Immune checkpoint inhibitor-associated nephritis - treatment standard.

Over the last 13 years, the use of immune checkpoint inhibitor (ICI) therapy has grown remarkably, owing to their unprecedented anti-tumor efficacy in certain tumor groups. With increased use of ICIs, we are seeing immune-related adverse events (irAE's) more frequently. Renal irAE's, such as ICI-associated acute kidney injury (ICI-AKI), are reported in 2-5% of patients treated with ICIs, with acute tubulointerstitial nephritis (ATIN) as the most common histopathologic lesion, though various forms of glomerulonephritis have also been reported. Modifiable risk factors for ICI-AKI include concurrent use of ATIN-associated drugs, like proton pump inhibitors, non-steroidal anti-inflammatory drugs and antibiotics, and dual ICI therapy with both CTLA-4 and PD1/PDL-1 blockade. Kidney biopsies remain the diagnostic modality of choice, though several promising non-invasive biomarkers, which have not yet been broadly clinically validated have emerged. The treatment of ICI-AKI involves holding ICIs, discontinuation of ATIN-associated drugs, and initiation of immunosuppression with corticosteroids as first-line therapy. With prompt treatment initiation, most patients achieve full or partial renal recovery, allowing for re-challenge with ICI. However, a subset of patients will require additional steroid-sparing therapies for corticosteroid-dependent or refractory ICI-AKI. Here we review developments in our understanding of the pathophysiology of ICI-AKI, the approach to diagnosis (with a focus on the emergence of novel diagnostic tools), prognostic factors and the current evidence for establishing treatment standards for ICI-AKI. As the evidence base remains largely retrospective, we identify questions that would benefit from future prospective studies in the diagnosis, management, and prognostication of ICI-AKI.

Management of urothelial cancer in patients with chronic kidney disease receiving platinum-based chemotherapy.

Despite recent advances in the management of urothelial cancer (UC), cisplatin-based combination chemotherapy regimens remain critical. However, their use can be complicated in patients with chronic kidney disease (CKD), which is not uncommon in UC patients. Based on the Galsky criteria for cisplatin ineligibility, most patients with CKD will be excluded from receiving cisplatin-based chemotherapy altogether. For patients with borderline kidney function, several strategies - such as the use of split-dose cisplatin, dose reductions, or extra hydration - may facilitate the use of cisplatin, but these need to be prospectively validated. This review highlights the critical need for a multidisciplinary team, including onco-nephrologists, to help manage renal complications and optimize delivery of cancer care in complex UC patients with CKD.

In patients with urothelial cancer, the presence of chronic kidney disease can significantly impact treatment options, eligibility for clinical trials, and overall patient outcomes. This review discusses key strategies and newer treatment options that can be used to optimize outcomes in patients who often can't receive standard treatments. Importantly, this article also highlights the critical importance and need for a multidisciplinary team of specialists, including kidney specialists with a focus on cancer patients, to help manage kidney function and deliver high-quality care to patients with urothelial cancer and chronic kidney disease.

Measurement of Glomerular Filtration Rate in Patients Undergoing Renal Surgery for Cancer: Estimated Glomerular Filtration Rate versus Measured Glomerular Filtration Rate in the Era of Precision Medicine.

BACKGROUND: In the era of precision medicine, determining reliable renal function assessment remains a critical and debatable issue, especially in nephrology and oncology. SUMMARY: This paper delves into the significance of accurately measured glomerular filtration rate (mGFR) in clinical practice, highlighting its essential role in guiding medical decisions and managing kidney health, particularly in the context of renal cancer (RC) patients undergoing nephrotoxic anti-cancer drugs. The limitations and advantages of traditional glomerular filtration rate (GFR) estimation methods, primarily using serum biomarkers like creatinine and cystatin C, are discussed, emphasizing their possible inadequacy in cancer patients. Specifically, newer formulae designed for GFR estimation in cancer patients may not perform at best in RC patients. The paper explores various methods for direct GFR measurement, including the gold standard inulin clearance and alternatives like iohexol plasma clearance. KEY MESSAGE: Despite the logistical challenges of these methods, their implementation is crucial for accurate renal function assessment. The paper concludes by emphasizing the need for continued research and innovation in GFR measurement methodologies to improve patient outcomes, particularly in populations with complex medical needs.

