Ofatumumab in post-transplantation recurrence of focal segmental glomerulosclerosis in a child.

FSGS is a potentially devastating form of nephrotic syndrome. Treatment of SRNS can be difficult, especially post-transplantation. The current therapy of post-transplant SRNS includes plasmapheresis, ACE-I, CNI, and monoclonal antibodies (rituximab). Patients who are refractory to these interventions have limited therapeutic alternatives. We present a case of a patient with SRNS secondary to FSGS. He did not respond to immunosuppressive medications prior to transplant, progressed to ESRD, and was started on chronic hemodialysis. He received a DDKT which was complicated by post-transplant FSGS recurrence. A course of plasmapheresis, rituximab, and CNI were administered with some response. Ofatumumab was then given to the patient. As a result, the patient achieved partial remission. Ofatumumab may be a safe and effective option for post-transplant recurrence of FSGS.

Mutations in EMP2 cause childhood-onset nephrotic syndrome.

Nephrotic syndrome (NS) is a genetically heterogeneous group of diseases that are divided into steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS). SRNS inevitably leads to end-stage kidney disease, and no curative treatment is available. To date, mutations in more than 24 genes have been described in Mendelian forms of SRNS; however, no Mendelian form of SSNS has been described. To identify a genetic form of SSNS, we performed homozygosity mapping, whole-exome sequencing, and multiplex PCR followed by next-generation sequencing. We thereby detected biallelic mutations in EMP2 (epithelial membrane protein 2) in four individuals from three unrelated families affected by SRNS or SSNS. We showed that EMP2 exclusively localized to glomeruli in the kidney. Knockdown of emp2 in zebrafish resulted in pericardial effusion, supporting the pathogenic role of mutated EMP2 in human NS. At the cellular level, we showed that knockdown of EMP2 in podocytes and endothelial cells resulted in an increased amount of CAVEOLIN-1 and decreased cell proliferation. Our data therefore identify EMP2 mutations as causing a recessive Mendelian form of SSNS.

Mycophenolate Mofetil Versus Prednisone for Induction Therapy in Steroid-Sensitive Idiopathic Nephrotic Syndrome in Children: An Observational Study.

Rationale & Objective: High-dose steroids are recommended for the induction of idiopathic nephrotic syndrome. The aim of this study was to compare standard induction therapy with Mycophenolate Mofetil (MMF). We hypothesized that MMF could be noninferior to steroids in maintaining steroid-induced remission. The second aim was to reduce steroid-induced side effects. Study Design: This was an observational study. Setting & Population: Patients 2-11 years with first episode of nephrotic syndrome who entered remission within 2 weeks of standard steroid treatment were eligible for enrollment. Patients in the experimental group completed 12-week induction with MMF, whereas the control group continued a standard 12-week steroid protocol. Exposures: MMF and prednisolone were used in the study. Outcomes: The primary study outcomes were relapse rate and relapse-free interval during a 52-week follow-up. Analytical Approach: Descriptive statistics were used for analysis. Results: Ten of 41 eligible patients consented to participate in the MMF group and 8 completed the study. The control group included 31 patients, with 23 patients who completed 52 weeks follow-up. During the induction phase, 3 out of 10 patients (30%) in the MMF group and 1 out of 31 (3%) in the control group (P = 0.04) developed relapse. During the 52 weeks follow-up period, 7 out of 10 patients (70%) in the MMF group and 19 out of 31 (61%) in the control group developed relapse (P = 0.72). The median relapse-free interval was 11 and 19 weeks in MMF and control groups, respectively (P = 0.60). No serious side effects were recorded in either group. Limitations: The limitations of the study were low patient numbers receiving MMF and single-center design. Conclusions: Our small cohort of patients treated with MMF reported a higher relapse rate during the induction phase. However, by 12 months of follow-up the relapse rate and relapse-free intervals were similar between both groups. All patients tolerated MMF without significant side effects, and those who relapsed remained steroid-sensitive.

Despite their known side effects steroids remain a standard induction therapy for new onset nephrotic syndrome in children. The aim of this study was to assess whether mycophenolate mofetil (MMF) can be as successful as steroids in maintaining steroid-induced remission. Patients who achieved remission within 2 weeks of steroid treatment had either continued steroids for an additional 10 weeks or switched to MMF. The results of the study showed a higher relapse and infection rate in the MMF group. By 12 months there were no differences in the relapse rate and relapse-free interval between the groups. Larger multicenter studies are underway to demonstrate noninferiority of MMF to steroids in steroid-sensitive nephrotic syndrome.

Mycophenolate Mofetil for Severe IgA Vasculitis Nephropathy in Children: An Observational Study.

