Primary IgA Nephropathy: New Insights and Emerging Therapies.

Primary IgA nephropathy (IgAN) is a common glomerular disorder defined by predominant mesangial IgA deposition. Once thought to follow a progressive course in 10-20% of those diagnosed, emerging evidence now suggests most will progress to kidney failure over their lifetimes. Although the lack of safe and effective treatments to impede disease progression continues to present a challenge, the landscape of IgAN has dramatically evolved over the last 2 years. Driven by fundamental changes to accepted end points for IgAN clinical trials as well as fascinating new insights into the pathophysiology of IgAN, a swathe of novel and repurposed therapies are currently being evaluated. Already, two novel drugs, targeted-release formulation budesonide and sparsentan, have received conditional approvals for the treatment of IgAN, with sodium glucose co-transporter 2 inhibitors establishing themselves as further options. Soon to join this ensemble are likely to be treatments that modulate the complement system and B-cell activity; several are currently undergoing clinical trials in IgAN with promising interim results. In this review, we provide an overview of evolving epidemiological insights, disease mechanisms, emerging therapies, and contemporary challenges surrounding the management of IgAN.

Anti-Glomerular Basement Membrane Disease: Recent Updates.

Anti-glomerular basement membrane disease is a small-vessel vasculitis involving the kidneys (∼90%) and the lungs (∼60%). Antibodies against the glomerular basement membrane are directly pathogenic in anti-glomerular basement membrane disease; however, recent research has highlighted the critical role of T cells. Novel autoantigens within the glomerular basement membrane are also now recognized. Atypical forms of the disease are reported along with preceding triggers, such as immune checkpoint inhibitors, immunomodulatory drugs, and vaccines. Kidney outcomes in anti-glomerular basement membrane disease remain poor despite significant improvement in patient survival in the last 2 to 3 decades. Treatment typically relies on combined plasmapheresis with intensive immunosuppression. Dialysis dependency at presentation is a dominant predictor of kidney outcome. Histologically, a low (<10%) percentage of normal glomeruli, 100% crescents, together with dialysis dependency at presentation, is associated with poor kidney outcomes. In such cases, an individualized approach weighing the risks and benefits of treatment is recommended. There is a need for better ways to stop the toxic inflammatory activity associated with this disease. In this narrative review, we discuss recent updates on the pathogenesis and management of anti-glomerular basement membrane disease relevant to patients of all ages.

Membranous-like glomerulopathy with masked monotypic IgG deposits: A single center case series.

BACKGROUND: Membranous-like glomerulopathy with masked monoclonal IgG deposits (MGMID) is a newly recognized condition predominantly observed in young females, and its understanding in the pediatric population remains limited. MATERIALS AND METHODS: Four cases of MGMID are reported, including three pediatric patients. RESULTS: All patients were female, with ages ranging from 12 to 26 years. None of the patients had malignancies. They presented with kidney dysfunction, proteinuria, or hematuria. Kidney biopsies of all cases exhibited a membranous pattern of injury with monoclonal IgG-κ restriction, "unmasked" by pronase digestion. Pediatric cases were treated conservatively, while the adult case underwent immunosuppressive treatment. All patients had favorable outcomes, and none reached end stage kidney disease (ESKD). CONCLUSION: MGMID can affect both adult and pediatric patients. Further studies are needed to fully characterize its risk factors, optimal therapy, and outcomes.

Hypercalcemia of malignancy: Cancer treatment can be a cause as well.

While the incidence of hypercalcemia of malignancy (HCM) is on the decline, it still occurs in up to 30% of patients with cancer. Immune checkpoint inhibitor (ICI)-related hypercalcemia is becoming increasingly recognized. We describe a case of cemiplimab-induced hypercalcemia in a patient with metastatic squamous cell carcinoma of the earlobe and discuss a management algorithm for HCM. Timely diagnosis and management of HCM is critical for optimal care and the prevention of complications.

Lupus nephritis: management challenges during pregnancy.

Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), leads to significant kidney inflammation and damage and drastically increases mortality risk. Predominantly impacting women in their reproductive years, LN poses specific risks during pregnancy, including pre-eclampsia, growth restrictions, stillbirth, and preterm delivery, exacerbated by lupus activity, specific antibodies, and pre-existing conditions like hypertension. Effective management of LN during pregnancy is crucial and involves carefully balancing disease control with the safety of the fetus. This includes pre-conception counseling and a multidisciplinary approach among specialists to navigate the complexities LN patients face during pregnancy, such as distinguishing LN flare-ups from pregnancy-induced conditions. This review focuses on exploring the complex dynamics between pregnancy and LN, emphasizing the management difficulties and the heightened risks pregnant women with LN encounter.

Real-World Experience With Avacopan in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Introduction: Postmarketing data on outcomes of avacopan use in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are lacking. Methods: We performed a multicenter retrospective analysis of 92 patients with newly diagnosed or relapsing AAV who received therapy with avacopan. The coprimary outcome measures were clinical remission at 26 and 52 weeks. We use descriptive statistics and univariate logistic regression to assess outcomes and predictors of remission, respectively. Results: Of the 92 patients, 23% (n = 21) had a baseline estimated glomerular filtration rate (eGFR) < 15 ml/min per 1.73 m2 and 10% on kidney replacement therapy at baseline. Among those with kidney involvement, mean (SD) enrollment eGFR was 33 (27) ml/min per 1.73 m2 with a mean (SD) change of +12 (25) and +20 (23) ml/min per 1.73 m2 at weeks 26 and 52, respectively. In addition to avacopan, 47% of patients received combination therapy of rituximab and low-dose cyclophosphamide, and 14% of patients received plasma exchange (PLEX). After induction, the median (interquartile range [IQR]) time to start avacopan was 3.6 (2.1-7.7) weeks, and the median time to discontinue prednisone after starting avacopan was 5.6 (3.3-9.5) weeks. Clinical remission was achieved in 90% of patients at week 26 and 84% of patients at week 52. Of the patients, 20% stopped avacopan due to adverse events, with the most common being elevated serum aminotransferases (4.3%). Conclusion: A high rate of remission and an acceptable safety profile were observed with the use of avacopan in the treatment of AAV in this postmarketing analysis, including the populations excluded from the ADVOCATE trial.

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

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

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.

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.

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.