Cancer therapy in patients with reduced kidney function.

Chronic Kidney Disease (CKD) and cancer constitute two major public health burdens and are on the rise. Moreover, the number of patients affected simultaneously by both conditions is growing. Potential nephrotoxic effect of cancer therapies is particularly important for patients with CKD, as they are also affected by several comorbidities. Therefore, administering the right therapy at the right dose for patients with decreased kidney function can represent a daunting challenge. We review in detail the renal toxicities of anti-cancer therapies i.e. conventional chemotherapy, targeted therapy, immune checkpoint inhibitors, and radioligand therapies, issue recommendations for patient monitoring along with guidance on when to withdraw treatment and suggest dosage guidelines for select agents in advanced stage CKD. Various electrolytes disturbances can occur as the result of the administration of anti-cancer agents in the patient with decreased kidney function. These patients are prone to developing hyponatremia, hyperkalemia, and other metabolic abnormalities because of a decreased GFR. Therefore, all electrolytes, minerals and acid base status should be checked at baseline and before each administration of chemotherapeutic agents. Moreover, studies on patients on kidney replacement therapy (KRT) are very limited and only single cases or small case series are published. Therefore, clinical therapeutical decisions in cancer patients with decreased function should be made by multidisciplinary teams constituted of medical oncologists, nephrologists, and other specialists. Onconephrology is an evolving and expanding subspecialty. It is crucial to consider anticancer drug treatment in these patients and offer them a chance to be treated effectively.

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.

Lung cancer-kidney cross talk induces kidney injury, interstitial fibrosis, and enhances cisplatin-induced nephrotoxicity.

Patients with cancer represent a unique patient population with increased susceptibility to kidney disease. Drug-induced acute kidney injury (AKI) in patients with cancer is a common problem. Cisplatin is a highly effective treatment used in many solid-organ cancers and causes AKI in 30% of patients, increasing the risk of chronic kidney disease development. Most preclinical cisplatin toxicity studies have been completed in mice without cancer. We believe that the physiology of patients with cancer is not adequately represented in preclinical models, and the objective of this study was to determine how lung cancer will alter the nephrotoxicity of cisplatin. A genetically engineered mouse model and a syngeneic xenograft model of lung cancer were used. Mice were divided into the following four groups: 1) noncancer/vehicle, 2) noncancer/cisplatin, 3) cancer/vehicle, and 4) cancer/cisplatin. Mice were administered cisplatin via intraperitoneal injection once a week for 4 wk. Animals were euthanized 72 h following their final cisplatin injection. Mice with lung cancer had increased renal toxicity, injury, and fibrosis following repeated low doses of cisplatin. In addition, lung cancer alone induced kidney injury and fibrosis in the kidney before cisplatin treatment. In conclusion, this is the first study that we are aware of that assesses the impact of cancer on the kidney in conjunction with the nephrotoxicity of cisplatin. We believe that cancer is providing the first hit to the kidney and the subsequent damage from repeated doses of cisplatin becomes unsurmountable, leading to AKI and progression to chronic kidney disease.NEW & NOTEWORTHY Patients with cancer have impaired kidney function and increased susceptibility to nephrotoxic agents. Cisplatin is a commonly used chemotherapeutic with nephrotoxicity as the dose-limiting side effect. Cisplatin nephrotoxicity is almost exclusively studied in mice without cancer. Our current preclinical models do not adequately represent the complexity of patients with cancer. This study demonstrates increased renal toxicity, injury, and fibrosis in mice with lung cancer, which is exacerbated with cisplatin treatment. These results highlight the necessity of using preclinical models that more accurately capture the altered physiology of patients with cancer treated with cisplatin.

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.

Long-Term Kidney and Cardiovascular Complications in Pediatric Cancer Survivors.

