Hypophosphatemia and FGF23 tumor-induced osteomalacia in two cases of metastatic breast cancer.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by factor-induced dysregulation of phosphate and vitamin D metabolism resulting in alterations in bone formation, leading to bone pain and fractures. While the true incidence is likely underestimated, less than 500 cases of TIO have been reported since initial description in 1947. TIO cases have classically been associated with mesenchymal tumors of bone and soft tissue, but have also rarely been linked to malignant tumors, with scant reports implicating non-mesenchymal tumors. TIO is mediated through inappropriate tumor overproduction of fibroblast growth factor 23 (FGF23). Increased FGF23 secretion leads to hypophosphatemia by (1) reduced phosphate reabsorption via activation of the proximal renal tubular epithelial cells to internalize sodium phosphate cotransporters and (2) reduced activation of vitamin D3 via inhibition of the renal enzyme 1-α hydroxylase. Low circulating levels of active vitamin D lead to reduced intestinal phosphate absorption and impaired mineralization of osteoid matrix. TIO in breast cancer poses a distinct diagnostic challenge due to the common adjunct oncologic management with bone protection therapy such as denosumab or bisphosphonates. These agents can be culprits of hypophosphatemia and hypocalcemia, rendering timely diagnosis of TIO difficult. Delay of diagnosis of TIO can result in worsening functional status, and early morbidity and mortality. To date, there has been one prior case report of TIO in breast cancer, and herein we describe two additional cases of TIO in this setting.

Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.

BACKGROUND: Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse. METHODS: We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI. RESULTS: Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. CONCLUSIONS: This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.

Kidney Complications of Immune Checkpoint Inhibitors: A Review.

Immunologic control of malignancy has long been recognized as an important determinant of disease progression. Recent advances in immunology have led to the focus on several mechanisms that can be targeted to achieve tumor suppression. In particular, checkpoint inhibition has evolved in less than a decade to become one of the most important strategies in cancer therapy, with a meaningful improvement in patient survival. Six agents have been approved for clinical use to date and many more are in the industry pipeline. The spectrum of malignancies responsive to immunotherapy ranges from advanced melanoma, for which the first immune checkpoint inhibitor ipilimumab was approved, to Hodgkin lymphoma, non-small cell lung cancer, renal cell carcinoma, and others. Notwithstanding its clinical benefits, checkpoint inhibition carries a risk for significant off-target toxicity stemming from the immune system activation. In this review, we discuss general principles of checkpoint inhibition, mechanisms of toxicity, and kidney complications of the treatment and propose diagnostic and treatment strategies when kidney injury occurs.

Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (CPIs), monoclonal antibodies that target inhibitory receptors expressed on T cells, represent an emerging class of immunotherapy used in treating solid organ and hematologic malignancies. We describe the clinical and histologic features of 13 patients with CPI-induced acute kidney injury (AKI) who underwent kidney biopsy. Median time from initiation of a CPI to AKI was 91 (range, 21 to 245) days. Pyuria was present in 8 patients, and the median urine protein to creatinine ratio was 0.48 (range, 0.12 to 0.98) g/g. An extrarenal immune-related adverse event occurred prior to the onset of AKI in 7 patients. Median peak serum creatinine was 4.5 (interquartile range, 3.6-7.3) mg/dl with 4 patients requiring hemodialysis. The prevalent pathologic lesion was acute tubulointerstitial nephritis in 12 patients, with 3 having granulomatous features, and 1 thrombotic microangiopathy. Among the 12 patients with acute tubulointerstitial nephritis, 10 received treatment with glucocorticoids, resulting in complete or partial improvement in renal function in 2 and 7 patients, respectively. However, the 2 patients with acute tubulointerstitial nephritis not given glucocorticoids had no improvement in renal function. Thus, CPI-induced AKI is a new entity that presents with clinical and histologic features similar to other causes of drug-induced acute tubulointerstitial nephritis, though with a longer latency period. Glucocorticoids appear to be a potentially effective treatment strategy. Hence, AKI due to CPIs may be caused by a unique mechanism of action linked to reprogramming of the immune system, leading to loss of tolerance.

