CD44 staining in parietal epithelial cells and early steroid response in patients with minimal change disease.
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ABSTRACT:
SUBMITTER: Morel A
PROVIDER: S-EPMC10387389 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
CD44 staining in parietal epithelial cells and early steroid response in patients with minimal change disease.
Morel Antoine A Remy Philippe P Sakhi Hamza H El Karoui Khalil K Sahali Dil D Audard Vincent V Moktefi Anissa A
Clinical kidney journal 20230405 8
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Project description:BackgroundActivation of parietal-epithelial cells (PECs) with neo-expression of CD44 has been found to play a relevant role in the development of focal and segmental glomerulosclerosis (FSGS). The aim of this study was to analyse whether the expression of CD44 by PECs in biopsies of minimal change disease (MCD) is associated with the response to corticosteroids, with kidney outcomes and/or can be considered an early sign of FSGS.MethodsThis multicentric, retrospective study included paediatric and adult patients with MCD. Demographic, clinical and biochemical data were recorded, and biopsies were stained with anti-CD44 antibodies. The association between PECs, CD44 expression and the response to corticosteroids, and kidney outcomes were analysed using logistic, Kaplan-Meier and Cox regression analyses.ResultsA total of 54 patients were included: 35 (65%) <18 years and 19 (35%) adults. Mean follow-up was 68.3 ± 37.9 months. A total of 19/54 patients (35.2%) showed CD44-positive staining. CD44-positive patients were younger (14.5 ± 5 versus 21.5 ± 13, P = 0.006), and showed a higher incidence of steroid-resistance [11/19 (57.8%) versus 7/35 (20%), P = 0.021; odds ratio: 5.5 (95% confidence interval 1.6-18), P = 0.007] and chronic kidney disease [9/19 (47.3%) versus 6/35 (17.1%), P = 0.021; relative risk: 3.01 (95% confidence interval 1.07-8.5), P = 0.037]. Follow-up re-biopsies of native kidneys (n = 18), identified FSGS lesions in 10/12 (83.3%) of first-biopsy CD44-positive patients versus 1/6 (16.7%) of first-biopsy CD44-negative patients (P = 0.026).ConclusionsIn patients with a light microscopy pattern of MCD, CD44-positive staining of PECs is associated with a higher prevalence of steroid resistance and worse kidney outcomes, and can be considered an early sign of FSGS.
| S-EPMC8862079 | biostudies-literature
Project description:Rationale & objectiveThe response to corticosteroid therapy may differ among patients with minimal change disease (MCD). Previous studies have suggested that glomerular hypertrophy or low areal glomerular density in biopsy specimens, which may be related to fewer nephrons, is associated with such a difference. We examined the associations between nephron number and the therapeutic response to corticosteroids in patients with MCD.Study designRetrospective cohort study.Setting & participants75 adult patients with a histologic diagnosis of MCD.ExposureNephron number per kidney estimated based on the combination of unenhanced computed tomography and nonsclerotic volumetric glomerular density in kidney biopsy specimens.OutcomesComplete remission and relapse following corticosteroid therapy.Analytical approachMultivariable Cox proportional hazard analyses of associations between factors, including nephron number, and outcomes.ResultsMean age of patients was 45.9 years and 60.0% were men. Patients had an estimated glomerular filtration rate of 64.6 mL/min/1.73 m2 and proteinuria of 8.7 g/d. The estimated total number of nonsclerotic glomeruli ranged from 1.07 to 18.77 ×105 per kidney among all patients. There were no significant differences in total amounts or selectivity of urinary protein excretion at biopsy among the tertile groups categorized by nephron number. All patients responded to corticosteroid therapy, but those with fewer nephrons had a delayed achievement of complete remission. Multivariable Cox proportional hazard analyses identified nephron number as a significant independent explanatory variable for the achievement of complete remission, with a hazard ratio of 1.10 (95% CI, 1.02-1.19)/100,000 nephrons per kidney. Nephron number in these patients was not associated with achievement of partial remission or relapse following complete remission.LimitationRetrospective design and sampling bias of needle biopsy.ConclusionsA small nephron number in patients with MCD is associated with longer time to complete remission.
| S-EPMC7568083 | biostudies-literature
Project description:BackgroundIn patients with adult minimal change disease (MCD), proteinuria relapse is a problem to solve. However, the optimal relapse treatment regimen remains unclear regarding steroid dose. We described the treatment pattern of adult MCD patients and evaluated the appropriate steroid dose for relapse treatment.MethodsThis retrospective multicenter cohort study included 192 patients with adult biopsy-proven MCD from 14 hospitals in Japan. The prescription pattern of immunosuppressive drugs in relapse was reviewed. To assess the association between steroid dose used for relapse and subsequent outcomes, data of patients with tapered prednisolone (PSL) dosage to <10 mg/day before the first relapse in whom the dose was subsequently increased to ≥10 mg/day were extracted and assigned to the High-PSL or Low-PSL groups, based on the median dose of 20 mg/day. Multivariate Cox proportional hazard model and propensity score analysis with multiple imputations were conducted to compare their clinical course.ResultsDuring a median observation period of 37.6 months, 186/192 (96.9%) patients achieved complete remission (CR) and 100 (52.1%) relapsed. The median urinary protein level at the first relapse was 3.12 g/gCr or g/day. The proportion of non-steroidal immunosuppressant use increased with relapses; cyclosporine was the most common. No significant differences were found in the second relapse, frequent relapses, or adverse events between High-PSL (n = 34) and Low-PSL (n = 36) groups. A multivariate Cox proportional hazard model revealed that the hazard ratios adjusted with propensity score for the second relapse were 0.94 (High-PSL vs. Low-PSL; 95% confidence interval, 0.42-2.10; P = 0.88) and 0.82 (PSL dose per 10 mg/day; 95% confidence interval, 0.58-1.16; P = 0.25).ConclusionsAmong patients in CR with PSL dose <10 mg/day, higher steroid dose (PSL >20 mg/day) was not associated with favorable outcomes after the first relapse as compared to lower dose (10-20 mg/day).