OBJECTIVE: The objective of this study was to describe the burden of adverse kidney and hypertension outcomes in patients evaluated by pediatric nephrology in a multidisciplinary survivorship clinic. STUDY DESIGN: Retrospective chart review of all patients followed up by nephrology in our multidisciplinary survivorship clinic from August 2013 to June 2021. Data included clinic blood pressure, longitudinal ambulatory blood pressure monitoring (ABPM), echocardiography, serum creatinine, and first-morning urine protein/creatinine ratios. For patients with multiple ABPMs, results of initial and most recent ABPMs were compared. RESULTS: Of 422 patients followed in the multidisciplinary cancer survivorship clinic, 130 were seen by nephrology. The median time after therapy completion to first nephrology visit was 8 years. The most common diagnoses were leukemia/myelodysplastic syndrome (27%), neuroblastoma (24%), and Wilms tumor (15%). At the last follow-up, 68% had impaired kidney function, 38% had a clinical diagnosis of hypertension, and 12% had proteinuria. There were 91 ABPMs performed in 55 (42%) patients. Patients with multiple ABPMs (n = 21) had statistically significant reductions in overall median blood pressure loads: systolic initial load 37% vs most recent 10% (P = .005) and diastolic load 36% vs 14% (P = .017). Patients with impaired kidney function were more likely to have received ifosfamide. Patients with hypertension were more likely to have received total body irradiation or allogeneic stem cell transplant. CONCLUSIONS: History of leukemia/myelodysplastic syndrome, neuroblastoma, and Wilms tumor was frequent among survivors seen by nephrology. There was significant improvement in cardiovascular measures with increased recognition of hypertension and subsequent treatment.

Onconephrology: Core Curriculum 2023.

Onconephrology focuses on management of kidney disease in cancer, which manifests itself in a variety of clinical syndromes, including acute kidney injury, chronic kidney disease, hypertension, proteinuria, and electrolyte disorders. Many of these syndromes result from cancer treatments including chemotherapy, immunotherapy, chimeric antigen receptor T cells, and stem cell transplant. Others are due to kidney-specific effects of the cancer, as seen with monoclonal gammopathy or glomerular diseases associated with malignancy. Further, cancer risk itself is heightened in patients with kidney disease, particularly kidney transplant recipients, and their care requires specific considerations. In this installment of AJKD's Core Curriculum in Nephrology, we review these and other core concepts in onconephrology, using a case-based approach to highlight clinical decision making.

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.

AA amyloidosis associated with cancers.

Systemic AA amyloidosis is associated with systemic inflammatory processes such as autoimmune disorders or chronic infections. In addition, AA amyloidosis can develop in a localized or systemic form in patients with malignant neoplastic disorders, and usually involves kidneys impacting renal function. Among solid tumors, renal cell carcinoma (RCC) appears to be responsible for one-quarter to half of all cancers associated with amyloidosis. Among other solid cancers, various clinical presentations and pathological types of lung cancer and basal cell carcinoma skin were reported with AA amyloidosis more often than isolated case reports on other cancers with AA amyloidosis. Symptoms from kidney involvement rather than from the tumor per se were the presenting manifestations in cases of RCC associated with AA amyloidosis. Among hematological malignancies, clonal B cell/plasma cell dyscrasias such as monoclonal gammopathy and lymphoma were noted to be associated with AA amyloidosis. In addition, AA amyloidosis was reported in a substantial number of cases treated with immune checkpoint inhibitors such as pembrolizumab and nivolumab. The mechanism of association of cancer and AA amyloidosis seems to be mediated by the immune response exacerbated from the tumor and its microenvironment or immune therapy. The mainstay of treatment consists of therapy directed against the underlying malignancy or careful withdrawal of the offending agent. This review will discuss this rare but highly morbid clinical condition.

Incidence of acute kidney injury and decreased estimated glomerular filtration rate according to the site of cancer.

