Acute Renal Failure

1. Acute Renal Failure Syed Rizwan, MD

2. Acute Renal Failure • Comprises a family of syndromes • Abrupt decrease in GFR(over hours to days)

3. MANIFFESTATIONS of ARF • Increase in BUN • Increase in creatinine • Oligouria(< 400 –500 cc)

4. DEFINITION • No consensus • Multiple • Relative rise in Serum Creatinine • > 0.5mg/dl if baseline creatinine is normal • > 1 mg/dl if baseline serum creatinine is high

5. Creatinine and GFR • Creatinine produced in muscles • Creatinine excretion depends on, • Glomerular filtration • Proximal tubular excretion • Change in Serum Creatinine with no change in GFR • Muscle wasting or amputation lowers creatinine • Medications(Trimethoprim, Cimetidine) increase creatinine by deceasing tubular excretion

6. Blood Urea and GFR • Increase BUN with no change in GFR • GI Bleed • Hyper catabolic states • Protein loading • Glucocorticoids • Tetracycline • Decrease BUN with no change in GFR • Protein Malnutrition • Severe Liver disease

7. ARF and Biomarker • Lack of sensitivity of BUN and creatinine • Need for Biomarkers • Kidney Injury Molecules-1(KIM-1) increased in Patients with Acute Tubular Necrosis • None available for cliniical utility yet

8. Epidemiology of ARF • Incidence, etiology and outcome varied depending on Population studied and Definition used • Mostly in-Patient than out –Patient • 5-7% of hospital admissions • Mortality varies between 20%-85% depending on cause

9. ARF Classification • Prerenal • Renal • Postrenal

10. Prerenal ARF • Hemodynamically mediated reduction in GFR in absence on Renal Parenchymal injury. • ARF resolves if hemodynamic insult is reversed • If hemodynamic insult is sustained, can result in overt renal injury

11. Renal ARF • Renal Parenchymal injury

12. Postrenal ARF • Acute obstruction to the Urinary Tract

13. Prerenal Azotemia • Decreased Glomerular perfusion(no renal injury) • True Volume Depletion e.g. Diarrhea • Effective Volume Depletion, cirrhosis • Altered Intrarenal Hemodynamics e.g. ACEI • Affenet dilatation • Efferent vasoconstriction

14. Prerenal Azotemia • True or Effective Volume depletion, • Neurohumoral vasoconstrictor • Increased catecholamine • Renin-angiotensin system activation • Increased vasopressin release

15. Renal Autoregulation • Maintains Glomerular Blood Flow and thus GFR • Afferent Vasodialtaion, • Prostaglandins • Kallikrein-kinin • Myogenic influence • Nitiric oxide • Efferent vasoconstriction • Angiotension 11

16. Prerenal Azotemia • Prerenal ARF presents with • Oligouria • Low Urine Na from Na retention • Increased BUN :creatinine ratio >20:1 • FENa < 1% • Existing Renal Insufficiency or Diuretic can alter this picture

17. ARF and ACEI &ARB • ACEI & ARB have greatest benefits in Patients with high risk of ARF • Old age • Diabetics • Cardiomyopathy • CHF with higher dose oh Diuretic • Renal Vascular disease • Chronic Kidney disease

18. Prerenal ARF with ACEI &ARB • Efferent Vasodilatation deceases GFRmedications • Lower GFR raises serum creatinie but usually less than 30% • Must monitor serum creatinine and electrolytes before and after starting or changing dose of these medications • Stop if ARF • Correct volume status • W/u for renal Artery Stenosios • Can reintroduce cautiously if reversible factors corrected

19. Prerenal ARF & NSAIDs • Both COX1/Cox!! Inhibitors cause lower Prostaglandins synthesis • Impairs Afferent vasodilatation decrease Glomerular perfusion • Effect greatest in high risk population • CHF • Cirrhosis • CKD • Vascular disease • elderly

