scholarly journals Enhancing clinical trial development for pediatric kidney diseases

2017 ◽  
Vol 82 (5) ◽  
pp. 727-732 ◽  
Author(s):  
H William Schnaper ◽  
Joseph T Flynn ◽  
Coleman Gross ◽  
Anne B Cropp ◽  
Bastian Dehmel ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kidney Diseases ◽  
Pediatric Kidney Diseases

A Uniform Clinical Trial Registration Policy for Journals of Kidney Diseases, Dialysis, and Transplantation

2005 ◽  
Vol 79 (7) ◽  
pp. 751 ◽  
Author(s):  
William Couser ◽  
Tilman Drueke ◽  
Phillip Halloran ◽  
Bertram Kasiske ◽  
Saulo Klahr ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kidney Diseases ◽  
Trial Registration ◽  
Clinical Trial Registration

Epidemiology of Pediatric Kidney Diseases

1996 ◽  
Vol 25 (5) ◽  
pp. 288-296 ◽  
Author(s):  
Robert J Wyatt ◽  
Lori Kagy ◽  
Stephen B Kritchevsky
Keyword(s):  
Kidney Diseases ◽  
Pediatric Kidney Diseases

scholarly journals Therapeutic Evaluation of Artesunate in IgA Nephropathy (TEATING) Study: A study protocol of a multicenter, double-blind, randomized, placebo-controlled trial

2021 ◽  
Author(s):  
Qi Chen ◽  
Zi Wang ◽  
Jicheng Lv ◽  
Lijun Liu ◽  
Hang Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Iga Nephropathy ◽  
Clinical Evidence ◽  
Kidney Diseases ◽  
Controlled Trial ◽  
Controlled Clinical Trial ◽  
Clinical Trial Registry ◽  
Double Blind ◽  
Patients At Risk ◽  
Stage Renal Disease

Abstract Background IgA nephropathy is the most common glomerular disease and a common cause of progression to end-stage renal disease in patients with kidney diseases. Proteinuria levels are critical to the prognosis of patients with IgA nephropathy, but many patients are still unable to effectively control proteinuria levels after receiving adequate RAAS blockers. Antimalarial drugs have shown good efficacy in the treatment of kidney disease in previous studies; however, there have been no strict designed randomized controlled trials to confirm the clinical efficacy of artesunate in IgA nephropathy patients. Therefore, we designed this clinical trial to compare the effect of artesunate versus placebo in patients with IgA nephropathy. Methods This study was a randomized, double-blind, three-group-parallel, placebo-controlled clinical trial. One hundred and twenty eligible IgA nephropathy patients at risk of progression were randomly divided into artesunate 100mg group, artesunate 50 mg group, and placebo group. Changes in proteinuria and renal function were measured after 6 months of intervention. The levels of Gd-IgA1, Anti-Gd-IgA1 in the patient's blood will also be tested to further understand possible immune mechanisms. Discussion Clinical evidence for artesunate treatment of IgA nephropathy is currently lacking, and we expect that the results of this trial will provide high-quality clinical evidence for artesunate as a treatment option for IgA nephropathy in the future. Trial registration: Chinese Clinical Trial Registry: ChiCTR2000038104, registration date: 10 September 2020. http://www.chictr.org.cn/edit.aspx?pid=61338&htm=4.

scholarly journals MO451GUANIDINYLATED APOLIPOPROTEIN C3 (APOC3) A NOVEL PLAYER IN CKD AND CKD-ASSOCIATED CARDIOVASCULAR DISEASES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Stefan Schunk ◽  
Juliane Hermann ◽  
Triem Sarah ◽  
Michaela Lellig ◽  
Eunsil Hahm ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Clinical Trial ◽  
Cardiovascular Diseases ◽  
Prospective Cohort ◽  
Kidney Diseases ◽  
Sterile Inflammation ◽  
Humanized Mice ◽  
Prospective Clinical Trial ◽  
Inflammasome Activation ◽  
Human Monocytes

Abstract Background and Aims Cardiovascular diseases (CVD) and chronic kidney diseases (CKD) are highly prevalent in Western populations and account for a substantial proportion of mortality. We found that apolipoprotein C-3 (ApoC3), a constituent of triglyceride-rich lipoproteins, induces alternative NLRP3 inflammasome activation in human monocytes and thus causes sterile inflammation. The aim of the present study was to screen ApoC3 for the presence of posttranslational protein modifications and to assess its relevance in vitro, in vivo, as well as in a prospective cohort of CKD patients. Method ApoC3 was subjected to proteomic analysis. The proinflammatory properties of ApoC3 were assessed in human monocytes and in humanized mice. Moreover, posttranslationally modified ApoC3 was quantified in prospective cohort of 543 patients with various etiologies of CKD and linked to kidney and cardiovascular outcomes. Results We identified posttranslational guanidinylation of lysine residues of ApoC3 (gApoC3) in patients after acute myocardial infarction and in patients with CKD. gApoC3 accumulates in kidneys and hearts after injury as determined by 2D-proteomic analyses. In human monocytes, guanidinylation enhanced the binding of ApoC3 to the cell surface and exerted substantially stronger pro-inflammatory effects as compared native ApoC3. In humanized mice, gApoC3 strongly induced kidney fibrosis and abolished the regeneration after vascular injury. In a prospective clinical trial of 543 patients, higher gApoC3 blood levels as determined by mass spectrometry were associated with increased mortality as well as cardiovascular and renal events during a long-term follow-up. Conclusion The present study provides evidence from preclinical models and a prospective clinical trial that gApoC3 plays an important role in the development of organ injury in patients with CKD, myocardial infarction and other clinical conditions. The clinical study represents one of the largest trials, in which the association of a specific PTM and clinically relevant outcomes was assessed. These findings highlight gApoC3 as a pathophysiologically relevant factor in development of organ dysfunction.

