BASIC OUTLINE Investigations MANAGEMENT PRINCIPLES Prerenal Vs ATN Vs ACN

1. ACUTE RENAL FAILURE IN PREGNANCY • BASIC OUTLINE • Investigations • MANAGEMENT PRINCIPLES • Prerenal Vs ATN Vs ACN • ROLE OF Nutrition Volume & metabolic control Diuretics : helpful or harmful ?? Dopamine : helpful or harmful ?? Dialysis : when & which ?? Renal biopsy ?? Delivery Conditions specific to pregnancy

2. DEFINITIONS OFARF • The syndrome is characterised by a sudden in parenchymal function (UOP<400ml/d;30ml/hr) which is usually but not always reversible • This produces disturbance of water, electrolyte, acid base balance and nitrogenous waste products& blood pressure.

3. Normal Physiologic Alterations of Pregnancy

4. Physiological changes in normal gestation • Kidney weight and size increase • Dilation of renal calyces, pelves, and ureters • Urinary stasis • Glomerular filtration, effective renal plasma flow, fractional clearance of urate increase • Bicarbonate reabsorption threshold decreases

5. Clinical relevance • Concentrations of serum creatinine, urea N, and uric acid of 0.9, 14, and 5.6 mg/dl, normal in nonpregnant subjects, are already suspiciously high in gravid women. • Asymptomatic bacteriuria - frank pyelonephritis. • PP reduction in size should not be mistaken for parenchymal loss • Post renal failure difficult to diagnose • S.bicarb lower,PCO2 10 mmHg lower

6. CausesEarly in Pregnancy Most common cause is pre-renal failure due to hyperemesis gravidarum ATN due to septic abortion

7. Causes - ARF Late in Pregnancy/Postpartum Thrombotic microangiopathy TTP-HUS Severe preeclampsia usually with HELLP syndrome Renal Cortical Necrosis Placenta previa Prolonged intrauterine fetal death Amniotic fluid embolism Intrinsic renal disease/autoimmune diseaes

8. ARF Late in Pregnancy/Postpartum Acute pyelonephritis ATN from septicemia or hypotension ARF from microabscesses Acute fatty liver of pregnancy ARF in up to 60% of cases Preeclampsia + hypoglycemia, hypofibrinogenemia, LFT abnormalities, prolonged PTT Obstructive uropathy Mild-moderate hydronephrosis is normal Occasionally, degree of obstruction sufficient to cause ARF. Nephrolithiasis if solitary functioning kidney

9. Causes - Severe Preeclampsia/HELLP Typically develops late in 3rd trimester; a few percent of cases can happen up to 48 hours post-partum. Preceded by hypertension, proteinuria, and severe edema ARF not typical unless marked DIC

10. Severe Preeclampsia/HELLP But, there are cases reported in which renal abnormalities begin post-partum WITHOUT prior proteinuria Typically, spontaneous recovery 2-3 days post-partum; complete recovery typical by 8 weeks post-partum. Corticosteroids have been utilized but no large randomized clinical trials

11. Causes - TTP-HUS Thrombocytopenia + microangiopathic hemolytic anemia + ARF Traditionally, TTP if neurologic symptoms are abundant; HUS if ARF is dominant. BUT, distinctions are often unclear and may not be important for management decisions

12. TTP-HUS Timing variable: 25% before mid-pregnancy 65% peri-partum 20% postpartum: may follow normal pregnancy or be preceded by findings indistinguishable from preeclampsia Can relapse if TTP-HUS occurred once prior to pregnancy; can occasionally relapse in subsequent pregnancy

13. TTP-HUS Plasma infusion +/- plasma exchange (plasmapheresis) In one series of 11 women: 2 died 4 with residual CKD 5 recovered completely Prior to use of plasmapheresis, 90% mortality rate reported

14. Causes - Renal Cortical Necrosis Bilateral cortical necrosis Severe renal ischemia or DIC with resultant endothelial damage Abruptio placenta, placenta previa, prolonged intrauterine death, amniotic fluid embolism THEN, patient develops acute onset of oliguria or anuria, gross hematuria, flank pain, and hypotension ANURIA, GROSS HEMATURIA, FLANK PAIN – triad that is unusual in other causes of renal failure

15. Renal Cortical Necrosis US or CT can be suggestive Biopsy can demonstrate necrosis No specific therapy – many patients require dialysis but 20-40% have partial recovery with CrCl between 15 and 50 mL/min.

