SARS-CoV-2 Infection in Children with Idiopathic Nephrotic Syndrome: A Multicentric Study.

A multicenter retrospective study was conducted to assess the clinical spectrum of 30 severe acute respiratory syndrome coronavirus (SARS-CoV-2)-positive children with idiopathic nephrotic syndrome. Difficult to treat nephrotic syndrome was found to be a high-risk group with a high incidence of acute kidney injury and mortality.

Comparison of the prophylactic antithrombotic effect of indobufen and warfarin in patients with nephrotic syndrome: a randomized controlled trial.

PURPOSE: The risk of thromboembolic events is elevated in patients with nephrotic syndrome, and warfarin use has been associated with an increased risk of bleeding. Indobufen, a selective cyclooxygenase-1 inhibitor, is currently being evaluated for the prevention of thromboembolic events in nephrotic syndrome. This study aimed to compare the efficacy and safety of indobufen with that of warfarin in patients with nephrotic syndrome. MATERIALS AND METHODS: This multicenter, randomized, three-arm, open-label, parallel controlled trial involved a total of 180 adult patients with nephrotic syndrome from four centers in China. Patients were randomly assigned to receive 100 mg indobufen (bid), 200 mg indobufen (bid), and 3 mg warfarin (qd) daily for 12 weeks. The primary endpoints included thromboembolic and bleeding events, while laboratory results and adverse events constituted secondary endpoints. RESULTS: No thromboembolic events occurred in the high-/low-dose indobufen and warfarin groups. Moreover, the use of a low dose of indobufen significantly reduced the risk of minor bleeding events compared with warfarin use (2% versus 18%, p < .05). Finally, adverse events were more frequent in warfarin-treated patients. CONCLUSIONS: This study found that indobufen therapy provided equivalent effects in preventing thromboembolic events compared with warfarin therapy, while low dose of indobufen was associated with a reduced risk of bleeding events, thus it should be recommended for the prevention of thromboembolic events in clinical practice in patients with nephrotic syndrome. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17013428.

Spontaneous remission of nephrotic syndrome associated with COVID-19 infection in an 8-year-old boy.

BACKGROUND: It is already known that viral infections, exclusively upper respiratory tract infections may trigger relapses of nephrotic syndrome. Recently, COVID-19 disease has also been reported to be related with relapse of nephrotic syndrome in a few pediatric cases Case. Here we present an 8-year-old boy who had relapse of nephrotic syndrome due to COVID-19 infection. He was asymptomatic except for mild edema. He was managed supportively, no medication was started and went into spontaneous remission in 7 days. CONCLUSIONS: Viral infections particularly upper respiratory tract infections may trigger relapse of nephrotic syndrome. COVID-19 has also been reported to be related with relapses of nephrotic syndrome in a few pediatric cases. Spontaneous remission in our patient indicates the importance of close monitoring of patients before starting long term treatment with steroids.

Treatment of Focal and Segmental Glomerulosclerosis Secondary to High Altitude Polycythemia with Acetazolamide.

Vizcarra-Vizcarra, Cristhian A., Eduardo Chávez-Velázquez, Carmen Asato-Higa, and Abdías Hurtado-Aréstegui. Treatment of focal and segmental glomerulosclerosis secondary to high altitude polycythemia with acetazolamide. High Alt Med Biol. 23:286-290, 2022.-Focal segmental glomerulosclerosis (FSGS) is a morphological pattern, caused by glomerular injury and is the leading cause of nephrotic syndrome in adults. We present the case of a 59-year-old female patient, resident of a high-altitude city (3,824 m), who had polycythemia and nephrotic syndrome. A renal biopsy was performed, and the findings were compatible with FSGS. The patient received phlebotomy 500 ml three times, which reduced, partially, the hemoglobin concentration. However, she had refractory proteinuria, despite the use of enalapril and spironolactone. We observed that proteinuria worsened with the increase in hemoglobin levels. So, she was treated with acetazolamide 250 mg bid for 4 months, which reduced proteinuria and hemoglobin. During the coronavirus disease 2019 (COVID-19) pandemic, the patient did not take acetazolamide and again, she had an increase in hemoglobin and proteinuria levels. We conclude that acetazolamide may be an effective treatment in FSGS due to high altitude polycythemia.

