Introduction: IgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) worldwide. However, patients with advanced CKD and significant fibrosis on biopsy have limited treatment options, and clinical trials studying targeted-release budesonide have excluded individuals with low estimated glomerular filtration rate (eGFR). Case presentation: We report a case of a 36-year-old male with biopsy-proven crescentic IgAN, initially diagnosed three years prior, who presented with progressive renal dysfunction and persistent proteinuria despite prior treatment with immunosuppression, including corticosteroids and rituximab. At evaluation, serum creatinine was 2.86 mg/dL with an eGFR of 28 mL/min/1.73 m², urine protein to creatinine ratio was 1.64 grams/day and microscopic hematuria was present. Repeat kidney biopsy demonstrated significant chronic changes with severe interstitial fibrosis and tubular atrophy. The Oxford classification score was M1, E1, S1, T2, C1. Targeted-release budesonide was initiated, after which hematuria resolved within one month, proteinuria decreased significantly reaching 0.29 g/day, and kidney function improved with a serum creatinine of 2.24 mg/dL and eGFR of 38 mL/min/1.73 m² at eight months into treatment. The patient tolerated therapy without major adverse events. Conclusion: This case demonstrates clinically meaningful improvement in both proteinuria and renal function following treatment with targeted-release budesonide, despite advanced chronicity but with disease acitivity and low eGFR, a population that remains underrepresented in clinical trials and prospective studies. Our findings highlight the importance of repeat biopsy and future studies addressing the potential benefit of targeted-release budesonide in select patients with advanced IgAN, who may retain a therapeutically targetable inflammatory component.

BACKGROUND:Immunoglobulin light chain (AL) cardiac amyloidosis carries high mortality, particularly when refractory to standard plasma cell-directed therapy. Deep hematologic remission is essential for heart transplant eligibility. CASE SUMMARY:A 37-year-old woman with advanced AL cardiomyopathy and refractory plasma cell dyscrasia did not respond to daratumumab-based therapy and could not tolerate venetoclax. She developed rapidly progressive, inotrope-dependent heart failure. Salvage therapy with a B-cell maturation antigen-directed bispecific antibody, teclistamab, induced a rapid, minimal residual disease-negative complete hematologic response within 2 weeks. This enabled successful heart transplantation during the same hospitalization, with excellent early post-transplant outcomes and sustained remission. DISCUSSION:B-cell maturation antigen-directed bispecific antibodies can achieve rapid and profound hematologic responses in refractory AL amyloidosis, even in patients with advanced cardiac involvement, thereby restoring transplant eligibility. TAKE-HOME MESSAGE:Teclistamab achieved a rapid minimal residual disease-negative complete response within weeks, demonstrating its potential as a fast-acting salvage therapy capable of restoring heart transplant eligibility in advanced cardiac AL amyloidosis.

Introduction B cell depletion with rituximab leads to complete or partial remission (CR/PR) in only ∼60% of patients with primary membranous nephropathy (PMN). Adding belimumab to rituximab may result in greater depletion of memory B cells, limit the re-emergence of autoreactive B cells, and improve clinical responses. Methods REBOOT Part A (NCT03949855) is a single arm, open-label, pharmacokinetic study where all participants had proteinuria ≥ 4g/day and detectable serum anti-phospholipase A2 receptor (anti-PLA2R) antibodies. Participants received belimumab 200 mg subcutaneously weekly for 52 weeks and rituximab 1000 mg intravenously at weeks 4 and 6. Assessments included belimumab exposure at week 4 and CR/PR at week 104. Results Seventeen participants started belimumab. Belimumab exposure was not significantly reduced in those with high (>8 g/day) proteinuria at week 4. Among all treated participants, 59% (10/17) achieved CR/PR at week 104, while in per protocol analyses, 91% (10/11) achieved CR/PR at week 104. All participants in per protocol analyses had normal serum albumin and undetectable serum anti-PLA2R by week 104. Circulating memory B cells increased before rituximab and were depleted by rituximab. B cell re-constitution occurred after week 52 with primarily naïve and transitional B cells. Belimumab with rituximab was well-tolerated, with one participant discontinuing belimumab due to infection. Conclusion In this study, a high proportion of participants receiving belimumab with rituximab achieved CR/PR. Thus, a multi-targeted approach to B cell depletion may improve immunologic and clinical outcomes in PMN and is being studied in a larger, randomized, placebo-controlled clinical trial.

