Citations

ABSTRACT Background and hypothesis The MENTOR trial (MEmbranous Nephropathy Trial Of Rituximab) showed that rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria and was superior in maintaining proteinuria remission. However, the cost of rituximab may prohibit first-line use for some patients and health-care payers. Methods A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of rituximab compared with cyclosporine for the treatment membranous nephropathy from the perspective of a health-care payer with a lifetime time horizon. The model was informed by data from the MENTOR trial where possible; additional parameters including cost and utility inputs were obtained from the literature. Sensitivity analyses were performed to evaluate the impact of reduced-cost biosimilar rituximab. Results Rituximab for the treatment of membranous nephropathy was cost effective (assuming a willingness-to-pay threshold of $50 000 per quality-adjusted life year (QALY) gained; in $US 2021) compared with cyclosporine, with an ICER of $8373/QALY over a lifetime time horizon. The incremental cost of rituximab therapy was $28 007 with an additional 3.34 QALYs compared with cyclosporine. Lower cost of rituximab biosimilars resulted in a more favorable ICER, and in some cases resulted in rituximab being dominant (lower cost and great benefit) compared to cyclosporine. Conclusions Despite the greater cost of rituximab, it may be a cost-effective option for the treatment of membranous nephropathy when compared with cyclosporine. The cost-effectiveness of rituximab is further improved with the use of less expensive biosimilars.

Plasma cell disorders are one of the most common hematologic malignancies. Monoclonal gammopathy of undetermined significance (MGUS) is defined by a serum monoclonal protein <3 g/dL, bone marrow plasma cell infiltration <10%, and most importantly absence of end-organ damage. The prevalence of MGUS in general population is estimated to be 1%–4% and its frequency increases with age with 3% among people above 50 y of age. The risk of progression to clinically significant plasma cell dyscrasia is estimated to be 1% per year. With aging population and increasing use of transplantation for the management of kidney disease in older adults, MGUS is being identified during the evaluation for kidney transplant candidacy or during the postkidney transplant follow-up. MGUS in patients with end-stage renal disease (ESRD) undergoing evaluation for kidney transplant can pose a complex management dilemma. In this article, we review the current state of knowledge about the prevalence of MGUS in ESRD population and the impact of kidney transplantation on the progression of MGUS to clinically significant plasma cell disorder. We make recommendations for the screening of ESRD patients undergoing kidney transplant evaluation and the management of MGUS after renal transplant.

Abstract 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.

Background The 2021 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend following anti-phospholipase A2 receptor (PLA2R) antibody levels as a marker of treatment response in membranous nephropathy; however, the optimal timing to evaluate antibody levels and how to combine them with other clinical variables are currently unknown. Methods We used a cohort of 85 patients from the Membranous Nephropathy Trial Of Rituximab (MENTOR) with anti-PLA2R antibodies ≥14 RU/ml to identify risk factors for not experiencing proteinuria remission after 12 months of treatment with cyclosporine or rituximab. Three landmark times were considered: at baseline and after 3 and 6 months of treatment. Logistic regression model performance was evaluated using C-statistics and model fit (Akaike information criterion [AIC], R 2 ). Results The model at baseline that best predicted no remission included anti-PLA2R antibodies >323 RU/ml and creatinine clearance; the best model after 3 months included the change from baseline in both antibody and albumin levels; and the best model after 6 months included antibody levels >14 RU/ml, creatinine clearance, and the change from baseline in albumin. Compared with the model at baseline, the model at 3 months had better model fit (AIC 70.9 versus 96.4, R 2 51.8% versus 30.1%) and higher C-statistic (0.93 versus 0.83, P = 0.008). The model at 6 months had no difference in performance compared with the model at 3 months (AIC 68.6, R 2 53.0%, C-statistic 0.94, P = 0.67). Conclusions In patients with membranous nephropathy treated with cyclosporine or rituximab in the MENTOR trial, we found that the optimal method to evaluate risk factors for the probability of treatment response was to use anti-PLA2R antibody levels combined with albumin levels after 3 months of treatment, which was significantly better than using antibody levels alone or risk factor evaluation at baseline, with no added benefit of waiting until 6 months of treatment. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_10_09_CJN0000000000000237.mp3

Hydralazine is a vasodilator used for the management of hypertension, heart failure, and hypertensive emergencies in pregnancy. It has been implicated in the causation of drug-induced lupus erythematosus (DLE) and rarely with ANCA-associated vasculitis (AAV), which may present as a pulmonary-renal syndrome and be rapidly fatal. Herein, we describe a case of hydralazine-associated AAV presenting as acute kidney injury with the use of early bronchoalveolar lavage (BAL) with serial aliquots to aid with diagnosis. Our case highlights how, in the correct clinical setting, BAL can act as a rapid diagnostic test to help guide quicker treatment to allow for better patient outcomes.