16. To summarise Causes • Bimodal distribution -peaks in the first trimester (related to unregulated and/or septic abortion,hyperemesis) and the late third trimester (related to obstetric complications APH,PPH,Preeclampsia, Chorioamnionitis,AFE etc).

17. ATN CORTICAL NECROSIS THOMBOTIC MICROANGIOPATHIES

19. The RIFLE classification (ADQI group) of ARF: • Risk (R) - Increase in serum creatinine level X 1.5 or decrease in GFR by 25%, or UO <0.5 mL/kg/h for 6 hours • Injury (I) - Increase in serum creatinine level X 2.0 or decrease in GFR by 50%, or UO <0.5 mL/kg/h for 12 hours • Failure (F) - Increase in serum creatinine level X 3.0, decrease in GFR by 75%, or serum creatinine level > 4 mg/dL; UO <0.3 mL/kg/h for 24 hours, or anuria for 12 hours • Loss (L) - Persistent ARF, complete loss of kidney function >4 wk • End-stage kidney disease (E) - Loss of kidney function >3 months

20. PHASES OLIGURIA POLYURIA RECOVERY

21. BLOOD CBC Urea,creatinine,uric acid Electrolytes LFT S.proteins Coagulation profile ABG RBS Osmolality URINE sp.gravity osmolality electrolytes proteins pigment casts c/s ECG Investigations

22. Management • Restore or maintain fluid balance • The maintenance of electrolytes and acid base balance • The maintenance of nutritional support • Prevention of infection • Avoid renal toxins (including NSAIDS) • Instigate renal replacement therapies

23. Prerenal failure • Adequately replace blood & fluid losses,maintain BP. • Control continuing blood loss • Mannitol (100ml, 25%) trial to d/d b/w reversible prerenal failure & established ATN (provided oliguria <48 hrs & U:P osmolality > 1.05) • If diuresis (>50ml/hr or doubling) established within 3 hrs,maintain NS infusion acc to UOP & replace electrolytes acc to urinary loss estimations. • If unsuccessful –objective is to support the functionally anephric pt till kidneys recover.

24. Volume control • IP/OP charting daily • State of hydration-wt,hct,protein • Input = Output/24hrs + 500ml(nonfebrile) + 200 ml/ deg C of inc. in Tem Balance : 0.3-0.5kg wt loss/d • Avoid overhydration : Rx diuretics,dialysis • CVP monitoring (b/w 10-15cm H2O)

25. Diuretics • Diuretics commonly have been given in an attempt to convert the oliguric state to a nonoliguric state. However, diuretics have not been shown to be beneficial, and they may worsen outcomes. • In the absence of compelling contradictory data from a randomized, blinded clinical trial, the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged. • Useful only in management of fluid-overloaded patients Cantarovich F, Rangoonwala B, Lorenz H, Verho M, Esnault VL. High-dose furosemide for established ARF: a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Am J Kidney Dis 2004;44:402-9. Kellum JA. Systematic review: The use of diuretics and dopamine in acute renal failure: a systematic review of the evidence. Critical Care1997;1(2):53–9.

26. DOPAMINE • Dopamine traditionally has been used to promote renal perfusion(1-5 mcg/kg/min ) • However, systematic reviews of dopamine treatment in critically ill patients and in patients with sepsis do not support the use of dopamine to prevent renal insufficiency, morbidity, or mortality. In the majority of ARF studies, dopamine was associated only with an increase in urine output. Kellum JA, Decker MJ. Use of dopamine in acute renal failure: a meta-analysis. Crit Care Med 2001;29:1526-31. Denton MD, Chertow GM, Brady HR. "Renal-dose" dopamine for the treatment of acute renal failure: scientific rationale, experimental studies and clinical trials. Kidney Int 1996;50:4-14.