Measuring intraperitoneal pressure (IPP) has been proposed as a means to help maintain optimal ultrafiltration and prevent complications such as hernias, peritoneal leaks, and gastroesophageal reflux, which are linked with high IPP levels. The Durand method is a commonly accepted method for measuring IPP; however, it is cumbersome and not routinely used in clinics due to its complexity. Here we report the outcome of a pilot study that evaluated the agreement between IPP measured using an in-line pressure transducer and IPP measured using the Durand method during in-clinic automated peritoneal dialysis (APD) therapy. This was an exploratory, descriptive, early feasibility study conducted among patients with a diagnosis of kidney failure who were on APD therapy. IPP was continuously measured using an investigational device (x-MIP transducer) and at fixed timepoints using the Durand method. The study included 10 patients with a median age of 47.0 years and a median body mass index of 28.1 kg/m2. The study population was predominantly female, comprising 70% of the participants. The transducer IPP showed a moderate agreement with manual IPP, as most differences in measurements were within ±3 cmH2O. Overall, IPP did not correlate with fill-volume. However, when examined on a per-patient level, six patients showed stronger correlations (ρ > 0.7) between IPP and fill-volume, while the remaining four patients had weaker correlations (ρ < 0.5). No safety concerns were identified in the study. In summary, this study indicates that a transducer-based IPP measurement device could serve as an alternative to the Durand method.

Primary membranous nephropathy (MN) is a common cause of nephrotic syndrome and is frequently associated with circulating antibodies against the M-type phospholipase A2 receptor (PLA2R). Anti–cluster of differentiation (CD)20 monoclonal antibodies, such as rituximab, are widely used in patients with high-risk disease; however, some patients remain refractory or develop intolerance to therapy. Obinutuzumab, a type II humanized anti-CD20 monoclonal antibody, has demonstrated enhanced B-cell depletion and is a promising option in treatment-resistant MN.We present the case of a 49-year-old man with type 2 diabetes and biopsy-proven PLA2R-associated MN who developed severe nephrotic syndrome and progressive kidney dysfunction despite multiple lines of therapy, including the Ponticelli regimen, calcineurin inhibitors, adrenocorticotropic hormone gel, and mycophenolate mofetil. Rituximab was attempted on 3 separate occasions but was discontinued because of rituximab-induced serum sickness. The patient subsequently experienced worsening proteinuria, at 19.9 g by urine protein-creatinine ratio (UPCR) and progressive decline in kidney function, with an estimated glomerular filtration rate (eGFR) falling to 16 ml/min per 1.73 m2. Given these reasons, treatment with obinutuzumab was initiated, after which the patient demonstrated reduction in proteinuria (5 g) and improvement in kidney function, with an increase in eGFR to 42 ml/min per 1.73 m2. Immunological remission was achieved with PLA2R antibodies declining to undetectable levels from a peak of 669 RU/ml.This case highlights the promising therapeutic role of obinutuzumab in refractory PLA2R-positive MN, particularly in patients intolerant to rituximab.

Introduction:IgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) worldwide. However, patients with advanced CKD and significant fibrosis on biopsy have limited treatment options, and clinical trials studying targeted-release budesonide have excluded individuals with low estimated glomerular filtration rate (eGFR). Case Presentation:We report a case of a 36-year-old male with biopsy-proven crescentic IgAN, initially diagnosed 3 years prior, who presented with progressive renal dysfunction and persistent proteinuria despite prior treatment with immunosuppression, including corticosteroids and rituximab. At evaluation, serum creatinine was 2.86 mg/dL with an eGFR of 28 mL/min/1.73 m2, urine protein-to-creatinine ratio was 1.64 grams/day, and microscopic hematuria was present. Repeat kidney biopsy demonstrated significant chronic changes with severe interstitial fibrosis and tubular atrophy. The Oxford classification score was M1, E1, S1, T2, C1. Targeted-release budesonide was initiated, after which hematuria resolved within 1 month, proteinuria decreased significantly reaching 0.29 g/day, and kidney function improved with a serum creatinine of 2.24 mg/dL and eGFR of 38 mL/min/1.73 m2 at 8 months into treatment. The patient tolerated therapy without major adverse events. Conclusion:This case demonstrates clinically meaningful improvement in both proteinuria and renal function following treatment with targeted-release budesonide, despite advanced chronicity but with disease activity and low eGFR, a population that remains underrepresented in clinical trials and prospective studies. Our findings highlight the importance of repeat biopsy and future studies addressing the potential benefit of targeted-release budesonide in select patients with advanced IgAN, who may retain a therapeutically targetable inflammatory component.

