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Immune checkpoint inhibitors (ICI) are now widely used in the treatment of many cancers, and currently represent the standard of care for multiple malignancies. These agents enhance the T cell immune response to target cancer tissues, and have demonstrated considerable benefits for cancer outcomes. However, despite these improved outcomes, there are important kidney immune-related adverse events (iRAEs) associated with ICI. Acute tubulo-interstitial nephritis remains the most frequent kidney iRAE, however glomerular lesions and electrolytes disturbances are increasingly being recognized and reported. In this review, we summarize clinical features and identify risk factors for kidney iRAEs, and discuss the current understanding of pathophysiologic mechanisms. We highlight the evidence basis for guideline-recommended management of ICI-related kidney injury as well as gaps in current knowledge. We advocate for judicious use of kidney biopsy to identify ICI-associated kidney injury, and early use of corticosteroid treatment where appropriate. Selected patients may also be candidates for re-challenge with ICI therapy after a kidney iRAE, in view of current data on recurrent rates of kidney injury. Risk of benefits of re-challenge must be considered on an individual considering patient preferences and prognosis. Lastly, we review current knowledge of ICI use in the setting of patients with end-stage kidney disease, including kidney transplant recipients and those receiving dialysis, which suggest that these patients should not be summarily excluded from the potential benefits of these cancer therapies.

Allogeneic hematopoietic cell transplantation (HCT) offers cure for some patients with hematological diseases but is associated with significant risk of morbidity and mortality. We investigated the incidence of AKI and its impact on transplant outcomes among 408 patients transplanted at Princess Margaret Hospital Cancer Centre, Toronto, Canada. The overall incidence of AKI at 100 days was 64.2%. Compared to those with no AKI, patients who developed AKI had inferior 2-y overall survival (OS), 44.7% vs. 62.4% (P = 0.0004), higher 2-y transplant related mortality (TRM) 36.8% vs. 18.7% (P = 0.0003), lower 2-y graft-vs-host disease (GVHD)- and relapse-free survival (GRFS), 21.0% vs. 39.8% (P = 0.0002), and higher 100-day grade 3-4 acute GVHD (aGVHD), 12.4% vs. 6.3% (P = 0.01). There was no difference in 2-y incidence of relapse between the AKI and non-AKI groups, 24.2% vs. 24.3% (P = 0.84), 100-day grade 2-4 aGVHD, 27.7% vs. 25.7 (P = 0.41) or 2-y moderate-severe chronic GVHD, 24.0% vs. 21.6% (P = 0.79). Patients who develop AKI within 100 days of HCT have inferior OS and GRFS with higher rates of TRM and grade 3-4 aGVHD. These results highlight the importance of close monitoring of renal function, multidisciplinary collaboration, and implementation of protective strategies throughout HCT to optimize transplant and kidney outcomes.

Background: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple providers, including primary care physicians (PCPs), specialists, and community pharmacists. Siloed traditional health systems limit access and collaboration between key clinicians, resulting in delays in diagnosis, access to treatment, and inefficient monitoring. These lead to poor medication adherence, adverse drug events, and ultimately, disempowered providers and patients. To date, only a handful of clinical teams have embraced a comprehensive, integrated care model to redesign a coordinated and collaborative team-based approach centred on the patient. Community pharmacists, for example, are not well integrated into the patient’s circle of care and often face communication barriers with physicians and patients to relay medication-related issues. With medication-related problems being one of the leading causes of death in patients with complex chronic diseases, it is an opportune time to harness the integrated delivery model to address these gaps in care.Objective: To assess the feasibility and impact of using an integrated and collaborative model between nephrologists and community pharmacists targeting medication outcomes in patients with kidney disease. Methods: University Health Network’s Division of Nephrology partnered with community pharmacists with McKesson Canada (Toronto, Canada) in patients at high risk of adverse drug events (co-existing kidney, cardiovascular and oncological diseases). We conducted an eight-month two-part observational, mixed-methods study. The first part consisted of iterative semi-structured interviews with patients or caregivers and clinicians (nephrologists and pharmacists) to provide feedback and assess their experience with the model of care. The second part involved a retrospective review of referrals with respect to types of referrals and outcomes measured using the Quadruple Aim Framework, particularly:1.Patient and Caregiver experience2.Provider experience – physicians and pharmacists3.Clinical outcomes specific to medication-related outcomes: (medication adherence, adverse drug events) 4.Value and efficiency: Access (time to treatment, medication reimbursement resolved) Results: In our eight-month observational study (February 1, 2021, to October 31, 2021), five nephrology clinics participated in this model of care. 54 patient referrals submitted during that period involved patients across the five clinics (72% male; Median age 60 [27,85]; Median medications 8 [4,13]). Compared to traditional models, access to treatment improved by 43% through resolved medication reimbursement issues with a turnaround time of 2 days, which otherwise would have denied drug treatment and access. 25% of patients who experienced an adverse drug event were intervened on to prevent any further potential or severe harm (e.g., uncontrolled blood pressure, prevention of acute kidney injury). Nephrologists revealed high satisfaction, citing efficiency, timely response, and collaboration with pharmacists as key facilitators. Ninety-eight percent of patients and caregivers were extremely satisfied with the service, demonstrating an improved patient experience. Conclusion: A collaborative and integrated model was feasible for providing access to nephrology care from the perspective of clinicians and patients. More importantly, efficiencies in care delivery addressing medication-related care gaps, patient experience, and healthcare outcomes improved in patients with complex diseases at high risk of adverse drug events.

BackgroundCorticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration.MethodsWe used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29–84 days).ResultsOf 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively).ConclusionA shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed.

Hyponatremia is the most common electrolyte disorder in patients with cancer and is associated with significant morbidity and mortality. Innovation in cancer therapies has led to substantial improvement in cancer outcomes, but also to new therapy-related toxicities, including electrolyte disturbance. Improvement in clinicians understanding of hyponatremia may mitigate adverse outcomes and improve quality of life in cancer patients. In this case-illustrated review, we discuss the mechanisms underlying drug-induced hyponatremia both in “classical” antineoplastic drugs and novel cancer therapies. Via these clinical cases, we describe hyponatremia caused by conventional chemotherapies (e.g. platinum compounds, vinca alkaloid, and alkylating agents) as well as hyponatremia related to tyrosine kinase inhibitors and other targeted therapies. We also focus on checkpoint inhibitors-induced hyponatremia, as these agents are increasingly used for a wide variety of malignancies. Lastly, we summarize therapy-related hyponatremia among recipients of newer treatments for multiple myeloma.

