Amit Lahoti

Hyponatremia in hospitalized cancer patients and its impact on clinical outcomes

BACKGROUND Hyponatremia is the most common electrolyte abnormality in clinical practice, yet little is known about its frequency in patients with cancer or its impact on their clinical outcomes. STUDY DESIGN Retrospective analysis of prospectively collected data. SETTING & PARTICIPANTS Patients with cancer admitted to the University of Texas M.D. Anderson Cancer Center in 2006 for 3 months. PREDICTOR Serum sodium levels categorized as eunatremia (serum sodium, 135-147 mEq/L) and mild (134-130 mEq/L), moderate (129-120 mEq/L), and severe (<120 mEq/L) hyponatremia. OUTCOMES (1) Length of hospital stay and (2) 90-day mortality. RESULTS In 4,702 admissions in 3,357 patients with cancer, hyponatremia (serum sodium <135 mEq/L) was noted in 47% of admissions. It was mild in 36%, moderate in 10%, and severe in 1%. Hyponatremia was acquired during the hospital stay in 24%. Using the first admission data, mean length of stay was 5.6 ± 5.0 days for patients with eunatremia and 9.9 ± 9.2, 13.0 ± 14.1, and 11.5 ± 12.6 days for those with mild, moderate, and severe hyponatremia, respectively. The respective HRs in the multivariate Cox model for longer hospital stay, using patients with eunatremia as reference, were 1.92 (95% CI, 1.75-2.13; P < 0.01), 2.94 (95% CI, 2.56-3.45; P < 0.01), and 2.32 (95% CI, 1.32-4.00; P = 0.01). 283 (8.4%) deaths occurred during 90 days, and in the multivariate model, the respective HRs for 90-day mortality for mild, moderate, and severe hyponatremia were 2.04 (95% CI, 1.42-2.91; P < 0.01); 4.74 (95% CI, 3.21-7.01; P < 0.01), and 3.46 (95% CI, 1.05-11.44; P = 0.04). These findings were consistent when analyses were repeated with sodium levels in tertiles. LIMITATIONS Observational study, retrospective, inability to adjust for all comorbid conditions. CONCLUSION Hyponatremia in patients with cancer is associated with longer hospital stay and higher mortality. Whether long-term correction of hyponatremia would improve these outcomes remains to be determined.

Autologous hematopoietic stem cell transplantation may reverse renal failure in patients with multiple myeloma.

Approximately 20% of patients with multiple myeloma (MM) have renal failure at diagnosis, and about 5% are dialysis-dependent. Many of these patients are considered ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) because of a high risk of treatment-related toxicity. We evaluated the outcome of 46 patient with MM and renal failure, defined as serum creatinine >2 mg/dL sustained for >1 month before the start of preparative regimen. Patients received auto-HSCT at our institution between September 1997 and September 2006. Median serum creatinine and creatinine clearance (CrCl) at auto-HSCT were 2.9 mg/dL (range: 2.0-12.5) and 33 mL/min (range: 8.7-63), respectively. Ten patients (21%) were dialysis-dependent. Median follow-up in surviving patients was 34 months (range: 5-81). Complete (CR) and partial responses (PR) after auto-HSCT were seen in 9 (22%) and 22 (53%) of the 41 evaluable patients, with an overall response rate of 75%. Two patients (4%) died within 100 days of auto-HSCT. Grade 2-4 nonhematologic adverse events were seen in 18 patients (39%) and included cardiac arrythmias, pulmonary edema, and hyperbilirubinemia. Significant improvement in renal function, defined as an increase in flomerular filtration rate (GFR) by 25% above baseline, was seen in 15 patients (32%). Kaplan-Meier estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 36% and 64%, respectively. In conclusion, auto HSCT can be offered to patients with MM and renal failure with acceptable toxicity and with a significant improvement in renal function in approximately one-third of the transplanted patients. In this analysis, a melphalan (Mel) dose of 200 mg/m(2) was not associated with an increase in toxicity or nonrelapse (Mel) mortality (NRM).