Proteinuria frequency and subsequent renal dysfunction in bevacizumab-treated patients: a single center, retrospective, observational study.

BACKGROUND: Proteinuria is a common adverse event observed during treatment with antivascular endothelial growth factor (VEGF) antibodies. Proteinuria is a risk factor for renal dysfunction and cardiovascular complications in patients with chronic kidney disease. However, the association between anti-VEGF antibody-induced proteinuria and renal dysfunction or cardiovascular complications remains unclear. METHODS: This retrospective, observational study included patients with cancer that were treated with bevacizumab (BV) at Kyoto University Hospital (Kyoto, Japan) between January 2006 and March 2018. Adverse event rates were compared between patients who developed qualitative ≥ 2 + proteinuria and those who developed < 1 + proteinuria. Adverse events were defined as renal dysfunction (i.e., ≥ 57% decrease in the eGFR, compared to the rate at the initial treatment) and hospitalization due to BV-associated cardiovascular complications and other adverse events. RESULTS: In total, 734 patients were included in this analysis. Renal dysfunction was more common in patients with ≥ 2 + proteinuria than in those with < 1 + proteinuria (13/199, 6.5% vs. 12/535, 2.3%). Seven of these 13 patients with ≥ 2 + proteinuria had transient reversible renal dysfunction. Only four (2.0%) patients had BV-associated renal dysfunction. Of the 734 patients, six patients, 16 patients, and 13 patients were hospitalized because of the adverse events of cardiovascular complications, thromboembolisms, and cerebrovascular complications, respectively. No relationship was observed between these adverse events and proteinuria. CONCLUSION: BV treatment-induced proteinuria was not associated with renal dysfunction or other adverse events. Continuing BV with caution is a possible treatment option, even after proteinuria develops, in patients with cancer and a limited prognosis.

Breast cancer, alcohol, and phosphate toxicity.

Alcohol consumption is associated with an increased risk of breast cancer, even at low alcohol intake levels, but public awareness of the breast cancer risk associated with alcohol intake is low. Furthermore, the causative mechanisms underlying alcohol's association with breast cancer are unknown. The present theoretical paper uses a modified grounded theory method to review the research literature and propose that alcohol's association with breast cancer is mediated by phosphate toxicity, the accumulation of excess inorganic phosphate in body tissue. Serum levels of inorganic phosphate are regulated through a network of hormones released from the bone, kidneys, parathyroid glands, and intestines. Alcohol burdens renal function, which may disturb the regulation of inorganic phosphate, impair phosphate excretion, and increase phosphate toxicity. In addition to causing cellular dehydration, alcohol is an etiologic factor in nontraumatic rhabdomyolysis, which ruptures cell membranes and releases inorganic phosphate into the serum, leading to hyperphosphatemia. Phosphate toxicity is also associated with tumorigenesis, as high levels of inorganic phosphate within the tumor microenvironment activate cell signaling pathways and promote cancer cell growth. Furthermore, phosphate toxicity potentially links cancer and kidney disease in onco-nephrology. Insights into the mediating role of phosphate toxicity may lead to future research and interventions that raise public health awareness of breast cancer risk and alcohol consumption.

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study.

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m2 , the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m2 were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m2 were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m2 revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m2 , with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.

A Predictive Model for Kidney Failure After Nephrectomy for Localized Kidney Cancer: The Kidney Cancer Risk Equation.

