#3618 CLINICAL SIGNIFICANCE OF MILD ABNORMALITIES IN GLOMERULAR FILTRATION BARRIER (GBM) DIAGNOSED BY RENAL BIOPSY

Abstract

Abstract Background and Aims The well-known GBM abnormalities without immunological reaction are Alport syndrome (ALPORT) and thin basement membrane disease (TMD). Two diseases occasionally share common genetic abnormalities, although, clinical outcomes are worse in ALPORT. Sometimes, there are also mild abnormalities of GBM unable to be classified into ALPROT or TMD without any immunological or hemodynamical abnormalities in the kidney. We compared clinical and pathologic findings among ALPORT, TMD, and GBM abnormalities not classified (GBM NOS) diagnosed by renal biopsy. Method Among 18,134 adult patients who underwent kidney biopsy from 1979 to 2018 in 17 hospitals in Korea (number of IRB: B1707/408-106), we selected patients with ALPORT, TMD, or GBM NOS diagnosed by renal biopsy. GBM NOS was defined as any abnormality of GBM structure of lamellation, thickness, and integrity by electron microscopic examination, which are not able to classify into specific pathologic diagnosis. We excluded ALPORT, TMD, and GBM NOS combined to the other pathologic diagnosis or showing electron dense deposit. We collected clinicopathologic findings at renal biopsy and the last visit to clinics and incidences of mortality and end stage renal disease during follow-up period. Results There were 179 (0.99%) TMDs, 33 (0.18%) ALPORTs, and 8 (0.04%) GBM NOSs among all patients. The clinico-pathologic findings were presented in Table 1. Age and gender proportion at renal biopsy were not different among groups. Patients with ALPORT showed the lowest level of estimated glomerular filtration rate by MDRD equation (eGFR) (p<0.001) and the highest level of urine protein to creatinine ratio (UPCR) (p<0.001). Patients with GBM NOS had similar levels of eGFR and UPCR compared to patients with TMD at renal biopsy. Under microscopic examinations, segmental sclerosis in glomeruli was most prevalent in patients with ALPORT compared to patients with the other disease. Global sclerosis in glomeruli was prevalent in patients with ALPORT and GBM NOS. Other glomerular changes, such as cellular infiltration and matrix change in mesangium, and ischemic glomerular change, were not different among groups. Patients with GBM NOS showed more severe change of interstitial fibrosis and tubular atrophy compared to patients with TMD but similar to patients with ALPORT. Patients with GBM NOS did not show vascular changes. Podocyte foot process effacement was present more frequently in patients with GBM NOS or ALPORT compared to patient with TMD (p<0.001). During 97.9 ± 61.8 months of follow-up period, one (3.0%) patient was dead and 10 (30.3%) patients must have renal replacement therapy (RRT) among patients with ALPORT. The other patients with GBM NOS or TMD had survived and did not need RRT. Conclusion Clinical findings of GBM NOS were similar to TMD, although pathologic changes of glomerular global sclerosis and tubulo-interstitial changes are more severe in GBM NOS compared to TMD. GBM changes in GBM NOS might be related to tubulo-interstitial damages which needs to be defined with more studies.