Acute Renal Failure

1. Acute Renal Failure Darrell Gray, II MD Internal Medicine Tenwek Hospital

2. Case #1 • 54yo M with AIDS (CD4 of 39) who presents to Tenwek with altered mental status and neurologic deficits. You do a thorough work-up but discover that you need to obtain a CT scan w/ contrast. His baseline creatinine is 1.4, but he returns from the CT scan and now has creatinine of 2.5, with decreased urine output.

3. Case #2 • 42yo F with no significant PMH presents to CCC c/o 4 days of nausea, vomiting and diarrhea, with fever to 101OF. She has been unable to keep any food down, and very little in the way of liquids. Her son is in primary school and had similar symptoms 1 week ago. Creatinine is 2.0. Last one was 0.9 about a year ago.

4. Case #3 • 75yo M with h/o prostate cancer diagnosed in 2006. It was metastatic to his ribs at the time, so he was not a candidate for prostatectomy. He has done well since then on hormone therapy in Nairobi, but presents to clinic today c/o abdominal pain and decreased urine output over the last 5 days, as well as irritability and back pain. His creatinine is 8.5, up from a baseline of 1.4.

5. How does it apply to you? • No matter what specialty you go into, you need to understand the kidneys • Surgery – post-operative renal failure • OB – proteinuria, ureteral reflux, pre-eclampsia, pyelo • Peds – ARF, HUS, polycystic kidney dz, minimal change • Radiology – contrast-induced ARF (what creatinine is safe to give contrast?), nephrogenic fibrosing dermopathy, RAS (dx on angiogram or MRI) • ENT – sinus disease and its connection with pulmonary/renal syndromes like Wegener’s • Pathology – identify underlying disease process

6. Definitions • Increase in serum creatinine (1mg/dL = 88.4umol/L) • By > 0.5mg/dL in < 2 weeks time • OR, > 20% increase if baseline creatinine is > 2.5mg/dL • Poor urine output • Oliguria (100-400mL in 24hrs) • Anuria (<100mL in 24hrs)

7. Tell me more about creatinine • An indirect marker of renal function • Is not elevated in early stages of kidney disease • Will not be raised above normal level until 60% loss of kidney function • Should be used to calculate the creatinine clearance for a more direct estimation of renal function • A small, elderly person may have a totally “normal” creatinine but a decreased creatinine clearance • Clearance declines predictably with age • It’s reflective of underlying muscle mass, which is why it can be deceptively “normal” in the elderly

8. Causes of deterioration in renal function • 3 major categories: • Pre-renal • Intrinsic renal • Post-renal Let’s go through each one…

9. Pre-renal • Characterized by decreased blood flow to the kidneys • Common causes: • Hypovolemia – ↑ losses, ↓ intake, diuresis • Hypotension – from vasodilation (sepsis, anaphylaxis, BP meds), poor cardiac output (heart failure; can actually be volume overloaded) • ACE inhibitors or ARBs – alterations in efferent arteriolar constriction change renal blood flow (RBF) • NSAIDs – afferent arteriolar constriction ↓ RBF • Renovascular – renal artery stenosis, fibromuscular dysplasia, hepatorenal syndrome

10. Intrinsic Renal • Damage to the kidney itself • Important causes: • Acute Tubular Necrosis (ATN) – contrast dye, severe hypotension (shock) • Acute Interstitial Nephritis (AIN) – medications (PCNs, sulfa drugs, NSAIDs) • Glomerular disease – numerous causes, including post-strep glomerulonephritis, vasculitis (like Wegeners), lupus nephritis, HIV, and other entities like minimal change disease, FSGS, etc. • Microvascular thrombosis – TTP, HUS, etc. • Embolic – cholesterol emboli (post-cath) • Infectious / depositional – pyelonephritis, nephrocalcinosis

11. Post-renal • Obstruction of ureter, bladder outlet, or of urethra • causes backup of urine and hydronephrosis • Common causes: • Bladder neck – BPH, prostate Ca, neurogenic bladder, anticholinergic meds • Ureteral obstruction – lymphadenopathy, malignancy, nephrolithiasis • Tubular – crystal precipitation

13. How do I apply this to my patient? • History and physical • Dehydration, fevers, vomiting or diarrhea, change in urine output, SOB, Edema, recent procedures, medications?? • Vital signs, signs of dehydration, skin rash?? • Laboratory data • Urinalysis w/ microscopic analysis, creatinine clearance, urine electrolytes, serology (if suspecting autoimmune process or vasculitis) • Imaging • Renal US or CT, bladder scan

14. High Yield Test Interpretation • Urinalysis – a wealth of information! • Components: • Specific gravity – tells you about dilution or concentration of urine (dehydration?) • Protein – points towards damaged machinery (nephrotic syndrome? Lupus? ) • Glucose – glucose diuresis? • Ketones – DKA? Not eating/drinking? • Blood / RBCs – kidney stone? Glomerular disease? • Nitrite – UTI? • Leukocyte esterase – UTI? • WBCs – UTI? Pyelo? • Bacteria – UTI?