Background: Ambulatory blood pressure monitoring (ABPM) is important for the diagnosis of hypertension (HTN) as well as variants such as nocturnal HTN (NH), masked HTN and a non-dipping pattern. NH and non-dipping, a failure of the normal circadian drop in blood pressure during sleep, have been associated with all-cause mortality and cardiovascular risk. Obstructive sleep apnea is associated with HTN and a growing body of evidence suggests that limb movement disorders of sleep may also influence cardiovascular morbidity. The present study investigates arousals of sleep disorders, limb movement or respiratory, and their relationship to ABPM measurements. Methods: A retrospective review (January 1, 2010 to December 31, 2014) was performed on patients that underwent both ABPM and polysomnography within a six months of each other. Socio-demographic data, results of 24 hour ABPM and polysomnography, concurrent medication use by class, comorbid conditions and laboratory data were recorded. Patients with incomplete polysomnography or ABPM measurements were excluded. Results: 330 individuals met criterion for inclusion; 59% male, 86% white. 211 (64%) were found to have NH, 106 (32%) had uncontrolled HTN and 202 (61%) had a non-dipping pattern. Patients with NH were more likely to have diabetes, hyperlipidemia and chronic kidney disease. Elevated arousal indices were more prevalent in those with NH, uncontrolled HTN and non-dippers. There was an association of NH with the total number of arousals per hour of sleep (p<0.01), whether related to respiratory disturbances or limb movements. Limb movement index (LMI) was related to age (p<0.0001) and was associated with all type arousals (p<0.0001). Conclusions: ABPM revealed a high prevalence of NH, non-dipping, masked and uncontrolled HTN in patients with sleep disorders. Arousals of all types, whether accompanying respiratory or limb movements, were associated with NH and also with LMI.

AbstractIn this study, the authors aimed to assess both nighttime and daytime blood pressure (BP) variability using 24‐hour ambulatory BP monitoring (ABPM) in persons with and without psychiatric conditions and with or without selective serotonin reuptake inhibitors (SSRIs) or serotonin‐norepinephrine reuptake inhibitors (SNRIs) treatment. In this retrospective study, patients who underwent psychiatric evaluation and ABPM within 6 months of each other between January 1, 2012 and December 31, 2017 were identified using billing data. Participants were divided into three groups—participants with no psychiatric diagnosis and no psychiatric medicine (−Diagnosis/−Medication), those with psychiatric diagnosis and on SSRIs/SNRIs (+Diagnosis/+Medication), and psychiatric diagnosis but no psychiatric medications (+Diagnosis/−Medication). Day and nighttime systolic and diastolic BPs were compared between groups controlling for relevant variables using multivariable linear regression models. A total of 475 participants met inclusion criteria including 135 in the −Diagnosis/−Medication group, 232 in the +Diagnosis/+Medication group, and 108 in the +Diagnosis/−Medication group. In adjusted multivariable analysis, the +Diagnosis/+Medication group had higher nighttime systolic BP (median 120 vs 110 mm (Hg); p = .01) and nighttime diastolic BP (median 68 vs 63 mm (Hg); p = .006) as compared to −Diagnosis/−Medication. No statistically significant differences in BPs between the −Diagnosis/−Medication and +Diagnosis/−Medication groups were observed, after adjustment. Use of SSRIs/SNRIs was associated with significantly higher nocturnal systolic and diastolic BP among patients with psychiatric diagnosis using SSRIs/SNRIs but not associated with psychiatric diagnosis without SSRI/SNRI use. SSRIs/SNRIs use may be associated with higher BP levels and this merits future prospective studies using ABPM to assess day and nighttime BP changes with SSRIs/SNRIs use.

Fibrillary glomerulonephritis (FGN) and complement 3 glomerulopathy (C3G) are rare forms of glomerulonephritis with distinct aetiologies. Both FGN and C3G can present with nephritic syndrome. FGN is associated with autoimmune disease, dysproteinaemia, malignancy and hepatitis C infection. C3G is caused by the unregulated activation of the alternative complement pathway. We present a rare case of diffuse necrotising crescentic glomerulonephritis with dominant C3 glomerular staining on immunofluorescence—consistent with C3G—but electron microscopy (EM) findings of randomly oriented fibrils with a mean diameter of 14 nm and positive immunohistochemistry for DNAJB9—suggestive of FGN. To the best of our knowledge, this is the first reported case of FGN to show dominant C3 glomerular deposits. This case report reaffirms the utility of EM in the evaluation of nephritic syndrome and highlights the value of DNAJB9—a novel biomarker with a sensitivity and specificity near 100% for FGN.