Jhaveri, Kenar D

Post-transplant thrombotic microangiopathy (PT-TMA) is a serious and underrecognized complication of kidney transplantation, associated with substantially reduced allograft survival. Its heterogeneous presentations, ranging from systemic to renal-limited forms, and multifactorial etiologies complicate timely diagnosis and management. Complement activation is central across all etiologies, either as a primary driver of disease in recurrent complement-mediated TMA (also known as atypical hemolytic uremic syndrome or aHUS) or as an amplifier in de novo PT-TMA (dnTMA). Accurate diagnosis requires a combination of clinical assessment, laboratory evaluation, and histopathologic examination, with particular attention to complement abnormalities, donor/recipient risk factors, and potential triggers. Management must be individualized, encompassing supportive care, optimization of immunosuppression, complement blockade, and plasmapheresis in select cases. Histologic features and clinical risk factors can guide prognosis, and scoring systems provide valuable tools for risk stratification. Despite advances in therapy, long-term outcomes remain suboptimal, particularly in antibody-mediated rejection (AMR)-related cases. Ongoing research is essential to clarify the optimal context for the use of anti-complement therapy, and to develop effective prophylactic and therapeutic strategies while maintaining adequate immunosuppression.

ABSTRACT Acute renal failure due to cast nephropathy (CAN) is a severe complication of multiple myeloma (MM). Here, we aimed to identify parameters associated with renal outcomes and survival in newly diagnosed MM patients with CAN‐related acute renal failure and to validate the IMWG criteria for renal response. CAN diagnosis was based on biopsy or clinical assessment. Of 787 registered patients, 354 met the inclusion criteria, requiring at least two therapy cycles with documented chemotherapy response, renal response, and eGFR. Baseline free light chain (FLC) levels (median 6825.65 mg/L) decreased below 500 mg/L in 67.8% of patients. According to IMWG classification, renal complete response, partial response, and minimal response were achieved in 33.9%, 19.5%, and 28.0% of patients, respectively. The best eGFR values > 60 mL/min/1.73 m 2 were observed in 33.9% of patients, while 33.3%, 22.3%, and 10.5% had best eGFR values of 30–59, 15–29, and < 15 mL/min/1.73 m 2 , respectively. Renal response correlated with baseline FLC levels, IgG kappa, eGFR, and ECOG status in multivariate analysis, as well as with myeloma response and FLC reduction in univariate analysis. Median overall survival was 77.6 months. Survival correlated with age, myeloma response, ECOG status, FLC kappa type, baseline eGFR, standard‐risk cytogenetics, and calcium levels, among other factors. A comparison of IMWG renal response criteria with classification based solely on best eGFR showed similar utility. Of 136 patients requiring dialysis, 80 (58.8%) were able to discontinue dialysis during therapy. Bortezomib containing myeloma therapy, along with significant FLC reduction, was associated with favorable outcome.

ABSTRACT Complement protein 3 (C3) glomerulopathy (C3G) is a rare and progressive kidney disease primarily affecting young individuals and frequently advancing to end-stage kidney disease (ESKD). For ESKD, kidney transplantation remains the optimal treatment option; however, C3G has a high recurrence rate post-transplantation, affecting over two-thirds of transplanted patients. Despite advances in our understanding of C3G, significant gaps persist regarding the optimal timing for transplantation and the best strategies for peri-transplant management. Currently, no clear evidence links functional complement levels to the risk of post-transplant recurrence. Genetic counseling is also complex, due to variable gene penetrance and weak genotype–phenotype correlations, which limit predictive accuracy. Transplant-related factors are believed to significantly influence C3G recurrence, yet there are no established methods for preventing recurrence after transplantation. Eculizumab has shown inconsistent efficacy in managing recurrent C3G. However, new proximal complement inhibitors, such as factor B and C3 inhibitors, are under investigation in clinical trials and show promise. Some of these trials include kidney transplant patients with C3G, and their outcomes could potentially shape future treatment protocols.

ABSTRACT Clonal hematopoiesis of indeterminate potential (CHIP) is a non-malignant state characterized by hematopoietic stem cells exhibiting clonality driven by acquired mutations during aging. Using next-generation sequencing, it has been reported that the prevalence of CHIP increases exponentially with age. Thus far, epigenetic mutations including DNMT3A, TET2 and ASXL1 are the most common mutations identified in driving CHIP. CHIP is considered a pre-malignant state, however with reports of its associations with non-malignant disease states, the clinical impact of CHIP has been of great interest, in particular its effect on the renal and cardiac systems. CHIP has been associated with a higher rate of estimated glomerular filtration rate decline and increased risk of acute kidney injury. CHIP and its driver mutations have also been shown to increase cardiovascular disease and atherosclerosis through various inflammatory pathways. In this review, we discuss the pathophysiology of CHIP through aging, its impact on kidney disease and implications on cardiovascular health. We also compare CHIP to another pre-malignant clonal disorder, monoclonal gammopathy of undetermined significance (MGUS).

ABSTRACT 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.

Onconephrology is an upcoming and expanding subspecialty that deals with the intersections between hematology/oncology and nephrology. With the paradigm shift in the understanding of cancer immunobiology and mechanisms of oncotherapeutic drug toxicities, it is important for a nephrologist to have a sound understanding of this field. Over the last 5 years, there have been immense developments in our understanding of kidney-related adverse events from various targeted, immuno- and cellular-based therapies. Pathogenic mechanisms of electrolyte imbalance, hypertension (oncohypertension), and AKI from multiple forms of cancer therapies have been explored. Significant research has also been conducted in the field of transplant onconephrology. In this review, we have tried to assimilate the most recent updates in the last 2 years in this ever-growing and fascinating field.