Incidence Rate, Clinical Correlates, and Outcomes of AKI in Patients Admitted to a Comprehensive Cancer Center

BACKGROUND AND OBJECTIVES Incidence of AKI in hospitalized patients with cancer is increasing, but reports are scant. The objective of this study was to determine incidence rate, clinical correlates, and outcomes of AKI in patients admitted to a cancer center. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Cross-sectional analysis of prospectively collected data on 3558 patients admitted to the University of Texas M.D. Anderson Cancer Center over 3 months in 2006. RESULTS Using modified RIFLE (Risk, Injury, Failure, Loss, ESRD) criteria, 12% of patients admitted to the hospital had AKI, with severity in the Risk, Injury, and Failure categories of 68%, 21%, and 11%, respectively. AKI occurred in 45% of patients during the first 2 days and in 55% thereafter. Dialysis was required in 4% of patients and nephrology consultation in 10%. In the multivariate model, the odds ratio (OR) for developing AKI was significantly higher for diabetes (OR, 1.89; 95% confidence interval [CI], 1.51-2.36), chemotherapy (OR, 1.61; 95% CI, 1.26-2.05), intravenous contrast (OR, 4.55; 95% CI, 3.51-5.89), hyponatremia (OR, 1.97; 95% CI, 1.57-2.47), and antibiotics (OR, 1.52; 95% CI, 1.15-2.02). In patients with AKI, length of stay (100%), cost (106%), and odds for mortality (4.7-fold) were significantly greater. CONCLUSION The rate of AKI in patients admitted to a comprehensive cancer center was higher than the rate in most noncancer settings; was correlated significantly with diabetes, hyponatremia, intravenous contrast, chemotherapy, and antibiotics; and was associated with poorer clinical outcomes. AKI developed in many patients after admission. Studies are warranted to determine whether proactive measures may limit AKI and improve outcomes.

Sustained Low Efficiency Dialysis in the Continuous Mode (C-SLED): Dialysis Efficacy, Clinical Outcomes, and Survival Predictors in Critically Ill Cancer Patients

BACKGROUND AND OBJECTIVES Oliguric, hypotensive patients who require large amounts of fluids may benefit from sustained low-efficiency dialysis performed continuously (C-SLED). C-SLED through higher clearance may improve survival, or through greater nutritional loss may worsen survival. No studies have assessed survival on C-SLED. The objective was to examine patient outcomes and survival predictors on C-SLED. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The data of 199 consecutive cancer patients treated with C-SLED were analyzed. The median duration of C-SLED was 50 h. With 48 h of C-SLED, the blood urea nitrogen (BUN) and serum creatinine levels had decreased by 80% and 73%, respectively. The mean arterial pressure (MAP) was maintained despite higher ultrafiltration and reduced vasopressor use. The 30-d mortality rate was 65%. Despite excellent dialysis, the sequential organ failure assessment (SOFA) score remained predictive of mortality. In the univariate model, higher SOFA scores and lower values for MAP, blood pH, and serum albumin and creatinine levels were associated with higher mortality. Administration of total parenteral nutrition (TPN) was, however, associated with lower mortality. RESULTS In the multivariate model, the higher SOFA score and lower blood pH, MAP and C-SLED duration were associated with higher mortality. In a subset analysis of 129 patients who received C-SLED for at least 48 h, those with higher BUN levels, which were associated with higher TPN infusion, had a lower mortality risk. CONCLUSION This first detailed report on C-SLED indicates that C-SLED can be effective and suggests a link between nutrition and survival.

Estimated glomerular filtration rate changes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors

Chronic use of tyrosine kinase inhibitors (TKIs) may lead to previously unrecognized adverse events. This study evaluated the incidence of acute kidney injury (AKI) and chronic kidney disease (CKD) in chronic‐phase (CP) chronic myeloid leukemia (CML) patients treated with imatinib, dasatinib, and nilotinib.

Tolvaptan in hospitalized cancer patients with hyponatremia: A double-blind, randomized, placebo-controlled clinical trial on efficacy and safety

The rate of hyponatremia is higher in hospitalized cancer patients than in hospitalized patients without cancer and is associated with poor clinical outcomes. The availability of V2 receptor antagonists has been a major breakthrough in the management of hyponatremia, but its efficacy and safety in treating hyponatremia in patients with cancer is not known.