A Single-Center Phase 2 Open-Label Trial Evaluating the Safety and Efficacy of Daratumumab in Treatment of Patients with Monoclonal Gammopathy of Renal Significance

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 43-44
Author(s):  
Ladan Zand ◽  
S. Vincent Rajkumar ◽  
Sanjeev Sethi ◽  
Nelson Leung ◽  
Fernando C. Fervenza
Keyword(s):  
Clinical Trial ◽  
Monoclonal Gammopathy ◽  
Conflicts Of Interest ◽  
Kidney Diseases ◽  
Primary Objective ◽  
Factor H ◽  
Complement Factor ◽  
Phase 2 ◽  
Safety And Efficacy ◽  
Secondary Objective

Proliferative glomerulonephritis with monoclonal immune deposits (PGNMID) and C3 glomerulopathy (C3G) with monoclonal gammopathy (MG) are kidney diseases related to monoclonal gammopathy of renal significance (MGRS). Rituximab or combination of cyclophosphamide, bortezomib and dexamethasone have been used with variable success but no clinical trial has been performed up to now. In this phase 2 trial, we evaluated the safety and efficacy of daratumumab (an anti-CD38 plasma therapy) in patients with PGNMID and C3G with MG. The primary objective was safety and tolerability of daratumumab. The secondary objective was the response rate to daratumumab. Response was defined by complete remission (CR) (proteinuria <500 mg/d and no more than 10% drop in eGFR) or partial remission (PR) (50% reduction in proteinuria with no more than 30% drop in eGFR) at 6 and 12 months. Daratumumab was administered intravenously at a dose of 16mg/kg once weekly for 8 weeks followed by once every other week for an additional 8 doses. Twelve patients were recruited. There was only one patient with C3G with MG recruited and one patient with PGNMID did not finish the first infusion of daratumumab. Both were excluded from evaluation of the secondary objective. The patient with C3G was excluded as later it was noted that the disease was not triggered by the MG but rather due to activation of her alternative complement pathway due to high-risk allele for complement Factor H (CFH) and C3. Mean age was 51.2 ± 22.6 (18-87) years. All patients were White and 5 were male. For the primary objective, there were five serious adverse events (SAE). Two were serious infections that occurred in the patient with C3G with MG. At the time of these infections, patient was receiving additional immunosuppression with tacrolimus, mycophenolate mofetil and prednisone. One was a febrile episode attributed to a virus that resolved with stopping additional immunosuppression, and another was an episode of C. difficile colitis that resolved following treatment. There were 3 episodes of uncomplicated UTI that resolved following antibiotic therapy and one episode of URI that required no treatment. The other two SAE were eye chemosis and headache in the same patient that resolved. Last SAE was an episode of acute closed angle glaucoma that occurred 45 min into the 1st infusion. This patient was withdrawn from the study. The most common side effect was infusion related reaction (with first infusion) that included cough, congestion, and throat irritation that resolved by the end of the infusion. There were no grade 3 or 4 anemia, thrombocytopenia or leukopenia. At 6 months, 2 patients achieved CR, 6 achieved PR and 2 had no response (NR). At 12 months, the 2 patients who had NR had entered PR and 2 additional patients that had achieved PR entered CR, but 3 patients relapsed (1 from CR and 2 from PR group). Overall, at 12 months, 3 patients achieved CR, 5 achieved PR and 2 had NR (due to relapse). The median 24hr baseline urinary protein declined from 4346 mg (3245 - 7943) to 702 mg (435 - 3057), at 6 months (p=0.001) and 1264 mg (463 - 3645) at 12 months (p = 0.004). There was also significant improvement in serum albumin, hemoglobin, total and LDL cholesterol, and complement 3 levels from baseline to 12 months follow-up (Table 1). Estimated GFR remained unchanged from 61.1 ± 31.9 to 65.0 ± 31.7 at 12 months (p=0.4). In this trial, daratumumab has shown to be safe and well tolerated. Daratumumab was also shown to be effective in reducing the proteinuria dramatically in patients with PGNMID secondary to MGRS along with stabilization of renal function. In conclusion, this is the first clinical trial of daratumumab in patients with MGRS and the promising results deserves further study. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Daratumumab - off label use for treatment of PGNMID

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