RATIONALE & OBJECTIVE: Nephrectomy is the mainstay of treatment for individuals with localized kidney cancer. However, surgery can potentially result in the loss of kidney function or in kidney failure requiring dialysis/kidney transplantation. There are currently no clinical tools available to preoperatively identify which patients are at risk of kidney failure over the long term. Our study developed and validated a prediction equation for kidney failure after nephrectomy for localized kidney cancer. STUDY DESIGN: Population-level cohort study. SETTING & PARTICIPANTS: Adults (n=1,026) from Manitoba, Canada, with non-metastatic kidney cancer diagnosed between January 1, 2004, and December 31, 2016, who were treated with either a partial or radical nephrectomy and had at least 1 estimated glomerular filtration rate (eGFR) measurement before and after nephrectomy. A validation cohort included individuals in Ontario (n=12,043) with a diagnosis of localized kidney cancer between October 1, 2008, and September 30, 2018, who received a partial or radical nephrectomy and had at least 1 eGFR measurement before and after surgery. NEW PREDICTORS & ESTABLISHED PREDICTORS: Age, sex, eGFR, urinary albumin-creatinine ratio, history of diabetes mellitus, and nephrectomy type (partial/radical). OUTCOME: The primary outcome was a composite of dialysis, transplantation, or an eGFR<15mL/min/1.73m2 during the follow-up period. ANALYTICAL APPROACH: Cox proportional hazards regression models evaluated for accuracy using area under the receiver operating characteristic curve (AUC), Brier scores, calibration plots, and continuous net reclassification improvement. We also implemented decision curve analysis. Models developed in the Manitoba cohort were validated in the Ontario cohort. RESULTS: In the development cohort, 10.3% reached kidney failure after nephrectomy. The final model resulted in a 5-year area under the curve of 0.85 (95% CI, 0.78-0.92) in the development cohort and 0.86 (95% CI, 0.84-0.88) in the validation cohort. LIMITATIONS: Further external validation needed in diverse cohorts. CONCLUSIONS: Our externally validated model can be easily applied in clinical practice to inform preoperative discussions about kidney failure risk in patients facing surgical options for localized kidney cancer. PLAIN-LANGUAGE SUMMARY: Patients with localized kidney cancer often experience a lot of worry about whether their kidney function will remain stable or will decline if they choose to undergo surgery for treatment. To help patients make an informed treatment decision, we developed a simple equation that incorporates 6 easily accessible pieces of patient information to predict the risk of reaching kidney failure 5 years after kidney cancer surgery. We expect that this tool has the potential to inform patient-centered discussions tailored around individualized risk, helping ensure that patients receive the most appropriate risk-based care.

Onco-nephrology: Physicians' Expectations About a New Subspecialty.

INTRODUCTION: Renal events are common in cancer patients and malignancy is a prevalent complication in both patients transplanted and under kidney replacement therapy (KRT). In recent years, onco-nephrology has been developed as a subspecialty whose scope has not been well established yet. The aim of our study was to assess resident and senior physicians' knowledge and expectations about onco-nephrology. METHODS AND MATERIALS: Two anonymous self-administered online questionnaires were developed by a multidisciplinary team and distributed to French residents and senior physicians. RESULTS: Two hundred twenty-eight physicians answered the survey, including 128 (56%) nephrologists, of which 98 (43%) were senior physicians and 130 (57%) were residents. Nephrologists rated their confidence in their ability to face onco-nephrological situation at 6/10 (interquartile range (IQR) 4.0-7.0) and oncologists at 6.0/10 (5.0-7.0). Managing cancer drugs in patients on KRT or in transplanted patients and discussion about introducing dialysis in cancer patients were designated as the most challenging topics. Asking if they had received appropriate learning, residents' median agreement was ranked at 3.0/10 (2.0-4.0). Forty-six percent of the respondents considered available resources as not appropriate. Specialized onco-nephrology consultations were accessible for 21% of the respondents. Finally, respondents thought there is a strong need for a national working group (8.3/10) with 87% of them expecting new reliable guidelines. CONCLUSION: The present survey revealed physicians' expectations about onco-nephrology implementation in France. An appropriate answer could be the creation of a national working group. Therefore, GRIFON (Groupe de Recherche Interdisciplinaire en OncoNéphrologie) has recently been created.

