Levamisole in steroid-sensitive nephrotic syndrome: usefulness in adult patients and laboratory insights into mechanisms of action via direct action on the kidney podocyte

Minimal change nephropathy (MCN) is the third most common cause of primary nephrotic syndrome in adults. Most patients with MCN respond to corticosteroid therapy, but relapse is common. In children, steroid-dependent patients are often given alternative agents to spare the use of steroids and to avoid the cumulative steroid toxicity. In this respect, levamisole has shown promise due to its ability to effectively maintain remission in children with steroid-sensitive or steroid-dependent nephrotic syndrome. Despite clinical effectiveness, there is a complete lack of molecular evidence to explain its mode of action and there are no published reports on the use of this compound in adult patients. We studied the effectiveness of levamisole in a small cohort of adult patients and also tested the hypothesis that levamisole’s mode of action is attributable to its direct effects on podocytes. In the clinic, we demonstrate that in our adult patient cohort levamisole is generally well tolerated and clinically useful. Using conditionally immortalized human podocytes, we show that levamisole is able to induce expression of glucocorticoid receptor (GR) and to activate GR signalling. Furthermore, levamisole is able to protect against podocyte injury in a puromycin aminonucleoside (PAN) treated cell model. In this model the effects of levamisole are blocked by the GR antagonist RU486, suggesting that GR signalling is a critical target of levamisole’s action. These results indicat...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research

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Abstract The present study tested the hypotheses that nephrotic syndrome (NS) leads to renal K+ loss due to augmented ENaC activity followed by down-regulation of renal K+- secretory pathways by suppressed aldosterone. The hypotheses were addressed by determining K+-balance and kidney abundance of K+- and Na+ transporter proteins in puromycin aminonucleoside (PAN)-induced rat nephrosis. Effect of amiloride and angiotensin II-AT1 and mineralocorticoid receptor (MR) antagonists were tested. Glucocorticoid-dependent MR activation was tested by suppression of endogenous glucocorticoid with dexamethasone. Urine and pla...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
Although the pathogenesis of steroid-sensitive nephrotic syndrome (SSNS) remains elusive, multiple epidemiologic, clinical, and experimental studies converge on the common theme of immune dysregulation. Initially, T-cell adaptive immunity was solely emphasized; however, the role of humoral immunity in nephrotic syndrome has gained recognition. The study by Colucci and colleagues provides preliminary evidence that production of deglycosylated IgM that is unable to regulate T-cell function in the presence or absence of corticosteroid may be responsible for a steroid-dependence course in SSNS.
Source: Kidney International - Category: Urology & Nephrology Authors: Tags: Commentary Source Type: research
ConclusionsKD is characterized by subcutaneous masses but it is also a systemic disease. Given the high rate of recurrence and reported association with lymphoma, patients require careful long-term follow-up.Key Points• Kimura disease (KD) is a rare inflammatory disorder of unknown etiology that is endemic in Asia.• Clinicians must regard and manage KD as a systemic disease.• There is no consensus on optimal treatments and further studies are necessary to improve outcomes.• Given the high rate of recurrence and reported association with lymphoma, patients require careful long-term follow-up.
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
Carotid intima-media thickness in children with idiopathic nephrotic syndrome: A single center cross-sectional study
. Clin Nephrol. 2019 May 13;: Authors: Skrzypczyk P, Kuźma-Mroczkowska E, Kułagowska J, Brzewski M, Okarska-Napierała M, Pańczyk-Tomaszewska M Abstract AIM: Our aim was to assess common carotid artery intima-media thickness (cIMT) in children with idiopathic nephrotic syndrome (INS) and to find relation between cIMT and clinical and biochemical parameters in these patients. MATERIALS AND METHODS: In 50 children with INS we retrospectively evaluated: cIMT ((mm) ...
Source: Clinical Nephrology - Category: Urology & Nephrology Authors: Tags: Clin Nephrol Source Type: research
Abstract BACKGROUND: Tacrolimus, a calcineurin inhibitor, is recommended by the recent guidelines from the Kidney Disease Improving Global Outcomes Group as the first-line treatment for steroid-resistant nephrotic syndrome (SRNS), but its clinical application in China is still limited. We investigated the efficacy and safety of tacrolimus combined with low-dose corticosteroids in a population of Chinese children with SRNS. METHODS: In this prospective non-randomized, non-controlled study, Chinese children with SRNS who failed the previous full-dose prednisone treatment were given tacrolimus (0.1 mg/kg/da...
Source: World Journal of Pediatrics : WJP - Category: Pediatrics Authors: Tags: World J Pediatr Source Type: research
Rationale: Crescent formation is rare in primary membranous nephropathy (MN). Anti-phospholipase A2 receptor (PLA2R) antibodies are detectable in these patients. The mechanism and treatments are unknown. Patient concerns: A 72-year-old female patient who presented with nephrotic syndrome, hematuria, and rapidly progressive kidney dysfunction. Diagnoses: Kidney biopsy was performed and the diagnosis was MN in combination with crescentic glomerulonephritis. Circulating anti-PLA2R IgG3 and IgG4 were detected of high level. Interventions: The patient received plasma exchange and rituximab besides corticosteroids. O...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
AbstractA 65-year-old male patient with nephrotic syndrome was admitted to our hospital due to worsening systemic edema and purpura on the limbs. He had an impaired renal function, low serum complement level, and elevated rheumatoid factor level. He was positive for cryoglobulin (monoclonal IgM- κ and polyclonal mixed-type IgG), and the results of his kidney biopsy showed a tissue profile of membranoproliferative glomerulonephritis (MPGN). Due to the fact that the secondary cause was unclear, he was diagnosed with MPGN due to essential mixed cryoglobulinemia. On hospital day 20, he was ini tiated on 50 mg/day ...
Source: CEN Case Reports - Category: Urology & Nephrology Source Type: research
Condition:   Nephrotic Syndrome in Children Intervention:   Drug: Corticosteroids Sponsors:   Wayne State University;   Children's Hospital of Fudan University;   Mansoura University Children Hospital;   Lady Hardinge Medical College;   Sawai Mansingh Medical College;   Sidra Medical and Research Center Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Recently, recessive mutations of MAGI2 were identified as a cause of steroid-resistant nephrotic syndrome (SRNS) in humans and mice. To further delineate the pathogenesis of MAGI2 loss of function, we generated stable knockout lines for the two zebrafish orthologues magi2a and magi2b by CRISPR/Cas9. We also developed a novel assay for the direct detection of proteinuria in zebrafish independent of transgenic background. Whereas knockout of magi2b did not yield a nephrotic syndrome phenotype, magi2a-/- larvae developed ascites, periorbital edema, and proteinuria, as indicated by increased excretion of low molecular weight protein.
Source: Kidney International - Category: Urology & Nephrology Authors: Tags: Basic Research Source Type: research
Conclusion: Although interstitial lung disease induced by CP is rare, with the current widespread usage of CP increases the risks of diffuse interstitial pneumonia and pulmonary fibrosis, which need to be noted in time to get early treatment. PMID: 30733918 [PubMed]
Source: Respiratory Care - Category: Respiratory Medicine Authors: Tags: Respir Med Case Rep Source Type: research
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