An integrated clinical approach for the identification, prevention, and treatment of tumor lysis syndrome.

Tumor lysis syndrome (TLS) is a potentially life-threatening metabolic disorder that occurs when tumor cells undergo rapid decomposition spontaneously or in response to cytoreductive therapy. Delayed recognition of the metabolic imbalances caused by the massive release of tumor cell contents may result in clinical complications such as acute kidney injury, seizures, and cardiac arrhythmias. Prevention, the key principle in TLS management, relies on the identification of patients at risk for developing TLS during chemotherapy or because of disease progression. TLS-related risk factors pertain to tumor type (particularly hematologic malignancies), specific tumor characteristics (e.g. bulky tumor, high cellular proliferation rate, sensitivity to cytoreductive therapy), and other host-related factors. A comprehensive grading system proposed by Cairo and Bishop classifies TLS syndromes into laboratory or clinical TLS, thus facilitating TLS prevention and management. The mainstays of TLS management include monitoring of electrolyte abnormalities, vigorous hydration, prophylactic antihyperuricemic therapy with allopurinol, and rasburicase treatment of patients at high TLS risk or with established hyperuricemia. Urine alkalinization and use of diuretics remain controversial clinical practices. In this review, we describe the incidence of, risk factors for, and diagnostic characteristics of TLS and summarize strategies for the prevention and management of TLS-associated metabolic abnormalities, particularly hyperuricemia. We specifically highlight recently published TLS management guidelines, which focus on the prevention of TLS and hyperuricemia based on a patient's level of risk, and the important role of nephrologists in the prevention and treatment of one of the most serious complications of TLS, acute kidney injury.

Renal disease in patients with cancer.

Kidney disease is very common in patients with cancer. Nephrologists are vital members of the multidisciplinary care team for these patients. Given the high prevalence of comorbidities in patients treated for active malignancy, it is not surprising that these individuals frequently develop renal diseases that are common among other hospitalized patients, such as those arising from sepsis, hypotension or use of nephrotoxic agents (e.g. radiocontrast or antimicrobial agents). The role of the nephrologist in these cases differs little with respect to the presence or absence of cancer. On the other hand, there are several renal syndromes that are unique to patients with cancer, being caused either by the cancer itself or by its treatment. These syndromes are reviewed here. In addition, patients who are receiving chemotherapy often require dialysis for either acute or chronic kidney disease. Unfortunately, there is very little information on the clearance characteristics of most chemotherapeutic agents. In cancer patients with renal disease, both the timing of administration and the dose-adjustment of chemotherapy must rely on clinical experience and close clinical observation.

Prolonged renal failure secondary to antithymocyte globulin treatment in severe aplastic anemia.

OBJECTIVE: To report a case of acute renal failure in a patient with severe aplastic anemia after administration of antithymocyte globulin (ATG). CASE SUMMARY: A 41-year-old man diagnosed with severe aplastic anemia was treated with ATG and cyclosporine. After one dose of ATG (3012 mg, 40 mg/kg), the patient developed anuric acute renal failure, with serum creatinine 3.4 mg/dL (1.2 mg/dL at baseline) and blood urea nitrogen (BUN) 29 mg/dL (13 mg/dL at baseline), which required intermittent hemodialysis. Renal failure resolved with cessation of the drug, serum creatinine and BUN returned to baseline levels, and the patient no longer required hemodialysis. DISCUSSION: ATG is a purified and concentrated gamma globulin, primarily a monomeric immunoglobulin G from hyperimmune serum of horses. It is widely used to treat severe aplastic anemia and to manage acute transplant rejection. This patient had no other confounding factors for the cause of the renal failure. An objective causality assessment using the Naranjo probability scale suggested that ATG was the probable cause of the acute renal failure. Primary glomerular disease was not excluded, as a renal biopsy was not performed. CONCLUSIONS: The association between renal injury and administration of ATG remains unclear; therefore, we recommend that renal function be assessed and carefully monitored prior to and after administration of ATG.

Interstitial nephritis secondary to bevacizumab treatment in metastatic leiomyosarcoma.

OBJECTIVE: To report a case of interstitial nephritis associated with the administration of bevacizumab. CASE SUMMARY: A 26-year-old man diagnosed with metastatic rectal leiomyosarcoma was treated with intravenous bevacizumab 5 mg/kg and received a total of 3 doses at 2 week intervals. His creatinine had increased from 1.0 mg/dL at baseline to 1.6 mg/dL after 2 doses of bevacizumab and to 4.7 mg/dL after the third dose, prompting admission. Acute renal failure was diagnosed, and hemodialysis was initiated. A renal biopsy revealed interstitial nephritis. Renal failure resolved with cessation of the drug, and the patient did not require further hemodialysis. DISCUSSION: Bevacizumab is a recombinant humanized monoclonal immunoglobulin G antibody to vascular endothelial growth factor. Bevacizumab has shown efficacy in treatment of patients with renal cell carcinoma and colorectal cancer and has been approved by the Food and Drug Administration as a first-line treatment for metastatic colorectal cancer. Our patient had no other confounding factors that might have caused renal failure. The presence of primary glomerular disease was excluded by biopsy. According to the Naranjo probability scale, bevacizumab was the probable cause of acute renal failure in this patient. CONCLUSIONS: Bevacizumab can cause acute renal failure by inducing interstitial nephritis. Renal function should be monitored during bevacizumab therapy.

Acute amphotericin B overdose.