27. Nutrition INTAKE 1500 cal (protein free) Oral/parenteral If vol limitation-50%D via central vein Essential L-aminoacids: K,Mg,P:Improve wound healing, hasten recovery Protein intake of 0.6 g per kg per day

28. Electrolyte & acid-base correction Hyperkalemia, which can be life-threatening, should be treated by • decreasing the intake of potassium, • delaying the absorption of potassium, • exchanging potassium across the gut lumen using potassium-binding resins, • controlling intracellular shifts • dialysis. Acidosis- sodabicarb ,dialysis

29. Treat coagulopathy with FFP for a prolonged aPTT, cryoprecipitate for a fibrinogen level less than 100 mg/dL, and transfuse platelets for platelet counts less than 20,000/mm3 • Timely identification of UTI, proper treatment & prevention using prophylactic antibiotics

30. Should we Initiate Dialysis in Pts w/Low Cr Clearance? Hou, S., Pregnancy in Women on Hemodialysis, 1994, revealed better outcomes of pregnancy in women w/ significant residual renal function or who initiate pregnancy before they need dialysis. May reduce incidence of polyhydramnios, lower urea and lowers water load, also reducing risk of dialysis-induced hypotension

31. Hou, et al, 1998

32. Hou, et al, 1998

33. Hou, et al, 1998

34. Indications for Kidney Replacement Therapy • Acidosis unresponsive to medical therapy • Acute, severe, refractory electrolyte changes (e.g., hyperkalemia) • Encephalopathy • Significant azotemia (blood urea nitrogen level >100 mg per dL [36 mmol per L]) • Significant bleeding • Uremic pericarditis • Volume overload

35. Allows more liberal fluid, protein & salt intake. Prevent hyperkalemic emergencies. infectious Cx. Improves comfort & survival Early “Prophylactic” Dialysis

36. Limited usefulness if hypotension C/I in actively bleeding pt. Controlled anticoagulation reqd Volume shifts-careful Faster correction Can be used in preg/PP pt. Easily available Simple,inexpensive Lower Cx rate Minimises rapid metabolic pertubations & fluid shifts Insert cath high direct vision Hemodialysis Vs Peritoneal dialysis

37. Delivery • Development of ARF in obs pt is indication of delivery in majority cases. • Deliver if UOP<20 ml/>2hrs despite adequate vol expansion & immediate delivery not expected • Redistribution of CO – better renal perfusion. • Remove fetus from hostile environment. • Neonate urea –osmotis diuresis -dehydration

38. Renal biopsy • Potentially v.risky in pregnancy • Defer until postpartum even if ACN( for prognostication). • Rare indication sudden renal failure before 32 wks with no obvious cause.

39. Preeclampsia A decrease in the GFR occurs secondary to intrarenal vasospasm. This may manifest as a "prerenal" picture. Acute renal failure (ARF) may develop, and acute tubular necrosis (ATN) may ensue if this hypoperfusion persists.

40. Pre-eclampsia: ManagementRenal problems • Hyperuricaemia and proteinuria are NOT indications for delivery per se • Consider delivery for progressive renal impairment (creatinine >0.09 mmol/L) • Care with fluids (pulmonary oedema can kill!) • Kidney Function is Criticalfor Drug Elimination

41. Pre-eclampsiaInvasive monitoring • CVP monitoring may NOT be helpful! • poor correlation between CVP and PCWP • PA catheters have risks! • rare indications: • pulmonary oedema resistant to diuretics • oliguric renal failure despite volume expansion

42. Idiopathic postpartum renal failure • Associated primarily with microangiopathic processes • Postpartum hemolytic-uremic syndrome. • These were often irreversible and were associated with substantial mortality. • Now improved outcome with plasma exchange,dialysis,prostacyclin infusion, correcting coagulopathy

43. ACUTE FATTY LIVER OF PREGNANCY • Associated with acute renal failure in up to 60 percent of cases. • The diagnosis should be suspected in a woman with preeclampsia who has jaundice,hypoglycemia, hypofibrinogenemia, and a prolonged PTT in the absence of abruptio placentae.

44. KEY RECOMMENDATIONS FOR PRACTICE • Identify & prevent at prerenal phase as early as possible • Dopamine should not be used to prevent acute renal failure. (Evidence level A) • Diuretics should not be used to treat oliguria in patients with acute renal failure unless volume overload (Evidence level B) • Early prophylactic dialysis should be strongly considered. • The maintenance of electrolytes,acid base balance & nutritional support plays vital role.

45. THANK YOU