BACKGROUND: The epidemiology of renal impairment in patients with cancer remains unclear. We aimed to clarify associations between various cancer sites and renal impairment. METHODS: We reviewed data from 5674 patients aged ≥ 18 years receiving cancer treatment at a single hospital facility. The primary endpoints were the occurrence of acute kidney injury (AKI), a 30% decrease in the estimated glomerular filtration rate (eGFR), or death. Survival time was defined as the time from study enrolment to AKI occurrence. Kaplan-Meier and Cox proportional hazard analyses were performed. RESULTS: Hazard ratios (HRs) for AKI occurrence and a ≥ 30% decline in eGFR were significantly higher for kidney, urinary tract, pancreatic, liver, and gallbladder cancers than for colon cancer. Compared with colon cancer, digestive tract cancer showed a significantly higher HR for AKI occurrence alone. The HRs for a ≥ 30% decline in eGFR were significantly higher for patients aged 71‒77 years or ≥ 78 years than for those aged < 68 years, and for patients with eGFR ≥ 90 mL/min/1.73 m2 or 30-44 mL/min/1.73 m2 than for those with eGFR = 45‒59 mL/min/1.73 m2. CONCLUSIONS: Kidney, urinary, hepatobiliary, or pancreatic cancer are associated with a higher risk of AKI development and eGFR decrease than other cancers. Renal function changes should be more closely monitored in patients with these cancers.

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.

Zoledronic Acid-Associated Fanconi Syndrome in Patients With Cancer.

Zoledronic acid (ZA) is an antiresorptive agent typically used for fracture prevention in postmenopausal osteoporosis, malignancy-associated metastatic bone lesions, and as a treatment for hypercalcemia. ZA is excreted almost entirely by the kidney; as a result, a reduction in renal clearance can lead to its accumulation and potential renal toxicity. Although uncommon, acute kidney injury (AKI) from intravenous bisphosphonates has been described, with different patterns including tubulointerstitial nephritis, acute tubular necrosis, as well as focal segmental glomerulosclerosis. Here we present 4 patients with an underlying malignancy who each developed evidence of generalized proximal tubular dysfunction, also known as Fanconi syndrome, approximately 1 week after receiving treatment with ZA. On presentation, all patients had AKI, low serum bicarbonate levels, abnormal urinary acidification, hypophosphatemia, hypokalemia, and increased urine amino acid excretion or renal glycosuria. Based on the temporal association between ZA infusion and the development of these electrolyte abnormalities, each case is highly suggestive of ZA-associated Fanconi syndrome. Due to the severity of presentation, all required discontinuation of ZA and ongoing electrolyte repletion. Nephrologists and oncologists should be aware of this complication and consider ZA as a possible trigger of new-onset Fanconi syndrome.

Kidney Transplant T Cell-Mediated Rejection Occurring After Anti-CD19 CAR T-Cell Therapy for Refractory Aggressive Burkitt-like Lymphoma With 11q Aberration: A Case Report.

Post-transplant lymphoproliferative disorder is a growing complication of kidney transplantation and is associated with a poor prognosis. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is an important new treatment option modifying the outcome of refractory hematological cancers. Here, we report the case of a 40-year-old kidney transplant recipient who developed a Burkitt-like lymphoma with 11q aberration 5 years after transplantation. After 3 unsuccessful lines of chemotherapy, it was decided to treat the patient with anti-CD19 CAR T cells as a salvage therapy. Three months after CAR T-cell infusion, she experienced a grade IIB T cell-mediated rejection with severe tubulitis (T3), slight interstitial inflammation (I1), and severe intimal arteritis (V2) with blood suffusion. Among T cells infiltrating the graft, some of them expressed the anti-CD19 CAR. CAR T cells within the graft and in blood samples were also detected by droplet digital polymerase chain reaction. Function of the kidney transplant improved after corticosteroid treatment and remained stable. However, lymphoma progressed, with a massive pulmonary mass leading to the patient's death 10 months after CAR T-cell infusion.

Outcomes of kidney transplantation in patients with myeloma and amyloidosis in the USA.