The occurrence of hyponatremia and its importance as a prognostic factor in a cross-section of cancer patients.

BACKGROUND: Hyponatremia is prognostic of higher mortality in some cancers but has not been well studied in others. We used a longitudinal design to determine the incidence and prognostic importance of euvolemic and hypervolemic hyponatremia in patients following diagnosis with lymphoma, breast (BC), colorectal (CRC), small cell lung (SCLC), or non-small cell lung cancer (NSCLC). METHODS: Medical record and tumor registry data from two large integrated delivery networks were combined for patients diagnosed with lymphoma, BC, CRC, or lung cancers (2002-2010) who had ≥1 administration of radiation/chemotherapy within 6 months of diagnosis and no evidence of hypovolemic hyponatremia. Hyponatremia incidence was measured per 1000 person-years (PY). Cox proportional hazard models assessed the prognostic value of hyponatremia as a time-varying covariate on overall survival (OS) and progression-free survival (PFS). RESULTS: Hyponatremia incidence (%, rate) was 76 % each, 1193 and 2311 per 1000 PY, among NSCLC and SCLC patients, respectively; 37 %, 169 in BC; 64 %, 637 in CRC, and 60 %, 395 in lymphoma. Hyponatremia was negatively associated with OS in BC (HR 3.7; P = <.01), CRC (HR 2.4; P < .01), lung cancer (HR 2.4; P < .01), and lymphoma (HR 4.5; P < .01). Hyponatremia was marginally associated with shorter PFS (HR 1.3, P = .07) across cancer types. CONCLUSIONS: The incidence of hyponatremia is higher than previously reported in lung cancer, is high in lymphoma, BC, and CRC and is a negative prognostic indicator for survival. Hyponatremia incidence in malignancy may be underestimated. The effects of hyponatremia correction on survival in cancer patients require further study.

Brincidofovir for polyomavirus-associated nephropathy after allogeneic hematopoietic stem cell transplantation.

Polyomavirus-associated nephropathy (PVAN) is common in patients who have undergone kidney transplantation and has been reported in hematopoietic stem cell (HSC) transplant recipients. Aside from reduction of immunosuppression, few therapeutic options exist for treatment of PVAN. We report a case of PVAN in a severely immunocompromised allogeneic HSC transplant recipient that was treated with brincidofovir without reduction of immunosuppression. We review our institutional experience of PVAN in HSC transplantation and discuss the potential use of brincidofovir for treatment.

Relationship of BK polyoma virus (BKV) in the urine with hemorrhagic cystitis and renal function in recipients of T Cell-depleted peripheral blood and cord blood stem cell transplantations.

Hematopoietic stem cell transplant (HSCT) recipients are at significant risk for BK virus (BKV) reactivation, hemorrhagic cystitis (HC), and renal dysfunction. We prospectively monitored 98 patients who had received HSCT by serial BKV PCR in the urine through day (D) +100 to analyze the relationship between BK viruria and HC, serum creatinine (Cr), and creatinine clearance (CrCl) through D +180 or death. Patients, median age 52 years (range, 20 to 73), received T cell-depleted (50%) or cord blood allografts (21%). Median pre-HSCT BKV IgG titers were 1:10,240. Incremental increase in BKV IgG titers correlated with developing BK viruria ≥ 10(7) copies/mL. By D +100, 53 (54%) patients had BK viruria. BKV load in the urine increased at engraftment and persisted throughout D +100. HC developed in 10 patients (10%); 7 of 10 with BK viruria. In competing risk analyses, BK viruria ≥ 10(7) copies/mL, older age, cytomegalovirus reactivation, and foscarnet use were risk factors for HC. Cr and CrCl at 2, 3, and 6 months after HSCT were similar between patients with and without BK viruria.

Derivation and external validation of a simple risk score for predicting severe acute kidney injury after intravenous cisplatin: cohort study.

OBJECTIVE: To develop and externally validate a prediction model for severe cisplatin associated acute kidney injury (CP-AKI). DESIGN: Multicenter cohort study. SETTING: Six geographically diverse major academic cancer centers across the US. PARTICIPANTS: Adults (≥18 years) receiving their first dose of intravenous cisplatin, 2006-22. MAIN OUTCOME MEASURES: The primary outcome was CP-AKI, defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of intravenous cisplatin. Independent predictors of CP-AKI were identified using a multivariable logistic regression model, which was developed in a derivation cohort and tested in an external validation cohort. For the primary model, continuous variables were examined using restricted cubic splines. A simple risk model was also generated by converting the odds ratios from the primary model into risk points. Finally, a multivariable Cox model was used to examine the association between severity of CP-AKI and 90 day survival. RESULTS: A total of 24 717 adults were included, with 11 766 in the derivation cohort (median age 59 (interquartile range (IQR) 50-67)) and 12 951 in the validation cohort (median age 60 (IQR 50-67)). The incidence of CP-AKI was 5.2% (608/11 766) in the derivation cohort and 3.3% (421/12 951) in the validation cohort. Each of the following factors were independently associated with CP-AKI in the derivation cohort: age, hypertension, diabetes mellitus, serum creatinine level, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose. A simple risk score consisting of nine covariates was shown to predict a higher risk of CP-AKI in a monotonic fashion in both the derivation cohort and the validation cohort. Compared with patients in the lowest risk category, those in the highest risk category showed a 24.00-fold (95% confidence interval (CI) 13.49-fold to 42.78-fold) higher odds of CP-AKI in the derivation cohort and a 17.87-fold (10.56-fold to 29.60-fold) higher odds in the validation cohort. The primary model had a C statistic of 0.75 and showed better discrimination for CP-AKI than previously published models, the C statistics for which ranged from 0.60 to 0.68 (DeLong P<0.001 for each comparison). Greater severity of CP-AKI was monotonically associated with shorter 90 day survival (adjusted hazard ratio 4.63 (95% CI 3.56 to 6.02) for stage 3 CP-AKI versus no CP-AKI). CONCLUSION: This study found that a simple risk score based on readily available variables from patients receiving intravenous cisplatin could predict the risk of severe CP-AKI, the occurrence of which is strongly associated with death.

Kidney tubular toxicity of maintenance pemetrexed therapy.

Pemetrexed is an antifolate agent approved for the treatment of advanced lung cancer. Major side effects include myelosuppression and neutropenia. Three patients developed kidney disease while being treated with maintenance pemetrexed. Kidney biopsy specimens showed tubulointerstitial injury with tubular simplification, shrinkage, loss of brush border, and tubular atrophy in a more advanced case. Kidney function remained impaired, but stable, after discontinuation of pemetrexed therapy in all cases.

Nephrotoxicities associated with the use of tyrosine kinase inhibitors: a single-center experience and review of the literature.

BACKGROUND: Sunitinib is an oral multitargeted tyrosine kinase receptor inhibitor (MTKI) used for the treatment of renal cell carcinoma. These small-molecule agents inhibit signaling through receptor tyrosine kinases such as vascular endothelial growth factor receptor, platelet-derived growth factor receptor and cytokine stem cell factor receptor, among others. Although the development of these novel molecular-targeted agents represents a substantial advance in the treatment of metastatic cancer, the spectrum of their adverse effects may be broader than initially predicted. METHOD: We performed a retrospective chart review of patients who had received sunitinib and developed renal insufficiency. RESULTS: We describe 4 patients with renal cell carcinoma and 1 patient with transitional cell carcinoma treated with sunitinib who experienced various degrees of nephrotoxicity including hypertension, proteinuria, thrombotic microangiopathy, and acute and chronic kidney injury which resolved upon cessation of MTKI. CONCLUSIONS: Nephrologists and oncologists should be aware of the potential for toxic renal effects, and we recommend guidelines for early recognition and treatment of these conditions in patients receiving MTKI.

Chronic kidney disease, thrombotic microangiopathy, and hypertension following T cell-depleted hematopoietic stem cell transplantation.

Chronic kidney disease (CKD) is now an accepted long-term complication of allogeneic hematopoietic stem cell transplantation. Calcineurin inhibitors (CNI), which are used for prophylaxis and treatment of graft-versus-host disease (GVHD), have been associated with the development of nephrotoxicity. Hypertension (HTN) and thrombotic microangiopathy (TMA) are 2 comorbidities linked to CKD. T cell depletion (TCD) of stem cell grafts can obviate the need for the use of CNI. We conducted a retrospective analysis of 100 patients who underwent TCD transplantation: 30 in group A were conditioned without total-body radiation (TBI) and 70 in group B received a TBI containing regimen. None of the patients received CNI. The median age was 55.5 and 45 years for groups A and B, respectively. Eleven patients developed TMA, all in group B. The 2-year cumulative incidence of sustained CKD was 29.2% and 48.8% in group A and group B, respectively, with a mean follow-up of at least 21 months. CKD free survival was better in the non-TBI group (P = .046). Multivariable survival analysis revealed that exposure to TBI, older age, and TMA were risk factors for CKD. The incidence of new onset or worsening HTN was 6.7% and 25.7% (P = .03) in group A and B, respectively. The use of TBI (P = .0182) and diagnosis of TMA (P = .0006) predisposed patients to the development of HTN using univariable logistic regression models. Thus, despite the absence of CNI, a proportion of these older patients in both groups developed CKD and HTN.

Management of Patients with Acute Methotrexate Nephrotoxicity with High-Dose Leucovorin.

BACKGROUND: Acute kidney injury complicating high-dose methotrexate (HDMTX) therapy increases the risk for severe mucositis, myelosuppression, and death. It is unclear whether high-dose leucovorin and supportive therapy without the use of glucarpidase can reduce toxicity from HDMTX. STUDY DESIGN: The charts of all patients at Memorial Sloan Kettering Cancer Center whose methotrexate (MTX) drug levels at 48 or 72 hours after administration were 10 times or more the toxic level were reviewed between January 2000 and December 2011. RESULTS: Eighty-eight patients (median age 51 years, range 9-90 years) who received 100 courses of HDMTX were identified. Serum creatinine increased by 2-fold from baseline (median, range 1- to 10-fold), but all patients recovered kidney function. Serum levels of MTX were 69 µmol/L (median, range 2.2-400), 6.9 µmol/L (1.3-64), and 2.0 µmol/L (0.05-26) at 24, 48, and 72 hours, respectively, after administration. A statistically significant correlation existed between MTX levels at 48, 72, 96, and 120 hours after administration but not between 24 and 72 hours or subsequent time points. High-dose leucovorin was given in 81% of courses in accordance with institutional protocols in most cases. Myelosuppression was present in 42%; grade III or higher neutropenia in 29%, and thrombocytopenia in 25%. Infectious complications, oral mucositis, and diarrhea occurred in 21%, 17%, and 6% of patients, respectively. Five deaths occurred, none directly attributed to complications from MTX administration. Seven additional patients received glucarpidase at the discretion of a treating physician during the study period, and results are reported separately. CONCLUSION: Patients who had 100 episodes of HDMTX-associated acute kidney injury were treated with a strategy that only included usual supportive measures and high-dose leucovorin. No deaths were directly attributed to complications related to HDMTX. Glucarpidase, an expensive drug, may not be necessary for a significant number of patients.

Kidney Toxicities Associated With Novel Cancer Therapies.

Targeted therapies that act via unique molecular pathways and interfere with cancer cell growth and tumor progression have dramatically changed the cancer treatment paradigm. However, although, ideally, these therapies intend to target only cancer cells, they do often affect nonmalignant tissue. Numerous renal side effects have been reported to date. This article will review clinical presentation, presumed pathophysiology, and treatment of kidney side effects of targeted therapies. Feasibility of the continuation of cancer therapy despite renal toxicity will also be addressed.

Hypertension and VEGF (Vascular Endothelial Growth Factor) Receptor Tyrosine Kinase Inhibition: Effects on Renal Function.

