Electron Microscopy and Clinicopathological Characteristics of Hereditary Nephritis, A 16-Years Single-Center Study

Background:Hereditary nephritis is an umbrella term for a group of congenital childhood diseases including but not limited to Alport Syndrome (AS), Thin Basement Membrane Disease (TBMD) and Fabry Disease (FD). The purpose of this study is a clinicopathologic investigation of AS, TBMD, and FD with a focus on the role of the diagnostic value of electron microscopy (EM) in the diagnosis.Methods:In this cross-sectional study, we investigated 22 out of 2865 kidney biopsies with a final diagnosis of either AS, TBMD or FD sent to the EM unit affiliated to Shiraz University of Medical Sciences from 2001 to 2016. EM and five stainings for light microscopy (LM) were done and corresponding clinical and paraclinical data were extracted from the patients’ medical charts. EM role was assessed in terms of necessary, helpful or non-necessary. All the statistical analysis performed in SPSS 19.0 and independent T-test, chi-square or Fisher’s exact test was used.Results:Among the 2865 kidney biopsies sent to the EM unit were 22 (0.77%) patients of hereditary nephritis including 15(0.52%) AS, 5(0.17%) TBMD and 2(0.07%) FD which were diagnosed by EM. Mean age of patients were 16.1 ± 9.0. EM was essential for the diagnosis of 19 (86.4%) of cases, helpful for 3(13.6%) and there was no case for which EM was non-necessary. LM findings were normal and non-specific at best for all three of the diseases and routine immunofluorescence studies were negative. The most common finding in AS was proteinuria(86.7%) followed by hematuria(60.0%) while all cases of TBMD had both hematuria and proteinuria, and in Fabry patient, both of the two cases had proteinuria while only one had hematuria. Most apparent extrarenal manifestations of AS were hearing loss in about half of the cases (53.3%) and eye involvement in a third (33.3%). Also, 40% of AS patients had hypertension. Results of the statistical correlations of clinicopathologic findings were, for the most part, unreliable due to low sample size except for a few. Those AS cases with hearing loss also had a higher chance of having hypertension (p=0.01) and similarly higher chance of hematuria (p=0.07).Conclusion:Considering the rate of misdiagnosis of hereditary diseases using LM and clinical findings alone, EM study has an essential role in the correct diagnosis in these patients. While TBMD patients don’t usually develop renal failure, prompt diagnosis of AS and FD patients using EM is pertinent for therapeutic decisions.

Keywords:

Nephritis , Hereditary , Fabry Disease , Microscopy , Electron , Transmission , Kidney , Hearing Loss