Harrison’s Manual of Medicine



Differential Diagnosis
Characteristic Findings and Diagnostic Workup

Acute renal failure (ARF), defined as a measurable increase in the serum creatinine (Cr) concentration (usually relative increase of 50% or absolute increase of 0.5 to 1.0 mg/dL), occurs in ~ 5% of hospitalized pts. It is associated with a substantial increase in in-hospital mortality and morbidity. ARF can be anticipated in some clinical circumstances (e.g., after radiocontrast exposure or major surgery), and there are no specific pharmacologic therapies proven helpful at preventing or reversing the condition. Maintaining optimal renal perfusion and intravascular volume appears to be important in most clinical circumstances.
Differential Diagnosis
The separation into three broad categories (prerenal, intrinsic renal, and postrenal failure) is of great clinical utility (Table 138-1). Prerenal failure is most common among hospitalized pts. It may result from true volume depletion (e.g., diarrhea, vomiting, GI or other hemorrhage) or “effective circulatory volume” depletion, i.e., reduced renal perfusion in the setting of adequate or excess blood volume. Reduced renal perfusion may be seen in CHF (due to reduced cardiac output and/or potent vasodilator therapy), hepatic cirrhosis (due most likely to arteriovenous shunting), nephrotic syndrome and other states of severe hypoproteinemia (total serum protein <5 g/dL), and renovascular disease (because of fixed stenosis at the level of the main renal artery or large branch vessels). Several drugs can reduce renal perfusion, most notably NSAIDs. ACE inhibitors and angiotensin II receptor antagonists may reduce GFR but do not tend to reduce renal perfusion.

Table 138-1 Common Causes of Acute Renal Failure

Causes of intrinsic renal failure depend on the clinical setting. Among hospitalized pts, especially on surgical services or in intensive care units, acute tubular necrosis (ATN) is the most common diagnosis. Allergic interstitial nephritis, usually due to antibiotics (e.g., penicillins, cephalosporins, sulfa drugs, quinolones, and rifampin) may also be responsible. These conditions are relatively uncommon in the outpatient setting. There, intrinsic disease due to glomerulonephritis or pyelonephritis predominates.
Postrenal failure is due to urinary tract obstruction, which is also more common among ambulatory rather than hospitalized pts. More common in men than women, it is most often caused by ureteral or urethral blockade. Occasionally, stones or renal papillae may cause more proximal obstruction.
Characteristic Findings and Diagnostic Workup
All pts with ARF manifest some degree of azotemia (increased BUN and Cr). Other clinical features depend on the etiology of renal disease. Pts with prerenal azotemia due to volume depletion usually demonstrate orthostatic hypotension, tachycardia, low JVP, and dry mucous membranes. Pts with prerenal azotemia and CHF may show jugular venous distention, an S3 gallop, and peripheral and pulmonary edema. Therefore, the physical exam is critical in the workup of pts with prerenal ARF. In general, the BUN/Cr ratio tends to be high (>20:1), more so with volume depletion and CHF than with cirrhosis. The uric acid may also be disproportionately elevated in noncirrhotic prerenal states (due to increased proximal tubular absorption overall). Urine chemistries tend to show low urine [Na+] (< 10–20 mmol/L, <<10 with hepatorenal syndrome) and a fractional excretion of sodium (FENa) << 1% (Table 138-2). The UA typically shows hyaline and a few granular casts, without cells or cellular casts. Renal ultrasonography is usually normal.

Table 138-2 Urine Diagnostic Indices in Differentiation of Prerenal versus Intrinsic Renal Azotemia

