Acute Kidney Injury (Case 12)

Pφ

Volume depletion activates central baroreceptors, which results in activation of the renin-angiotensin-aldosterone system, release of antidiuretic hormone (ADH), and activation of the sympathetic nervous system. These mechanisms result in systemic vasoconstriction and sodium and water retention, which maintains renal blood flow. Within the kidney, renal hypoperfusion causes dilatation of the afferent arterioles and constriction of the efferent arterioles, maintaining GFR. In cases of prolonged hypoperfusion, these mechanisms are overwhelmed and decompensation develops, resulting in decreased GFR and resultant AKI.

TP

Patients present with a history of volume loss (i.e., vomiting, diarrhea, diuretic use, bleeding). On exam they are often hypotensive, tachycardic, and orthostatic.

Dx

Expected laboratory findings include an elevated BUN and creatinine with a BUN/Cr ratio > 20 : 1, FeNa < 1%, and UNa < 20 mmol/L. Urine sediment is bland.

Pφ

Even though circulatory volume is overloaded on exam, decreased cardiac output results in a decreased effective circulation. The central baroreceptors become activated, resulting in the same neurohumoral response the body has to volume depletion. Initially the body compensates by systemic vasoconstriction with sodium and water retention, but if these mechanisms are overwhelmed, decreased GFR and AKI will develop.

TP

Patients may have extensive cardiac histories with low ejection fractions. They usually present with decompensated heart failure with jugular venous distension, pulmonary edema, and lower extremity swelling.

Dx

Expected laboratory findings include an elevated BUN and creatinine with a BUN/Cr ratio > 20 : 1, FENa < 1%, and UNa < 20 mmol/L. Urine sediment is bland.

Pφ

TTP and HUS are characterized by fibrin and platelet thrombi in the microvasculature of various organs, primarily affecting the kidneys and brain. The inciting event appears to be injury to the endothelium, resulting in dysregulation of the coagulation/complement system and unchecked thrombosis. In typical HUS, the mechanism is associated with exotoxins found in certain bacteria that bind microvascular endothelium, leading to vascular damage and thrombi formation. With TTP and atypical forms of HUS, the underlying mechanism results from defects in proteinases or other factors that are crucial to the coagulation system.

TP

The classic findings associated with both TTP and HUS consist of thrombocytopenia, microangiopathic hemolytic anemia, renal failure, neurologic symptoms, and fevers. The degree of renal failure varies between these two entities; HUS more commonly presents with overt renal failure. Neurologic symptoms include confusion, headaches, seizures, and even coma. In typical HUS, additional symptoms may include abdominal pain and bloody diarrhea.

Dx

Diagnosis is primarily based on clinical assessment of the above constellation of symptoms. The microangiopathic anemia demonstrates signs of hemolysis (i.e., elevated lactate dehydrogenase [LDH], low haptoglobin, elevated bilirubin). Schistocytes can be seen on examination of the peripheral smear.

Pφ

Acute glomerulonephritis (GN) occurs as a result of glomerular inflammation. When the inflammation is so profound that it causes renal failure in days to weeks, the syndrome is called rapidly progressive GN. The pathologic finding in acute GN is cellular proliferation around the glomerular tuft, which is termed crescent formation. Crescent formation occurs when glomerular injury results in breaks in the glomerular basement membrane, allowing deposition of fibrin in Bowman space. The fibrin deposition causes epithelial cell proliferation and macrophage infiltration, which results in crescent formation. The etiologies of acute GN are varied and include both vasculitides (e.g., Wegener granulomatosis, microscopic polyangiitis) and immune complex diseases (e.g., SLE, post-streptococcal GN, endocarditis, IgA nephropathy).

TP

Patients with acute GN typically present with hypertension, proteinuria, microscopic hematuria, and acute renal failure (ARF). The ARF can be oliguric or nonoliguric. If the acute GN is part of a systemic illness such as lupus or endocarditis, the patient will have additional symptoms suggestive of those clinical entities.

Dx

Expected laboratory findings include an elevated BUN and creatinine. The urinalysis reveals an active urine sediment with microscopic hematuria, proteinuria, and red blood cell casts. A serologic evaluation and a kidney biopsy are often necessary to determine the cause of the acute GN.

Pφ

The histologic finding in AIN is an inflammatory cell infiltrate within the renal interstitium in response to a medication or infection. The inflammatory cell infiltrate, which is made up primarily of lymphocytes, leads to interstitial edema and tubular damage. Although the provoking factor varies, animal studies have shown that both cellular and humoral mechanisms are important in its pathogenesis.

TP

Patients with drug-induced AIN present with ARF occurring days to weeks after starting a new medication. The ARF can range from mild elevations in creatinine to oliguric renal failure requiring dialysis. Affected individuals may report associated fevers, rash, arthralgias, or flank pain.

Dx

Expected laboratory findings include an elevated BUN and creatinine. Urinary sediment typically reveals microscopic hematuria, non-nephritic–range proteinuria, pyuria, and WBC casts. Eosinophiluria is a hallmark of this disease but also can be seen with other renal injuries. Definitive diagnosis can be made only through renal biopsy.

Pφ

ATN can be caused by prolonged hypoperfusion, exogenous nephrotoxins (medications, contrast agents), or endogenous nephrotoxins (myoglobin, hemoglobin, or uric acid), resulting in direct tubular damage and irreversible cellular injury. ATN commonly occurs within a hospital setting.

TP

Ischemia is the most common cause of ATN, and affected patients may present with hypotension and marked volume depletion. When ATN is the result of a nephrotoxic injury, the patient will often have a history of a recent contrast study, evidence of trauma, or a history of tumor lysis syndrome.

Dx

Laboratory studies show an elevated BUN and creatinine with a BUN/Cr ratio < 20 : 1. In addition, high UNa and an FENa >1% characterize ATN. The urine sediment shows tubular epithelial cells and granular casts. A definitive diagnosis can be made with renal biopsy but is rarely necessary.

Pφ

Obstruction at any level of the urinary tract, irrespective of the etiology, will increase pressure in the collecting systems resulting in compensatory dilatation proximal to the lesion. If left untreated, this will result in a decreased net glomerular filtration pressure and overall decline in GFR. The extent of injury is determined by the severity and duration of the obstruction.

TP

Presentations may vary widely. Patients may give a history of flank or suprapubic tenderness depending on the etiology and site of obstruction. If obstruction is complete, anuria may be reported. Patients with partial obstruction may complain of urgency or frequency. Obstruction is commonly seen in patients with enlarged prostates, history of stones, or neurogenic bladders.

Dx

Laboratory findings include an elevated creatinine. Chemistries may reveal hyperkalemia and suggest type IV renal tubular acidosis (RTA). Sonography of the kidneys and bladder will show the site of obstruction.