Autosomal dominant polycystic kidney disease (ADPKD), the most prevalent genetic kidney disorder, is characterized by diffuse kidney cysts, hypertension, and progressive kidney function decline, often leading to kidney failure by the age of 60 years. Compared with the general population, patients with ADPKD have an increased risk for development of saccular intracranial aneurysms (IAs), which can lead to intracranial bleeding and result in significant disability and mortality. Of both modifiable and nonmodifiable risk factors, the most significant is a family history of IAs or aneurysm rupture. Other contributing factors include hypertension, cigarette smoking, age, and sex. Most IAs currently detected during screening tests are small and located in the anterior circulation. Intracranial aneurysms can be manifested with thunderclap headache, which may be indicative of subarachnoid hemorrhage. Less commonly, IAs cause symptoms related to mass effect with focal neurologic deficits. Subarachnoid hemorrhage is particularly concerning, given its high case-fatality rate, which remains around 35% despite advances in neurologic care. Therefore, control of risk factors, early detection, and treatment when indicated are important to prevent adverse outcomes. Screening for IAs in ADPKD remains controversial and can be approached either universally (screening of all ADPKD patients) or selectively (screening of high-risk patients). The preferred imaging modality is brain magnetic resonance angiography without contrast enhancement or alternatively computed tomography angiography. This review provides a practical guide for medical teams managing patients with ADPKD, detailing the characteristics of IAs and their associated symptoms. It presents an algorithm for risk assessment and screening along with recommendations for treatment and follow-up care.

BACKGROUND:Cardiac amyloidosis is a restrictive cardiomyopathy caused by myocardial deposition of insoluble amyloid fibrils. The 2 most frequent types are transthyretin amyloid cardiomyopathy (ATTR-CM) and light-chain amyloid cardiomyopathy (AL-CM). AL-CM is a type of plasma cell dyscrasia characterized by overproduction of light chains by a plasma cell clone. Some plasma cell dyscrasias, such as monoclonal gammopathy of undetermined significance, are common in patients with ATTR-CM; however, the coexistence of multiple myeloma and ATTR is rarely described in the literature. CASE SUMMARY:We describe 2 patients with confirmed plasma cell disorders: one with smoldering multiple myeloma and another with multiple myeloma receiving chemotherapy. Both exhibited cardiac imaging findings of infiltrative cardiomyopathy and were initially suspected to have AL-CM due to concomitant multiple myeloma. However, after bone marrow biopsy and fat pad aspiration did not show evidence of amyloidosis, an endomyocardial biopsy was performed that led to the diagnosis of ATTR-CM. DISCUSSION:These cases underscore the necessity of tissue confirmation when evaluating cardiac amyloidosis in the context of plasma cell dyscrasias. Adhering to guideline-directed diagnostic pathways is essential to distinguish ATTR-CM from AL-CM, as misclassification may result in delayed or inappropriate therapy. TAKE-HOME MESSAGES:ATTR-CM can occur in patients with multiple myeloma. Endomyocardial biopsy is essential to accurately distinguish ATTR-CM from AL-CM in the presence of plasma cell dyscrasia and to ensure appropriate and timely treatment.

Rationale & Objective: Ventricular assist devices (VADs) are used for advanced heart failure, but their impact on kidney function remains unclear. This study evaluated changes in kidney function following VAD implantation, including acute kidney injury (AKI) incidence and need for kidney replacement therapy (KRT). Study Design: A retrospective cohort study analyzing longitudinal kidney function outcomes post-VAD placement. Setting & Participants: Adult patients who underwent durable VAD placement (2009-2019) at a single center were included. Patients were stratified into chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2) and non-CKD (eGFR ≥60 mL/min/1.73m2) groups. Exposures & Predictors: The VAD implantation was the primary intervention, with baseline kidney function modifying its impact on post-VAD kidney function. Outcomes: Primary outcomes were changes in eGFR and creatinine at 3-months and 12-months post-VAD. Secondary outcomes included AKI incidence, KRT requirement, and postdischarge AKI within 1 year. Analytical Approach: Descriptive statistics and comparative analyses, including Wilcoxon rank sum, χ2, and paired t tests, were used to assess differences. Significance was set at P < 0.05. Results: Among 160 patients (82% male and 69% White), patients with CKD were older with a higher prevalence of diabetes, vasodilator use, and inotrope use. At 3 months, kidney function improved in patients with CKD (eGFR +17, P < 0.001) but declined by 12 months (eGFR +7, P = 0.03). The non-CKD group had a smaller improvement at 3 months (eGFR +8, P = 0.004) that was not sustained. AKI requiring KRT occurred in 14%, with 45% in-hospital mortality; and 41% discontinued KRT before discharge. Post-VAD AKI occurred in 21%. Half of the patients underwent heart transplant, which was associated with worsening kidney function at 1-year. Limitations: Single-center design limits generalizability. Conclusions: The VAD placement initially improves kidney function, particularly in CKD patients, but this effect diminishes over time. AKI and KRT use are common, highlighting the need for close kidney monitoring post-VAD. Plain-Language Summary: Ventricular assist devices (VADs) help patients with advanced heart failure by supporting heart function, but their impact on kidney health is not well understood. Because kidney disease is common in heart failure and linked to worse outcomes, we studied how kidney function changes after VAD placement. We compared patients with and without chronic kidney disease and found that kidney function improved in the first 3 months, especially in those with chronic kidney disease. However, this benefit declined over the first year. Some patients developed acute kidney injury requiring dialysis, which significantly increased their risk of death. These findings highlight the importance of closely monitoring kidney health in VAD patients to improve long-term outcomes.