The current treatment paradigm for muscle-invasive bladder cancer (MIBC) consists of cisplatin-based neoadjuvant chemotherapy followed by local definitive therapy, or local definitive therapy alone for cisplatin-ineligible patients. Given that MIBC has a high propensity for distant relapse and is a chemotherapy-sensitive disease, under-utilization of chemotherapy is associated with suboptimal cure rates. Cisplatin eligibility criteria are defined for patients with metastatic bladder cancer by the Galsky criteria, which include creatinine clearance ≥60 ml/min. However, consensus is still lacking regarding cisplatin eligibility criteria in the neoadjuvant, curative MIBC setting, which continues to represent a substantial barrier to the standardization of patient care and clinical trial design. Jiang and colleagues accordingly suggest an algorithm for assessing cisplatin eligibility in patients with MIBC. Instead of relying on an absolute renal function threshold, their algorithm emphasizes a multidisciplinary and patient-centred approach. They also propose mitigation strategies to minimize the risk of cisplatin-induced nephrotoxicity in selected patients with impaired renal function. This new framework is aimed at reducing the inappropriate exclusion of some patients from cisplatin-based neoadjuvant chemotherapy (which leads to under-treatment) and harmonizing clinical trial design, which could lead to improved overall outcomes in patients with MIBC. Many patients with muscle-invasive bladder cancer are currently excluded from cisplatin-based neoadjuvant chemotherapy owing to renal impairment. Here, Jiang and colleagues present an update on cisplatin-induced nephrotoxicity in muscle-invasive bladder cancer and highlight a multidisciplinary and patient-centred approach to treatment decision-making.

Introduction Immune checkpoint inhibitors (ICIs) are increasingly used to treat cancers. Kidney immune-related adverse events (IRAEs) are now well recognized, with the incidence of IRAEs ranging from 2% to 5%. Most of the initial data related to kidney IRAEs have focused on acute interstitial nephritis (AIN). There are minimal data on the types and relative frequencies of glomerular diseases associated with ICIs, their treatment, and outcomes. Methods We performed a systematic review and meta-analysis of all biopsy-proven published cases/series of glomerular pathology associated with ICIs. We searched the MEDLINE, EMBASE, and Cochrane databases from inception to February 2020. We abstracted patient-level data, including demographics, cancer and ICI therapy details, and characteristics of kidney injury. Results After screening, 27 articles with 45 cases of biopsy-confirmed ICI-associated glomerular disease were identified. Several lesion types were observed, with the most frequent being pauci-immune glomerulonephritis (GN) and renal vasculitis (27%), podocytopathies (24%), and complement 3 GN (C3GN; 11%). Concomitant AIN was reported in 41%. Most patients had ICIs discontinued (88%), and nearly all received corticosteroid treatment (98%). Renal replacement therapy (RRT) was required in 25%. Most patients had full (31%) or partial (42%) recovery from acute kidney injury (AKI), although 19% remained dialysis-dependent, and approximately one-third died. Complete or partial remission of proteinuria was achieved in 45% and 38%, respectively. Conclusion Multiple forms of ICI-associated glomerular disease have been described. Pauci-immune GN, podocytopathies, and C3GN are the most frequently reported lesions. ICI-associated glomerular disease may be associated with poor kidney and mortality outcomes. Oncologists and nephrologists must be aware of glomerular pathologies associated with ICIs and consider obtaining a kidney biopsy specimen when features atypical for AIN are present., Graphical abstract

Solid organ transplant recipients on long-term immunosuppressive medication are at increased risk of developing malignancy, and treatment of advanced cancers with angiogenesis inhibitors in this context has not been widely studied. We present a case of recurrent high-grade serous ovarian carcinoma treated with paclitaxel and bevacizumab in the context of prior renal transplantation where the patient responded well to treatment with controlled toxicities, discussing the potential for increased rates of adverse events and drug interactions in this select population.

Targeted radionuclide therapies (TRNT) are novel cancer treatments that deliver radiation selectively to cancer cells and the immediate tumor microenvironment. These agents consist of radiation-emitting radionuclides conjugated with monoclonal antibodies, peptides, or small molecules, each of which are able to specifically target tumor-associated antigens and hence allow for delivery of radiation directly, and almost exclusively, to tumor cells. The radiation emitted by these radionuclide particles causes DNA damage, triggering cancer cell death. Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed at high levels in prostatic cancer, compared with the low levels of expression seen in a variety of tissue, including normal prostate and kidneys.1 Even higher levels are seen in metastatic and castration-resistant disease, allowing for targeted therapy. Radionuclide agents targeting PSMA include alpha (e.g., actinium-225) and beta emitters (e.g., lutetium-177). Alpha particle emissions like actinium-225 (225Ac) are more effective in targeted killing of tumor cells compared with beta emitters, due to greater energy generated, coupled with shorter path length.2 Unfortunately, kidney toxicity may result from tubular nuclide accumulation, intrinsic affinity of actinium for the kidney, and low-level kidney PSMA expression.2,3,S1 As seen in animal models, the multiple alpha particles generated in the decay chain of 225Ac, termed daughter nuclides, can accumulate in the kidney and lead to a progressive nephropathy.4 Promising therapeutic efficacy has been demonstrated with 225Ac-PSMA617 in patients with metastatic castration-resistant prostate cancer (mCRPC).5,S2 There are few data, however, on clinical renal toxicity associated with 225Ac-PSMA617. We report our experience with 225Ac-PSMA617 therapy in 2 patients with mCRPC who received these novel agents and developed progressive kidney disease.

Recent advances in the fields of hematology and oncology over the past decades are truly astounding. Higher response rates have increased the overall and progression free survival, and for certain cancers, have brought the possibility of a cure within reach. While this represents great news for many cancer patients, their longer survival is creating new challenges. Cancer patients can now live long enough to develop chronic kidney disease (CKD), receive long term dialysis, and even a kidney transplantation. There are important and significant knowledge gaps in the care of the cancer patient with CKD or end stage renal disease (ESRD). The subspecialty of Onco-Nephrology was created with the goal of optimizing the care of cancer patients with CKD or ESRD by (1) identifying crucial knowledge gaps in the proper care of these patients by (2) engaging in basic science and clinical research independently and in partnership with cancer specialists to attenuate these gaps, and (3) by educating future onco-nephrologists.

