Acute Renal Failure

1. Internal Medicine Resident Half-Day Ahsan Alam, MD Acute Renal Failure

2. Internal Medicine Resident Half-Day Ahsan Alam, MD AcuteKidneyInjury

3. What is Acute Kidney Injury Abrupt decline in GFR Increase in serum creatinine PUF = (PGC - PT) - (pGC - pT) Varying definitions (RIFLE, AKIN, etc)

4. Rising Prevalence of AKI

5. Why do we care about AKI? Mortality with hospital-acquired AKI Mortality post cardiac surgery Nash K et al. Am J Kidney Dis 2002;39(5):930-936 Lassnigg, A. et al. J Am Soc Nephrol 2004;15:1597-1605

6. Case #1 A 76 yr old female presents to ED with abdominal pain and dyspnea Serum creatinine is 135 mmol Does she have AKI?

7. Diagnostic Approach Time of onset – prior serum creatinine Careful review of history and physical exam Comorbidities Medications Current illness (vomiting, diarrhea, blood loss, etc) BP, volume status, skin lesions, flank/abdominal signs

8. Case #1 DM2, HTN, CAD (CABG 2004), CVA 2000 (right CEA 2009), hypothyroidism Medications telmistartan 80 mg, ramipril 10 mg, furosemide 40/80 mg, metoprolol, clonidine, atorvastatin, clopidogrel, insulin, thyroxine If this is AKI, what are the most likely diagnoses?

9. Causes of Hospital-Acquired AKI and Mortality 4,622 consecutive patients 7.3% with AKI Nash K et al. Am J Kidney Dis 2002;39(5):930-936

10. Case #1 The patient undergoes investigations for her symptoms in hospital…

11. Case #1 *CI-AKI

12. Case #1 *CI-AKI *Stage 2-3 AKI

13. AKI Network (AKIN) Classification Lopes, J. A. et al. Crit Care 2008;12(4):R110

14. Risk Factors for AKI Lameire et al. NDT. 2008;6:392

15. Consistent Risk Factors • Age • Hypovolemia • Hypotension • Sepsis • CKD • Hepatic dysfunction • Cardiac dysfunction • DM • Exposure to nephrotoxins

16. Differential Diagnosis of AKI Pre-renal Renal Post-renal

17. Pre-renal Hypovolemia Diuretics, trauma, surgery, burns, hemorrhage, pancreatitis, GI loss, etc. Decreased effective circulating volume Nephrotic sydrome, cirrhosis, CHF, tamponade, massive PE, etc. Renovascular obstruction RAS/atherosclerosis/thrombosis/embolism, dissecting aneurysm, vasculitis, compression Impaired glomerular autoregulation NSAIDs, ACEi/ARB, calcineurin inhibitors

18. Intrinsic Renal Glomerular and small vessel diseases Rapidly progressive GN, endocarditis, post-strep GN, vasculitides, scleroderma/malignant HTN, HUS, PET, DIC Interstitial nephritis Infection-related, inlammation, drug-induced, infiltrative (lymphoma, leukemia, sarcoidosis) Tubular Lesions Post-ishemia, nephrotoxic (drugs, contrast, anesthetics, heavy metals), pigment nephropathy, light chain, hypercalcemia

19. Post-renal Bladder flow obstruction Urethral, bladder neck (BPH), neurogenic bladder Ureteral obstruction (bilateral or single kidney) Stones, clots, tumours, papillary necrosis, retroperitoneal fibrosis, surgical ligation

20. Urine Output and AKI Anuric < 50 cc / 24 hrs Oliguric < 500 cc / 24 hrs Non-olguric Normal urine output, but inadequate clearance GFR 2 ml/min will produce ~3L of urine/day if there is no tubular reabsorption

21. Diagnostic Approach Urine dipstick Urine microscopy Cellular elements RBC, WBC, Renal tubular epithelial cells Other (squamous, vaginal) Casts Hyaline, granular, waxy, RBC, WBC, tubular cell Organisms Bacteria, yeast Crystals Lipiduria Specific gravity pH Leukocytes Nitrites Protein Glucose Ketones Urobilinogen Bilirubin Blood

