Kidney disease in lymphoma

Prerenal acute kidney injury

Prerenal AKI is the most common kidney injury in patients with lymphoma. Prerenal AKI is most often caused by volume depletion from poor oral fluid intake (78%), anorexia (64%), early satiety (50%), emesis (23%), or diarrhea (16%). In addition, the use of certain medications in the setting of volume depletion may exacerbate or magnify the severity of prerenal AKI in a patient with lymphoma. Medications that affect kidney afferent and efferent tone, including renin-angiotensin blockade or nonsteroidal antiinflammatory medications, or diuretics may worsen the kidney injury. Prerenal AKI is often suspected based on clinical context and history, and supported with physical examination demonstrating orthostatic hypotension or tachycardia, and laboratory data demonstrating an elevated blood urea nitrogen (BUN) and creatinine, often with a BUN to creatinine ratio greater than 20. Urine studies usually show and elevated specific gravity, a low urine sodium (often less than 20 mEq/L), low fractional excretion of sodium (< 1%), and bland urine sediment with occasional hyaline casts or renal tubular epithelial cells. Treatment of prerenal AKI is supportive, with intravenous crystalloid expansion and removal of exacerbating factors that lead to injury.

Postrenal acute kidney injury

In patients with lymphoma, obstruction may result from direct compression or encasement of ureteral outflow by tumor or lymph nodes, retroperitoneal fibrosis, or nephrolithiasis from tumor lysis syndrome. ^, The retroperitoneum has many lymph nodes that can become affected by systemic disease. Anuric kidney failure should raise the concern for bilateral urinary tract obstruction, which is possible with lymphoma and extensive disease burden. Kidney ultrasound or CT scan should demonstrate varying degrees of hydronephrosis depending on the extent of obstruction ( Fig. 38.1 ). Treatment should happen quickly with immediate decompression with nephrostomy tubes to prevent permanent tubular atrophy and interstitial fibrosis.

Acute tubular necrosis

ATN is the most common cause of intrinsic AKI in lymphoma, with more than 75% of patients with AKI having ATN. ATN can often be diagnosed through clinical history and urinary sediment, which will show renal tubular epithelial cells or granular casts, but at times a biopsy may be necessary to exclude other causes of intrinsic AKI ( Fig. 38.2 A and B ). Although the majority of patients with ATN will have ischemia-induced tubular injury, other causes of AKI exist, including drug-related nephrotoxicity and tumor lysis syndrome.

Tumor lysis syndrome occurs when intracellular potassium, phosphate, and nucleic acids are released into the serum from cancer cells. This can be spontaneous release from the death of rapidly growing cancer cells or the direct effect of chemotherapy. Purine nucleic acids that are released are converted to xanthine and then to uric acid by xanthine oxidase. At high levels uric acid crystals can precipitate within the renal tubules and directly injure renal tubule epithelial cells from an associated inflammatory response. This can be detected on the urine sediment by the presence of uric acid crystals that polarize brightly under a polarization filter ( Fig. 38.3 A and B ). In addition, uric acid can also function as a vasoconstrictor, leading to ischemic renal tubular damage through the recruitment of proinflammatory cytokines to the renal interstitium. The risk of tumor lysis syndrome can be mitigated with adequate hydration with nonbicarbonate-containing fluids or xanthine oxidase inhibitors, such as allopurinol or febuxostat, in at risk patients. However, if uric acid levels increase substantially (upwards of 10 mg/dL), rasburicase, a recombinant urate oxidase, can be used to convert uric acid to allantoin, a nonnephrotoxic metabolite that is highly soluble in the urine.