Rationale & Objective Surveillance blood work is routinely performed in maintenance hemodialysis (HD) recipients. Although more frequent blood testing may confer better outcomes, there is little evidence to support any particular monitoring interval. Study Design Retrospective population-based cohort study. Setting & Participants All prevalent HD recipients in Ontario, Canada, as of April 1, 2011, and a cohort of incident patients commencing maintenance HD in Ontario, Canada, between April 1, 2011, and March 31, 2016. Exposure Frequency of surveillance blood work, monthly versus every 6 weeks. Outcomes The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiovascular events, all-cause hospitalization, and episodes of hyperkalemia. Analytical Approach Cox proportional hazards with adjustment for demographic and clinical characteristics was used to evaluate the association between blood testing frequency and all-cause mortality. Secondary outcomes were evaluated using the Andersen-Gill extension of the Cox model to allow for potential recurrent events. Results 7,454 prevalent patients received care at 17 HD programs with monthly blood sampling protocols (n=5,335 patients) and at 8 programs with blood sampling every 6 weeks (n=2,119 patients). More frequent monitoring was not associated with a lower risk for all-cause mortality compared to blood sampling every 6 weeks (adjusted HR, 1.16; 95% CI, 0.99-1.38). Monthly monitoring was not associated with a lower risk for any of the secondary outcomes. Results were consistent among incident HD recipients. Limitations Unmeasured confounding; limited data for center practices unrelated to blood sampling frequency; no information on frequency of unscheduled blood work performed outside the prescribed sampling interval. Conclusions Monthly routine blood testing in HD recipients was not associated with a lower risk for death, cardiovascular events, or hospitalizations as compared with testing every 6 weeks. Given the health resource implications, the frequency of routine blood sampling in HD recipients deserves careful reassessment.

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.

Supplemental material, sj-docx-1-cjk-10.1177_20543581221130156 for KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors: Description of Clinical Research Protocol of the KINDEST-CCS Study by Adree Khondker, Michael Groff, Sophia Nunes, Carolyn Sun, Natasha Jawa, Jasmine Lee, Vedran Cockovski, Yasmine Hejri-Rad, Rahul Chanchlani, Adam Fleming, Amit Garg, Nivethika Jeyakumar, Abhijat Kitchlu, Asaf Lebel, Eric McArthur, Luc Mertens, Paul Nathan, Rulan Parekh, Serina Patel, Jason Pole, Raveena Ramphal, Tal Schechter, Mariana Silva, Samuel Silver, Lillian Sung, Ron Wald, Paul Gibson, Rachel Pearl, Laura Wheaton, Peter Wong, Kirby Kim and Michael Zappitelli in Canadian Journal of Kidney Health and Disease

Introduction and Objective: Amyloidoses are a heterogeneous group of disorders resulting from deposition of amyloid fibrils into extracellular tissues. While the kidneys are one of the most frequent sites of amyloid deposition, amyloid deposits can also affect a wide range of organ systems, including the heart, liver, gastrointestinal tract, and peripheral nerves. The prognosis of amyloidosis, especially with cardiac involvement, remains poor; however, a collaborative approach applying new tools for diagnosis and management may improve outcomes. In September 2021, the Canadian Onco-Nephrology Interest Group hosted a symposium to discuss diagnostic challenges and recent advances in the management of amyloidosis from the perspectives of the nephrologist, cardiologist, and onco-hematologist. Methods and Sources of Information: Through structured presentations, the group discussed a series of cases highlighting the varied clinical presentations of amyloidoses affecting the kidney and heart. Expert opinions, clinical trial findings, and publication summaries were used to illustrate patient-related and treatment-related considerations in the diagnosis and management of amyloidoses. Key findings: (1) Overview of the clinical presentation of amyloidoses and the role of specialists in performing timely and accurate diagnostic workup; (2) review of best practices for multidisciplinary management of amyloidosis, including prognostic variables and determinants of treatment response; and (3) update on new and emerging treatments in the management of light chain and amyloid transthyretin amyloidoses. Limitations: This conference featured multidisciplinary discussion of cases, and learning points reflect the assessments by the involved experts/authors. Implications: Identification and management of amyloidoses can be facilitated with a multidisciplinary approach and higher index of suspicion from cardiologists, nephrologists, and hemato-oncologists. Increased awareness of clinical presentations and diagnostic algorithms for amyloidosis subtyping will lead to more timely interventions and improved clinical outcomes.

Patients with chronic kidney disease (CKD) may be at increased risk for cancer. CKD may also be associated with worse cancer outcomes. This study examined cancer incidence and mortality across the spectrum of CKD.Population-based cohort study.All adult Ontario residents with data on estimated glomerular filtration rate (eGFR) or who were receiving maintenance dialysis or had received a kidney transplant (2007-2016).Patients were categorized as of the first date they had 2 eGFR assessments or were registered as receiving maintenance dialysis or having received a kidney transplant. eGFR levels were further categorized as ≥60, 45-59, 30-44, 15-29, and 15 mL/min/1.73 mOverall and site-specific cancer incidence and mortality.Fine and Gray subdistribution hazard models.Among 5,882,388 individuals with eGFR data, 29,809 receiving dialysis, and 4,951 having received a kidney transplant, there were 325,895 cancer diagnoses made during 29,993,847 person-years of follow-up. The cumulative incidence of cancer ranged between 10.8% and 15.3% in patients with kidney disease. Compared with patients with eGFR ≥60 mL/min/1.73 mPossible unmeasured confounding and limited ability to infer causal associations.Cancer incidence in the setting of kidney disease is substantial. Cancer risk was increased in mild to moderate CKD and among transplant recipients, but not in advanced kidney disease. Cancer-related mortality was significantly higher among patients with kidney disease, particularly urologic cancers and myeloma. Strategies to detect and manage these cancers in the CKD population are needed.

This study aims to evaluate genetic risk factors for cisplatin-induced nephrotoxicity by investigating not previously studied genetic risk variants and further examining previously reported genetic associations. A genome-wide study (GWAS) was conducted in genetically estimated Europeans in a discovery cohort of cisplatin-treated adults from Toronto, Canada, followed by a candidate gene approach in a validation cohort from the Netherlands. In addition, previously reported genetic associations were further examined in both the discovery and validation cohorts. The outcome, nephrotoxicity, was assessed in two ways: (i) decreased estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) and (ii) increased serum creatinine according to the Common Terminology Criteria for Adverse Events v4.03 for acute kidney injury (AKI-CTCAE). Four different Illumina arrays were used for genotyping. Standard quality control was applied for pre- and post-genotype imputation data. In the discovery cohort (n = 608), five single-nucleotide polymorphisms (SNPs) reached genome-wide significance. The A allele in rs4388268 (minor allele frequency = 0.23), an intronic variant of the BACH2 gene, was consistently associated with increased risk of cisplatin-induced nephrotoxicity in both definitions, meeting genome-wide significance (β = −8.4, 95% CI −11.4–−5.4, p = 3.9 × 10−8) for decreased eGFR and reaching suggestive association (OR = 3.9, 95% CI 2.3–6.7, p = 7.4 × 10−7) by AKI-CTCAE. In the validation cohort of 149 patients, this variant was identified with the same direction of effect (eGFR: β = −1.5, 95% CI −5.3–2.4, AKI-CTCAE: OR = 1.7, 95% CI 0.8–3.5). Findings of our previously published candidate gene study could not be confirmed after correction for multiple testing. Genetic predisposition of BACH2 (rs4388268) might be important in the development of cisplatin-induced nephrotoxicity, indicating opportunities for mechanistic understanding, tailored therapy and preventive strategies.

Background Advances in allogeneic hematopoietic stem cell transplant (HSCT) have increased patient survival, although substantial treatment-related toxicity remains, including chronic kidney disease (CKD). We assessed the association between CKD and survival and transplant-specific outcomes in HSCT recipients. Methods We conducted a retrospective study of all 408 adult patients with allogenic HSCT at Princess Margaret Cancer Centre (Toronto, Canada, 2015–18). We used logistic regression to identify risk factors for CKD at 1 year post-transplant. Associations between CKD at 1 year and overall survival, relapse-free survival, graft-versus-host-disease (GVHD)-free/relapse-free survival, relapse and transplant-related mortality were examined using extended time-varying Cox models. In a sensitivity analysis, we restricted the cohort to survivors at 1 year, using standard Cox proportional hazard models to examine associations between CKD and overall survival, relapse-free survival and GVHD-free/relapse-free survival, and Fine and Gray's competing risk models to determine associations between CKD and relapse/transplant-related mortality. Results The prevalence of CKD at 1 year was 19% (46 patients) with median follow-up of 23 months. Multivariable regression identified age at transplant [adjusted OR (aOR) 1.09, 95% confidence interval (95% CI) = 1.05–1.14; P Conclusions CKD adversely affects the long-term prognosis for allogeneic HSCT recipients, with increased mortality risk and worse GVHD-free/relapse-free survival.

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. METHODS: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. RESULTS: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. CONCLUSIONS: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Background The most frequently reported malignancies after solid organ transplant are cutaneous, but data on the risk in pediatric populations varies across studies. Objectives To perform a systematic review including reported features and outcomes of skin cancers in pediatric solid organ transplant recipients. Methods EMBASE and MEDLINE were systematically searched (Prospero CRD42020201659). Results The review summarizes data from 20 studies on 337 patients, with a median age ranging from 15.0 to 19.5 years as reported in 4 studies, who developed skin malignancies after pediatric solid organ transplantation. Median ages at transplant and skin cancer diagnosis ranged from 1.5 to 17.0 years and 15.3 to 33.5 years, respectively. Squamous cell carcinoma (SCC) was most commonly reported (218 cases), followed by basal cell carcinoma (BCC) (91 cases), melanoma (18 cases), and unspecified keratinocyte carcinomas (2 cases). The median latency period between transplantation and cancer diagnosis ranged from 2.2 to 21.0 years. Overall, 4 studies reported 17 cases of metastasis in total, and recurrence was reported in one case. Six deaths were reported in one study related to SCC and melanoma metastases. The incidence rate of skin cancer after pediatric transplantation per 100 person-years of follow-up was 2.1 based on 5 studies. Conclusion The most frequent post-transplant malignancy in pediatric organ transplant recipients was SCC.

Nephrectomy is the mainstay of treatment for many kidney cancers, but has been correlated with increased incidence of acute kidney injury (AKI) and chronic kidney disease (CKD). Recently, sodium-glucose cotransporter-2 (SGLT2) inhibition has been shown to decrease the incidence of end-stage kidney disease and death in people with type 2 diabetes mellitus (T2D). However, at present, there has been no description of the use of SGLT2 inhibition in patients with T2D and solitary kidney despite the high risk of CKD progression.To characterize the use of SGLT2 inhibition and kidney function in a series of patients with T2D with prior nephrectomy for renal cell carcinoma (RCC).Retrospective case series.University hospital outpatient onco-nephrology clinic.Patients post-nephrectomy for RCC with T2D who were prescribed an SGLT2 inhibitor.Serum creatinine, albumin to creatinine ratio (ACR), HgA1c, and blood pressure measurements.Patients post-nephrectomy with incident use of SGLT2 inhibitor were identified from an existing registry of patients followed in the Onco-Nephrology Clinic at our institution from May 2019 to March 2021. Demographics, medication use, time since nephrectomy, cancer diagnosis, serum creatinine, ACR measurements, and blood pressure measurements were extracted from electronic medical records.Five patients were identified who had initiated SGLT2 inhibition post-nephrectomy. All patients were male, had T2D, and a prior history of hypertension. Renal cell carcinoma was the clinical indication for nephrectomy in all patients. None of patients were prescribed diuretics, and all were receiving renin-angiotensin system (RAS) inhibition therapies. The time from nephrectomy to SGLT2 inhibitor initiation ranged from 5 to 74 months. Baseline mean estimated glomerular filtration rate (eGFR) values were 49 mL/min/1.73 mSmall sample size, lack of a comparison group, and the variable timing of clinical data collection, including eGFR levels following initiation of SGLT2 inhibition.SGLT2 inhibition is becoming a standard component of nephrology care to reduce kidney function decline, cardiovascular risk, and mortality. To our knowledge, our report is the first to provide longitudinal data on SGLT2 inhibitor usage in patients with T2D and solitary kidneys post-nephrectomy. Larger prospective studies are needed to determine the efficacy and safety of SGLT2 inhibition strategies for kidney protection in patients post-nephrectomy.La néphrectomie est le traitement de référence pour de nombreux cancers rénaux, mais elle est corrélée à une incidence accrue d’insuffisance rénale aiguë (IRA) et d’insuffisance rénale chronique (IRC). On a récemment montré que l’inhibition du cotransporteur sodium-glucose de type 2 (SGLT2) réduisait l’incidence de l’insuffisance rénale terminale et la mortalité chez les personnes atteintes de diabète de type 2 (DB2). À l’heure actuelle, malgré le risque élevé de progression vers l’IRC, il n’existe aucune description de l’utilisation des inhibiteurs du SGLT2 chez les patients DB2 ayant un seul rein.Caractériser la fonction rénale et l’utilisation des inhibiteurs du SGLT2 chez une série de patients atteints de DB2 ayant subi une néphrectomie pour traiter un carcinome rénal (CR).Série de cas rétrospective.Clinique externe d’onconéphrologie d’un hôpital universitaire.Patients atteints de DB2 ayant subi une néphrectomie pour un CR et à qui on a prescrit un inhibiteur du SGLT2.Créatinine sérique, rapport albumine/créatinine (RAC), HgA1c et mesures de la pression artérielle.Les patients ayant subi une néphrectomie et ayant utilisé un inhibiteur du SGLT2 ont été identifiés dans le registre des patients suivis à la clinique d’onconéphrologie de notre établissement entre mai 2019 et mars 2021. Les données suivantes ont été extraites des dossiers médicaux : données démographiques, consommation de médicaments, temps écoulé depuis la néphrectomie, diagnostic du cancer, taux de créatinine sérique, mesures du RAC et de la pression artérielle.Cinq patients avaient amorcé l’inhibition du SGLT2 après la néphrectomie. Tous les sujets étaient des hommes atteints de diabète de type 2 et présentant des antécédents d’hypertension. Le CR était dans tous les cas l’indication clinique pour la néphrectomie. Aucun des patients n’avait reçu une prescription de diurétiques et tous suivaient un traitement avec un inhibiteur du système rénine-angiotensine (SRA). Le délai entre la néphrectomie et l’amorce de l’inhibition du SGLT2 variait entre cinq et soixante-quatorze mois. Le DFGe initial moyen s’établissait à 49 ml/min/1,73 mÉchantillon de petite taille, absence d’un groupe de comparaison et synchronisation variable de la collecte des données cliniques, notamment du DFGe, après le début de l’inhibition du SGLT2.L’inhibition du SGLT2 devient une partie intégrante des soins néphrologiques visant à réduire le déclin de la fonction rénale, les risques cardiovasculaires et la mortalité. À notre connaissance, notre rapport est le premier à fournir des données longitudinales sur l’utilisation des inhibiteurs du SGLT2 chez les patients atteints de diabète de type 2 ayant subi une néphrectomie. Des études prospectives de plus grande envergure sont nécessaires pour examiner l’efficacité et l’innocuité des stratégies d’inhibition du SGLT2 visant la protection rénale des patients post-néphrectomie.