20. Abdominal Compartment Syndrome • Unusual cause of ARF • Associated with increased intra-abdominal pressure • Manifestations, • Respiratory compromise • Decreased cardiac output • Intestinal ischemia • Hepatic Dysfunction • Oliguric ARF • Increased renal venous pressure • Recovery with decreased intraabdominal pressure

21. Post-Renal ARF • Obstruction – complete or Partial • Anuria or variable urine output • Recovery depends on duration of obstruction • Conditions Sonogram may not show obstruction, • Retroperitoneal fibrosis • Tumors • Adenopathy • Encasing ureter prevent dilatation

22. ARF- Renal • Useful to categorize according to Anatomical injury. • Primary sites, • Glomerulus- Acute Glomerulonephritis • Tubules- Acute Tubular Necrosis • Interstitium- Acute Interstial Nephritis • Vascular- Atheroembolism • ATN- most common • U/A-Protein, RBC,Casts,pigments

23. Acute Tubular Necrosis • Ischemic vs Nephrotoxic • Most frequently multi-factorial • Medical vs Surgical • Ischemic- Hypotension,shock • Nephrotoxic- Dye induced, Rhabdomyolysis

24. Acute Tubular Necrosis • Initiation, maintenance, recovery Phases • Mortality from very low to very high • Potentially Preventable • Long –term outcome in survivors very good

25. ATN- Specific Syndromes • Radiocontrast Nephropathy • Rhabdomyolysis • Aminoglycoside Related • Amphotericin B associated

26. Radiocontrast Nephropathy • 10% of Hospital acquired ATN • Mild and Transient in Majority • Risk factors, • Amount of Dye(> 100cc) • Volume Depletion • Renal Insufficiency • DM • Old Age • CHF • ACEI or NSAIDs

27. Radiocontrast Nephropathy • Risks higher with higher creatinine • Normal- negligible risks • Mild- Moderate RI(Creatinine< 2)– 5-10% risks • Mild- Moderate RI with DM- 10-40% risks • Advanced Renal Disease- >50%

28. Radiocontrast Nephropathy • Pathogenesis incompletely understood • Severe Renal vasoconstriction within seconds of contrast administration • Direct Renal Tubular injury • FENa < 1%

29. Radiocontrast Nephropathy • Independent risk factor of death • Prevention in high risk Patients • Consider Alternate imaging.g. MRI • Volume repletion with Saline • Minimize amount of Dye • Low Osmolality contrast media? • N-Acetylcysteine(Mucomyst)? • Fenoldopam-Selective Dopamine agonist? • Lasix, Mannitol, Dopamine –not helpful, may be risky • Prophylactic Hemodialysis- not helpful

30. Radiocontrast Nephropathy • N-Acetylcysteine – reducing agent, scavenge reactive oxygen species(ROS) • No good large randomized trial to prove its efficacy • Impact on morbidity and mortality unknown • Used commonly in practice b/o potential benefits and lack of Toxicity

31. Aminoglycoside Nephrotoxicity • Usually after 7-10 days • Depends on dose and frequency • Direct Proximal Tubular injury • Once a day dosing may be less Nephrotoxic • K. Ca. MG wasting • Risk factors- age, Renal insufficiency, Dose,Volume depletion

32. ARF from Rhabdomyolysis • Muscle injury leading to ARF • Most cases subclinical • Myoglobinuria cause, • Renal vasoconstriction • Proximal tubular damage • Intratubular cast (Obstruction) • Hypovolemia(Third Spacing) • Metabolic Acidosis, • Electrolyte Imbalance(K,Ca,P)

33. ARF from Rhabdomyolysis • Subclinical causes more common • Drugs • PVD • Seizure • FENa < 1% • U/A- Heme/+vie but no RBC • Aggressive Volume replacement • Urinary Alkalization?, Mannitol?

