Acute Renal Failure Fall Medical/ Surgical Conference Lubbock-Crosby-Garza County Medical Society Sandra Sabatini PhD, MD Neil A Kurtzman MD

Acute Kidney Injury now the preferred term It's imprecise Some forms of ARF are not associated with tissue injury We'll stick with ARF

An elevated serum creatinine during hospitalisation is an independent risk factor for mortality, progression to CKD, end-stage renal disease, and reduced long-term survival. Patients with chronically elevated serum creatinine (i.e., impaired baseline renal function) have a higher risk for acute kidney injury during hospital stays and are more often dialysis-dependent at hospital discharge than those without.

ARF is an acute decline in the glomerular filtration rate (GFR) from baseline, with or without oliguria/anuria. It may be due to various insults such as impaired renal perfusion, exposure to nephrotoxins, outflow obstruction, or intrinsic renal disease.

Three General Mechanisms Pre-renal Renal Post-Renal

ARF vs CRF adaptation BP Edema - fluid overload Acid-Base RBC Ca PO4 K

Pre-Renal Decreased renal perfusion Contracted EABV CHF Blood loss Vomiting Diarrhea Sweating Decreased fluid intake Cirrhosis Pre-glomerular vascular disease

Evaluation History PE - Pulse and BP - Edema - Signs of other diseases Urine NaCl BUN/Cr Uric Acid

Treatment and Implications Depends on cause Fluid loss different from CHF different from Cirrhosis Vol contraction predisposes to ATN - more soon

Post Renal Prostatism Advanced Cervical Cancer Retroperitoneal Fibrosis Retroperitoneal Lymphoma Bilateral Renal Calculi

Features Anuria if complete Collecting duct dysfunction

Polyuria - NDI Metabolic acidosis Hyperkalemia NaCl loss

Treatment Relieve obstruction if possible Dialysis and supportive care if obstruction is irreversible

Renal Acute glomerulonephritis Acute vasculitides Acute interstitial nephritis Toxins Acute tubular necrosis (ATN) Acute papilary necrosis

Toxins -Ethylene Glyco l

Ethylene Glycol - Anti-Freeze

Dog kidney - polarized light

Manifestations CNS Metabolic Acidosis Renal failure

Diagnosis History CNS - "drunk", seizures Anion gap metabolic acidosis Oxaluria Acute renal failure

Treatment Ethanol Fomepizole (inhibits alcohol dehydrogenase) Hemodialysis Prognosis - good early treatment Prognosis - bad late treatment

Acute Interstitial Nephritis Can be infectious Usually non-infectious inflammatory Commonly drug induced

Allergic reaction to a drug (acute interstitial allergic nephritis) Autoimmune disorders such as anti-tubular basement membrane disease, Kawasaki’s disease, Sjogren syndrome, systemic lupus erythematosus, or Wegener’s granulomatosis Acetaminophen, aspirin, NSAIDS

Penicillin, ampicillin, methicillin, sulfonamide Furosemide, thiazide diuretics, omeprazole, triamterene, and allopurinol Hypokalemia Hypercalcemia, hyperuricemia

Kidney International (2001) 60, 804–817

Treatment Stop offending drug Treat underlying disease Steroids may hasten recovery

Acute Papillary Necrosis Chronic more common Diabetes Infection Often a catastrophic illness

ATN Requires an underperfused kidney Nephrotoxins (Hg, Pt) Major surgery (due to multiple factors) Third-degree burns covering > 15% of BSA The heme pigments myoglobin and hemoglobin Tumor lysis or multiple myeloma Herbal and folk remedies, such as ingestion of fish gallbladder in Southeast Asia (uncommon)

Am J Med Sci. 2007, 334(2): Cisplatin nephrotoxicity: a review. Yao X1, Panichpisal K, Kurtzman N, Nugent K.

Common nephrotoxins include the following: Aminoglycosides Amphotericin B Cisplatin and other chemotherapy drugs Radiocontrast agents NSAIDs Colistimethate Calcineurin inhibitors (cyclosporine, tacrolimus)

ATN

ATN is more likely to develop in patients with the following: Preexisting hypovolemia or poor renal perfusion Preexisting chronic kidney disease Diabetes mellitus Older age

Crush Syndrome

J Am Soc Nephrol 11: 1553–1561, 2000

Contrast Induced ARF Systolic blood pressure <80 mm Hg Intraarterial balloon pump Congestive heart failure Age >75 y Hematocrit level <39% for men and <35% for women

Diabetes especially with ↑Cr Contrast media volume Renal insufficiency Serum creatinine level >1.5 g/dL Estimated Glomerular filtration rate < 60 ml/min Gadolinium enhance MRI risks NSF and CRI

Prevention Avoid use in high risk patients Isotonic saline Saline and furosemide if CHF present HCO 3 of uncertain utility N-acetylcysteine probably ineffective Prophylactic hemodialysis not proven effective

Prostaglandins and the Kidney

NSAIDS and Renal Disease AIN Pre renal azotemia ATN Nephrotic Syndrome Hyperkalemia Hyponatremia

NSAIDS and ARF Relatively uncommon Incidence increases with age ACE inhibitors and ARBs increase incidence Volume contraction Diuretics Pre-existing renal disease

Prognosis 65% recover to baseline in 7-10 days Dialysis needed <1% of patients 18% who need HD remain on it Maioli M, Toso A, Leoncini M, Gallopin M, Musilli N, Bellandi F. Persistent renal damage after contrast-induced acute kidney injury: incidence, evolution, risk factors, and prognosis. Circulation. Jun ;125(25):

The Centre for Adverse Reactions Monitoring, NZ 2000

Antibiotic induced ARF Aminoglycosides Martínez-Salgado et al. / Toxicology and Applied Pharmacology 223 (2007), 86–98

Renal Under perfusion always present

Amphotericin Nephrotoxicity Renal Underperfusion Hypokalemia Renal tubular acidosis Liposomal formulation likely lower incidence Acute renal failure

Pre-renalATN UTO Urine Na ↓Urine Na ↑ Urine K ↑ Urine K ↓ Urine Osm ↑Urine Osm ↓

Fractional Excretion FE x = C x /C cr X 100 C x = U x V/P x FE Na (<0.5%) FE urea (<35%)

Rx Oliguric ARF A fluid challenge is a substitute for thought HD a soon as diagnosis is made Daily until clinical status improves Better avoided than treated

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