Background and objectives Survivors of AKI are at higher risk of CKD and death, but few patients see a nephrologist after hospital discharge. Our objectives during this 2-year vanguard phase trial were to determine the feasibility of randomizing survivors of AKI to early follow-up with a nephrologist or usual care, and to collect data on care processes and outcomes. Design, setting, participants, & measurements We performed a randomized controlled trial in patients hospitalized with Kidney Disease Improving Global Outcomes (KDIGO) stage 2–3 AKI at four hospitals in Toronto, Canada. We randomized patients to early nephrologist follow-up (standardized basket of care that emphasized BP control, cardiovascular risk reduction, and medication safety) or usual care from July 2015 to June 2017. Feasibility outcomes included the proportion of eligible patients enrolled, seen by a nephrologist, and followed to 1 year. The primary clinical outcome was a major adverse kidney event at 1 year, defined as death, maintenance dialysis, or incident/progressive CKD. Results We screened 3687 participants from July 2015 to June 2017, of whom 269 were eligible. We randomized 71 (26%) patients (34 to nephrology follow-up and 37 to usual care). The primary reason stated for declining enrollment included hospitalization-related fatigue (n=65), reluctance to add more doctors to the health care team (n=59), and long travel times (n=40). Nephrologist visits occurred in 24 of 34 (71%) intervention participants, compared with three of 37 (8%) participants randomized to usual care. The primary clinical outcome occurred in 15 of 34 (44%) patients in the nephrologist follow-up arm, and 16 of 37 (43%) patients in the usual care arm (relative risk, 1.02; 95% confidence interval, 0.60 to 1.73). Conclusions Major adverse kidney events are common in AKI survivors, but we found the in-person model of follow-up posed a variety of barriers that was not acceptable to many patients. Clinical Trial registry name and registration number: Nephrologist Follow-up versus Usual Care after an Acute Kidney Injury Hospitalization (FUSION), NCT02483039 CJASN 16: 1005–1014, 2021. doi: https://doi.org/10.2215/CJN.17331120

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.

Purpose of review Hyponatremia is seen commonly in patients with cancer and is associated with increased mortality and morbidity. Understanding the proper diagnosis and therapy of cancer-associated hyponatremia is critical to ensure improved outcomes. Recent findings The most common cancers associated with hyponatremia are the various forms of lung cancer with incidences approaching 25-45%. The most common causes of hyponatremia in cancer patients are the syndrome of inappropriate antidiuretic hormone secretion [syndrome of inappropriate antidiuretic hormone (ADH)] and volume depletion. Proper diagnosis rests on clinical information supplemented by laboratory studies and is critical to ensure appropriate therapy. In recent years, the development of drugs that specifically antagonize the vasopressin type 2 receptor in the distal tubule have offered targeted and highly effective therapies for syndrome of inappropriate ADH. Summary Hyponatremia in cancer patients generally indicates advanced or severe disease but proper therapy that targets the underlying process can improve outcomes.

In Africa, about 70 percent of the total population still lives without electricity. Significant resources are needed to meet the gap. Demand-side management is crucial to curb the increasing demand even in developing countries. A traditional approach is to raise prices, but promoting energy-efficient products such as compact fluorescent lamp (CFL) bulbs is also a win-win proposition. While end-users can reduce their spending, power utilities can avoid costly investments in new generation capacity. This paper estimates the effects of progressive pricing as well as CFL distribution program in Ethiopia. It is found that the increasing block tariff structure reduced the demand: the price elasticity is estimated at 0.29. This is particularly useful to influence large-volume users, who are presumably the rich. The CFL program is also found effective to contain the electricity demand. The estimated impact is about 45 kWh per customer. This is significant energy savings particularly for low-volume users.

Background: Extraction or sample preparation is the first step in any research related to natural products and the objectives of the research could be seriously jeopardized if the extract prepared is not the true representative of the original crude material. The work reports a microwave assisted extraction model for the rapid extraction of phenolics and flavonoid bioactives from the leaves of Taraxacum officinale which is an edible plant with profound ethobotanical significance. The work aims to showcase new technological ventures to the nutraceutical industries for large scale production of such components which are greatly used as dietary supplements. Methods: The process optimization of the proposed method has been carried out using Taguchi L9 orthogonal array approach and total phenolics content (μg/gm dried extract in terms of chlorogenic acid equivalent) was used as the performance evaluation parameter. SEM reports and test of integrity of biological activity has also been reported. Results: Eight phenolic/flavonoid bioactives were identified using HPTLC. The final optimum conditions for rapid microwave assisted extraction of phenolics were reported as 160 W microwave power, 6 min irradiation time, 50 °C temperature and 2 min soak time. Results in terms of yield of total phenolics were very superior compared to 36 hours of conventional Soxhlet and maceration extraction. SEM images clearly indicated cellular ruptures, thus facilitating easy exit of bioactives from inside the cell to the external bulk solvent. Conclusions: The work basically attempts to encourage researchers in adapting to green technologies so that science, industry and environment can progress in tandem.