34. Amphotericin B Nephrotoxiciy • Very high incidence of ARF • Binds to sterol in cell membrane • Multiple sites in Nephrons • Distal Tubular Acidosis • Mg and K wasting • Dose dependent • Liposomal Amphotercin formulation less toxic • Saline loading helpful

35. Postoperative ARF • ARF after vascular,cardiac and major abdominal surgery. • Very high mortality • Multifactorial • 1-5% after CABG. • Risk factors, • Renal disease, cardiogenic shock,emergent surgery, Left main disease etc,

36. Acute Interstitial Nephritis • Classical triad(fever rash & eosinophilia) not usually seen • Mostly Drug related e.g. Cipro • Infection : Strept., Staph, CMV, EB virus, Hantaan virus etc • Systemic Diseases : SLE, Sarcoidosis. • Eosinophiluria may be absent • Dx by renal Biopsy. • Rx supportive, Hold Drug, Steroids ?

37. Atheroembolic ARF • Require high degree of suspicion • Cholesterol emboli • Renal failure – acute or subacute • Multisystem disorder • Lived reticularis • Digital Ischemia(Blue Toe Syndrome) • GI bleed, TIA, Rahbdomyolysis

38. Atheroembolic ARF • ARF after vascular procedure • ARF can be abrupt needing dialysis within few days. • Can be subacute occurring in staggered steps separated by stable renal function. • Patients on Anticoagulants are at high risk • Eosinphilia, eosinphiluria, low complement. • High mortality

39. Hepatorenal Syndrome • Profound renal vasoconstriction • Resemble Pre-renal Azotemia • Volume Expansion fail to improve renal function. • Pathogenesis incompletely understood • Oligiuric ARF, FENa low • Diagnosis of exclusion

40. Hepatorenal Syndrome • Two Types • Type 1 HRS: rapid ARF, hospitalized Pt.,>90% mortality • Type 11 HRS : insidious onset, slow progression of RI, refractory ascites, better prognosis. • ATN vs HRS • Low FENa I n ATN • casts in Bilirubinemia with HRS

41. Hepatorenal Syndrome • Rx difficult • Volume expansion with Albumin • Terlipressin(vasopressin analogue) • Midodrine (selective alpha 1 adrenergic agonist)+ octreotide(a somstoastatin analogue) • TIPS, Liver Transplantation • Dialysis in selective Patients

42. ARF in HIV/AIDS • Prerenal Azotemia • Renal salt wasting from Adrenal Insufficiency. • HIV Nephropathy • High risk for ATN • Drug side effects e.g. Pentamidine.Crystal nephropathy(indinavir) • TTP(prognosis worse ) • Rhabomyolysis

43. ARF from RPGN • Less common • Rapidly Progressive Glomerulonephritis include vasculitis, SLE, Wagner's • Active Urinary sediments(RBC cast diagnostic) • Higher degree of Proteinuria • Serology helpful(ANCA, ANA,IgMantibodyetc0 • Renal Biopsy usually required. • Early diagnosis essential to prevent ESRD • Rx with Steroids and Cytoxan

44. Rx of ARF • No proven Drugs • Many cause preventable • Volume expansion • Withdrawal of Drugs • Diuretics help in management but not curative • Dopamine potentially harmful

45. RRT in ARF • Renal Replacement Therapy usually the only option in severe ARF. • Indication of RRT • HYPERKALEMIA • METABOLIC Acidosis • Uremic Symptoms • Fluid Load • “Prophylactic” • RRT • Intermittent Hemodialysis • CVVHD • Extended Daily Dialysis(6-12h) • Peritoneal Dialysis- not favored

46. CVVHD vs Hemodialysis • HD – • more stable Pt, SBP >90, no heparin, allows larger amount of fluid removal in3-4 hours • CVVHD • Unstable Pt., low BP with high dose Pressers, allows gradual removal of fluids 24h • EDD • Allows no heparin dialysis, gradual removal of fluids, but expensive b/o Nursing Support

47. RRT- how to improve outcome? • Lot of Questions to answer • Frequency of Dialysis • Quantification of Dialysis • Type of Membrane of Dialysis • Synthetic vs. Cellulose • Does Erythropoietin improves outcome? • Faster fluid removal vs. slow fluid removal?