Risk of Kidney Failure in Patients With Cancer: A South Korean Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Reduced kidney function is associated with an increased risk of cancer; however, it is unclear if cancer increases the risk of kidney failure with replacement therapy (KFRT). We assessed the risk of KFRT among patients with various types of cancer collectively and with specific types of cancer. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: A total of 2,473,095 participants with (n = 824,365) or without (n = 1,648,730) cancer registered in the Korean National Health Insurance Service database. PREDICTORS: Cancer and cancer subtypes defined using International Classification of Diseases, 10th Revision, Clinical Modification, codes. OUTCOMES: Primary outcome was KFRT defined as the initiation of hemodialysis or peritoneal dialysis or kidney transplantation. ANALYTICAL APPROACH: For each patient with cancer, 2 controls matched for age, sex, estimated glomerular filtration rate, diabetes, and hypertension were included. To address the competing risk of death, a competing risk survival analysis was conducted using the Fine and Gray method. RESULTS: Occurrence of KFRT was higher in patients with cancer than in controls without cancer (incidence rates of 1.07 vs 0.51 cases per 1,000 person-years). Competing risk analysis showed that cancer was significantly associated with an increased risk of KFRT after adjusting for other potential predictors (adjusted hazard ratio, 2.29 [95% CI, 2.20-2.39]). Multiple myeloma, leukemia, lymphoma, and kidney, ovarian, and liver cancer were most significantly associated with an increased KFRT risk, with multiple myeloma conferring the highest risk across age and sex groups. All subgroups of patients with cancer (based on age, sex, smoking, alcohol, exercise, obesity, and comorbid conditions) exhibited a higher risk of KFRT. LIMITATIONS: Causal association between cancer and kidney outcomes could not be confirmed. CONCLUSIONS: Patients with cancer, particularly those with multiple myeloma, exhibited an increased risk of KFRT after accounting for the competing risk of death.

Spectrum of cancer patients receiving renal biopsy.

BACKGROUND: The frontier of onco-nephrology, particularly renal complications of cancer and treatment, remains unexplored. We revisit the fundamental tool of diagnosing kidney disease, renal biopsy, in cancer patients with renal manifestation. METHODS: Patients who received renal biopsy from July 2015 to July 2019 were analyzed. Primary outcomes included end-stage renal disease (ESRD), mortality, and catastrophic outcome defined as either ESRD or mortality. A Cox proportional hazards model and Kaplan-Meier technique were used to assess the association with outcome measurements and survival analyses. Immunosuppression after renal biopsy and response to the treatment were evaluated. RESULTS: Among the 77 patients, the median age was 66 years (interquartile range [IQR] 59-73 years) and 46 (59.7%) were male. At the time of renal biopsy, 57 patients (74%) had various degrees of renal insufficiency. Tubulointerstitial damage score, quantified by renal pathology, were associated with higher hazards of ESRD (hazard ratio [HR], 1.77; 95% confidence interval [95% CI], 1.20 to 2.61; P = 0.004) and catastrophic outcome (HR, 1.30; 95% CI, 0.99 to 1.70; P = 0.058). The response rate to immunosuppression was lower in those diagnosed with tubulointerstitial nephritis (1 of 4 patients, 25%) than those with glomerulopathy (10 of 20 patients, 50%). CONCLUSION: Renal biopsy may improve diagnostic accuracy and assist in treatment guidance of cancer patients with renal manifestation. Renal biopsy should be encouraged with clinical indication. Collaboration between oncologists and nephrologists is of paramount importance to provide more comprehensive care for caner patients.

The renal effects of ALK inhibitors.

Anaplastic lymphoma kinase 1 (ALK-1) is a member of the insulin receptor tyrosine kinase family. In clinical practice, three small molecule inhibitors of ALK-1 are used, namely crizotinib, ceritinib and alectinib. Several more agents are in active pre-clinical and clinical studies. Crizotinib is approved for the treatment of advanced ALK-positive non-small cell lung cancer (NSCLC). According to the package insert and published literature, treatment with crizotinib appears to be associated with kidney failure as well as an increased risk for the development and progression of renal cysts. In addition, this agent is associated with development of peripheral edema and rare electrolyte disorders. This review focuses on the adverse renal effects of Crizotinib in clinical practice.

Thrombotic microangiopathy, cancer, and cancer drugs.

