CBP: Nephrology – Diseases of the kidneys!

1. CBP: Nephrology – Diseases of the kidneys!

2. CBP: Nephrology • A 48-year-old man, otherwise healthy, presents with severe unspecific abdominal pain and vomiting of 2 days duration. • He is a stable bipolar personality disorder on lithium. • an X smoker, has history of alcohol use,

3. CBP: Nephrology • On physical examination, restless, dehydrated HR 130 and BP 90/60 (Supine), RR 28, T 37.4. Chest and heart exams are unremarkable. Abd. exam revealed mild-moderate epigastric abdominal tenderness without peritoneal signs. Rest of the exam is unremarkable. • Lab: WBC is 16,500, and the HCT is 49. Cr 188 (67 base line), BUN 12.3 , K 5.5 and the rest of electrolyte values are normal.

4. CBP: Nephrology • Intubated on admission due to altered LOC and inability to protect his airway as well as impending hypoxemic respiratory failure, remains on multiple vasoactive agents, and is in oliguric-to-anuric renal failure • Admitted to ICU and adequately resuscitated • Patient remains anuric despite the adequate fluid resuscitation

5. Question 1 • Any role for increasing doses of Lasix in an anuric patient? Any harm? Any benefit? (Eric)

6. Diuretics in AKI

7. Diuretics in AKI • Three part question: • Electrolyte management • Fluid management • Conversion of oliguric to non-oliguric RF

8. Electrolytes & Fluid* • Paucity of data answering these specific questions • Remains clinical decision and therapeutic option * Differentiate fluid management from urine output

9. Conversion of oliguric to non-oliguric RF Ravindra LM et al., Diuretics, Mortality, and Nonrecovery of Renal Function in Acute Renal Failure, JAMA. 2002;288(20):2547-2553

10. Confounders • Diuretic use at the time of consultation was significantly associated with older age, presumed nephrotoxic (rather than ischemic or multifactorial) ARF origin, a lower BUN level, acute respiratory failure, and a history of congestive heart failure.

11. Cause vs Correlate • After adjusting for covariates associated with the risk of death, diuretic use was significantly associated with in-hospital mortality an non-recovery of renal function, even after adjustment for nonrandom treatment assignment using propensity scores.

12. Diuretics in AKI • Three part question: • Electrolyte management ✓/ ✗ • Fluid management ✓/ ✗ • Conversion of oliguric to non-oliguric RF ✗

13. Question 2 • Define Acute Kidney Injury (Eric)

14. Definitions of AKI

15. The dilemma “More than 35 definitions of AKI currently exist in the literature”

16. AKI vs Acute/Chronic RF Crit Care Med 2010; 38:261–275

18. RIFLE vs AKIN Bagshaw et al., A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients, Nephrol Dial Transplant (2008) 23: 1569–1574

19. Bottom Line • Both the RIFLE and AKIN criteria were developed to facilitate clinical investigation and comparison across study populations. • To date, most interventional studies (e.g. NAC, NaHCO3, etc.) to prevent or mitigate AKI have not used these definitions.

20. Question 3 • What is the incidence of AKI in the ICU and how does it affect patient outcomes?( yahya)

21. Incidence of AKI in the ICU • AKI occurs in ~ 7% of all hospitalized patients, whereas it occurs in 36% – 67% of critically ill patients. • On average, 5 % of ICU patients with AKI require renal replacement therapy. Dennen P, Douglas IS, Anderson R. Acute kidney injury in the intensive care unit: an update and primer for the intensivist. Crit Care Med. 2010 Jan;38(1):261-75

22. AKI and mortality • In most studies, mortality rates rise proportionally with severity of AKI. • Even small increases in serum creatinine have been associated with increasing mortality in various ICU populations despite adjusting for severity of illness and comorbidities. • In patients with AKI requiring RRT, mortality rates reach 50% to 70%. Dennen P, Douglas IS, Anderson R. Acute kidney injury in the intensive care unit: an update and primer for the intensivist. Crit Care Med. 2010 Jan;38(1):261-75

23. AKI and other outcomes • AKI is also associated with: • Increased length of stay • Increased incidence of CKD and end-stage kidney disease • Increased cost • For example, an increase in SCr of 0.5 mg/dl (38 mmol/L)was associatedwith a: • 6.5-fold increasein the odds of death • 3.5 day increase in LOS • nearly $7500in excess hospital costs Dennen P, Douglas IS, Anderson R. Acute kidney injury in the intensive care unit: an update and primer for the intensivist. Crit Care Med. 2010 Jan;38(1):261-75 Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005 Nov;16(11):3365-70

24. Question 4 • What are the methods for detecting acute kidney injury?( yahya)

25. Traditional methods for detecting AKI • Currently available measures do not detect actual kidney injury the way troponin detects myocardial injury: • Creatinine • Urea • Urine output • Rather they are markers of abnormal renal function, that can be used to presume kidney inury has occurred. Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007 Dec;13(6):638-44.

26. Serum creatinine • Used to estimate GFR • Pros • Produced at a relatively constant rate • Freely filtered by glomerulus • Not reabsorbed or metabolized by the kidney. Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007 Dec;13(6):638-44.