BACKGROUND: Recent improvement in treatment and patient survival has opened the eligibility of kidney transplantation to patients who developed end-stage kidney disease (ESKD) from plasma cell dyscrasias (PCDs). Data on clinical outcomes in this population are lacking. METHODS: We conducted a retrospective study of United Network for Organ Sharing/Organ Procurement and Transplantation Network dataset (2006-2018) to compare patient and graft outcomes of kidney transplant recipients with ESKD due to PCD versus other causes. RESULTS: Among 168 369 adult first kidney transplant recipients, 0.22-0.43% per year had PCD as the cause of ESKD. The PCD group had worse survival than the non-PCD group for both living and deceased donor types {adjusted hazard ratio [aHR] 2.24 [95% confidence interval (CI) 1.67-2.99] and aHR 1.40 [95% CI 1.08-1.83], respectively}. The PCD group had worse survival than the diabetes group, but only among living donors [aHR 1.87 (95% CI 1.37-2.53) versus aHR 1.16 (95% CI 0.89-1.2)]. Graft survival in patients with PCD were worse than non-PCD in both living and deceased donors [aHR 1.72 (95% CI 1.91-2.56) and aHR 1.30 (95% CI 1.03-1.66)]. Patient and graft survival were worse in amyloidosis but not statistically different in multiple myeloma compared with the non-PCD group. CONCLUSION: The study data are crucial when determining kidney transplant eligibility and when discussing transplant risks in patients with PCD.

Acute kidney injury as a risk factor for mortality in oncological patients receiving checkpoint inhibitors.

BACKGROUND: Checkpoint inhibitors (CPIs) have drastically improved metastatic cancer outcomes. However, immunotherapy is associated with multiple toxicities, including acute kidney injury (AKI). Data about CPI-related AKI are limited. Our aim was to determine risk factors for CPI-related AKI as well as its clinical characteristics and its impact on mortality in patients undergoing immunotherapy. METHODS: All patients under CPI at our centre between March 2018 and May 2019 and with a follow-up through April 2020 were included. Demographic, clinical and laboratory data were collected. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines. We performed a logistic regression model to identify independent risk factors for AKI and actuarial survival analysis to establish risk factors for mortality in this population. RESULTS: A total of 759 patients were included, with a median age of 64 years. A total of 59% were men and baseline median creatinine was 0.80 mg/dL. The most frequent malignancy was lung cancer and 56% were receiving anti-programmed death protein 1 (PD-1). About 15.5% developed AKI during the follow-up. Age and baseline kidney function were identified as independent risk factors for CPI-related AKI. At the end of follow-up, 52.3% of patients had died. The type of cancer (not melanoma, lung or urogenital malignance), type of CPI (not cytotoxic T-lymphocyte-associated protein 4, PD-1, programmed death-ligand 1 or their combination) and the presence of an episode of AKI were identified as risk factors for mortality. CONCLUSIONS: A total of 15.5% of patients under immunotherapy presented with AKI. A single AKI episode was identified as an independent risk factor for mortality in these patients and age and baseline renal function were risk factors for the development of AKI.

Kidney transplantation in patients with multiple myeloma: narrative analysis and review of the last two decades.

There have been significant advances in the treatment of multiple myeloma in the last two decades. Approximately 25% of patients with newly diagnosed myeloma have some degree of kidney impairment. During the course of illness, nearly 50% of myeloma patients will develop kidney disease. Moreover, ∼10% of myeloma patients have advanced kidney disease requiring dialysis at presentation. Hemodialysis is associated with a significantly reduced overall survival (OS). In the setting of prolonged long-term OS due to the use of newer immunotherapeutic agents in the treatment of myeloma, patients with myeloma and advanced kidney disease may benefit from more aggressive management with kidney transplantation (KTx). Unfortunately, most data regarding outcomes of KTx in patients with myeloma come from single-center case series. With the advent of novel treatment choices, it remains unclear if outcomes of kidney transplant recipients with myeloma have improved in recent years. In this descriptive systematic review, we coalesced published patient data over the last 20 years to help inform clinicians and patients on expected hematologic and KTx outcomes in this complex population. We further discuss the future of KTx in patients with paraproteinemia.

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.