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

The evolving landscape of cancer treatments has introduced new challenges, particularly related to adverse events associated with chemotherapeutic agents. To address these challenges, the fields of cardio-oncology and onco-nephrology have arisen, focusing on the management of cardiotoxicity and nephrotoxicity attributable to anti-cancer drugs. Numerous intersections between these disciplines exist, including onco-hypertension and cardiorenal toxicities induced by chemotherapeutic agents. Additionally, immune checkpoint inhibitors may cause myocarditis and nephritis. Multidisciplinary collaboration among oncologists, cardiologists, nephrologists, and other healthcare professionals is crucial for developing tailored approaches to optimize treatment efficacy while minimizing the risk of cardiovascular and renal complications, ultimately enhancing patient outcomes in modern oncology practice.

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

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

Pitfalls of Current Diagnostic Criteria of Tumor Lysis Syndrome.

BACKGROUND: Tumor Lysis syndrome (TLS) is a well-recognized medical emergency in patients with cancer diagnosis. The diagnostic criteria of TLS have been revised many times since it was recognized, but still have many drawbacks limit diagnosis accuracy. SUMMARY: Autopsy studies in patients with perimortem diagnoses of TLS have shown that they may not have actually had TLS. Therefore, many cancer patients who are at risk for TLS, clinical and laboratory criteria may be fulfilled due to other causes of acute kidney injury. In this review, we aim to cast a spotlight on the shortcomings and pitfalls of the current diagnostic criteria for TLS, and propose a roadmap for developing a more rigorous criteria that improve on the diagnostic accuracy. KEY MESSAGES: Causes of AKI in patients with cancer other than TLS should be considered. Because current diagnostic criteria may miss those differential diagnosis, specific biomarkers that can tell when TLS is the underlying process is an important need, besides appropriate criteria that can jump over the pitfalls in the current criteria and enhance the recognition of TLS among other causes.

Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study.

PURPOSE: To characterize the incidence of kidney failure associated with intravitreal anti-VEGF exposure; and compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab. DESIGN: Retrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network. SUBJECTS: Subjects aged ≥ 18 years with ≥ 3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion). METHODS: The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random effects meta-analysis was performed to combine each database's hazard ratio (HR) estimate into a single network-wide estimate. MAIN OUTCOME MEASURES: Incidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure. RESULTS: Of the 6.1 million patients with blinding diseases, 37 189 who received ranibizumab, 39 447 aflibercept, and 163 611 bevacizumab were included; the total treatment exposure time was 161 724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100 000 persons (range, 0-2389), and incidence rate 742 per 100 000 person-years (range, 0-2661). The meta-analysis HR of kidney failure comparing aflibercept with ranibizumab was 1.01 (95% confidence interval [CI], 0.70-1.47; P = 0.45), ranibizumab with bevacizumab 0.95 (95% CI, 0.68-1.32; P = 0.62), and aflibercept with bevacizumab 0.95 (95% CI, 0.65-1.39; P = 0.60). CONCLUSIONS: There was no substantially different relative risk of kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk of kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Kidney and Urinary Tract Involvement in Chronic Myelomonocytic Leukemia.

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy affecting the bone marrow and resulting in peripheral blood monocytosis. Kidney and urinary tract involvement is common and can present dramatically with life-threatening consequences. Kidney involvement can be the result of direct or indirect mechanisms, including prerenal azotemia, glomerular disease, tubulointerstitial involvement, and renovascular disorders. Urinary tract involvement, electrolyte and acid-base disorders, as well as nephrotoxicity from treatment of the disorder can also occur. Given this multifactorial pathogenesis involving several mechanisms concomitantly, nephrologists must exercise heightened awareness and maintain a low threshold for kidney biopsy. There is a pressing need for future research endeavors to elucidate and target the manifestations of CMML that involve the kidneys with the ultimate goal of augmenting overall prognosis and therapeutic outcomes.

Management of hypertension in patients with cancer: challenges and considerations.

The survival rates of many cancers have significantly improved due to recent advancements in cancer screening and therapeutics. Although better cancer outcomes are encouraging, additional health challenges have surfaced, the utmost of which is the burden imposed by various cardiovascular and renal toxicities of anticancer therapies. To improve the overall outcome of patients with cancer, it is essential to understand and manage these treatment-related adverse effects. The cardiovascular side effects of antineoplastic therapies are well-known and include left ventricular dysfunction, heart failure, myocardial ischaemia, QT prolongation, arrhythmia and hypertension. Among these, hypertension is the most common complication, prevalent in about 40% of all cancer patients, yet frequently overlooked and undertreated. This review explores the intricate connection between cancer and hypertension and provides distinct approaches to diagnosing, monitoring and managing hypertension in patients with cancer. We also outline the challenges and considerations that are relevant to the care of patients receiving anticancer drugs with prohypertensive potential.

Frequency and characteristics of chemotherapy-associated thrombotic microangiopathy: Analysis from a large pharmacovigilance database.

