Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy.

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).

Can ferric citrate lead to iron overload in peritoneal dialysis patients?
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Ferric citrate (FC), a novel oral phosphate binder, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of hyperphosphatemia in end-stage renal disease (ESRD) patients receiving dialysis. FC binds to dietary phosphate in the gastrointestinal (GI) tract producing ferric phosphate that is excreted in feces. However, a small quantity of iron is systemically absorbed. There are limited data regarding the safety of the maximum approved dose of FC among peritoneal dialysis (PD) patients. We present a series of 3 PD patients who developed iron overload while receiving FC for management of hyperphosphatemia. These cases highlight the importance of close monitoring of iron studies and question whether a lower maximum dose of FC should be recommended in PD patients. Further studies are needed to assess the safety of the maximum approved dose of FC among PD patients.

Trends in multiple myeloma presentation, management, cost of care, and outcomes in the Medicare population: A comprehensive look at racial disparities.

BACKGROUND: Outcomes have improved significantly in multiple myeloma (MM), but racial disparities in health care access and survival exist. A comprehensive analysis exploring MM care and racial disparities is warranted. METHODS: Patients with MM from 1991 to 2010 in the Surveillance, Epidemiology, and End Results-Medicare database were evaluated for racial trends in clinical myeloma-defining events (MDEs), the receipt of treatment (drugs and stem cell transplantation; [SCT]), the cost of care, and overall survival (OS). RESULTS: Among 35,842 patients, the frequency of all MDEs at diagnosis increased over time; whereas, in recent years (2006-2010), all MDEs with the exception of renal dialysis decreased. Blacks had highest rates for all MDEs except bone fractures, which were highest in whites. Over time, the proportion of patients who received any treatment, multiple agents, and SCT increased significantly, and the largest increase was observed in the receipt of immunomodulatory drugs and steroids. There was greater receipt of bortezomib and SCT among whites and blacks and higher receipt of immunomodulatory drugs among Hispanics and Asians (P < .001). Medicare claims were highest during first 6 months after MM diagnosis for blacks and at any time after MM diagnosis for Hispanics. Over time, Medicare claims increased most steadily for Hispanics (P < .001). Hypercalcemia, renal dysfunction, and bone fractures were associated with inferior OS. Blacks and Asians had superior OS compared with whites, but racial differences in OS became less pronounced during 2006 through 2010 (P = .182) compared with prior years (P < .01). Better OS was noted among patients who had higher median incomes. CONCLUSIONS: The current results indicate that there have been significant changes in the management of patients with MM over time and provide an in-depth understanding of the factors that may help explain racial disparities. Cancer 2018;124:1710-21. © 2018 American Cancer Society.

Behçet's syndrome and focal segmental glomerulosclerosis with nephrotic syndrome - successful treatment with etanercept
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Behçet's syndrome (BS) often presents with aphthous and genital ulcers, uveitis, and erythema nodosum. Renal involvement has been reported with most cases presenting with renal amyloidosis, IgA nephropathy, or crescentic glomerulonephritis. We describe a case of a 49-year-old woman with relapsing BS symptoms coinciding with new-onset development of nephrotic syndrome. Renal biopsy showed focal segmental glomerulosclerosis (FSGS) that was treated with prednisone and etanercept for BS therapy. Both proteinuria and BS symptoms responded to treatment with complete remission. To our knowledge, our report is the first to show evidence of a possible connection between BS and FSGS and discusses the pathophysiologic mechanism that explains this link.
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Protecting a Diamond Quantum Memory by Charge State Control.

In recent years, solid-state spin systems have emerged as promising candidates for quantum information processing. Prominent examples are the nitrogen-vacancy (NV) center in diamond, phosphorus dopants in silicon (Si:P), rare-earth ions in solids, and VSi-centers in silicon-carbide. The Si:P system has demonstrated that its nuclear spins can yield exceedingly long spin coherence times by eliminating the electron spin of the dopant. For NV centers, however, a proper charge state for storage of nuclear spin qubit coherence has not been identified yet. Here, we identify and characterize the positively charged NV center as an electron-spin-less and optically inactive state by utilizing the nuclear spin qubit as a probe. We control the electronic charge and spin utilizing nanometer scale gate electrodes. We achieve a lengthening of the nuclear spin coherence times by a factor of 4. Surprisingly, the new charge state allows switching of the optical response of single nodes facilitating full individual addressability.