| S-EPMC6005527 | biostudies-literature
Project description: Not available
| S-EPMC9276299 | biostudies-literature
Project description:The glycoprotein CD44 is barely detected in normal mouse and human glomeruli, but is increased in glomerular parietal epithelial cells following podocyte injury in focal segmental glomerulosclerosis (FSGS). To determine the biological role and regulation of CD44 in these cells, we employed an in vivo and in vitro approach. Experimental FSGS was induced in CD44 knockout and wild-type mice with a cytotoxic podocyte antibody. Albuminuria, focal and global glomerulosclerosis (periodic acid-Schiff stain), and collagen IV staining were lower in CD44 knockout compared with wild-type mice with FSGS. Parietal epithelial cells had lower migration from Bowman's capsule to the glomerular tuft in CD44 knockout mice with disease compared with wild type mice. In cultured murine parietal epithelial cells, overexpressing CD44 with a retroviral vector encoding CD44 was accompanied by significantly increased collagen IV expression and parietal epithelial cell migration. Because our results showed de novo co-staining for activated ERK1/2 (pERK) in parietal epithelial cells in experimental FSGS, and also in biopsies from patients with FSGS, two in vitro strategies were employed to prove that pERK regulated CD44 levels. First, mouse parietal epithelial cells were infected with a retroviral vector for the upstream kinase MEK-DD to increase pERK, which was accompanied by increased CD44 levels. Second, in CD44-overexpressing parietal epithelial cells, decreasing pERK with U0126 was accompanied by reduced CD44. Finally, parietal epithelial cell migration was higher in cells with increased and reduced in cells with decreased pERK. Thus, pERK is a regulator of CD44 expression, and increased CD44 expression leads to a pro-sclerotic and migratory parietal epithelial cell phenotype.
| S-EPMC5357449 | biostudies-literature
Project description:To search for biomarkers to differentiate Adult-Onset Steroid Sensitive focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD).
2017-01-04 | GSE69814 | GEO
Project description:To search for biomarkers to differentiate Adult-Onset Steroid Sensitive focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Compared the profiles of glomerular transcriptomes between patients with FSGS and patients with MCD using microarray analysis. This dataset is part of the TransQST collection.
2017-01-04 | E-GEOD-69814 | biostudies-arrayexpress
Project description:ObjectiveTo search for biomarkers to differentiate primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD).MethodsWe isolated glomeruli from kidney biopsies of 6 patients with adult-onset steroid sensitiveFSGS and 5 patients with MCD, and compared the profiles of glomerular transcriptomes between the two groups of patients using microarray analysis.ResultsAnalysis of differential expressed genes (DEGs) revealed that up-regulated DEGs in FSGS patients compared with MCD patients were primarily involved in spermatogenesis, gamete generation, regulation of muscle contraction, response to unfolded protein, cell proliferation and skeletal system development. The down-regulated DEGs were primarily related to metabolic process, intracellular transport, oxidation/reduction andestablishment of intracellular localization. We validated the expression of the top 6 up-regulated and top 6 down-regulated DEGs using real-time PCR. Membrane metallo-endopeptidase (MME) is a down-regulated gene that was previously identified as a key gene for kidney development. Immunostaining confirmed that the protein expression of MME decreased significantly in FSGS kidneys compared with MCD kidneys.ConclusionsThis report was the first study to examine transcriptomes in Chinese patients with various glomerular diseases. Expressions of MME both in RNA and protein level decreased significantly in glomeruli of FSGS kidneys compared with MCD kidneys. Our data suggested that MME might play a role in the normal physiological function of podocytes and a decrease in MME expression might be related to podocyte injury. We also identified genes and pathways specific for FSGS versus MCD, and our data could help identify potential new biomarkers for the differential diagnosis between these two diseases.
| S-EPMC4633097 | biostudies-literature
Project description:The horseshoe kidney is a frequent urological birth defect. The most frequent complications are urinary tract infections, stones and hydronephrosis. The occurrence of glomerular disease in horseshoe kidney is rare. Therefore, we report the first case of minimal change disease occurring in a patient with horseshoe kidney in literature. A 22-year-old Caucasian man without personal or family medical history admitted to the pneumology department for a pulmonary artery embolism. In presence of a generalized oedema, a biological assessment was performed yielding intense nephrotic syndrome with urine protein excretion 22g/day. The abdominal ultrasound revealed a horseshoe kidney. Hence a scanno-guided kidney biopsy was taken yielding minimal change disease. High dose steroids were started, then gradually tapered with good response. Horseshoe kidney is the most common renal fusion anomaly, with a prevalence of 0.25% among the general population. The occurrence of glomerular nephropathy in horseshoe kidney has been reported in few cases. We report the first case of minimal change disease occurring in a patient with horseshoe kidney in literature. The mechanism of the association between the horseshoe kidney and these renal pathologies could not be explained in the previous reports. There is no literature data indicating a high rate of glomerulonephritis in horseshoe kidneys. The co-incidence of two renal diseases in this patient can be only a coincidence. The question that arises is whether this glomerulopathy is associated or not with this anatomical abnormality. Further studies are needed to answer this question.
| S-EPMC5491730 | biostudies-other
Project description:This study aimed to shed light on the potential pathophysiology of MCD by using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies from two groups of samples: control (CTR) and MCD. Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digest method was used to improve yield and protein identifications.
2024-03-12 | MSV000094293 | MassIVE