Clinical groupings showing podocyte depletion in ASC.

Clinical parameters are shown to the left side and podometric parameters to the right side of the Table. Since age impacts podometric parameters the control group (n = 17 biopsies from deceased kidney donors aged 4–17 years) is appropriate for the ASC group (n = 26 biopsies from 21 patients aged 2–17 years). For cross-sectional analysis where more than one biopsy data set is available from one patient a single averaged value is used. Clinical parameters shown are from the time point at which the biopsy was performed. eGFR and urine protein:creatinine ratio (Urine PCR) data are not available (NA) for the control group. For each data set the mean (above in bold) and 1SD (below) are shown. Statistical comparisons of each data set compared to control using t-tests are shown by superscripted asterisks, while comparisons between sub-groups using analysis of variance are shown by asterisks in the area between the two sub-groups being compared. (* = PGroup Comparison: All ASC subjects (n = 21) compared with control (n = 17) shows that glomerular volume was not different. However, podocyte number per glomerular tuft, podocyte nuclear density and podocyte cell (Glepp1 area density) were all decreased in ASC biopsies compared to control. Mean podocyte cell volume and mean podocyte nuclear diameter were not statistically significantly increased in ASC glomeruli. GBM appearance: Alport GBM is defined as typical alternating thin and thick GBM with lamellated lamina densa. Both the Thin GBM group (n = 5) and the Alport GBM group (n = 16) had significantly reduced podocyte number per tuft and Glepp1 area density compared to controls. The Thin GBM and Alport GBM groups were not significantly different from each other by any parameter (probably because one patient in the Thin GBM group progressed to ESKD in association with podocyte depletion). Histologic appearance: Biopsies containing only normal-appearing glomeruli without FSGS contained fewer podocytes and lower podocyte cell (Glepp1) area density than control. Biopsies with FSGS and/or global glomerulosclerosis (GGS) had significantly fewer podocytes (podocyte number per glomerulus, density or podocyte area density) than both control and ASC biopsies with normal appearing glomeruli. “Non-progressors” vs Progressors: Biopsies from people who did not progress (“Non-progressors”) as judged by retaining eGFR within the normal range by follow-up of 3 or more years (mean follow-up 7.4±3.9 years, n = 8) had significant podocyte depletion (reduced number of podocyte per glomerulus and reduced podocyte area [Glepp1 area density] compared to control. Biopsies from people who subsequently progressed to ESKD requiring renal replacement therapy (n = 7 patients) had significantly increased podocyte depletion at time of biopsy (reduced podocyte number per glomerulus, podocyte nuclear density and Glepp1 area density and larger podocytes) than those that did not progress.