Single-spin stochastic optical reconstruction microscopy.

We experimentally demonstrate precision addressing of single-quantum emitters by combined optical microscopy and spin resonance techniques. To this end, we use nitrogen vacancy (NV) color centers in diamond confined within a few ten nanometers as individually resolvable quantum systems. By developing a stochastic optical reconstruction microscopy (STORM) technique for NV centers, we are able to simultaneously perform sub-diffraction-limit imaging and optically detected spin resonance (ODMR) measurements on NV spins. This allows the assignment of spin resonance spectra to individual NV center locations with nanometer-scale resolution and thus further improves spatial discrimination. For example, we resolved formerly indistinguishable emitters by their spectra. Furthermore, ODMR spectra contain metrology information allowing for sub-diffraction-limit sensing of, for instance, magnetic or electric fields with inherently parallel data acquisition. As an example, we have detected nuclear spins with nanometer-scale precision. Finally, we give prospects of how this technique can evolve into a fully parallel quantum sensor for nanometer resolution imaging of delocalized quantum correlations.

Addressing single nitrogen-vacancy centers in diamond with transparent in-plane gate structures.

For many applications of the nitrogen-vacancy (NV) center in diamond, the understanding and active control of its charge state is highly desired. In this work, we demonstrate the reversible manipulation of the charge state of a single NV center from NV(-) across NV(0) to a nonfluorescent, dark state by using an all-diamond in-plane gate nanostructure. Applying a voltage to the in-plane gate structure can influence the energy band bending sufficiently for charge state conversion of NV centers. These diamond in-plane structures can function as transparent top gates, enabling the distant control of the charge state of NV centers tens of micrometers away from the nanostructure.

Nailfold videocapillaroscopy in antineutrophil cytoplasmic antibody-associated vasculitis.

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.

Performance Evaluation of an Automated Peritoneal Dialysis Solution Generation System in Patients Using Automated Peritoneal Dialysis.

Introduction: Most patients on peritoneal dialysis (PD) in the United States are on automated PD (APD) utilizing several liters of PD solution daily for their treatment. The ordering, delivery, and storage of PD solutions can be challenging and is an important factor that can dissuade patients from doing PD. The generation of PD solutions at home is a strategy that could potentially be used to overcome this problem. The APD Solution Generation System (SGS) allowed for PD solution generation using tap water in patients' homes. Methods: In this study, we set out to evaluate the performance of the SGS in prevalent, adult patients with end-stage kidney disease, who are on maintenance PD. We evaluated the primary safety (microbiological testing) and efficacy (chemical composition) of the product water generated by the SGS device. Results: Twenty-two patients from 12 different United States centers were enrolled, of which 14 patients completed the study. The results of the primary safety and efficacy end point analyses of the product water showed that all 64 samples met the International Organization for Standardization (ISO) specifications. Secondary safety analysis found a total of 34 adverse events (AEs) in 12 patients. Of these AEs, 3, namely, culture negative peritonitis, bacterial peritonitis, and atrial fibrillation were deemed serious treatment-emergent AEs. Conclusion: This study demonstrated that the SGS can successfully generate PD solution in patients' homes, while meeting chemical composition and ISO microbiological standards. Lessons learned from this clinical trial will be useful in optimizing product development and future clinical trials.

Quantum sensors for biomedical applications.

Quantum sensors are finding their way from laboratories to the real world, as witnessed by the increasing number of start-ups in this field. The atomic length scale of quantum sensors and their coherence properties enable unprecedented spatial resolution and sensitivity. Biomedical applications could benefit from these quantum technologies, but it is often difficult to evaluate the potential impact of the techniques. This Review sheds light on these questions, presenting the status of quantum sensing applications and discussing their path towards commercialization. The focus is on two promising quantum sensing platforms: optically pumped atomic magnetometers, and nitrogen-vacancy centres in diamond. The broad spectrum of biomedical applications is highlighted by four case studies ranging from brain imaging to single-cell spectroscopy.