Pts with intrinsic renal disease present with varying complaints. Glomerulonephritis (GN) is often accompanied by hypertension and mild to moderate edema (associated with Na retention and proteinuria, and sometimes with hematuria). The urine chemistries may be indistinguishable from those in pts with prerenal failure; in fact, some pts with GN have renal hypoperfusion (due to glomerular inflammation and ischemia) with resultant hyperreninemia leading to hypertension. The urine sediment is most helpful in these cases. RBC, WBC, and cellular casts are characteristic of GN; RBC casts are rarely seen in other conditions (i.e., high specificity). In the setting of inflammatory nephritis (GN or interstitial nephritis, see below), there may be increased renal echogenicity on ultrasonography, so-called medical renal disease. Unlike pts with GN, pts with interstitial diseases are less likely to have hypertension or proteinuria. Hematuria and pyuria may present on UA; the classic sediment finding in allergic interstitial nephritis is a predominance (>10%) of urinary eosinophils with Wright’s or Hansel’s stain. WBC casts may also be seen, particularly in cases of pyelonephritis.
Pts with postrenal ARF due to urinary tract obstruction are usually less severely ill than pts with prerenal or intrinsic renal disease, and their presentation may be delayed until azotemia is markedly advanced (BUN > 150, Cr > 12–15 mg/dL). An associated impairment of urinary concentrating ability often “protects” the pt from complications of volume overload. Urinary electrolytes typically show a FENa > 1%, and microscopic examination of the urinary sediment is usually bland. Ultrasonography is the key diagnostic tool. More than 90% of pts with postrenal ARF show obstruction of the urinary collection system on ultrasound (e.g., dilated ureter, calyces); false negatives include hyperacute obstruction and encasement of the ureter and/or kidney by tumor, functionally obstructing urinary outflow without structural dilatation.

This should focus on providing etiology-specific supportive care. For example, pts with prerenal failure due to GI fluid loss may experience relatively rapid correction of ARF after the administration of IV fluid to expand volume. The same treatment in prerenal pts with CHF would be counterproductive; in this case, treatment of the underlying disease with vasodilators and/or inotropic agents would more likely be of benefit.
There are relatively few intrinsic renal causes of ARF for which there is safe and effective therapy. ARF associated with vasculitis may respond to high-dose glucocorticoids and cytotoxic agents (e.g., cyclophosphamide); plasmapheresis and plasma exchange may be useful in other selected circumstances [e.g., Goodpasture’s syndrome and hemolytic-uremic syndrome/ thrombotic thrombocytopenic purpura (HUS/TTP), respectively]. Antibiotic therapy may be sufficient for the treatment of ARF associated with pyelonephritis or endocarditis. There are conflicting data regarding the utility of glucocorticoids in allergic interstitial nephritis. Many practitioners advocate their use with clinical evidence of progressive renal insufficiency despite discontinuation of the offending drug, or with biopsy evidence of potentially reversible, severe disease.
The treatment of urinary tract obstruction often involves consultation with a urologist. Interventions as simple as Foley catheter placement or as complicated as multiple ureteral stents and/or nephrostomy tubes may be required.
Dialysis for ARF and Recovery of Renal Function Most cases of community- and hospital-acquired ARF resolve with conservative supportive measures, time, and patience. If nonprerenal ARF continues to progress, dialysis must be considered. Traditional indications include: volume overload refractory to diuretic agents; hyperkalemia; encephalopathy not otherwise explained; pericarditis, pleuritis, or other inflammatory serositis; and severe metabolic acidosis, compromising respiratory or circulatory function. The inability to provide requisite fluids for antibiotics, inotropes and other drugs, and/or nutrition should also be considered an indication for dialysis.
Dialytic options for ARF include (1) intermittent hemodialysis (IHD), (2) peritoneal dialysis (PD), and (3) continuous renal replacement therapy (CRRT, i.e., continuous arteriovenous or venovenous hemodiafiltration). Most pts are treated with IHD. The use of a noncellulosic membrane for IHD may limit renal injury in selected pt groups and has been associated with enhanced renal recovery. At many centers, CRRT is prescribed only in pts intolerant of IHD, usually because of hypotension; other centers use it as the modality of choice for pts in intensive care units.


For a more detailed discussion, see Brady HR, Brenner BM: Acute Renal Failure, Chap. 269, p. 1541, in HPIM-15.


2 comments on “138 ACUTE RENAL FAILURE

  1. […] more so with volume depletion and CHF than with cirrhosis. … Read the original here: 138 ACUTE RENAL FAILURE « Free Medical Textbook ← Immunodeficiency, Gastrointestinal Candidiasis, Wheat and Dairy […]

  2. this text is very well written, you must be a really intelligent person, keep up the good work.http://www.emoferta.org

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )


Connecting to %s

%d bloggers like this: