Assessment of Glomerular Filtration Rate in Patients with Cancer: A Statement from the American Society of Onco-Nephrology.

Accurate assessment of glomerular filtration rate (GFR) is crucial to guiding drug eligibility, dosing of systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. Up to 32% of cancer patients have baseline chronic kidney disease (CKD), and both malignancy and treatment may cause kidney injury and subsequent CKD. To date, there has been lack of guidance to standardize approaches to GFR estimation in the cancer population. In this two-part statement from the American Society of Onco-Nephrology, we present key messages for estimation of GFR in patients with cancer, including the choice of GFR estimating equation, use of race and body surface-area (BSA)-adjustment, and anticancer drug dose-adjustment in the setting of CKD. These key messages are based on a systematic review of studies assessing GFR estimating equations using serum creatinine and cystatin C in patients with cancer, against a measured GFR comparator. The preponderance of current data involving validated GFR estimating equations involves the CKD-EPI equations, with 2,508 patients in whom CKD-EPI using serum creatinine and cystatin C was assessed (8 studies) and 15,349 in whom CKD-EPI with serum creatinine was assessed (22 studies). The former may have improved performance metrics and be less susceptible to shortfalls of eGFR using serum creatinine alone. Since included studies were moderate quality or lower, the ASON Position Committee rated the certainty of evidence as low. Additional studies are needed to assess the accuracy of other validated eGFR equations in patients with cancer. Given the importance of accurate and timely eGFR assessment we advocate for the use of validated GFR estimating equations incorporating both serum creatinine and cystatin C in patients with cancer. Measurement of GFR via exogenous filtration markers should be considered in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials.

Cancer drugs and acute kidney injury: new therapies and new challenges.

PURPOSE OF REVIEW: Cancer therapies continue to evolve at a rapid pace and although novel treatments, including immunotherapies and targeted therapies have allowed for substantial improvements in cancer survival, they carry associated risks of acute kidney injury (AKI). We aim to summarize the existing literature on AKI associated with the spectrum of systemic cancer treatments, including conventional chemotherapies, newer immunotherapies, and the growing number of targeted cancer therapies, which may be associated with both AKI and 'pseudo-AKI'. RECENT FINDINGS: Conventional cytotoxic chemotherapies (e.g. cisplatin and other platinum-based agents, methotrexate, pemetrexed, ifosfamide, etc.) with well recognized nephrotoxicities (predominantly tubulointerstitial injury) remain in widespread use. Immunotherapies (e.g., immune checkpoint inhibitors and CAR-T therapies) may be associated with kidney immune-related adverse events, most often acute interstitial nephritis, and rarely, glomerular disease. Recently, multiple targeted cancer therapies have been associated with reduced renal tubular secretion of creatinine, causing elevations in serum creatinine and apparent 'pseudo-AKI'. To complicate matters further, these agents have had biopsy-proven, 'true' kidney injury attributed to them in numerous case reports. SUMMARY: Clinicians in nephrology and oncology must be aware of the various potential kidney risks with these agents and recognize those with clinically meaningful impact on both cancer and kidney outcomes.

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.

Virtual Pharmacy: An Integrated Collaborative Redesign Targeting Medication-Related Problems in Patients with Chronic Kidney Disease.

INTRODUCTION: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple providers. Siloed traditional health systems often result in delays, barriers to treatment access, and inefficient monitoring. METHODS: We conducted a 1-year observational mixed-methods study. We included all consecutive referrals except for patients without telephone access. We assessed 4 domains of outcomes: (1) patient and caregiver experience, (2) provider experience (e.g., physicians and pharmacists), (3) clinical outcomes specific to medication-related outcomes (e.g., adherence, adverse drug events [ADEs]), and (4) value and efficiency (i.e., medication access, defined as time to treatment and resolution of medication reimbursement issues). RESULTS: Sixty-five patients were referred to the integrated virtual pharmacy (iVRx) model. Most (72%) patients were male. Patients had a median (min, max) age of 60 (27, 85) years and were taking 8 (4, 13) medications. Compared with traditional care delivery models, medication access improved for 56% of participants. Direct home delivery of medication resulted in 91% of patients receiving prescriptions within 2 days of a nephrologist visit. During more than 2,000 pharmacist-patient encounters, 208 ADEs were identified that required clinician intervention to prevent patient harm. When these ADEs were classified by severity, 53% were mild, 45% were moderate (e.g., delaying dose titration in patients initiated on glucagon-like peptide 1 (GLP-1) agonists due to intolerable gastrointestinal side effects), and the remaining 2% of ADEs were severe, meaning clinical intervention was required to prevent a serious outcome (e.g., uncontrolled blood pressure, prevention of acute kidney injury). Nephrologists reported high satisfaction with iVRx, citing efficiency, timely response, and collaboration with pharmacists as key facilitators. Of the 65 patient participants, 98% reported being extremely satisfied. CONCLUSIONS: The iVRx is an acceptable and feasible clinical strategy. Our pilot program was associated with improved kidney care by increasing medication access for patients and avoiding potential harms associated with ADEs.

Immunotherapy in oncology and the kidneys: a clinical review of the evaluation and management of kidney immune-related adverse events.

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.

Amyloidoses in Onco-Nephrology Practice: A Multidisciplinary Case-Based Conference Report.

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.

Introduction et objectifs: Les amyloïdoses sont un groupe hétérogène de troubles résultant du dépôt de fibrilles amyloïdes dans les tissus extracellulaires. Les reins sont un des sites les plus fréquents de dépôts amyloïdes, mais ces derniers peuvent également affecter un large éventail de systèmes et d'organes, notamment le cœur, le foie, le tractus gastro-intestinal et les nerfs périphériques. Le pronostic de l'amyloïdose, en particulier en cas d'atteinte cardiaque, est mauvais. Les résultats peuvent cependant être améliorés par une approche collaborative utilisant de nouveaux outils de diagnostic et de prise en charge. En septembre 2021, le Canadian Onco-Nephrology Interest Group (groupe canadien d'intérêt en onco-néphrologie) a organisé un symposium pour discuter des défis liés au diagnostic de l'amyloïdose et des récents progrès dans la gestion de cette maladie du point de vue du néphrologue, du cardiologue et de l'hémato-oncologue. Méthodologie et sources de l'information: Au moyen de présentations structurées, le groupe a discuté d'une série de cas mettant en évidence les diverses présentations cliniques d'amyloïdoses affectant les reins et le cœur. Les opinions d'experts, les résultats des essais cliniques et les résumés des publications ont été utilisés pour illustrer les facteurs liés au patient et au traitement à considérer dans le diagnostic et la prise en charge des amyloïdoses. Principaux résultats: 1) Aperçu de la présentation clinique des amyloïdoses et du rôle des spécialistes dans la réalisation d'un bilan diagnostic précis et en temps opportun (2) Examen des meilleures pratiques de gestion multidisciplinaire de l'amyloïdose, y compris des variables pronostiques et des déterminants de la réponse au traitement (3) Mise à jour sur les traitements nouveaux et émergents dans la prise en charge des amyloïdoses à chaîne légère (AL) et à transthyrétine (ATTR). Limites: Ce symposium a donné lieu à une discussion multidisciplinaire de cas; les points d'apprentissage reflètent les évaluations des experts/auteurs concernés. Conclusion: L'identification et la prise en charge des amyloïdoses peuvent être facilitées par une approche multidisciplinaire et un indice de suspicion plus élevé de la part des cardiologues, des néphrologues et des hémato-oncologues. Une meilleure connaissance des présentations cliniques et des algorithmes de diagnostic pour le sous-typage de l'amyloïdose permettra d'intervenir plus rapidement et d'améliorer les résultats cliniques.

Cardiovascular Drug Use After Acute Kidney Injury Among Hospitalized Patients With a History of Myocardial Infarction.

Introduction: Patients who survive acute kidney injury (AKI) may receive fewer cardioprotective drugs. Our objective was to measure the difference in time to dispensing of evidence-based cardiovascular drugs in patients with a history of myocardial infarction (MI) with and without AKI. Methods: This was a population-based cohort study of patients 66 years of age and older with a history of MI who survived a hospitalization complicated with AKI, propensity-score matched to patients without AKI. The primary outcome was time to outpatient dispensing of an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB), statin, or ß-blocker within 1 year of hospital discharge. Results: We identified 28,871 patients with AKI, of whom 21,452 were matched 1:1 to patients without AKI. In the matched cohort, mean age was 80 years, 40% were female, and 34% had an MI during the index hospitalization. AKI was associated with less frequent dispensing of all 3 cardiovascular drug classes within 1 year of hospital discharge (subdistribution hazard ratio [sHR], 0.93; 95% confidence interval [CI], 0.91-0.95). This association was most pronounced in patients with stage 2 (sHR, 0.81; 95% CI, 0.75-0.88) and stage 3 (sHR, 0.71; 95% CI, 0.64-0.79) AKI. We observed less frequent dispensing of statins in patients with stage 2 (sHR, 0.87; 95% CI, 0.81-0.92) and stage 3 (sHR, 0.85; 95% CI, 0.78-0.93) AKI and less frequent dispensing of ß-blockers in patients with stage 3 AKI (sHR, 0.86; 95% CI, 0.79-0.94). Conclusion: In patients with a history of MI, survivors of AKI were less likely to receive prescriptions for ACEi/ARB, statins, or ß-blockers within 1 year of hospital discharge. This association was most pronounced in patients with stages 2 and 3 AKI.

KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors: Description of Clinical Research Protocol of the KINDEST-CCS Study.

Background: Approximately 30% of childhood cancer survivors (CCSs) will develop chronic kidney disease (CKD) or hypertension 15 to 20 years after treatment ends. The incidence of CKD and hypertension in the 5-year window after cancer therapy is unknown. Moreover, extent of monitoring of CCS with CKD and associated complications in current practice is underexplored. To inform the development of new and existing care guidelines for CCS, the epidemiology and monitoring of CKD and hypertension in the early period following cancer therapy warrants further investigation. Objective: To describe the design and methods of the KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors study, which aims to evaluate the burden of late kidney and blood pressure outcomes in the first ~10 years after cancer therapy, the extent of appropriate screening and complications monitoring for CKD and hypertension, and whether patient, disease/treatment, or system factors are associated with these outcomes. Design: Two distinct, but related studies; a prospective cohort study and a retrospective cohort study. Setting: Five Ontario pediatric oncology centers. Patients: The prospective study will involve 500 CCS at high risk for these late effects due to cancer therapy, and the retrospective study involves 5,000 CCS ≤ 18 years old treated for cancer between January 2008 and December 2020. Measurements: Chronic kidney disease is defined as Estimated glomerular filtration rate <90 mL/min/1.73 m2 or albumin-to-creatinine ratio ≥ 3mg/mmol. Hypertension is defined by 2017 American Academy of Pediatrics guidelines. Methods: Prospective study: we aim to investigate CKD and hypertension prevalence and the extent to which they persist at 3- and 5-year follow-up in CCS after cancer therapy. We will collect detailed biologic and clinical data, calculate CKD and hypertension prevalence, and progression at 3- and 5-years post-therapy. Retrospective study: we aim to investigate CKD and hypertension monitoring using administrative and health record data. We will also investigate the validity of CKD and hypertension administrative definitions in this population and the incidence of CKD and hypertension in the first ~10 years post-cancer therapy. We will investigate whether patient-, disease/treatment-, or system-specific factors modify these associations in both studies. Limitations: Results from the prospective study may not be generalizable to non-high-risk CCS. The retrospective study is susceptible to surveillance bias. Conclusions: Our team and knowledge translation plan is engaging patient partners, researchers, knowledge users, and policy group representatives. Our work will address international priorities to improve CCS health, provide the evidence of new disease burden and practice gaps to improve CCS guidelines, implement and test revised guidelines, plan trials to reduce CKD and hypertension, and improve long-term CCS health.

Shorter versus longer corticosteroid duration and recurrent immune checkpoint inhibitor-associated AKI.

BACKGROUND: Corticosteroids 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. METHODS: We 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). RESULTS: Of 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). CONCLUSION: A 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.

Chronic kidney disease, survival and graft-versus-host-disease-free/relapse-free survival in recipients of allogeneic hematopoietic stem cell transplant.

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 < 0.0001), female gender (aOR 2.83, 95% CI = 1.34-5.97; P = 0.006) and acute kidney injury during the first 100 days (aOR 3.86, 95% CI = 1.70-8.73; P = 0.001) as risk factors for CKD at 1 year. Patients with CKD at 1 year had significantly poorer overall survival than those without CKD, when adjusted for relevant covariates [adjusted HR (aHR) 1.93, 95% CI = 1.02-3.66; P = 0.04 in the time-varying Cox model, and aHR 2.06, 95% CI = 1.04-4.07; P = 0.04 using the standard Cox model]. CKD at 1 year was also associated with worse GVHD-free/relapse-free survival (aHR 1.65, 95% CI = 1.04-2.61; P = 0.03). Conclusions: CKD adversely affects the long-term prognosis for allogeneic HSCT recipients, with increased mortality risk and worse GVHD-free/relapse-free survival.

Acute kidney injury within 100 days post allogeneic hematopoietic cell transplantation is associated with increased risk of post-transplant complications and poor transplant outcomes.

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.

Pegylated Liposomal Doxorubicin and Kidney-Limited Thrombotic Microangiopathy in a Kidney Transplant Recipient: A Case Report.

A 64-year-old man with Kaposi sarcoma in clinical remission after treatment with pegylated liposomal doxorubicin and a history of deceased-donor kidney transplantation 4 years prior presented with a slowly progressive increase in his serum creatinine level, well-controlled hypertension, stable subnephrotic-range proteinuria, and bland urinary sediment. An allograft kidney biopsy demonstrated thrombotic microangiopathy, without clinical or laboratory features of systemic involvement. Based on the timing of drug initiation preceding thrombotic microangiopathy, complete recovery after drug withdrawal, and the absence of other etiologies, it was concluded that pegylated liposomal doxorubicin was the likely cause of kidney-limited thrombotic microangiopathy. When pegylated liposomal doxorubicin was resumed, the patient developed hypertension and kidney allograft dysfunction. A new kidney biopsy was not performed because of the overall risk benefit. The case highlights the importance of recognizing novel etiologies of thrombotic microangiopathy in kidney transplant patients with malignancy. Although Kaposi sarcoma has not been linked to thrombotic microangiopathy, pegylated liposomal doxorubicin has been increasingly associated with drug-induced thrombotic microangiopathy. To our knowledge, this is the first case report that etiologically links pegylated liposomal doxorubicin to kidney-limited thrombotic microangiopathy in a kidney transplant patient.

Cancer Risk and Mortality in Patients With Kidney Disease: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: 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. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: 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). EXPOSURE: 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 m2; the latter 4 groups are consistent with KDIGO (Kidney Disease: Improving Global Outcomes) CKD categories G3a, G3b, G4, and G5, respectively. OUTCOMES: Overall and site-specific cancer incidence and mortality. ANALYTICAL APPROACH: Fine and Gray subdistribution hazard models. RESULTS: 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 m2, adjusted hazard ratios (AHRs) for a cancer diagnosis among patients with CKD G3a, G3b, G4, and G5 were 1.08 (95% CI, 1.07-1.10), 0.99 (95% CI, 0.97-1.01), 0.85 (95% CI, 0.81-0.88), and 0.81 (95% CI, 0.73-0.90), respectively. The AHRs for patients receiving dialysis and who had received a transplant were 1.01 (95% CI, 0.96-1.07) and 1.25 (95% CI, 1.12-1.39), respectively. Patients with kidney disease had higher proportions of stage 4 cancers at diagnosis. Patients with CKD G3a, G3b, and G4 and transplant recipients had increased risks of cancer-specific mortality (AHRs of 1.27 [95% CI, 1.23-1.32], 1.29 [95% CI, 1.24-1.35], 1.25 [95% CI, 1.18-1.33], and 1.48 [95% CI, 1.18-1.87], respectively). The risks of bladder and kidney cancers and multiple myeloma were particularly increased in CKD, and mortality from these malignancies increased with worsening kidney function. LIMITATIONS: Possible unmeasured confounding and limited ability to infer causal associations. CONCLUSIONS: 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.

Cisplatin Nephrotoxicity: Novel Insights Into Mechanisms and Preventative Strategies.

Cisplatin is a highly effective chemotherapeutic agent that has been used for more than 50 years for a variety of cancers; however, its use is limited by toxicity, including nephrotoxicity. In this in-depth review, we discuss the incidence of cisplatin-associated acute kidney injury, as well as common risk factors for its development. Cisplatin accumulates in the kidney tubules and causes AKI through various mechanisms, including DNA damage, oxidative stress, and apoptosis. We also discuss the spectrum of nephrotoxicity, including acute and chronic impairment of kidney function, electrolyte disturbances, and thrombotic microangiopathy. We discuss the limited options for the diagnosis, prevention, and management of these complications, along with factors that may impact future therapy with or without cisplatin. We conclude with directions for future research in this expanding and important area.

Cancer Screening in Solid Organ Transplant Recipients: A Focus on Screening Liver, Lung, and Kidney Recipients for Cancers Related to the Transplanted Organ.

Over the last few decades, the life expectancy of solid organ transplant recipients (SOTRs) has improved significantly. With SOTRs living longer, more recipients are dying from cancer. There is a reported 2- to 3-fold increased risk of cancer-specific mortality in SOTRs compared with the general population. Cancer in an SOTR can be de novo, recurrent, or donor-derived. Cancer screening in this population is crucial, as early detection and treatment may improve outcomes. In the absence of randomized controlled trials dedicated to SOTRs, clinicians rely on clinical practice guidelines from regional and national transplant societies; however, these may vary considerably across jurisdictions and transplanted organ. At present, no widely accepted consensus exists for cancer screening protocols in SOTRs, particularly with regard to screening for malignancy related to transplanted organ. Some SOTRs may be at higher risk of malignancies within the allograft. This is particularly the case in lung and liver recipients, though less common in kidney recipients who are at increased risk of developing renal cell cancer in their native kidneys. This increased risk has not been uniformly incorporated into screening recommendations for SOTRs. In this review, we summarize the cancer screening recommendations for SOTRs from various transplant organizations based on transplanted organ. This review also discusses the complexity and controversies surrounding screening of cancer in the allograft and future avenues to improve cancer detection in this context. More studies specific to SOTRs are required to form generalizable and evidence-based cancer screening guidelines, particularly with respect to cancer screening in the allograft.

Outcomes of skin cancers in pediatric solid organ transplant patients: A systematic review.

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.