Thrombotic microangiopathy (TMA) is a complication that can develop directly from certain malignancies, but more often results from anticancer therapy. Currently, the incidence of cancer drug-induced TMA during the last few decades is >15%, primarily due to the introduction of anti-vascular endothelial growth factor (VEGF) agents. It is important for clinicians to understand the potential causes of cancer drug-induced TMA to facilitate successful diagnosis and treatment. In general, cancer drug-induced TMA can be classified into 2 types. Type I cancer drug-induced TMA includes chemotherapy regimens (ie, mitomycin C) that can potentially promote long-term kidney injury, as well as increased morbidity and mortality. Type II cancer drug-induced TMA includes anti-VEGF agents that are not typically associated with cumulative dose-dependent cell damage. In addition, functional recovery of kidney function often occurs after drug interruption, assuming a type I agent was not given prior to or during therapy. There are no randomized controlled trials to provide physician guidance in the management of TMA. However, previously accumulated information and research suggest that endothelial cell damage has an underlying immunologic basis. Based on this, the emerging trend includes the use of immunosuppressive agents if a refractory or relapsing clinical course that does not respond to plasmapheresis and steroids is observed.

Onco-nephrology: current concepts and future perspectives.

Onco-nephrology is a new and evolving subspecialized area in nephrology that deals with kidney diseases in cancer patients. As many newer cancer therapies emerge in the field of oncology, cancer patients are surviving longer than ever before. However, the benefits of the remarkable advances in cancer management have not been fully appreciated. Not only is cancer often associated with abnormalities that affect the kidney, but cancer therapy often leads to both acute and chronic kidney diseases. The development of cancer-associated kidney complications is associated with poor prognosis, whereas prompt recognition and treatment initiation are associated with improved outcomes in this population. Therefore, both nephrologists and oncologists should be familiar with the diagnosis and management of cancer-associated kidney complications. Another unique aspect of onco-nephrology is that significant improvements in predialysis and dialysis care in recent years have led to prolonged survival and a higher incidence of patients with chronic kidney disease suffering from cancer. Therefore, research is urgently needed to establish treatment for patients with chronic kidney disease. This update addresses the pathophysiology and treatment of various cancer-associated kidney complications, and highlights cancer treatment for patients with chronic kidney disease.

Immune Checkpoint Inhibitor-Associated Nephrotoxicity.

CONTEXT: The clinical indications for immune checkpoint inhibitors (ICIs) are rapidly expanding. However, adverse events affecting multiple organs, including kidneys leading to ICI-associated acute kidney injury (AKI), remain a significant challenge with ICI therapy. Although AKI is considered a rare complication, it can be severe and result in treatment interruption or discontinuation of ICIs. Despite a generally favorable kidney prognosis, the possibility of re-challenging ICI therapy remains a subject of debate, particularly for patients who have exhausted other treatment options or experienced severe AKI. Subject of Review: In a recent review article, Sprangers et al. provide a comprehensive overview of the possible mechanisms and clinical manifestations of ICI-associated AKI [Nat Rev Nephrol. 2022;18(12):794-805]. The authors propose a practical strategy for diagnosing and managing suspected cases of ICI-associated AKI, which includes identifying a subset of eligible patients who may be re-exposed to ICIs following an episode of AKI. Second Opinion: The authors of the review article offer several recommendations on the diagnosis and treatment of ICI-associated nephrotoxicity. While we generally agree with the recommendations proposed by the authors, it is important to acknowledge that the available data primarily rely on small retrospective studies, as the authors have recognized. In addition, there are two key questions that need be carefully addressed in future studies: (1) the optimal dose and duration of corticosteroids and the use of alternative immunosuppressive agents in patients with ICI-associated nephrotoxicity and (2) a clear guideline for restarting ICI treatment in patients with AKI who have not fully recovered their kidney function.

Primary Renal Lymphoma: A Rare Cause of Bilateral Renal Enlargement and Acute Renal Failure in a Patient With Rheumatoid Arthritis.