Kidney-related adverse drug effects from chemotherapeutic agents can cause acute kidney injury that may influence cancer treatment and patient outcomes. Many current chemotherapy drugs are associated with acute kidney injury, including methotrexate which causes dose-dependent tubular injury. In this review, we will focus on the manifestations of kidney disease secondary to methotrexate and discuss management strategies. In particular, we will review the use of high-flux hemodialysis versus glucarpidase for reducing toxic serum levels of methotrexate.

This cohort study identifies the risk factors for and the incidence of keratinocyte carcinoma among patients who underwent solid organ transplant during childhood compared with the general population in Ontario, Canada.

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes. ispartof: KIDNEY INTERNATIONAL vol:100 issue:1 pages:196-205 ispartof: location:United States status: published

Background and objectives Anticoagulation with either a vitamin K antagonist or a direct oral anticoagulant may be associated with AKI. Our objective was to assess the risk of AKI among elderly individuals with atrial fibrillation newly prescribed a direct oral anticoagulant (dabigatran, rivaroxaban, or apixaban) versus warfarin. Design, setting, participants, & measurements Our population-based cohort study included 20,683 outpatients in Ontario, Canada, ≥66 years with atrial fibrillation who were prescribed warfarin, dabigatran, rivaroxaban, or apixaban between 2009 and 2017. Inverse probability of treatment weighting on the basis of derived propensity scores for the treatment with each direct oral anticoagulant was used to balance baseline characteristics among patients receiving each of the three direct oral anticoagulants compared with warfarin. Cox proportional hazards regression was performed in the weighted population to compare the association between the prescribed anticoagulant and the outcomes of interest. The exposure was an outpatient prescription of warfarin or one of the direct oral anticoagulants. The primary outcome was a hospital encounter with AKI, defined using Kidney Disease Improving Global Outcomes thresholds. Prespecified subgroup analyses were conducted by eGFR category and by the percentage of international normalized ratio measurements in range, a validated marker of anticoagulation control. Results Each direct oral anticoagulant was associated with a significantly lower risk of AKI compared with warfarin (weighted hazard ratio, 0.65; 95% confidence interval, 0.53 to 0.80 for dabigatran; weighted hazard ratio, 0.85; 95% confidence interval, 0.73 to 0.98 for rivaroxaban; and weighted hazard ratio, 0.81; 95% confidence interval, 0.72 to 0.93 for apixaban). In the subgroup analysis, the lower risk of AKI associated with each direct oral anticoagulant was consistent across each eGFR strata. The risk of AKI was significantly lower among users of each of the direct oral anticoagulants compared with warfarin users who had a percentage of international normalized ratio measurements ≤56%. Conclusions Direct oral anticoagulants were associated with a lower risk of AKI compared with warfarin.

Immune checkpoint inhibitors (ICIs), immunomodulatory antibodies that are used to enhance the immune system, have substantially improved the prognosis of patients with advanced malignancy. As the use of ICI therapy becomes increasingly widespread across different types of cancer, their use in patients receiving dialysis is likely to increase. In this review we summarize the current literature on the use of ICIs in end-stage kidney disease (ESKD) patients and provide aggregate data from reported cases and series. Based on available pharmacological information, ICIs require no dosing adjustment in ESKD patients. Analysis of the reported cases in the literature demonstrates a similar incidence of immune-related adverse events in patients with ESKD receiving dialysis as compared with the general population (49%). Severe reactions graded as 3 and 4 have been seen in 15 patients (16%). As such, it is important that these patients are monitored very closely for immune-related adverse events; however, the risk of these adverse events should not preclude patients on dialysis from receiving these therapies. Cancer remission (complete and partial) was seen in close to 30% of patients, stable disease was seen in 28% and progression of disease in ∼36%. One-third of the patients died. Urothelial and renal cell cancer represented approximately half of all treated cancers and accounted for ∼50% of all deaths reported. Additional data in the dialysis population with the use of ICIs and involvement in prospective studies are needed to better assess outcomes, particularly within specific cancer types. ispartof: Clin Kidney J vol:14 issue:9 pages:2012-2022 ispartof: location:England status: Published online

2584 Background: Cancer immune checkpoint inhibitor (ICI) therapy may be associated with kidney immune-related adverse events (IRAEs) and other causes of acute kidney injury (AKI). In clinical trials, the frequency of AKI events was uncommon, however, further real-world study is warranted. Methods: We evaluated the proportion of AKI events among patients with advanced cancer (bladder, head and neck, lung, kidney and malignant melanoma) treated with ICI therapy in Ontario, Canada from 2012 - 2018. AKI was defined by a rise in the concentration of serum creatinine as per Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A multivariable regression model was used to identify predictors of AKI while accounting for the competing risk of death. Results: A total of 4,380 patients received ICI therapy. In follow-up, 1,283 (29%) had recorded AKI event (any stage AKI) and 289 (7%) had a severe AKI event (≥ stage 2). Median time to AKI was 6 months (Interquartile Range 2-16 months) and ≤ 1 % of patients received dialysis therapy. Within 30 days of any observed AKI event, 853 (58%) discontinued ICI therapy, 372 (29%) were hospitalized and 266 (21%) died. Mortality was significantly higher among patients who experiencing a severe AKI event (≥ stage 2) as compared to patients with a less severe AKI event (stage 1) or no observed AKI event. Among patients alive at 30 days following an AKI event, 14% received an outpatient corticosteroid or immunosuppressive therapy prescription, 7% had a visit with a nephrologist. Characteristics associated with a higher risk of AKI included female sex, bladder or kidney cancer (reference malignant melanoma), history of hypertension or diabetes, higher Charlson comorbidity score, a baseline estimated glomerular filtration rate less than 30 mL/min/1.73 m2, or outpatient prescription for either a proton pump inhibitor or non-steroidal anti-inflammatory drug. Among patients with an AKI event and treatment discontinuation, re-challenge of ICI therapy was infrequent (16%) with a significant risk of a recurrent AKI event (57%). Conclusions: In a population-based study among patients with cancer receiving ICI therapy, the rate of AKI was common (29%) but severe AKI was less frequent (7%). Rates of ICI discontinuation, hospitalization and death are substantial following an AKI event. Kidney function should be monitored carefully among patients undergoing ICI therapy who have common risk factors for developing renal disease. Nephrology consultation may be optimized among patients who develop a severe AKI event, especially among individuals who are considered for ICI therapy re-challenge.

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.

