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Introduction
Acute renal failure (ARF) is a serious disease with a multiplicity of etiological factors. The incidence varies with the clinical situation: it accounts for 1% of hospital admissions, occurs in 2-5% of hospitalized patients and may occur in as many as 15% of patients after cardio-pulmonary bypass. The overall mortality is high -50% and reflects the presence of multi-organ dysfunction kidney failure or dialysis.
The syndrome is often reversible if properly diagnosed and managed.
Definitions
Acute renal failure implies a rapid decline of renal function (occurring over days to 1-2 weeks) manifested by azotemia, with or without uremia.
Acute renal failure is not synonymous with acute tubular necrosis (ATN) which is but one cause of ARF. Oliguria may or may not be present. Oliguric ARF implies a urine output of <400 cc/day (the minimal urine volume that can accommodate the osmotic load that needs to be excreted in a day).
Non-oliguric ARF does occur commonly and in the patients with ATN implies there is less damage to the kidney and consequently a more favorable prognosis. These patients are also easier to manage since fluid retention and hyperkalemia occur less often than in oliguric patients.
Epidemiology
Despite major improvements in medical technology, the mortality of ARF has not changed over three decades of observation. However, the clinical setting in which ARF occurs has changed in recent years: there are very few obstetric-related cases of ARF. A declining incidence of ARF in surgical patients has been offset by a sharp increase in the number of cases in the medical setting.
Etiology
The etiology of ARF may be divided into:
Pre-renal (decreased per fusion)
Renal (renal parenchymal involvement) or
Post-renal (obstruction to urine flow).
Acute Tubular Necrosis (ATN) is the commonest cause of ARF.
Pre-Renal ARF is characterized by a decrease in renal perfusion pressure leading to a fall in the GFR.
Pre-Renal ARF: Hepatorenal Syndrome
This form of renal failure may be subacute or acute in onset. There is generally evidence of advanced liver disease (acute or chronic). There is intense renal vasoconstriction of unknown
Post-renal ARF
Since obstruction to urinary flow is readily treatable, this cause should be considered in every patient with ARF. Urinary obstruction may occur at the bladder neck (due to prostatic enlargement or bladder denervation) and can be clinically evaluated by suprapubic percussion and by measuring post-void residuals with urinary catheterization or bladder ultrasonography. To cause ARF, the ureters need to be obstructed bilaterally (or in a single kidney). Retroperitoneal space-occupying lesions, accidental ligation, or occlusion (stones, papillary necrosis, clots or pus)may lead to
Renal ARF
After pre and post-renal causes of ARF have been excluded, one can then consider diseases of the kidney itself. The four structural components of the kidney are: vascular, interstitial, glomerulus and tubules. Dysfunction of any these components may lead to ARF.
Vascular: Thrombotic Microangiopathy
In this group of diseases, ARF occurs with clinical evidence of: Intravascular hemolysis (anemia with reticulocytosis, elevated LDH and indirect bilirubin, absent haptoglobin and schistocytes in the peripheral smear). Widespread fibrin deposition in the small vessels leading to mechanical fragmentation of
Vascular: Atheroembolic Disease
With the widespread use of invasive radiologic procedures the incidence of atheroembolic ARF is increasing; however the diagnosis is frequently overlooked. There is dislodgment of material from atheromatous plaques during the procedure resulting in a syndrome resembling systemic vasculitis: fever, skin manifestations(livedo reticularis, rashes), eosinophilia, hypocomplementemia,
Interstitial: Acute Interstitial Nephritis (AIN)
Typically A1N is drug-induced (virtually any drug may cause AIN), but may also occur with infections, sarcoidosis, hypercalcemia. Drug-induced AIN may be accompanied by the triad of fever, rash and eosinophilia. The onset occurs 7-14 days after starting the medication (or earlier if there is prior exposure to the drug) and is accompanied by hematuria and moderate proteinuria. The
Glomerular: Rapidly Progressive Glomerulonephritis
A glomerular pathology for ARF should be suspected when there are signs of glomerulonephritis ie, significant hematuria with dysmorphic RBCs or RBC casts in the urine Daily protein excretion of >3 grams. Further workup of such cases will proceed along lines of glomerular disease with complement measurements, serologies and perhaps a renal biopsy. Early diagnosis and
Renal: Crystal-Induced ARF
The passage of poorly soluble material through the kidney may lead to crystal precipitation within the tubules causing ARF. Uric acid nephropathy usually occurs in the setting of chemotherapy which causes the tumor lysis syndrome. Ethylene glycol ingestion leads to the formation of oxalic acid, which is deposited in the brain, heart and kidney. Methotrexate, acyclovir, indinavir, and
Tubular: Acute Tubular Necrosis (ATN)
ATN is usually a diagnosis of exclusion after pre-renal and obstructive causes are eliminated. ATN is caused by ischemic or toxic insults to the kidney and is usually seen in hospitalized patients. All pre-renal causes of ARF if not corrected could potentially lead to ATN. The duration of ischemia is important.
