Nabeel Aslam

A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR).

Background: Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. Methods and Design: Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with IV rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. Discussion: This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy.

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

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.

Career interest and perceptions of nephrology: A repeated cross-sectional survey of internal medicine residents

Background Interest in nephrology careers among internal medicine residents in the United States is declining. Our objective was to assess the impact of the presence of a nephrology fellowship training program on perceptions and career interest in nephrology among internal medicine residents. A secondary objective was to identify commonly endorsed negative perceptions of nephrology among internal medicine residents. Methods This was a repeated cross-sectional survey of internal medicine residents before (Group 1) and 3 years after (Group 2) the establishment of nephrology fellowship programs at two institutions. The primary outcome was the percentage of residents indicating nephrology as a career interest in Group 1 vs. Group 2. Secondary outcomes included the frequency that residents agreed with negative statements about nephrology. Results 131 (80.9%) of 162 residents completed the survey. 19 (14.8%) residents indicated interest in a nephrology career, with 8 (6.3%) indicating nephrology as their first choice. There was no difference in career interest in nephrology between residents who were exposed to nephrology fellows during residency training (Group 2) and residents who were not (Group 1). The most commonly endorsed negative perceptions of nephrology were: nephrology fellows have long hours/burdensome call (36 [28.1%] of residents agreed or strongly agreed), practicing nephrologists must take frequent/difficult call (35 [27.6%] agreed or strongly agreed), and nephrology has few opportunities for procedures (35 [27.3%] agreed or strongly agreed). More residents in Group 2 agreed that nephrology is poorly paid (8.9% in Group 1 vs. 20.8% in Group 2, P = 0.04), whereas more residents in Group 1 agreed that nephrologists must take frequent/difficult call (40.0% in Group 1 vs. 18.1% in Group 2, P = 0.02). Conclusions The initiation of a nephrology fellowship program was not associated with an increase in internal medicine residents’ interest in nephrology careers. Residents endorsed several negative perceptions of nephrology, which may affect career choice.

Novel variants in COL4A4 and COL4A5 are rare causes of FSGS in two unrelated families

We report two female patients with focal segmental glomerulosclerosis and chronic kidney disease. The first patient was found to have a heterozygous, de novo, pathogenic variant in COL4A5 (c.141+1G>A, IVS2+1G>A), which is associated with Alport syndrome. The second patient was found to have a heterozygous, likely pathogenic variant in COL4A4 (c.2842G>T). Both these variants in COL4A5 and COL4A4 are novel, and they were detected using whole exome sequencing and gene panel testing, respectively. Additionally, we discuss the complexities of diagnosis in such cases and the benefits of using the abovementioned diagnostic approaches.Kidney dysfunction: Identifying mutations linked with focal segmental glomerulosclerosisResearchers in the USA have identified two mutations linked with unrelated cases of the kidney disease focal segmental glomerulosclerosis (FSGS) and compared different diagnostic techniques. This disease is involved in roughly 40% of adult kidney dysfunction. Using sequencing of all protein-coding genes, Paldeep Atwal’s team at the Mayo Clinic, Jacksonville, identified a novel mutation in an FSGS patient. The mutation was not inherited, indicating that the patient’s siblings are not at increased risk. There were also mutations in other genes which may account for the patient’s vision loss. The team tested a second FSGS patient by screening kidney-related genes specifically, revealing a novel mutation in a different gene. Although the targeted approach is cheaper and quicker, these findings highlight the diagnostic benefits of full sequencing, which can reveal relevant mutations in unexpected genes.

Correction: Novel variants in COL4A4 and COL4A5 are rare causes of FSGS in two unrelated families

The originally published version of this Article contained an error in the name of the author Nabeel Aslam, which was incorrectly given as Aslam Nabeel. This has now been corrected in both the PDF and HTML versions of the Article.

Behçet's syndrome and focal segmental glomerulosclerosis with nephrotic syndrome - Successful treatment with etanercept

Behçets 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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Transection versus infection: acute appendicitis in a peritoneal dialysis patient presenting as catheter dysfunction and discontinuity on X-ray

Acute appendicitis in peritoneal dialysis patients generally presents as abdominal pain and cloudy dialysate. We report a case of acute appendicitis in a peritoneal dialysis patient that presented as poor dialysate fluid drainage and an abnormal abdominal X-ray showing breakage in the continuity of the catheter. Catheter dysfunction in this case was caused by acute appendicitis leading to the formation of adhesions with peritoneal dialysis catheter trapped in it. This resulted in radiological appearance of catheter breakage, although catheter itself was intact. Clinicians should be aware of this rare presentation of acute appendicitis—poor drain alarm and radiological appearance of catheter discontinuity.