22. Urine Findings WBC casts - pyelonephritis WBC

23. Urine Findings Crystalluria – uric acid Crystalluria – calcium oxalate (ethylene glycol toxicity)

24. Urine Findings RBC casts - GN Dysmorphic RBC - GN

25. Urine Findings Muddy brown casts – acute tubular necrosis

26. Urine Findings 1.030 Specific gravity pH 5.0 Leukocytes Nitrites Protein Glucose Ketones + Urobilinogen Bilirubin Blood ++++ 80 yo female found on the floor of her apartment after 2 days, SCr 400 mol/L, K 6.8 mmol/L, CK 54,000

27. Urine Indices

28. Urine Indices

29. FeNa Limitations of FeNa Diuretic use Post-ischemic ATN who have less severe disease AKI on chronic pre-renal disease (cirrhosis, CHF) Contrast or pigment nephropathy Acute GN or vasculitis Alternatives FE of urea, lithium, uric acid FeNa = UNa/PNa x 100 UCr/PCr

30. Imaging Assess kidney size/morphology Hydronephrosis

31. Kidney Biopsy Intrinsic renal AKI Indications Isolated glomerular hematuria with proteinuria Nephrotic syndrome Acute nephritic syndrome Unexplained acute or rapidly progressive AKI

32. Kidney Biopsy Crescentic GN

34. Principles of AKI Management • Identify AKI • Avoid further nephrotoxic injury • Optimize renal hemodynamics • Treat complications • Fluid balance, electrolytes, uremia • Nutritional support • Renal Support (RRT) • Monitoring after AKI

35. Medications • Pre-renal • Calcineurin inhibitors, radiocontrast, ACEi/ ARB, NSAIDS, amphotericin B • Intra-renal • aminoglycosides, amphotericin B, cisplatin, cephalosporins, sulfa, rifampin, NSAIDS, interferon • Post-renal • acyclovir, MTX, indinavir, sulfadiazine • Review renal dosing of medications

36. Fluid Management • Correct fluid deficit • Will not guarantee AKI prevention • Studies of PA catheters did not reduce AKI • High urine flow in specific conditions • Myoglobinuria, tumour lysis, contrast media, etc. • Little evidence on fluid choice • Crystalloids • Hypooncotic colloids (4% albumin) • Hyperoncotic solutions (HES, dextrans) carry risk of renal dysfunction

37. Renal Perfusion and Vasoactive Agents • No support for • Loop diuretics • Dopamine • Selected use of • Mannitol (Rhabdomyolysis, post-cardiac surgery) • Unclear support for • Natriuretic peptides (ANP, BNP) • Fenoldopam (DA agonist) • Theophylline (adenosine antagonist)

38. Renal Perfusion • Vasopressors • Inotropes to improve low cardiac function • Target MAP needs to be individualized • Commonly 65 mmHg • Higher in elderly where autoregulation impaired

39. Nutrition in AKI • AKI is a catabolic state • Inadequate nutritional support can delay renal recovery • Cochrane review 2010: • “There is not enough evidence to support the effectiveness of nutritional support for AKI…” • Adequate calorie delivery in anuric patient will necessitate RRT

40. Treat Complications • Monitor and correct electrolytes, acidosis • Renal replacement therapy • If indicated, do not withhold until patient is anuric

41. Indications for Dialysis A E I O U Acidosis Electrolyte disturbance Ingestions Overload (volume) Uremia

42. New Paradigm for AKI CKD AKD AKI

43. Natural history of AKI Cerda et al. cJASN. 2008;

44. Follow up after AKI

45. Questions?

46. Case #1 *CI-AKI *Stage 2-3 AKI

47. Fluids – Isotonic vs. Hypotonic Isotonic saline (0.9%) more protective than half normal (0.45%) 1,620 pts undergoing cardiac catheterization Goal is to achieve ‘good’ urine flow Mueller C et al. Arch Intern Med. 162: 329-336, 2002

48. Fluids Optimal rate and duration is not clear IV rate >1-1.5 ml/kg/hr to achieve urine flow >150 ml/hr At least 1hr (3-12hr) prior and 3-6hr (6-12hr) after contrast

49. Bicarbonate vs Saline Zoungas S et al. Ann Intern Med 2009;151:631-638

50. Bicarbonate vs Saline Zoungas S et al. Ann Intern Med 2009;151:631-638