Evaluation of Daily Low-Dose Prednisolone During Upper Respiratory Tract Infection to Prevent Relapse in Children With Relapsing Steroid-Sensitive Nephrotic Syndrome: The PREDNOS 2 Randomized Clinical Trial.

IMPORTANCE: In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an upper respiratory tract infection reduced the risk of relapse, but the generalizability of their findings is limited by location of the studies and selection of study population. OBJECTIVE: To investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection-related relapses. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled randomized clinical trial (Prednisolone in Nephrotic Syndrome [PREDNOS] 2) evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. Data from the modified intention-to-treat population were analyzed from July 1, 2020, to December 31, 2020. INTERVENTIONS: At the start of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of first upper respiratory tract infection-related relapse. Secondary outcomes included overall rate of relapse, changes in background immunosuppressive treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, and quality of life. RESULTS: The modified intention-to-treat analysis population comprised 271 children (mean [SD] age, 7.6 [3.5] years; 174 [64.2%] male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 of 131 (42.7%) in the prednisolone arm and 58 of 131 (44.3%) in the placebo arm (adjusted risk difference, -0.02; 95% CI, -0.14 to 0.10; P = .70). No evidence was found that the treatment effect differed according to background immunosuppressive treatment. No significant differences were found in secondary outcomes between the treatment arms. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40-1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81-1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P = .09). CONCLUSIONS AND RELEVANCE: The results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK. Further work is needed to investigate interethnic differences in treatment response. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN10900733; EudraCT 2012-003476-39.

Splanchnic venous thrombosis in a nephrotic patient following COVID-19 infection: a case report.

BACKGROUND: As the COVID-19 pandemic spread worldwide, case reports and small series identified its association with an increasing number of medical conditions including a propensity for thrombotic complications. And since the nephrotic syndrome is also a thrombophilic state, its co-occurrence with the SARS-CoV-2 infection is likely to be associated with an even higher risk of thrombosis, particularly in the presence of known or unknown additional risk factors. Lower extremity deep vein thrombosis (DVT) and pulmonary embolism (PE) are the most common manifestations of COVID-19-associated hypercoagulable state with other venous or arterial sites being much less frequently involved. Although splanchnic vein thrombosis (SVT) has been reported to be 25 times less common than usual site venous thromboembolism (VTE) and rarely occurs in nephrotic patients, it can have catastrophic consequences. A small number of SVT cases have been reported in COVID-19 infected patients in spite of their number exceeding 180 million worldwide. CASE PRESENTATION: An unvaccinated young adult male with steroid-dependent nephrotic syndrome (SDNS) who was in a complete nephrotic remission relapsed following contracting SARS-CoV-2 infection and developed abdominal pain and diarrhea. Abdominal US revealed portal vein thrombosis. The patient was anticoagulated, yet the SVT rapidly propagated to involve the spleno-mesenteric, intrahepatic and the right hepatic veins. In spite of mechanical thrombectomy, thrombolytics and anticoagulation, he developed mesenteric ischemia which progressed to gangrene leading to bowel resection and a complicated hospital course. CONCLUSION: Our case highlights the potential for a catastrophic outcome when COVID-19 infection occurs in those with a concomitant hypercoagulable state and reminds us of the need for a careful assessment of abdominal symptoms in SARS-CoV-2 infected patients.

Coronavirus Disease-2019 in Children with Primary Kidney Disease: A Case series.