ATN: Radiocontrast Nephropathy
Radiologic contrast (except, perhaps in large doses) have little effect on healthy people. The presence of pre-existing renal impairment (especially diabetic nephropathy), multiple myeloma, and pre-renal azotemia are associated with a higher risk of experiencing ATN.
The pathogenesis is not clear but is related to both renal vasoconstriction and tubular toxicity. The amount of dye and level of hydration are important determinants of severity of ARF.
ATN: Heme Pigment Induced ATN
Hemoglobin and myoglobin although not directly toxic to renal tubules may cause ATN. The mechanism is uncertain and is always accompanied by volume depletion which "primes" the kidney.
ATN: Pathogenesis
Current pathogenetic theories suggest a tubular and/or a vascular basis for renal failure. Tubular obstruction from sloughed cells and back-leak of glomerular filtrate across damaged renal tubular
Diagnosis of ARF: Urinary Indices
Pre-renal azotemia is associated with avid Na retention with oliguria due to intact functioning renal tubules. The opposite occurs in oliguric ATN patients.
Although urine electrolytes are commonly requested, there is considerable overlap: Pre-renal patients who have been administered diuretics, osmotic agents or dopamine may have FENa >1%. Likewise, in early ATN from contrast, heme-pigment and in acute glomerulonephritis, the FENa may be low.
Note: Urine lytes are valid only in oliguric patients
Diagnosis of ARF: Acute vs Chronic Renal Failure
Patients with an elevated creatinine at time of presentation may have preexisting chronic renal failure or ARF.
The presence of chronic symptoms such as nocturia due to the inability of the damaged kidney to concentrate urine, or foamy urine (implying heavy proteinuria) suggests chronic renal disease.
A chronically high calcium x phosphate product can lead to visible deposition in the cornea (band keratopathy). Radiologic evidence of secondary hyperparathyoidism is also suggestive of long-standing renal failure.
Small kidneys on a renal USG are suggestive of chronicity; however, in amyloidosis, diabetic glomerulosclerosis, HIV nephropathy, and polycystic kidney disease the kidneys may be normal-sized or enlarged.
Workup of Renal Failure
With a detailed history, physical examination, urine examination and a renal sonogram one can proceed in a systemic manner to elucidate the cause of renal failure:
ARF in Special Situations: Pregnancy
Certain disorders unique to pregnancy may occur.
Septic abortions are fortunately rare.
Severe preeclampsia rarely leads to renal failure in conjunction with the HELLP syndrome and typically occurs in the 3rd trimester. Thrombotic thrombocytopenic purpura usually occurs before 24 weeks and hemolytic uremic syndrome is usually found post-partum. Diffuse cortical necrosis is associated with severe complications of pregnancy (abruptio, placenta previa etc.) and has a uniformly poor prognosis. Functional hydronephrosis which can be found in normal pregnancies may rarely cause ARF. Acute fatty liver of pregnancy is a rare disorder associated with ARF in 60% of cases. Clinical features include coagulopathy with hypofibrinogenemia and hypoglycemia.
ARF in Special Situations: HIV-infected Patients
Pre-renal azotemia can occur secondary to diarrhea, drug-induced renal tubular concentrating defects and hypocortisolism.
Collapsing focal & segmental glomerulosclerosis can occur, sometimes resulting in a rapid decline of renal function and massive proteinuria.
Drug-induced ARF is usually reversible with withdrawal of therapy.
Treatment:
There is no specific treatment of ATN-ARF.
In oliguric pts, K and Na restriction is needed, with fluid restriction if hyponatremic. Acidosis may require bicarbonate therapy.
Negative nitrogen balance may be minimized by adequate caloric intake (35K cal/kg-increased by 50% in sepsis, burns or surgery) protein intake of 0.6g/kg (increase to lg/kg if dialysis).
All potential nephrotoxins should be carefully looked for and avoided.
Dialysis
Dialysis should be initiated early if recovery is not anticipated. In some studies, the institution of early dialysis appeared to decrease mortality. The absolute indications of dialysis are indicated.
The choice of dialysis modality depends on patients' hemodynamic stability (peritoneal dialysis and continuous modalities in unstable patients), access, and catabolic state of patient (PD is relatively ineffective in catabolic patients).
Course and Outcome of ATN
Recovery from ARF is heralded by an increase in urine volumes which usually precedes a falling creatinine.
During the diuretic phase, there may be significant losses of fluid and electrolytes and these should be carefully monitored and replaced.
Recovery is generally complete in ATN if the
Prevention of ATN
Rapid correction of pre-renal factors is the key to preventing ischemic ATN."Renal dose" dopamine although in widespread use has not been convincingly shown to be effective.
Atrial natriuretic peptide is ineffective in contrast nephropathy and there is some evidence of its efficacy in oliguric ischemic ATN.
Future Directions
In the last decade, several new and important pathophysiological mechanisms for ATN have been discovered the role of both calcium and calcium-dependent enzymes, oxidant stress, loss of polarity of the tubular cell, tubular obstruction and arginine-glycine-aspartic acid (RGD) peptides, neutrophils, intracellular adhesion molecules (ICAM), and growth factors.
Emerging therapies will focus on these mechanisms and preliminary work is in