Nephrology                                                                  ISSN 1930-6741   



 

 

                         Acute Renal Failure

Author: Zafar Iqbal, MD

Sudden decrease in GFR remains the definition of acute renal failure. Oliguria means urine output of less than 500 ml/d and anuria is called if urine output is less than 100 ml/d. It requires a methodical clinical approach and laboratory-data to uncover the etiology and provide appropriate treatment. Time- honored classification into prerenal, renal and postrenal acute renal failure remains the cornerstone of the workup.

 

PRERENAL AZOTEMIA: Prerenal azotemia is either due to decrease perfusion pressure to the kidneys or due to increase in renal vasoconstriction. Volume depletion leading to decrease in perfusion occurs in hemorrhage, gastrointestinal fluid losses and overdiuresis. Third spacing (hypoproteinemia, ascites, peritonitis, pancreatitis, burns) will decrease perfusion pressure, however patient may be total body fluid overloaded. Reduced cardiac input can occur in congestive heart failure, acute myocardial infarction, and pericardial effusion with tamponade and in acute pulmonary embolism. Sepsis and excessive antihypertensive therapy will increase the capacitance of vasculature and decrease perfusion to the kidneys. Increase in resistance of renal arteries can also decrease perfusion to the kidneys. This occurs with anesthesia, postsurgery, hepatorenal syndrome, ace inhibitors and use of NSAIDS.

 

APPROACH TO PRERENAL AZOTEMIA: Prerenal azotemia is common in-hospital cause of acute renal failure, however treatment of pre-renal azotemia can be diametrically opposite depending upon the cause. Prerenal azotemia should be differentiated from intrinsic renal failure and postrenal causes prior to getting into differential diagnosis of pre-renal azotemia.

History and Physical examination remains pivotal role in formulating a plan to determine the correct cause. Urinary examination should be the first step including volume in the last 24 hours and simple dipstick examination. Examination of the sediment though should be bland in prerenal azotemia is extremely important to rule out active inflammation of the kidneys.  Postvoid residual urine (bladder neck obstruction) and renal ultrasound (hydronephrosis) will in most cases will rule out any significant obstruction. Fractional excretion of sodium differentiates prerenal azotemia from acute tubular necrosis: Urinary Sodium x Serum Creatinine  / Serum Sodium x Urinary Creatinine X 100.

Effective Circulatory Volume: The cardiac output and state of peripheral resistance are two determinants of the effective circulatory volume. Acute response to decrease in effective circulatory volume is an increase in angiotensin II and increase in catecholamines, while chronic response is secondary hyperaldosteronism and increase in total body sodium and water. So patients with lower effective circulatory volume have prerenal azotemia but could be total body fluid overloaded, treatment in this situation should be after-load reduction and judicious use colloid-diuretic combination.

Summary: Prerenal azotemia induced by true dehydration is easy to recognize and treat; however differentiation from obstructive uropathy and intrinsic renal disease should be made. Difficult situation arises when patient has prerenal azotemia with total body fluid overload like in congestive heart failure, nephrotic syndrome, cirrhosis and sepsis. Each preceding situation should be recognized and treated differently. Hepatorenal syndrome is a unique presentation where there is increase in renal vascular resistance causing fractional sodium to be <1%, this should be differentiated from true dehydration. Uosm >500(mos/kg H2O, U/P >40, U/P Urea >8, UNa <20Meq/L, FENA <1%

 

POST- RENAL AZOTEMIA:

Bladder neck obstruction is the commonest cause in men. Prostratic hypertrophy and urethral stricture is common causes. Over age 60 benign prostratic hypertrophy is found in most men but prostrate cancer should present with obstruction at bladder neck or obstruct internal urethral meati with infiltration in trigone area. Urethral strictures are primarily caused by gonococcal infection repeated urinary tract instrumentation and self-catheterization. In women, tumors of the pelvis particularly cervical malignancy can cause bilateral obstruction.  Neurogenic bladder can cause obstruction and can be caused by upper motor neuron lesion (spastic bladder), lower motor neuron lesion (diabetic cystopathy) or by drugs (antihistamines, anticholinergics, and diazepam). Intraureteral causes of obstruction in men include stones, blood clots, sloughed papilla, transitional cell carcinoma, and post-retrograde edema. Extraureteral causes include retroperitoneal fibrosis, retroperitoneal lymphadenopathy, invasive carcinomas (cervical, prostrate, bladder). Pregnancy is physiologic cause of obstruction of right kidney and does not cause azotemia and usually resolve in 3 Ė 4 months after delivery. Ovarian (tumors and abscesses) and uterus (prolapse and endometrioses) may cause obstruction. Acute uric acid nephropathy and acylovir toxicity can present as obstructive crystal disease.

APPROACH TO OBSTRUCTIVE UROPATHY

The diagnosis to obstuctive uropathy is typically made from the history however ultrasound performed for an unrelated reason may surprise the physician. Digital examination of the rectum will suggest prostrate hypertrophy and should never be omitted; palpable urinary bladder and rarely kidneys will suggest obstruction. Postvoid residual volume> 70 ml is suggestive of bladder obstruction or cystopathy. Ultrasonography is the most appropriate initial imaging procedure but false negative (8% to 20%) and false positive (7% to 10%) do occur. Computed topography is sensitive and should be performed without contrast if renal insufficiency exist. Retrograde pyelography should be considered in this setting however risk of introducing infection should be weighed against the information required. CT intravenous urography is more sensitive than IVP in patients with normal renal function for upper urinary tract obstruction. Cystocopy should be performed as first choice in older men.

SUMMARY:  History and digital examination will usually provide sufficient information to proceed with postvoid residual volume. Ultrasonogaphy is simple and noninvasive to be performed as the first imaging procedure. Cystoscopy is appropriate with higher residual volume which is confirm prostrate hypertrophy urethral stricture and bladder CA. Retrograde pyelography can be performed in the same sitting and small stones, sloughed papilla or clot can be removed. Ureteral catheters can be inserted in ureteral obstruction not relieved immediately. Failure to insert ureteral catheters or obstructed ureteral catheters will require bilateral or unilateral nephrostomy. Cystogram will confirm cystopathy and  treated with self-catherization.

 

INTRINSIC RENAL DISEASE: By definition intrinsic renal failure cannot be reversed by eliminating prerenal and postrenal factors. Parenchymal disease or injury which may involve tubules, glomeruli and interstitium.

Vasomotor nephropathy (ATN) can occur in hypotension caused by: Hemorrhage, trauma, rhabdomyolysis, sepsis, third-spacing losses (pancreatitis). Nephrotoxic agents such as aminoglycosides, radiocontrast materials, NSAIDís, ethylene glycol and heavy metal poisoning are the next largest group of disorders. Interstitial nephritis is under recognized and difficult to diagnosis short of renal biopsy most of the times. RPGN (rapidly progressive glomerulonephritis) presents with rapid progressive renal failure, on kidney biopsy, crescents present in Bowmanís space. Idiopathic RPGN is associated with positive ANCA in 80% of case, Anti-GBM disease is rare and is associated with anti-GBM antibody in serum, immune complex RPGN is less likely to have positive ANCA. Wagenerís granulamatosis (Usually with positive C-ANCA) and SLE can present with acute renal failure. TTP can be diagnosed with blood smear.

Atheroembolic renal disease is also under recognized disease and is often confused with ATN, the recovery of renal function is poor and it needs a kidney biopsy to appreciate this disease.

ATN: Mostly proximal tubular injury with, most often loss of or internalization of apical microvilli, epithelial cell flattening and necrosis of scattered tubular cells seen on histology. Proximal tubular cells are described as polar i.e. they move particles only in one direction. This polarity is temporarily lost in sublethal ischemic injury. The correlation of these structural and biochemical changes of ARF is not fully understood. The common pathway of intratubular cast formation is due to partial of complete release of proximal tubular contents in the lumen of the tubules. Interaction of tubular contents with the Tamm-Harsfall protein leads to formation of obstructing casts. Traditionally thought to be perfusion defect of the cortex cause ATN, however medullary hypoxia is most likely a cause of in necrosis of the straight portion of proximal tubule. In normal cell, the Ca-ATPase and Na-Ca ATPase maintain intracellular calcium to a very low level. In injured cells intracellular calcium disrupting functions of organelles and finally death of the cell. Thus Ca-channel blockers may have protective effect in early part of ATN. Free oxygen radicals produced in renal ischemia have been implicated in renal injury. However, there are as yet no clinically relevant antioxidants for use in preventing renal failure.

PIGMENT INDUCED RENAL FAILURE: Rhabdomyolysis is the principal factors in causing pigment induce renal failure followed by hemolysis. Traumatic crush injuries are the most common precursor, however, pressure necrosis from prolonged coma (alcohol, barbiturates), muscle tremors (Parkinsonsís disease, phencyclidine, amphetamine, cocaine) may cause muscle damage and ARF. CPK of more than 15,000 or more usually cause ATN, mannitol-alkaline diuresis appears to reduce incidence of ARF.

ATHEROEMBOLIC DISEASE: Cholesterol embolization provoked by angiography-induced vascular trauma or cardiovascular surgery can cause acute renal failure, which does not recover. Another form of similar disorder is called MCES (multiple cholesterol embolization syndromes) results from the release of cholesterol crystals or microemboli from surface of ulcerated plaques.

 

DRUG INDUCED OR TOXIN INDUCED NEPHROPATHIES:

AMINOGLYCOSIDES: 15 Ė20 % of patients who receive aminoglycosides develop nephrotoxicity. The dose and the duration of drug received are the determinant factors. A high serum peak does not predispose to nephrotoxity, once daily dosing has shown to be less nephrotoxic in clinical trials. Risk factors for nephrotoxicity are old age, volume contraction, renal insufficiency, coadministration of other nephrotoxins, potassium depletion and hepatic dysfunction. Pharmacokinetic computer programs should be utilized for dosing however it does not guarantee prevention of nephrotoxicity.

RADIOCONTRAST INDUCED RENAL FAILURE: Risk factors include dehydration, advanced age, SCr >2.0, multiple myeloma, congestive heart failure, and volume of dye used > 125 ml. Non-ionic radiocontrast dye is less nephrotoxic though more expensive.  Most episodes of nephrotoxicity are mild reversible rise of SCr 1 Ė3 mg/dl; dialysis is usually needed in-patients with underlying renal disease. Urinary sodium is low with contrast-induced renal failure, which distinguishes from ischemic renal failure. Prevention of ARF includes judicious hydration with 0.45% saline and lowest-possible use of contrast volume.

ACE INHIBITORS: Development of ARF with ACE inhibitors heralds vascular abnormality of bilateral or unilateral renal artery stenosis. Less frequently these agents can cause ARF in low-output cardiac failure, hypertension, cirrhosis and polycystic renal disease. Whether ACE inhibitors should be permanently held in these patients is unclear.

NSAIDs: These drugs may cause a reversible, functional form of ARF in patients with ECF volume depletion, congestive heart failure, cirrhosis, hypoalbuminemia and chronic renal insufficiency. Elderly patients on diuretics have been identified as a group particularly at risk. Sulindac, the only NSAID not affecting prostacycline should be used in patients with renal insufficiency. Acute poisoning with NSAIDís can cause oliguric ARF in normal patients. Interstitial nephritis with NSAIDís can present clinically resembling functional ARF but diagnosed with histology.

AMPHOTERICIN : Distal tubular toxicity results in hypokalemia and hypomagnesemia initially followed by increase in SCr. Saline loading will tend to minimize renal damage.

CISPLATIN: 25% of patients exposed to this drug will develop nephrotoxicity. Sodium depletion increases this risk of nephrotoxicity. Hypomagnesemia occurs in 50% of patients accompanied by hypocalcemia and hypocalcemia. Carboplatin is preferable with lower nephrotoxicity.

 TUBULO-INTERSTITIAL NEPHRITIS: It predominantly affects the interstitium and tubules of kidney with relative sparing of the sparing. Light microscopy typically shows interstitial edema with polymorphonuclear infiltrate particularly eosinophils. Most cases of interstitial nephritis are due to drugs. Antibiotics (penicillins, cephalosporins, sulfonamides, ciprofloxacins), commonly used drugs (NSAIDís, lithium, allopurinol, phenytoin, thiazide, furosemide, chlorthalodone), heavy metals (lead, cadmium).

APPROACH TO INRINSIC RENAL FAILURE: History and physical provides the important clues to the diagnosis. Prerenal azotemia and postrenal azotemia has to be excluded prior to institution of more aggressive workup. Examination of the sediment remains single most non-invasive tool prior to resorting histology of the kidney, which provides the diagnosis. ATN though with multiple etiologies should be diagnosed without renal biopsy since therapeutically it will not contribute much. Urinary indices pointing to intrinsic renal disease are Uosm <350 mosm/kg H2O, U/P Cr <20, U/P urea <3, UNa >40 Meq/L, FENA <3%. Renal biopsy should not be withheld since serology results usually take valuable days and loss of specific treatment.

 

    

Dr. ZAFAR IQBAL, MD

Zafar is a Board Certified Nephrologist. He is a leading  kidney specialist in Pennsylvania US . He is an Instructor in Medicine in the University of Pittsburgh Medical Center and a great clinician.

 

 

May 5th,2006

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