15. High Yield Test Interpretation • Urine microscopy • Under-appreciated and under-utilized • Can give you incredibly valuable information about underlying processes • Analysis of “casts” • “Sediment” • Bland = no significant casts • Active = red cell casts, white cell casts, “muddy brown” or granular casts • Hyaline casts = often pre-renal, or CKD (“waxy casts”) • Can point towards pyelo (white cell casts), glomerulonephritis (red cell casts)

16. Casts Hyaline = pre-renal cause (usually) Granular, “muddy brown” = acute tubular necrosis!

17. High Yield Test Interpretation • Chemistry • BUN : Cr ratio – if >20:1, is strongly suggestive of pre-renal azotemia • Urine sodium and creatinine • Allows you to calculate the fractional excretion of sodium (FeNa) • If < 1%, this is c/w pre-renal cause • If >2%, this is c/w intrinsic renal cause • Urine urea • Useful when patients on diuretics to calculate FeUrea • <35% suggests pre-renal cause

18. High Yield Test Interpretation • Urine eosinophils • Very specific for acute interstitial nephritis • Bladder scan • A rudimentary ultrasound device that gives a mL reading of urinary bladder content • Have patient void, then scan bladder, or insert foley and record “post-void residual” volume if no machine • High post-void residual is suggestive of prostatism or neurogenic bladder • If > 180-250mL, data show risk of UTI is increased • If VERY high (500-1000mL), is clearly c/w post-renal cause

19. Treatment by Cause • Pre-renal • Volume expansion • Normal saline, to enhance renal perfusion (or LR) • Follow chemistry (BUN, creatinine), urine output • Hold BP meds to ensure good renal perfusion (within reason) • Intrinsic renal • If AIN, stop potentially offending agent • Or, if active sediment, consider special studies (lupus labs, ANCA for vasculitis, etc) • Supportive care, especially for ATN • Watch lytes, UOP (beware post-ATN diuresis!) • Biopsy as last resort, if indicated

20. Treatment by Cause (cont’d) • Post-renal • Foley placement! (if you can; sometimes it’s not so easy) • Follow BUN, creatinine • Should improve slowly over several days • If not improved, consider abdominal imaging for mass lesion compressing bladder outlet, ureters, etc.

21. Don’t forget to . . . • Hold nephrotoxic meds • Stop ACE inhibitor / ARB – these can be harmful in acute renal failure • No NSAIDs • Renally dose the meds • Can have catastrophic consequences • Example: morphine has a toxic, renally cleared metabolite, morphine 6-glucoronide; can cause seizures in ARF • Lots of medicines need to be re-dosed (antibiotics like cipro or Keflex or Zosyn or Vanc, zantac, neurontin, atenolol, lovenox, etc.)

22. When to Start Dialysis? • At what creatinine should you begin HD? • Trick question; creatinine doesn’t matter • An easy acronym: AEIOU • Acidosis – metabolic • Electrolytes – hyperkalemia • Intoxication – if dialyzable (lithium…) • Overload – pulmonary edema, CHF… • Uremia – pericarditis, “frost,” AMS

23. Questions?

24. Case #1 • 54yo M with AIDS (CD4 of 39) who presents to Tenwek with altered mental status and neurologic deficits. You do a thorough work-up but discover that you need to obtain a CT scan w/ contrast. His baseline creatinine is 1.4, but he returns from the CT scan and now has creatinine of 2.5, with decreased urine output.

25. Questions • Is this renal failure? • What type is it most likely to be? • What tests might you order? • How would you manage this? • Answers: Yes, ATN from contrast, urine microscopy to look for “muddy brown” / granular casts, supportive care • Bonus: how might you have prevented this? (intern level) • Pre-hydration and N-acetylcystine (Mucomyst) prophylaxis

26. Case #2 • 42yo F with no significant PMH presents to CCC c/o 4 days of nausea, vomiting and diarrhea, with fever to 101OF. She has been unable to keep any food down, and very little in the way of liquids. Her son is in primary school and had similar symptoms 1 week ago. Creatinine is 2.0. Last one was 0.9 about a year ago.

27. Questions • Is this renal failure? • What type is it most likely to be? • What tests might you order? • How would you manage this? • Answers: • Yes • pre-renal from dehydration / volume depletion • Orthostatic vitals, BUN:Cr ratio, FeNa • Give fluids (saline saline saline!), follow creatinine

28. Case #3 • 75yo M with h/o prostate cancer diagnosed in 2006. It was metastatic to his ribs at the time, so he was not a candidate for prostatectomy. He has done well since then on hormone therapy in Nairobi, but presents to clinic today c/o abdominal pain and decreased urine output over the last 5 days, as well as irritability and back pain. His creatinine is 8.5, up from a baseline of 1.4.

29. Questions • Is this renal failure? • What type is it most likely to be? • What tests might you order? • How would you manage this? • Answers: • Yes • Post-renal, from prostatic obstruction • Bladder scan or post-void residual; renal ultrasound • Foley placement, give fluids, follow UOP and creatinine