OBJECTIVE: To report the clinical course of a woman with cryptococcal meningitis and no previous cardiac disease who developed a fatal cardiac arrhythmia after an acute overdose of amphotericin B and to review its toxicity. CASE SUMMARY: A 41-year-old woman with a history of proliferative glomerulonephritis from systemic lupus erythematosus was admitted with a diagnosis of cryptococcal meningitis. Liposomal amphotericin B was prescribed at the standard dose of 5 mg/kg/day; however, amphotericin B deoxycholate 5 mg/kg was inadvertently administered (usual dose of the deoxycholate formulation is 0.5-0.8 mg/kg/day). The patient developed cardiac arrhythmias, acute renal failure, and anemia. The medication error was noticed after she had received 2 doses of amphotericin B deoxycholate, and it was then discontinued. Despite treatment in the intensive care unit, the woman died on the sixth day after admission. DISCUSSION: Amphotericin B deoxycholate has been reported to produce significant cardiac toxicity, with ventricular arrhythmias and bradycardia reported in overdoses in children and in adults with preexisting cardiac disease, even when administered in conventional dosages and infusion rates. Use of the Naranjo probability scale indicated a highly probable relationship between the observed cardiac toxicity and amphotericin B deoxycholate therapy in this patient. CONCLUSIONS: Given the fulminant course of amphotericin B deoxycholate overdosage and lack of effective therapy, stringent safeguards against its improper administration should be in place.

Acute renal failure secondary to imatinib mesylate treatment in prostate cancer.

OBJECTIVE: To report a case of acute renal failure associated with the administration of imatinib mesylate. CASE SUMMARY: A 64-year-old man diagnosed with prostate cancer was enrolled in a Phase I trial of imatinib mesylate plus taxotere on a protocol that required a run-in period of imatinib mesylate alone. During therapy with imatinib mesylate, the patient developed acute renal failure, requiring hemodialysis. A renal biopsy revealed tubular vacuolization. Renal failure resolved with cessation of imatinib mesylate. DISCUSSION: Imatinib mesylate is a protein tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the receptor tyrosine kinases for platelet-derived growth factor, and stem cell factor c-kit. Prostate cancer has been identified as a target for therapy with imatinib mesylate. This patient had no other confounding factors for the cause of the renal failure. An objective causality assessment determined that imatinib mesylate was the probable cause of the acute renal failure. The presence of a primary glomerular disease was excluded by biopsy. CONCLUSIONS: Imatinib mesylate-induced acute renal failure has now been linked to toxic effects on renal tubular cells in 3 cases. Renal function should be closely monitored during imatinib mesylate therapy.

Safety of regional citrate anticoagulation for continuous sustained low efficiency dialysis (C-SLED) in critically ill patients.

BACKGROUND: Sustained low efficiency dialysis (SLED) is a hybrid therapy that uses a conventional hemodialysis machine to deliver lower solute clearance over prolonged periods of time, typically 8 to 12 hours per treatment, and utilizes the same sodium and bicarbonate concentrations as intermittent hemodialysis. The therapy has been shown to be an effective dialysis mode for the critically ill patient with acute renal failure and hemodynamic instability. At our institution, critically ill patients requiring renal replacement therapy receive SLED on a continuous, 24-hour schedule (C-SLED). The higher dialysis dose with C-SLED compared to continuous venovenous hemodiafiltration (CVVHDF) or traditional SLED would likely alter the prescription needed to provide regional citrate anticoagulation and the incidence of hypernatremia and metabolic alkalosis. OBJECTIVE: To evaluate the safety of utilizing regional citrate anticoagulation with continuous SLED in critically ill patients who frequently clot the hemofilter and have contraindications to systemic anticoagulation with heparin. We hypothesized that the higher dialysis dose with C-SLED would affect the prescription of citrate anticoagulation and the development of hypernatremia and metabolic alkalosis. DESIGN: We prospectively followed the first 20 patients who received regional citrate anticoagulation on C-SLED for acute renal failure in the intensive care unit. Important outcomes measured included serum sodium, bicarbonate, ionized calcium concentration, serum pH, and PCO2. The number of clotting episodes for each patient while on regional citrate anticoagulation was recorded. Setting. Surgical and medical intensive care units at The University of Texas MD Anderson Cancer Center. RESULTS: In over 2200 hours of continuous dialysis with citrate anticoagulation none of the 20 patients had derangements in the serum sodium or acid base status requiring cessation of regional citrate anticoagulation. In 14 patients, no clotting occurred during 1500 hours of SLED with the citrate infusion. There were eight episodes of hemofilter clotting in six patients during 750 hours of C-SLED. CONCLUSION: Regional citrate anticoagulation is a safe method of anticoagulation in critically ill patients on continuous SLED.

Advances in genetic detection of kidney disease.

The Human Genome Project has provided a vast amount of molecular genetic information for the analysis of normal and diseased genes. This new information provides new opportunities for precise diagnosis, assessment of predisposition and risk factors, and novel therapeutic strategies. At the same time, this constantly expanding knowledge base represents one of the most difficult challenges in molecular medicine. For monogenic diseases, nearly 2000 human disease genes have thus far been identified. Most of these conditions are characterized by large mutational variation and even greater phenotypic variation. In nephrology, several genetic diseases have been elucidated that provide new insight into the structure, function and developmental biology of the glomerulus, tubules and urogenital tracts, as well as renal cell tumors. Great improvements in the diagnostic resolution of genetic disease have been achieved, such that single base pair mutations can be readily detected. Because of accurate diagnosis and risk assessment, genetic testing may be valuable in improving disease management and preventive care when genotype-specific therapies are available. Moreover, such testing may identify de novo mutations and potentially aid in understanding the disease process. This review summarizes recent advances in the renal genetic database and methods for genetic testing of renal diseases.