Onconephrology is a new and evolving field that deals with kidney complications in patients with cancer as well as the management of cancer in patients with preexisting kidney disease. With increasing numbers of patients with cancer with kidney-related complications, the field has garnered increased attention. Thus, an annual Greater Toronto Area Onconephrology Interest Group symposium was held in May 2019. The objective of the meeting was to demonstrate the junctures between oncology and nephrology by highlighting recent data regarding (1) kidney impairment in solid organ malignancies, (2) management and treatment of kidney cancer, (3) kidney impairment in hematologic malignancies, (4) malignancy and kidney transplantation, and (5) hyponatremia in patients with cancer.Through a structured presentation, the group explored key topics discussed at a Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on Onconephrology. Expert opinions, clinical trial findings, and publication summaries were used to illustrate patient and treatment-related considerations in onconephrology.Kidney complications in patients with cancer are a central theme in onconephrology. An estimated 12% to 25% of patients with solid organ malignancies have chronic kidney disease (CKD), although in certain cancers, the prevalence of CKD is higher. Kidney impairment is also a common complication of some hematologic malignancies. The incidence of renal failure in patients with multiple myeloma is estimated at 18% to 56% and light chain cast nephropathy is seen in approximately 30% of these patients. In addition, there appears to be a bidirectional relationship between kidney cancer and CKD, with some data sets suggesting the risk increases as kidney function declines. Cancer is also of concern in patients with preexisting kidney disease. Kidney transplant recipients have a greater risk of cancer and a higher risk of cancer-related mortality. Kidney complications have also been associated with novel cancer therapies, such as immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy. An estimated 2% to 4% of patients initiating an immune checkpoint inhibitor may develop nephrotoxicity, whereas up to 40% of patients on CAR T-cell therapy experience cytokine release syndrome (CRS). Tumor lysis syndrome and electrolyte abnormalities, such as hyponatremia, have also been reported with CAR T-cell therapy. While the incidence and prevalence of hyponatremia vary depending on the cancer type and serum sodium cutoff point, hyponatremia may be seen in up to 46% of patients hospitalized in cancer centers.Onconephrology is a developing field and the themes arising from this meeting indicate a need for greater collaboration between oncologists and nephrologists. Educational symposia and onconephrology fellowship programs may allow for improved cancer care for patients with kidney disease.L’onconéphrologie est une discipline nouvelle et évolutive qui traite les complications néphrologiques chez les patients atteints d’un cancer et assure également la prise en charge des patients soignés en oncologie et présentant une néphropathie préexistante. En mai 2019, le symposium duPar le biais d’une présentation structurée, le groupe s’est penché sur les thèmes clés discutés lors d’une conférence du KDIGO portant sur les controverses entourant l’onconéphrologie. Des avis d’experts, des résultats d’essais cliniques et des résumés de publications ont été utilisés pour illustrer les considérations relatives aux patients et aux traitements en onconéphrologie.Les complications rénales chez les patients atteints d’un cancer sont un thème central en onconéphrologie. On estime qu’environ 12 à 25 % des patients présentant une tumeur maligne touchant les organes solides sont atteints d’insuffisance rénale chronique (IRC), bien que la prévalence soit plus élevée pour certains cancers. L’insuffisance rénale s’avère également une complication fréquente de certaines tumeurs malignes hématologiques. L’incidence d’IRC chez les patients atteints d’un myélome multiple est estimée entre 18 et 56 %, et une néphropathie à chaînes légères est observée chez environ 30 % de ces patients. En outre, on soupçonne l’existence d’une relation bidirectionnelle entre le cancer du rein et l’IRC; certains ensembles de données suggérant que le risque de cancer augmenterait avec le déclin de la fonction rénale. Le cancer est également préoccupant chez les patients ayant une néphropathie préexistante. Enfin, les receveurs d’une greffe rénale présentent un risque accru de cancer et de mortalité liée au cancer. Les complications rénales ont également été associées aux nouveaux traitements contre le cancer, comme les inhibiteurs du point de contrôle immunitaire et les thérapies par cellules CAR T. Environ 2 à 4 % des patients amorçant un traitement par les inhibiteurs de point de contrôle immunitaire pourraient développer une néphrotoxicité, alors que jusqu’à 40 % des patients traités par cellules CAR T présentent un syndrome de relargage de cytokines. Le syndrome de lyse tumorale et des anomalies électrolytiques, comme l’hyponatrémie, ont également été observés chez les patients traités par cellules CAR T. Bien que l’incidence et la prévalence de l’hyponatrémie varient en fonction du type de cancer et du seuil de natrémie, jusqu’à 46 % des patients hospitalisés dans les centres de cancérologie présentent cette anomalie.L’onconéphrologie est une discipline en évolution et les thèmes issus de ce colloque soulignent le besoin d’accroître la collaboration entre les oncologues et les néphrologues. Les symposiums à caractère éducatif et les programmes de bourses d’études et de recherche en onconéphrologie pourraient améliorer les soins oncologiques prodigués aux patients atteints de néphropathies.

Background Patients with AKI may require interhospital transfer to receive RRT. Interhospital transfer may lead to delays in therapy, resulting in poor patient outcomes. There is minimal data comparing outcomes among patients undergoing transfer for RRT versus those who receive RRT at the hospital to which they first present. Methods We conducted a population-based cohort study of all adult patients (≥19 years) who received acute dialysis within 14 days of admission to an acute-care hospital between April 1, 2004 and March 31, 2015. The transferred group included all patients who presented to a hospital without a dialysis program and underwent interhospital transfer (with the start of dialysis ≤3 days of transfer and within 14 days of initial admission). All other patients were considered nontransferred. The primary outcome was time to 90-day all-cause mortality, adjusting for demographics, comorbidities, and measures of acute illness severity. We also assessed chronic dialysis dependence as a secondary outcome, using the Fine and Gray proportional hazards model to account for the competing risks of death. In a secondary post hoc analysis, we assessed these outcomes in a propensity score–matched cohort, matching on age, sex, and prior CKD status. Results We identified 27,270 individuals initiating acute RRT within 14 days of a hospital admission, of whom 2113 underwent interhospital transfer. Interhospital transfer was associated with lower rate of mortality (adjusted hazard ratio [aHR], 0.90; 95% CI, 0.84 to 0.97). Chronic dialysis dependence was not significantly different between groups (aHR, 0.98; 95% CI, 0.91 to 1.06). In the propensity score–matched analysis, interhospital transfer remained associated with a lower risk of death (HR, 0.88; 95% CI, 0.80 to 0.96). Conclusions Interhospital transfer for receipt of RRT does not confer higher mortality or worse kidney outcomes.