Primary renal lymphoma (PRL) is a rare non-Hodgkin's lymphoma (NHL) involving the kidneys without evidence of extra-renal involvement. We describe a 66-year-old female who presented with bilateral pleural effusions, and acute renal failure and was diagnosed with primary renal diffuse large B-cell lymphoma (DLBCL). She presented with shortness of breath due to bilateral pleural effusions and acute renal failure. Computed tomography (CT) of the chest reported bilateral pleural effusions. Thoracocentesis and subsequent fluid analysis reported non-malignant effusion. Her kidney function worsened during her hospital stay, requiring dialysis. Nonspecific findings such as bilateral renal enlargement on imaging prompted a renal biopsy. Histopathology reported mixed tubulointerstitial atypical lymphocytic CD 20 and BCL-6 positive cell infiltrates, confirming non-Hodgkin diffuse large B-cell lymphoma. Whole-body positron emission tomography/CT (PET/CT) and brain magnetic resonance imaging (MRI) ruled out the involvement of any other organs or lymph nodes, confirming our diagnosis of PRL. She was treated with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Her kidney function recovered fully and remained normal at the one-year follow-up. We highlight the importance of recognizing PRL as an underlying cause of renal failure and its association with autoimmune diseases. Prompt investigation with timely diagnosis and treatment can result in improved morbidity and mortality in these patients.

Effects of a Personalized Diet on Nutritional Status and Renal Function Outcome in Nephrectomized Patients with Renal Cancer.

Nutritional therapy (NT) based on a controlled protein intake represents a cornerstone in managing chronic kidney disease (CKD). However, if a CKD patient is at the same time affected by cancer, oncologists and nutritionists tend to suggest a dietary regimen based on high protein intake to avoid catabolism and malnutrition. International guidelines are not clear when we consider onco-nephrological patients and, as a consequence, no clinical shared strategy is currently applied in clinical practice. In particular, no precise nutritional management is established in nephrectomized patients for renal cell carcinoma (RCC), a specific oncological cohort of patients whose sudden kidney removal forces the remnant one to start a compensatory mechanism of adaptive hyperfiltration. Our study aimed to investigate the efficacy of a low-normal-protein high-calorie (LNPHC) diet based on a Mediterranean model in a consecutive cohort of nephrectomized RCC patients using an integrated nephrologist and nutritionist approach. A consecutive cohort of 40 nephrectomized RCC adult (age > 18) patients who were screened for malnutrition (malnutrition screening tool, MST < 2) were enrolled in a tertiary institution between 2020 and 2022 after signing a specific informed consent form. Each patient underwent an initial nephrological and nutritional evaluation and was subsequently subjected to a conventional CKD LNPHC diet integrated with aproteic foods (0.8 g/Kg/die: calories: 30-35 kcal per kg body weight/die) for a period of 6 months (±2 months). The diet was structured after considering eGFR (CKD-EPI 2021 creatinine formula), comorbidities, and nutritional status. MST, body mass index (BMI), phase angle (PA), fat mass percentage (FM%), fat-free mass index (FFMI), body cell mass index (BCMI), extracellular/intracellular water ratio (ECW/ICW), extracellular matrix/body cell mass ratio (ECM/BCM), waist/hip circumference ratio (WHC), lab test exams, and clinical variables were examined at baseline and after the study period. Our results clearly highlighted that the LNPHC diet was able to significantly improve several nutritional parameters, avoiding malnutrition and catabolism. In particular, the LNPHC diet preserved the BCM index (delta on median, ΔM + 0.3 kg/m2) and reduced the ECM/BCM ratio (ΔM - 0.03 *), with a significant reduction in the ECW/ICW ratio (ΔM - 0.02 *), all while increasing TBW (ΔM + 2.3% *). The LNPHC diet was able to preserve FFM while simultaneously depleting FM and, moreover, it led to a significant reduction in urea (ΔM - 11 mg/dL **). In conclusion, the LNPHC diet represents a new important therapeutic strategy that should be considered when treating onco-nephrological patients with solitary kidney due to renal cancer.

Cardiorenal Impact of Anti-Cancer Agents: The Intersection of Onco-Nephrology and Cardio-Oncology.