Kidney Outcomes Following Utilization of Molecular Adsorbent Recirculating System.

Introduction: Molecular adsorbent recirculating system (MARS) is an extracorporeal system combining conventional veno-venous hemodiafiltration and adsorption to provide rescue support in fulminant hepatic failure. Acute kidney injury (AKI) is common in patients with hepatic failure warranting continuous kidney replacement therapy (CKRT). Our primary aim was to characterize a cohort of patients who received MARS therapy and examine kidney events given the current paucity of available data. Methods: Patients initiating MARS in a tertiary care setting from January 2014 through December 2020 were assessed for treatment indications, transplantation, CKRT, kidney recovery, and death. Data was collected using the REDCAP software. Results: A total of 49 patients (67% female; 75% White) received MARS therapy with 29 patients (59%) requiring concomitant CKRT. Hepatic encephalopathy (HE) was the most common indication for MARS initiation (55%). In-hospital mortality was 41% (12/29) among patients who received CKRT versus 10% (2/20) among those not requiring CKRT (relative risk [RR] 4.15, 95% confidence interval [CI] 1.04 to 16.52, P = 0.044); this persisted following adjustment for prespecified patient characteristics (all RR ≥ 3.76, all P ≤ 0.060). One-year mortality post-MARS initiation was high overall but highest among the CKRT group (59% [17/29] vs. 25% [5/20] unadjusted RR 2.92, 95% CI 1.08 to 7.94, P = 0.035). Liver transplant after MARS occurred in 41% of patients (20/49). After CKRT, 39% of patients (9/29) recovered kidney function prior to hospital discharge. Conclusions: Patients requiring MARS frequently have AKI warranting the use of concomitant CKRT, which is associated with a high rate of in-hospital and 1-year mortality.

The Utility of Bronchoscopy in Hydralazine-Induced ANCA-Associated Vasculitis.

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.

Anti-PLA2R Antibody Levels and Clinical Risk Factors for Treatment Nonresponse in Membranous Nephropathy.

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.

Sarcoidosis-associated renal AA amyloidosis and crescentic necrotizing glomerulonephritis.

Sarcoidosis has a rare and independent association with renal AA amyloidosis and crescentic necrotizing glomerulonephritis. However, coexisting entities in sarcoidosis have not been previously described. Herein, we report a 66-year-old Caucasian woman who presented with generalized fatigue, weight loss, and acute kidney injury in the setting of likely sarcoidosis. Renal biopsy revealed AA amyloid fibrils with fibrocellular crescents. The patient's clinical symptoms and laboratory results improved with high-dose glucocorticoids and azathioprine.

Kidney Transplantation and Monoclonal Gammopathy of Undetermined Significance.

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.

Malignancy-Associated Membranous Nephropathy with Positive Anti-PLA2R Autoantibodies: Coincidence or Connection.

Membranous nephropathy (MN) is currently classified as either primary - often associated with positive anti-phospholipase-A2 receptor (PLA2R) autoantibodies - or as secondary - associated with malignancy, infection, medications, or autoimmune disease. We present a case of biopsy-proven MN with very high serum titer of anti-PLA2R autoantibodies in a patient with a synchronous diagnosis of poorly differentiated esophageal adenocarcinoma and renal cell carcinoma who presented with nephrotic syndrome. Based on the current classification, MN in the presence of active malignancy is diagnosed as secondary and unlikely to have positive anti-PLA2R autoantibodies. This raises several questions: whether this patient has secondary MN associated with malignancy and coincidentally discovered anti-PLA2R autoantibodies, primary MN due to anti-PLA2R autoantibodies with coincidentally discovered malignancy, or whether malignancy can induce the formation of anti-PLA2R autoantibodies that result in MN. This case report highlights the importance of age-appropriate cancer screening, even in patients with presumed primary MN and positive anti-PLA2R autoantibodies.

Fibrillary glomerulonephritis or complement 3 glomerulopathy: a rare case of diffuse necrotising crescentic glomerulonephritis with C3-dominant glomerular deposition and positive DNAJB9.

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.

Assessment of psychiatric comorbidities and serotonergic or noradrenergic medication use on blood pressure using 24-hour ambulatory blood pressure monitoring.

In 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.