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Background Sustained low efficiency dialysis (SLED) has emerged as an alternative to continuous renal replacement therapy (CRRT) for the treatment of acute kidney injury (AKI) in critically ill patients. However, there is limited information on the short- and long-term outcomes of SLED compared to CRRT. Methods We conducted a retrospective cohort study of patients with AKI who commenced either SLED or CRRT in ICUs at a tertiary care hospital in Toronto, Canada. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at one year, and dialysis dependence at 90 days and one year. All outcomes were ascertained by linkage to provincial datasets. Results We identified 284 patients, of whom 95 and 189 commenced SLED and CRRT, respectively. Compared to SLED recipients, more CRRT recipients were mechanically ventilated (96% vs 86%, p = 0.002) and receiving vasopressors (94% vs 84%, p = 0.01) at the time of RRT initiation. At 90 days following RRT initiation, 52 (55%) and 126 (67%) SLED and CRRT recipients, respectively, died (adjusted risk ratio (RR) 0.91, 95% CI 0.75–1.11). There was no inter-modality difference in time to death through 90 days (adjusted hazard ratio 0.90, 95% CI 0.64–1.27). Among patients surviving to Day 90, a higher proportion of SLED recipients remained RRT dependent (10 (23%) vs 6 (10%) CRRT recipients, adjusted RR 2.82, 95% CI 1.02–7.81). At one year, there was no difference in mortality or dialysis dependence. Conclusions Among critically ill patients with acute kidney injury, mortality at 90 days and one year was not different among patients initiating SLED as compared to CRRT.

Education policy makers around the world marvel at Vietnam’s success in access to general education and learning outcomes. Despite the country’s relatively low level of economic development, Vietnamese students outperform students in Organization for Economic Co-operation and Development (OECD) countries on average in the program for international student assessment. What are the factors that have allowed Vietnam to achieve such success? This note shows that Vietnam’s education system shares common characteristics with other successful education systems in East Asia. While some of these factors are sociocultural - which may not be easily replicable in other countries - others are policy decisions from which leaders of other countries may learn. Following the evolution of education in postwar Vietnam, from 1975 to the present, this note highlights the key reforms pursued by the government and the resulting achievements, as well as the obstacles encountered along the way. The note also discusses challenges that Vietnam’s education system faces today in reaching its full potential as a knowledge-based economy.

BackgroundImmune checkpoint inhibitors (ICPi) are a novel and promising anti-cancer therapy. There are limited data on the incidence, risk factors and outcomes of acute kidney injury (AKI) in patients receiving ICPi.MethodsWe conducted a cohort study of patients receiving ICPi at our center between 2010 and 2017 via electronic health record. The primary outcome was AKI (increase of >50% from baseline serum creatinine (sCr)). Risk factors for AKI were assessed using logistic regression. Survival among those with and without AKI was compared using the Kaplan-Meier method.ResultsAmong 309 patients on ICPi, 51 (16.5%) developed AKI (Kidney Disease Improving Global Outcomes (KDIGO) stages 1: 53%, 2: 22%, 3: 25%). AKI was associated with other immune-related adverse events (IRAE) (OR 3.2, 95% CI 1.6 to 6; pConclusionAKI is a common complication in patients receiving ICPi treatment. The development of other IRAE and previous diagnosis of hypertension were associated with increased AKI risk. AKI was not associated with worse survival. Distinguishing kidney IRAE from other causes of AKI will present a frequent challenge to oncology and nephrology practitioners. Kidney biopsy should be considered to characterize kidney lesions and guide potential therapy.

As life expectancy among pediatric solid organ transplant recipients (SOTRs) improves, the risk of comorbid conditions such as malignancy post-transplantation has also increased. SOTRs are at elevated risks of post-transplantation lymphoproliferative disorders (PTLDs), and skin and solid cancers. PTLDs typically occur early following transplantation, while skin and solid cancers frequently arise in young adulthood (25-40 years). By 30 years following transplantation, 26-41% of pediatric SOTRs have developed cancer. Different risk factors exist for PTLD, and skin and solid cancers, which are modified by cumulative immunosuppression, infections, transplanted organ, and the underlying disease process associated with initial organ failure (e.g., kidney failure). Optimal cancer treatment strategies depend on the specific cancer type, stage, and patient comorbidities. Immunosuppression reduction may be beneficial for certain cancers but must be considered against the risks of acute and chronic rejection and allograft loss. Lifestyle counseling regarding smoking avoidance and sun protection, as well as human papillomavirus vaccination, is an important aspect of cancer prevention. Currently, no cancer screening guidelines exist specifically for pediatric SOTRs. Adult population screening guidelines have not been validated in transplant populations. Therefore, an individualized approach should be taken to cancer screening for pediatric SOTRs, accounting for other cancer risk factors.

The bidirectional relationship between cancer and chronic kidney disease (CKD) is complex. Patients with cancer, particularly those with hematological malignancies such as multiple myeloma and lymphoma, are at increased risk of developing acute kidney injury and CKD. On the other hand, emerging evidence from large observational registry analyses have consistently shown that cancer risk is increased by at least 2- to 3-fold in kidney transplant recipients, and the observed increased risk occurs not only in those who have received kidney transplants but also in those on dialysis and with mild- to moderate-stage CKD. The interactions between cancer and CKD have raised major therapeutic and clinical challenges in the management of these patients. Given the magnitude of the problem and uncertainties, and current controversies within the existing evidence, Kidney Disease: Improving Global Outcomes (KDIGO) assembled a global panel of multidisciplinary clinical and scientific expertise for a controversies conference on onco-nephrology to identify key management issues in nephrology relevant to patients with malignancy. This report covers the discussed controversies in kidney disease in hematological malignancies, as well as cancer after kidney transplantation. An overview of future research priorities is also discussed. © 2020 Kidney Disease: Improving Global Outcomes (KDIGO)

The bidirectional relationship between cancer and chronic kidney disease (CKD) is complex. Patients with cancer, particularly those with hematological malignancies such as multiple myeloma and lymphoma, are at increased risk of developing acute kidney injury and CKD. On the other hand, emerging evidence from large observational registry analyses have consistently shown that cancer risk is increased by at least 2- to 3-fold in kidney transplant recipients, and the observed increased risk occurs not only in those who have received kidney transplants but also in those on dialysis and with mild- to moderate-stage CKD. The interactions between cancer and CKD have raised major therapeutic and clinical challenges in the management of these patients. Given the magnitude of the problem and uncertainties, and current controversies within the existing evidence, Kidney Disease: Improving Global Outcomes (KDIGO) assembled a global panel of multidisciplinary clinical and scientific expertise for a controversies conference on onco-nephrology to identify key management issues in nephrology relevant to patients with malignancy. This report covers the discussed controversies in kidney disease in hematological malignancies, as well as cancer after kidney transplantation. An overview of future research priorities is also discussed.