BACKGROUND: The evolving landscape of cancer treatments has introduced new challenges, particularly related to adverse events associated with chemotherapeutic agents. To address these challenges, the fields of cardio-oncology and onco-nephrology have arisen, focusing on the management of cardiotoxicity and nephrotoxicity attributable to anti-cancer drugs. SUMMARY: Numerous intersections between these disciplines exist, including onco-hypertension (HTN) and cardiorenal toxicities induced by chemotherapeutic agents. Additionally, immune checkpoint inhibitors (ICIs) may cause myocarditis and nephritis. This paper aimed to explore the intersection between cardio-oncology and onco-nephrology. A detailed review will be undertaken, focusing on onco-HTN and the cardiorenal toxicities of chemotherapeutic agents, with a specific emphasis on the adverse effects associated with ICIs. KEY MESSAGES: Multidisciplinary collaboration among oncologists, cardiologists, nephrologists, and other healthcare professionals is crucial for developing tailored approaches to optimize treatment efficacy while minimizing the risk of cardiovascular and renal complications, ultimately enhancing patient outcomes in modern oncology practice.

CAR T-cell therapy and the onco-nephrologist.

Cell therapy, specifically the revolutionary chimeric antigen receptor (CAR) T-cell therapy, has transformed the landscape of oncology, making substantial strides in practical treatment approaches. Today, established guidelines for diseases such as lymphomas, myelomas, and leukemias actively advocate the utilization of these once-unconventional therapies. The practical impact of these therapies is underscored by their unparalleled efficacy, reshaping the way we approach and implement treatments in the realm of oncology. However, CAR T-cell therapy, with its performance in anti-tumor aggression through cellular action and inflammatory response, also comes with various adverse events, one of which is kidney injury. Therefore, the management of these side effects is extremely important. The integration of knowledge between oncologists and specialized nephrologists has led to the emergence of a new sub-area of expertise for onco-nephrologists specializing in managing kidney complications from immune effector therapies.

Inclusion of patients with chronic kidney disease in randomized phase 3 clinical trials in patients with prostate, breast, lung, and colorectal cancer.

The objective of this study was to determine the proportion of phase 3 clinical trials investigating a systemic therapy for patients with prostate, breast, lung, or colorectal cancer that excluded patients with Chronic Kidney Disease (CKD) and the exclusion criteria chosen, if any. A search was conducted using the ClinicalTrials.gov database to identify eligible studies. Of the 268 included trials, 185 (69%) had at least one renal exclusion criteria. Of these 185 trials, 116 (63%) had an undefined exclusion criterion. Only disease site was associated with exclusion of patients with CKD in the univariate analysis, but no factors in the multivariate analysis. There are several potential barriers to including patients with CKD in clinical trials. Nevertheless, solutions can be proposed to allow the inclusion of these patients. This would allow them to access to innovative therapeutic strategies, but also allow a better applicability of trial results to this patient population.

BK Viremia and Changes in Estimated Glomerular Filtration Rate in Children and Young Adults after Hematopoietic Cell Transplantation.

Kidney disease in allogeneic hematopoietic cell transplantation (HCT) recipients is associated with increased mortality rates. BK virus (BKV) viremia has been associated with kidney dysfunction in pediatric HCT recipients; however, few studies have investigated longer-term kidney outcomes in association with BKV in this population. Here we assessed the relationship between BK viremia and changes in estimated glomerular filtration rate (eGFR) in children in the first year post-HCT. We selected 136 patients age ≤26 years who underwent HCT in 2007 to 2018 at a single center and had plasma BK viral load data available at 2 time points, weeks 4 to 7 post-HCT and weeks 10 to 13 post-HCT from prospectively collected stored plasma samples. A total of 272 samples were analyzed for BKV using quantitative PCR. We used multivariate linear models to determine the association of BK viremia and change in eGFR by 1 year post-HCT. Forty percent of the patients (54 of 136) had BKV detection in weeks 4 to 7, 13% of whom (7 of 54) had a BK viral load of ≥10,000 copies/mL, and 46% (62 of 136) had BKV detected in weeks 10 to 13, 34% (21 of 62) of whom had a BK viral load of ≥10,000 copies/mL. The mean decline in eGFR was 25.73 mL/min/1.73 m2 by 1 year post-HCT. In multivariate models, a BK viral load of ≥10,000 copies/mL during weeks 4 to 7 was associated with a mean decline in eGFR of 30.6 mL/min/1.73 m2 (95% confidence interval, -55.94 to -5.17; P = .019) compared with a BK viral load <10,000 copies/mL. In adjusted analyses, a high BK viral load in the blood (≥10,000 copies/mL) was associated with a significant decline in eGFR by 1 year post-HCT.