27. Serum creatinine • Used to estimate GFR • Cons • 10-40% is secreted by the tubules • Relatively insensitive (may need a 50% reduction in function before a detectable rise in SCr is seen) • Creatinine production varies based on age/sex/muscle mass/diet • Certain disease states can increase production (rhabdo) • Certain drugs can decrease secretion (cimetidine, trimethoprim) • Certain factorsmay affect assay (ketoacidosis, cefoxitin, flucytosine) • Does not reflect real-time changes in GFR Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007 Dec;13(6):638-44.

28. Urea • Rate of production is not constant • Increases with protein intake • Increases in critical illness (burns/sepsis/trauma) • GI Bleed • Steroids • 40% - 50 % of urea is reabsorbed by the kidney (even more when dry) Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007 Dec;13(6):638-44.

29. Urine output • Pros • A dynamic gauge of kidney function. • May be a barometer for change in kidney perfusion • Cons • Poor sensitivity and specificity • Can have severe AKI with normal or increased urine output Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007 Dec;13(6):638-44.

30. Summary of novel markers Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care 13:638–644.

31. CBP: Nephrology • Patient continues to have increasing ventilation support requirments and is now on .85 FiO2. His K+ is now 5.6. He is given routine hyperK+ therapy. He has been started on vasopressors because of declining MAP

32. Question 6 • When should RRT be started? (Indication and timing) (Brian)

33. Historical aspects • Use of HD in ARF started in the years immediately following WWII (1947-1950) • Initial indications: advanced symptoms of renal failure – clinical uremia, severe hyperkalemia, pulmonary edema • Reduction in mortality could not be demonstrated, with high complication rates • Teschan et al reported improved survival with “prophylactic dialysis” in 1960

34. “Indisputable” indications • Volume overload • Hyperkalemia • Metabolic acidosis • Uremic signs or symptoms • Refractory to medical management • No specific objective criteria

35. Other Indications • Progressive azotemia in the absence of uremia (no consensus) • Other electrolyte disturbances (Na, Mg,PO4, Uric acid)

36. Timing of initiation of RRT • Competing risks • Risk of delay in therapy • Potential harm of therapy, including complications of therapy and the potential that dialysis may prolong the course of ARF

37. Teschan et al. Prophylactic hemodialysis in the treatment of acute renal failure. Ann Int Med 1960. • Paul Teschan of US Army Medical Corps after the Korean War introduced the concept of “prophylactic dialysis”, applied before overt uremic symptoms appeared • N=15, uncontrolled trial, initiation of dialysis before serum Urea Nitrogen reached 100 mg/dl • Twin coil cellulosic dialyzers at BF 75-250ml/min to maintain BUN less than 75mg/dl • All cause mortality 33%, mortality due to hemorrhage or sepsis 20% • No control group. However, investigators reported that the result represented “dramatic” increase in survival cf their past experience in pt in whom dialysis was not initiated until “conventional” indications were present

38. Early studies

41. Bouman et al (CCM 2002) • 2 center RCT (n=106). ICU pts on MV with vasopressor dependent circulation and oliguric ARF • ARF: CrCl<20, UO<180ml/6h • Early: CVVH within 12h after onset of liguria • Late: urea>40mmol/l, pulmonary edema with PaO2/FiO2<150 despite PEEP 10 • Many issues

42. Jiang, et al (2005) • RCT (n=37) in severe pancreatitis WITHOUT documented evidence of ARF • Early: CVVH within 48 hours onset of abdo pain • Late: within 96 hours • Improved hemodynamics and 14d survival

43. Gettings et al (ICM 1999) • Retrospective nonrandomized cohort study (n=100) • Trauma patients • “Timing” defined by BUN level • Early: RRT started at a mean BUN 15mmol/l • Late: at BUN 34 mmol/L • Survival: 39% Early, 20% Late

44. Piccini et al. (ICM 2006) • Retrospective study (n=80) • Patients with septic shock and oliguric AKI • Historical control • Early: <12h after ICU admission • Late: Urea>35 mmol/l or Cr>600 • Improved hemodynamics, gas exchange, 28d survival

45. Elahi et al. (2004) • Retrospective cohort study (n=80) • Cardiac surgery patients • Early: CVVH when UO<100ml/8h despite lasix • Late: Urea>30 mmol/l, Cr>250, or K>6 regardless of UO • Survival 44% early, 22% late, p<0.05

46. Demirkilic et al. (2004) • Retrospective study (n=61) • ARF following cardiac surgery • Historical control • Early: CVVHDF if UO<100ml/8h • Late: Cr>444 • Hospital mortality 23.5% Early 55% late p=0.02

47. Summary • Trend towards better outcome with earlier timing of RRT • Methodology poor • Nonuniform definition of timing • Heterogeneity of population • Heterogeneity of RRT

48. Summary • Nonuniform and arbitrary definition of ARF prevents direct comparison of trials • But how about using RIFLE criteria and AKIN definition?

50. Shiao et al. (2009) • Multicenter prospective observational study • N=98 who underwent RRT according to local indications for post-major abdo surgery AKI • Early: sRIFLE – 0 or Risk • Late: sRIFLE – I or F