We used the information component (IC), a disproportionate Bayesian analysis comparing the number of observed versus expected adverse drug reactions, to determine the potential association between anti-neoplastic agents and thrombotic microangiopathy (TMA). The IC025 indicates the lower end of 95% of IC, in which a value >0 suggests a disproportionality signal between the drug of interest and the adverse drug reaction. Carfilzomib had the highest IC025 for TMA among all studied chemotherapies followed by gemcitabine, mitomycin, bevacizumab, and bortezomib.

COVID-19 outcomes in patients with a history of immune-mediated glomerular diseases.

Introduction: Patients with immune-mediated glomerular diseases are considered at high risk for severe COVID-19 outcomes. However, conclusive evidence for this patient population is scarce. Methods: We created a global registry and retrospectively collected clinical data of patients with COVID-19 and a previously diagnosed immune-mediated glomerular disease to characterize specific risk factors for severe COVID-19 outcomes. Results: Fifty-nine patients with a history of immune-mediated glomerular diseases were diagnosed with COVID-19 between 01.03.2020 and 31.08.2021. Over a mean follow-up period of 24.79 ± 18.89 days, ten patients (16.9%) developed acute kidney injury. Overall, 44.1% of patients were managed in an outpatient setting and therefore considered as having "non-severe" COVID-19, while 55.9% of patients had severe COVID-19 requiring hospitalization including worse outcomes. Comparing both groups, patients with severe COVID-19 were significantly older (53.55 ± 17.91 versus 39.77 ± 14.95 years, p = .003), had lower serum albumin levels at presentation (3.00 ± 0.80 g/dL versus 3.99 ± 0.68 g/dL, p = .016) and had a higher risk of developing acute kidney injury (27% versus 4%, p = .018). Male sex (p <.001) and ongoing intake of corticosteroids at presentation (p = .047) were also significantly associated with severe COVID-19 outcomes, while the overall use of ongoing immunosuppressive agents and glomerular disease remission status showed no significant association with the severity of COVID-19 (p = .430 and p = .326, respectively). Conclusion: Older age, male sex, ongoing intake of corticosteroids and lower serum albumin levels at presentation were identified as risk factors for severe COVID-19 outcomes in patients with a history of various immune-mediated glomerular diseases.

Kidney dysfunction due to AA amyloidosis in a morbidly obese female.

Kidneys are commonly involved in systemic amyloidosis. Systemic AA amyloidosis is known to be associated with states of chronic inflammation such as autoimmune conditions, chronic infections, and malignancies. Obesity is increasingly recognized to be a risk factor for low-grade, chronic inflammation. We report a 48-year-old female with morbid obesity who presented with unexplained persistent mild kidney dysfunction and low-grade proteinuria. Attempt at evaluating the cause of kidney dysfunction included performing kidney biopsy despite technical challenges. Kidney biopsy showed AA amyloidosis with predominant vascular deposition, explaining the absence of nephrotic-range proteinuria. Evaluation for secondary causes of systemic AA amyloidosis was negative. While our patient was treated with sleeve gastrectomy for morbid obesity with reasonable response, it is likely that ongoing chronic inflammation, reflected by her laboratory markers, resulted in AA amyloidosis. Treatment with anakinra, an interleukin-1 antagonist, led to improvement in the laboratory markers in the next 6 months, and her kidney function remained stable. This report highlights an important cause of kidney dysfunction in morbid obesity, an atypical presentation of AA amyloidosis, and emphasizes the value of kidney biopsy in such patients.

Atypical Anti-Glomerular Basement Membrane Disease.

Atypical anti-glomerular basement membrane (anti-GBM) disease is characterized by linear immunoglobulin G (IgG) deposition along the GBM without circulating IgG anti-GBM antibodies. Compared to classic anti-GBM disease, atypical anti-GBM disease tends to be milder with a more indolent course in certain cases. Moreover, pathologic disease pattern is much more heterogenous in atypical anti-GBM disease than in the classic type, which is uniformly characterized by diffuse crescentic and necrotizing glomerulonephritis. Although there is no single well-established target antigen in atypical anti-GBM disease, the target antigen (within the GBM) and the autoantibody type are hypothesized to be different from the classic type. Some patients have the same antigen as the Goodpasture antigen that are detected only by a highly sensitive technique (biosensor analysis). Some cases of atypical anti-GBM disease have autoantibodies of a different subclass restriction like IgG4, or of monoclonal nature. Antibodies targeting antigen/epitope structure other than the Goodpasture antigen can be detected using modified assays in some cases. Patients with IgA- and IgM-mediated anti-GBM disease are known to have negative circulating antibodies because conventional assays do not detect these classes of antibodies. A significant proportion of cases with atypical anti-GBM disease do not have any identifiable antibodies despite extensive evaluation. Nevertheless, extensive evaluation of atypical autoantibodies using modified assays and sensitive techniques should be attempted, if feasible. This review summarizes the recent literature on atypical anti-GBM disease.