Rationale & Objective: Individuals with IgA vasculitis nephritis (IGAVN) may develop rapidly progressive glomerulonephritis and/or nephrotic-range proteinuria, which are associated with worse prognosis. We report our experience of treatment of children with IGAVN with nephrotic-range proteinuria. Study Design: Case series. Setting & Participants: We retrospectively analyzed all children who presented with IGAVN, cutaneous purpura, and nephrotic-range proteinuria from January 1, 2000 until December 31, 2018. Outcome: We evaluated time required to achieve remission of proteinuria, resolution of hematuria, and glomerular filtration rate (GFR) at 12 months and last follow-up. Results: Twelve patients, 8 boys and 4 girls, mean age 7.5 years (range 4-15) were included in the study. Mean urinary protein to creatinine ratio (UPC) was 12.5 ± 8.7 mg/mg and GFR 90.7 ± 19.1 mL/min/1.73 m2 before initiation of immunosuppression. All patients were treated with steroids and mycophenolate mofetil. Mean UPC declined progressively from 12.5 mg/mg to 4.6, 2.7, 0.3, and 0.2 mg/mg after 1, 3, 6, and 12 months, respectively. All patients achieved remission of proteinuria (UPC <0.3 mg/mg) and normalization of kidney function (GFR 102.2 ± 8.0 mL/min/1.73 m2) at 12 months. Immunosuppression was successfully withdrawn in all patients, and at last follow-up (mean 33.5 months), all patients except one remained in remission. All patients except one that relapsed maintained normal GFR at the last follow-up. Limitations: Retrospective study, single-center experience, no standard immunosuppressive protocol, lack of control group. Conclusions: Remission can be achieved in patients with IGAVN and nephrotic-range proteinuria using mycophenolate mofetil-based immunosuppression. Magnitude of proteinuria is a key laboratory finding that correlates with time to achieve remission. Prolonged follow-up of patients with severe IGAVN is warranted.

Management of severe hyponatremia with low-dose continuous kidney replacement therapy and peripheral D5W in an infant with acute kidney injury.

We report a 7-month-old female infant who presented with anuric acute kidney injury and severe hyponatremia (serum sodium 110 mEq/L). The patient was treated with low-dose continuous kidney replacement therapy (CKRT), that is, 85% of total clearance dose divided equally between normonatric (Na 140 mEq/L) replacement and dialysate fluids. The remaining 15% of the clearance was provided by peripheral infusion of dextrose 5% (D5W). The patient's sodium was maintained between 119 mEq/L and 121 mEq/L for the first 24 hours of CKRT. Over the next 2 days, the rate of D5W infusion was slowly decreased while replacement and dialysis flow rates were proportionately increased. Serum sodium was normalised by day 2 of the therapy. The patient had no neurologic sequelae associated with this therapy.

COVID-19 in Children With Kidney Disease: A Report of 2 Cases.

The presentation of novel coronavirus disease 2019 (COVID-19) in children with kidney disease is largely unknown. We report on 2 children with kidney disease not receiving long-term immunosuppression who were hospitalized due to COVID-19. The first case is an infant with end-stage kidney disease secondary to bilateral cystic dysplastic kidneys and posterior urethral valves receiving peritoneal dialysis, with a history of prematurity previously requiring mechanical ventilation in the neonatal intensive care unit, who presented with fever, hypertension, and emesis. He had no respiratory symptoms and recovered with supportive care. His hypertension was managed well with amlodipine. The second case is a child with steroid-sensitive nephrotic syndrome who presented with a relapse of nephrotic syndrome with concurrent peritonitis and sepsis caused by Streptococcus agalactiae. He was treated with antibiotics and prophylactic anticoagulation therspy. Steroid therapy was initiated after 48 hours of antibiotic therapy. Neither child required mechanical ventilation or developed COVID-19-related multisystem inflammatory syndrome.

Renal function and proteinuria after successful immunosuppressive therapies in patients with FSGS.

BACKGROUND AND OBJECTIVES: In the FSGS Clinical Trial, 22 cyclosporine-treated and 20 mycophenolate/dexamethasone-treated patients experienced a complete or partial remission after 26 weeks, completed 52 weeks of treatment, and were studied through 78 weeks. Herein, changes in the urine protein/creatinine ratio (UP/C) and estimated GFR (eGFR) throughout the entire study period are defined. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The FSGS Clinical Trial, which was conducted from November 2004 to January 2010, enrolled patients aged 2-40 years, with eGFR ≥40 ml/min per 1.73 m(2) and UP/C >1 mg/mg after ≥4 weeks of corticosteroid therapy. Both groups received lisinopril or losartan throughout the study. UP/C and eGFR were measured at 0, 26, 52, and 78 weeks. RESULTS: The median UP/C in the cyclosporine- and mycophenolate/dexamethasone-responsive patients fell by 89.8% and 82.7% at 52 weeks; the fall was largely sustained at 78 weeks (74.7% and 80.3%, respectively). The mean eGFR fell by 19.4% in the cyclosporine group and rose by 7.0% in the mycophenolate mofetil/dexamethasone group at 52 weeks, but subsequently rose by 16.4% and fell by 2.6%, respectively, in the two groups from 52 to 78 weeks. CONCLUSIONS: In this subset of responding FSGS patients, the improvement in UP/C after cyclosporine or mycophenolate/dexamethasone treatment was largely sustained for 6 months after therapy. Reduction in eGFR in the cyclosporine group was improved 6 months after cyclosporine was stopped although the levels were lower than baseline in seven patients who entered the study with decreased eGFR.