Background Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. Methods Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys. Results Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice. Conclusion These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis characterized by diffuse deposits of IgM in the glomerular mesangium. However, its renal prognosis remains unknown. We compared renal outcomes of IgMN patients with those of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or mesangial proliferative glomerulonephritis (MsPGN) from a prospective observational cohort, with 1791 patients undergoing native kidney biopsy in eight hospitals affiliated with The Catholic University of Korea between December 2014 and October 2020. IgMN had more mesangial proliferation and matrix expansion than MsPGN and more tubular atrophy and interstitial fibrosis than MCD. IgMN patients had decreased eGFR than MCD patients in the earlier follow-up. However, there was no significant difference in urine protein or eGFR among all patients at the last follow-up. When IgMN was divided into three subtypes, patients with FSGS-like IgMN tended to have lower eGFR than those with MCD-like or MsPGN-like IgMN but higher proteinuria than MsPGN-like IgMN without showing a significant difference. The presence of hypertension at the time of kidney biopsy predicted ≥20% decline of eGFR over two years in IgMN patients. Our data indicate that IgMN would have a clinical course and renal prognosis similar to MCD, FSGS, and MsPGN

Background and Aims Few studies have investigated the impact of a change in metabolic syndrome (MetS) components on clinical renal outcomes in the general population. Method Using nationally representative data from the Korean National Health Insurance System, 13,310,924 subjects who underwent two health examinations over 2 years and were free from end-stage renal disease (ESRD) from 2009 to 2012 were followed to the end of 2016. The subjects were divided into four groups according to the change in MetS components between the two visits over 2 years: no MetS (–/–), post-MetS (–/+), pre-MetS (+/–), and both MetS (+/+). Results After a median follow up of 5.11 years, 18,582 incident ESRD cases were identified. In the multivariate adjusted model, the hazard ratio (HR) and 95% confidence interval (CI) for the development of ESRD in the both-MetS (+/+) group compared with the no-MetS (–/–) group was 5.65 (95% CI, 5.42–5.89), which was independent of age, sex, and baseline estimated glomerular filtration rate. Additionally, the HR for the pre-MetS (+/-) group versus the no-MetS (–/–) group was 2.28 (2.15–2.42). In subgroup analysis according to renal function, the impact of a change in MetS on the incidence of ESRD was more pronounced in individuals with advanced renal dysfunction. Subjects with resolved MetS components had a decreased risk of ESRD, but not as low as those that never had MetS components. Conclusion This provides evidence supporting the strategy of modulating MetS in the general population to prevent the development of ESRD.