Evaluation and Management of BK Virus-Associated Nephropathy Following Allogeneic Hematopoietic Cell Transplantation

BK virus nephropathy is a common cause of graft loss in kidney transplant recipients. Cases of BK nephropathy following allogeneic hematopoietic cell transplantation (HCT) are underreported. An increased incidence of BK virus-associated nephropathy is being seen in the setting of more profound and prolonged immunosuppression following solid organ transplantation and HCT. We will review diagnostic and treatment modalities for BK-associated nephropathy following allogeneic HCT.

Onconephrology: the need and the emergence of a subspecialty in nephrology

Onconephrology is a new and evolving field of subspecialization in nephrology that deals with the study of kidney diseases in cancer patients, and, by extension, a nephrologist who further specializes in onconephrology can be considered as an onconephrologist. Remarkable advances in cancer medicine have required many cancer programs to become subspecialized, for example, into lymphoma/myeloma, leukemia, stem-cell transplantation (SCT), and various solid-tumor programs. Onconephrology, however, is a broad term that currently encompasses kidney diseases in any cancer setting, whether the tumor is liquid or solid, although further specialization—for example, onconephrology in hematological cancer—remains a possibility.

Topical cidofovir–induced acute kidney injury in two severely immunocompromised patients with refractory multidrug-resistant herpes simplex virus infections

Cidofovir, a nucleoside analog of deoxycytidine monophosphate, is a water-soluble polar molecule that exhibits antiviral activity against a broad range of DNA viruses. Cidofovir for injection is approved for the treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. The safety and efficacy of topical cidofovir has been described in a limited number of patients. We present two cases of multidrug-resistant herpes simplex virus infections that responded to topical cidofovir therapy yet resulted in irreversible acute kidney injury.

Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias

Micro‐Abstract We evaluated the incidence of renal adverse events and estimated glomerular filtration rate in patients with Philadelphia chromosome‐positive leukemias receiving first‐line bosutinib (n = 248) or imatinib (n = 251), or second‐line or later bosutinib (n = 570). Results show that long‐term bosutinib treatment is associated with an apparently reversible decline in renal function with frequency and characteristics similar to those observed with long‐term imatinib. Background: The purpose of the study was to assess renal function in patients with Philadelphia chromosome‐positive leukemias receiving bosutinib or imatinib. Patients and Methods: Patients received first‐line bosutinib (n = 248) or imatinib (n = 251; phase III trial), or second‐line or later bosutinib (phase I/II trial; n = 570). Adverse events (AEs) and changes from baseline in estimated glomerular filtration rate (eGFR) and serum creatinine were assessed. Results: Time from the last patients first dose to data cutoff was ≥ 48 months. Renal AEs were reported in 73/570 patients (13%) receiving second‐line or later bosutinib, and in 22/248 (9%) and 16/251 (6%) receiving first‐line bosutinib and imatinib, respectively. eGFR in patients receiving bosutinib declined over time with more patients developing Grade ≥ 3b eGFR (< 45 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease method) with second‐line or later bosutinib (139/570, 24%) compared with first‐line bosutinib (26/248, 10%) and imatinib (25/251, 10%); time to Grade ≥ 3b eGFR was shortest with second‐line or later bosutinib. Similar proportions of patients receiving second‐line or later bosutinib (74/139, 53%), first‐line bosutinib (15/26, 58%), and first‐line imatinib (15/25, 60%) improved to ≥ 45 mL/min/1.73 m2 eGFR as of the last follow‐up. In a regression analysis, first‐line treatment with bosutinib versus imatinib was not a significant predictor of Grade ≥ 3b eGFR. Conclusion: Long‐term bosutinib treatment is associated with an apparently reversible decline in renal function with frequency and characteristics similar to renal decline observed with long‐term imatinib treatment. Patients with risk factors for Grade ≥ 3b eGFR should be monitored closely.