Underlying comorbid illness is a known risk factor for severe coronavirus disease-2019 (COVID-19). Clinical course of COVID-19 in children with primary kidney disease is not well understood. We present the clinical profile and management of COVID-19 in three children at a COVID hospital in India. These children had nephrotic syndrome, hemolytic uremic syndrome, and chronic kidney disease, respectively. The first two were immunosuppressed, mandating to stop their immunosuppressive medications temporarily. Both had mild course of illness. Third child presented with respiratory distress requiring oxygen support, falling into moderate disease. Renal functions were normal in all of them. They all responded well to oral azithromycin and supportive management. None of them received chloroquine, corticosteroids, or monoclonal antibodies. All three recovered without complications.

Concomitant nephrotic syndrome and tubulointerstitial nephritis in a child with Epstein-Barr virus mononucleosis.

Acute kidney injury (AKI) and nephrotic syndrome (NS) are uncommon manifestations of Epstein-Barr virus (EBV) mononucleosis. We report a 4-year-old boy with Infectious mononucleosis (IM) who presented with dialysis-requiring AKI and NS. Renal biopsy showed severe acute tubular necrosis, mild chronic interstitial nephritis and focal podocyte foot processes effacement. EBV early RNA was not detected in the renal tissue. However, immunophenotyping of peripheral lymphocytes showed increased cytotoxic T cell activity and increased memory B cells. Treatment with steroid led to rapid resolution of NS within 3 weeks. Renal function stabilised. EBV viral capsid antigen (VCA) IgM remained elevated until 4 months before starting to decline when VCA IgG and nuclear antigen started appearing. B lymphocytes are the predominant target cells in EBV infection and additionally may also act as antigen presenting cells to T lymphocytes, thereby eliciting the strong immune response and leading to podocyte and tubulointerstitial injury.

Nephrotic syndrome relapse in a boy with COVID-19.

Clinical data on coronavirus disease-19 (COVID-19) in children during the management of nephrotic syndrome (NS) is lacking. Patients on prednisolone are compromised hosts at the risk of severe infections. Some infections may induce NS relapse. We describe the clinical course of a child with NS and COVID-19. A 3-year-old boy was admitted with clinical and laboratory findings indicative of NS. Induction therapy with prednisolone (2 mg/kg/day) induced complete remission. While tapering the dose, he was infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). He developed a high fever and periorbital edema. Urinalysis revealed proteinuria (protein-creatinine ratio: 6.3 g/gCr). He was transferred to our hospital for the concurrent management of COVID-19 and NS relapse. As proteinuria worsened, the prednisolone dose was increased to 2 mg/kg/day. Proteinuria gradually improved, and remission was noted a week after initiating full-dose steroid treatment. The fever subsided after 2 days without treatment for COVID-19. Anti-SARS-CoV-2 antibody including IgG levels decreased in the early convalescent phase. To the best of our knowledge, this is the first reported case with the recurrence of NS triggered by the SARS-CoV-2 infection in Asia. SARS-CoV-2 infection may induce NS relapse. Daily administration of full-dose of prednisolone may be effective for managing the recurrence of NS associated with SARS-CoV-2 infection.

COVID-19 associated with onset nephrotic syndrome in a pediatric patient: coincidence or related conditions?

BACKGROUND: COVID-19 is less frequent in children than in adults and affects the former less severely; despite the fact that respiratory symptoms are the most frequent, in some cases unusual manifestations can be seen. CASE-DIAGNOSIS: We present a 15-year-old boy who tested positive for SARS-COV-2 infection and onset of nephrotic syndrome, without antecedent of kidney disease and who had normal urine tests shortly before being affected by COVID-19. CONCLUSIONS: The patient described in this report, who was admitted due to nephrotic syndrome and respiratory syndrome, tested positive for COVID-19. He, based on the data review by the researchers, is the first reported case of COVID-19 with simultaneous onset of complete picture of nephrotic syndrome. The presence of both diagnoses could be a coincidence or an unusual form of presentation of COVID-19.