VEGF (vascular endothelial growth factor) receptor tyrosine kinase inhibitors have become first-line therapy for metastatic renal cell carcinoma. Their use commonly leads to hypertension, but their effects on long-term renal function are not known. In addition, it has been suggested that the development of hypertension is linked to treatment efficacy. The objective of this study was to determine the effects of these drugs on long-term renal function, especially in those with renal dysfunction at baseline, and to examine the role of hypertension on these effects. Serum creatinine measurements were used to calculate the estimated glomerular filtration rate for 130 renal cell carcinoma patients who were treated with this class of tyrosine kinase inhibitors. New or worsening hypertension was defined by documented start or addition of antihypertensive medications. Overall, the use of tyrosine kinase inhibitors in patients with estimated glomerular filtration <60 or ≥60 mL/min per 1.73 m2 was not associated with a decline in long-term renal function. During follow-up, 41 patients developed new or worsening hypertension within 30 days from first drug administration, and this was not linked to further reductions in glomerular filtration. These patients seemed to survive longer than those who did not develop hypertension within 30 days, although this was not statistically significant (P=0.07). Our findings suggest that the use of VEGF tyrosine kinase inhibitors does not adversely affect long-term renal function even in the setting of new-onset hypertension or reduced renal function at baseline.

Renal Toxicities of Novel Agents Used for Treatment of Multiple Myeloma.

Survival for patients with multiple myeloma has significantly improved in the last decade in large part due to the development of proteasome inhibitors and immunomodulatory drugs. These next generation agents with novel mechanisms of action as well as targeted therapies are being used both in the preclinical and clinical settings for patients with myeloma. These agents include monoclonal antibodies, deacetylase inhibitors, kinase inhibitors, agents affecting various signaling pathways, immune check point inhibitors, and other targeted therapies. In some cases, off target effects of these therapies can lead to unanticipated effects on the kidney that can range from electrolyte disorders to AKI. In this review, we discuss the nephrotoxicities of novel agents currently in practice as well as in development for the treatment of myeloma.

Two cases of spontaneous remission of non-parasitic chyluria.

OBJECTIVES: Chyluria is a medical condition with presence of chyle in urine. The disease is most prevalent in South East Asian countries mostly caused by parasitic (Wuchereria bancrofti) infections. Our objective was to investigate the spontaneous remission of non-parasitic chyluria. DESIGN AND METHODS: The spontaneous remission of non-parasitic chyluria cases were worked up with diagnostic investigations, clinical assessment and studied in detail with respect to their natural evolution. RESULTS: We present two patients who were evaluated in the nephrology clinic with symptoms of milky urine and painless hematuria. Midnight blood smear was negative for filarial parasites. Urine culture was without mycobacteria. Urine cytology and IgG western blot for cysticercus were negative. Imaging for a lymphatic leak by lymphoscintigraphy was unrevealing. Chyluria resolved spontaneously in both patients. CONCLUSIONS: In our cases, radiologic visualization via lymphoscintigraphy was unrevealing. The patients were managed conservatively and fortunately underwent spontaneous remission marked by the disappearance of chyluria within several months of her initial diagnosis. In our opinion this spontaneous remission could be due to unrevealed lymphatico-renal fistula collapse or sclerosis of lymphatics caused by contrast media.

Hypophosphatemia after Hepatectomy or Pancreatectomy: Role of the Nicotinamide Phosphoribosyltransferase.