Key PointsThis study demonstrates that peritoneal dialysis is a safe and feasible option for patients with autosomal dominant polycystic kidney disease, even with high cystic organ volumes.Larger organ volumes, including height-adjusted cumulative kidney and liver volume, were not associated with increased peritoneal dialysis-related complications.BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder and the fourth leading cause of kidney failure. Peritoneal dialysis (PD), preferred for its home-based convenience and cost-effectiveness, is often underutilized in ADPKD because of concerns over enlarged kidneys and heightened risk of complications.MethodsThis retrospective cohort study used data from the Mayo Clinic Polycystic Kidney Disease Database to evaluate individuals with ADPKD undergoing PD. We analyzed demographics, clinical parameters, and PD-related parameters. Complications were correlated with kidney and liver volumes derived from pre-kidney failure imaging.ResultsA total of 155 individuals with ADPKD on PD were included, of whom 45.1% were male. The mean age at PD initiation was 54.3 +/- 12.8 years, and the mean body mass index was 28.0 +/- 7.0 kg/m2. The median duration of PD was 24.3 months (interquartile range [IQR], 10.7-43.1), with 21.9% transitioning to hemodialysis. The most common complications were abdominal hernias (30.3%) and peritonitis (23.9%), with a peritonitis rate of 0.11 episodes per patient-year. Imaging analyses performed on a subset of 50 patients showed a median height-adjusted total kidney liver volume of 2731.9 ml/m (IQR, 2102.5-3131.1) and a median height-adjusted total kidney volume of 1303.5 ml/m (IQR, 733.1-1829.4). Kaplan-Meier analysis demonstrated no differences in complications rates on the basis of height-adjusted total kidney liver volume or height-adjusted total kidney volume (above versus below median values) or body mass index categories. Multivariate Cox regression analysis revealed that higher height-adjusted cumulative organ volume was associated with a lower risk of PD-related complications (hazard ratio=0.56, P = 0.026).ConclusionsPD is a safe and feasible treatment option for patients with ADPKD, with no increased risk of PD-related complications associated with larger height-adjusted cumulative organ volumes. Infectious complication rates in this cohort were within International Society of Peritoneal Dialysis guideline thresholds, further supporting the safety of PD in this population.

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy secondary to amyloid fibril deposition in the myocardium. The two precursor proteins that most frequently infiltrate the heart resulting in cardiac amyloidosis are immunoglobulin light chains (AL) and transthyretin (ATTR). Regardless of the type of amyloidosis, cardiac involvement portends a worse prognosis, and those patients with symptoms of advanced heart failure should be referred to a heart failure specialist for further evaluation and management. Given the lack of formalized guidelines for heart transplantation in CA, we propose recommendations for the pretransplant evaluation and posttransplant management within the context of the best current evidence in addition to expert opinion.

Objective Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is a group of illnesses that cause inflammation and alterations to small vessels in the body. Some of the most common and detrimental manifestations, including alveolar hemorrhage and glomerulonephritis, are caused by this capillary inflammation. We sought to clarify whether patients with AAV would have abnormal nailfold capillaries when evaluated with nailfold videocapillaroscopy. Methods Patients with a current diagnosis of AAV and a control group were identified for enrollment. Nailfold videocapillaroscopy images were used for a semiquantitative analysis on capillary density, morphology, dilation, and microhemorrhage after review by 2 rheumatologists. Disease characteristics, occurrence of recent disease flare, and presence of ANCA were recorded. Results Thirty-three patients with a diagnosis of AAV and 21 controls were recruited. The AAV group had a median age of 59 and 17 (52%) were women. Granulomatosis with polyangiitis was the most common diagnosis (19 [58%]), followed by eosinophilic granulomatosis with polyangiitis (7 [21%]) and microscopic polyangiitis (7 [21%]). Twenty-seven patients (82%) had positive ANCA tests. After assessment of capillary density, dilation, morphology, microhemorrhages, and disorganization, there were no statistically significant differences between the 2 groups. Conclusion There was no evidence of differences in nailfold capillaroscopy abnormalities between those diagnosed with AAV and the control group. While this cohort was relatively small, we did not find a high enough prevalence or specific phenotype of capillary abnormalities that could aid in diagnosis or prognostication of these diseases in the clinical setting.