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Dysbiosis in the Salivary Microbiome Associated with IgA Nephropathy-‍A‍ ‍Japanese Cohort Study.

ABSTRACT: IgA nephropathy is one of the leading causes of chronic kidney disease in Japan. Since the origin and mechanisms by which IgA nephropathy develops currently remain unclear, a confirmed disease diagnosis is currently only possible by highly invasive renal biopsy. With the background of the salivary microbiome as a rich source of biomarkers for systemic diseases, we herein primarily aimed to investigate the salivary microbiome as a tool for the non-invasive diagnosis of IgA nephropathy. In a comparison of salivary microbiome profiles using 16S rRNA amplicon sequencing, significant differences were observed in microbial diversity and richness between IgA nephropathy patients and healthy controls. Furthermore, recent studies reported that patients with IgA nephropathy are more likely to develop inflammatory bowel diseases and that chronic inflammation of the tonsils triggered the recurrence of IgA nephropathy. Therefore, we compared the salivary microbiome of IgA nephropathy patients with chronic tonsillitis and ulcerative colitis patients. By combining the genera selected by the random forest algorithm, we were able to distinguish IgA nephropathy from healthy controls with an area under the curve (AUC) of 0.90, from the ulcerative colitis group with AUC of 0.88, and from the chronic tonsillitis group with AUC of 0.70. Additionally, the genus Neisseria was common among the selected genera that facilitated the separation of the IgA nephropathy group from healthy controls and the chronic tonsillitis group. The present results indicate the potential of the salivary microbiome as a biomarker for the non-invasive diagnosis of IgA nephropathy.

SUBMITTER: Khasnobish A

PROVIDER: S-EPMC8209455 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionRenin-angiotensin system (RAS) blockade using angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) is first-line therapy for IgA nephropathy (IgAN). There is a paucity of information on the predictors and magnitude of response to this treatment.MethodsIn a prospective study, treatment-naive patients with IgAN with urinary protein ≥ 1 g/d and estimated glomerular filtration rate (eGFR) ≥ 30 ml/min per 1.73 m2 received supportive treatment including ACEi (ramipril) or ARB (losartan) in patients intolerant to ACEi, and optimal blood pressure (BP) control to ≤130/80 mm Hg, with a follow-up of 6 months. The primary outcome was remission of proteinuria. Complete remission (CR) was defined as proteinuria < 0.5 g/d and partial remission (PR) as proteinuria < 1g/d with at least a 50% decline from the baseline with stable renal function (≤ 25% reduction in eGFR).ResultsA total of 96 patients were analyzed, with a mean age of 33.3 ± 10.2 years, baseline eGFR 74.0 ± 30.9 ml/min per 1.73 m2, and urinary protein 2.6 ± 1.2 g/d. In all, 71.9% patients received ≥ 75% of the maximum approved dose of ACEi/ARB. Remission was observed in 36.5% (CR, 6.3%) patients at 3 months and in 55.2% (CR, 31.3%) at 6 months. Patients who failed to achieve remission had lower baseline eGFR (P = 0.002) and serum albumin levels (P< 0.001), asymptomatic hyperuricemia (P < 0.001), and higher proteinuria (P = 0.076). E1 (P= 0.053) and T1/T2 (P = 0.009) lesions were more frequent on histology. The ACEi/ARB had to be discontinued in 17 (17.7%) patients. These patients were older (P= 0.085) with lower eGFR (P < 0.002) and serum albumin levels (P = 0.001) and more E1 (P = 0.012) and T1/T2 (P = 0.001) lesions on histology.ConclusionMeticulous supportive therapy with optimal use of ACEi/ARB achieved remission in half of IgAN patients in this study. Increasing the treatment duration to 6 months improved remission rates. Patients with severe clinical and histological disease were less likely to tolerate and respond to treatment with RAS blockade.

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Dysbiosis in the Salivary Microbiome Associated with IgA Nephropathy-‍A‍ ‍Japanese Cohort Study.

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