: >300 mg/24h • Dipstick test (Reagent strips) • Alb/Cr : 30-300 µg/mg (Microalbuminuria)

16. Prevention • Antihypertensives • Dietary Protein Restriction • Treatment of Dyslipoproteinemia • Intensive Glu Control (in Diabetic patients)

17. HTN & CRF • HTN is both a cause and a result of RF • HTN causes glumerolarhyperperfusion leading to progressive renal damage • Goal of BP: • 130/85 (in patients with some degree of renal failure) • 125/75 (in patients with proteinuria >1gr)

18. Prevention:Which Antihypertensives? • ACEIs (Enalapril, Captopril, Lisinopril) • Ag II play a central role in glomerular capillary pressure • ARAs (Losartan, Irbesartan, Valsartan, Candesartan, Eprosartan, Telmisartan) • CCBs (Diltiazem, Verapamil are superior to Nifedipine) • Effects on renal hemodynamic, cytoprotective & antiproliferative properties • ACEIs+CCBs

19. Prevention: Dietary Protein Restriction • There is an association between “Proteiningestion” &“GFR” and “Renal Plasma Flow” • For GFR>25 or in Diabetics → 0.6-0.8 g/kg/day • GFR<25 or in Diabetics with RF → 0.3-0.6 g/kg/day • Protein restriction may delay development of ESRD, but no definitive conclusions could be made

20. Prevention:Treatment of Dyslipoproteinemia • ↑TG (Up to 70% of patients), ↓HDL, ↔ Total-C • Progression of renal disease • Cardiovascular morbidity & mortality • Treatment: • Based on individual lipid profile, generally NCEP guidelines are used • Gemfibrozil (Clofibrate accumulates in CRF) • Statines

21. ESRD • Uremic Toxins: • urea, guanidine, purine & pyridine derivatives, aliphatic & aromatic amines, PTH • Secondary Complications: • Mild Renal Dysfunction: • fluid overload, HTN • Mod to Severe Renal Dysfunction: • ↑ K, ↑ P, ↓Ca, Metabolic acidosis, • Anemia

22. Metabolic Effects of Uremia • Fluid/Electrolytes/Acid-Base: • Fluid retention, ↑K, ↑Mg, ↑P, ↓Ca, Metabolic acidosis • Hematologic: • Anemia, Hemostaticabnorm., Immune suppresion • CVS: • HTN, CHF, Pericarditis, Atherosclerosis, Arrhytmia, ↓ exercise tolerance • Endocrine: • Hyperpara, Altered thyroid function, Hypophyseal-gonadaldysfunc, Erythropoietin deficiency

23. Metabolic Effects of Uremia (Cont.) • GI: • Anorexia, Nausea, Vomiting, Delayed gastric emptying, Ulcers, GI bleeding • Musculoskeletal: • Renal bone disease, Amyloidosis, Extraskeletal calcification • Neurologic: • Lethargy, Tremor, Asterixix, Cramp, Motor weakness, Peripheral neuropathy • Skin: • Altered pigmentation, Pruritus • Psychologic: • Depression, Anxiety, Psychosis

24. Treatment • Dialysis (HD, PD) • Transplant

25. Pharmacotherapy • To Slow the rate of progression • To manage secondary complications

26. Conclusion