BACKGROUND: Postoperative hypophosphatemia is common and is associated with a lower risk of liver failure after hepatectomy, but higher morbidity after pancreatectomy. Whether different physiologic mechanisms underlie the hypophosphatemia associated with these very different clinical outcomes is unclear. This study aims to evaluate the underlying mechanism in postoperative hypophosphatemia. STUDY DESIGN: We prospectively enrolled 120 patients who underwent major hepatectomy (n = 30), minor hepatectomy (n = 30), pancreatectomy (n = 30), and laparotomy without resection (control group, n = 30). Preoperative and postoperative serum and urinary phosphorus, calcium, and creatinine, as well as phosphaturic factors, including serum nicotinamide phosphoribosyltransferase (NAMPT), fibroblast growth factor-23, and parathyroid hormone were measured. In addition, we evaluated urinary levels of nicotinamide catabolites, N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide. RESULTS: We found that significant hypophosphatemia occurred from postoperative day (POD) 1 to POD 2 in all 4 groups and was preceded by hyperphosphaturia from preoperative day to POD 1. Phosphate level alterations were associated with a significant increase in NAMPT levels from preoperative day to POD 2 in all 3 resected groups, but not in the control group. The fibroblast growth factor-23 levels were significantly decreased postoperatively in all 4 groups, and parathyroid hormone levels did not change in any of the 4 groups. Urine levels of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide decreased significantly in all 4 groups postoperatively. CONCLUSIONS: This study demonstrates that the mechanism of hypophosphatemia is the same for both liver and pancreas resections. Postoperative hypophosphatemia is associated with increased NAMPT. The mechanism that upregulates NAMPT and its role on disparate clinical outcomes in postoperative patients warrant additional investigation.

Paraprotein-Related Kidney Disease: Diagnosing and Treating Monoclonal Gammopathy of Renal Significance.

Paraprotein-related kidney disease represents a complex group of diseases caused by an abnormal paraprotein secreted by a clone of B cells. The disease manifestations range from tubulopathies, such as the Fanconi syndrome, to a spectrum of glomerular diseases that can present with varying degrees of proteinuria and renal dysfunction. Diagnosis of these diseases can be challenging because of the wide range of manifestations as well as the relatively common finding of a serum paraprotein, especially in elderly patients. Thus, renal biopsy along with detailed hematologic workup is essential to link the presence of the paraprotein to the associated renal disease. Recent advances in treatment with more effective and targeted chemotherapies, as well as stem cell transplantation, have improved the renal and overall prognosis for many of these disorders.

Long-Term Renal Outcomes after Cisplatin Treatment.

BACKGROUND AND OBJECTIVES: Nephrotoxicity remains the dose-limiting side effect of cisplatin, an effective chemotherapeutic agent with applications across diverse tumor types. This study presents data on renal outcomes across multiple tumor types in 821 adults. We report on incidence of AKI, initial and long-term changes in eGFR after cisplatin, and relationships between cumulative dose, initial eGFR, age, sex, and long-term renal function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective study of adult patients treated with cisplatin from January 1, 2000 to September 21, 2011 who had survived ≥5 years after initial dose. The Modification of Diet in Renal Disease equation was used to calculate eGFR. AKI was defined as an increase from the baseline creatinine of >25% within 30 days after the first cycle of cisplatin. Chi-squared tests were done to evaluate the relationships between categorical or ordinal variables; ANOVAs or t tests were used to evaluate continuous or categorical variables. Changes in eGFR over time were evaluated in a growth curve model. RESULTS: Mean follow-up was 6 years (25th and 75th percentiles, 4 and 9 years). AKI occurred in 31.5% of patients, with a median initial decline in eGFR of 10 ml/min per 1.73 m(2) (25th and 75th percentiles, -41.5 and -23.3 ml/min per 1.73 m(2)). At any time point after the first cycle of cisplatin, <3% of patients progressed to eGFR<29 ml/min per 1.73 m(2), and none were known to be on dialysis. Age was associated with a higher risk for AKI after cisplatin. Compared with age <25 years old, the odds ratios for AKI versus no AKI are 1.22 for >26-44 years old (95% confidence interval [95% CI], 0.60 to 2.4), 1.54 for >45-65 years old (95% CI, 0.78 to 3), and 2.96 for >66 years old (95% CI, 1.4 to 6.1). The lowest dose categories of cisplatin (≤100 and 101-250 mg/m(2)) are associated with increases in eGFR (P=0.06 and P=0.02, respectively) compared with the highest dose category (>701 mg/m(2)). CONCLUSIONS: This is the largest study of adult patients with cancer who received cisplatin for treatment across multiple tumor types. Most patients experience small but permanent declines in eGFR, but none progressed to ESRD requiring hemodialysis.