Date Published: June 12, 2019
Publisher: Public Library of Science
Author(s): Lívia Helena de Morais Pereira, Crislaine Aparecida da Silva, Maria Luíza Gonçalves dos Reis Monteiro, Liliane Silvano Araújo, Laura Penna Rocha, Marcelo Bernardes da Rocha Reis, Fernando Silva Ramalho, Rosana Rosa Miranda Corrêa, Marcos Vinicius Silva, Marlene Antonia Reis, Juliana Reis Machado, Stuart E. Dryer.
There are controversies whether Minimal Change Disease (MCD) and Focal and Segmental Glomerulosclerosis (FSGS) are distinct glomerular lesions or different manifestations within the same spectrum of diseases. The uPAR (urokinase-type plasminogen activator receptor) and some slit diaphragm proteins may be altered in FSGS glomeruli and may function as biomarkers of the disease in renal biopsies. Thus, this study aims to evaluate the diagnostic potential of uPAR and glomerular proteins for differentiation between MCD and FSGS in renal pediatric biopsy. Renal biopsies from 50 children between 2 and 18 years old were selected, with diagnosis of MCD (n = 29) and FSGS (n = 21). Control group consisted of pediatric autopsies (n = 15) from patients younger than 18 years old, with no evidences of renal dysfunction. In situ expressions of WT1, nephrin, podocin and uPAR were evaluated by immunoperoxidase technique. Renal biopsy of patients with MCD and FSGS expressed fewer WT1 (p≤0.0001, F = 19.35) and nephrin (p<0.0001; H = 21.54) than patients in the control group. FSGS patients expressed fewer podocin than control (p<0.0359, H = 6.655). FSGS cases expressed more uPAR than each of control and MCD (p = 0.0019; H = 12.57) and there was a positive and significant correlation between nephrin and podocin (p = 0.0026, rS = 0.6502) in these cases. Podocin had sensitivity of 73.3% and specificity of 86.7% (p = 0.0068) and uPAR had sensitivity of 78.9% and specificity of 73.3% (p = 0.0040) for diagnosis of FSGS patients. The main limitation of the study is the limited number of cases due to the difficulty in performing biopsy in pediatric patients. Podocin and uPAR are good markers for FSGS and differentiate these cases from MCD, reinforcing the theory of distinct glomerular diseases. These findings suggest that podocin and uPAR can be used as biomarkers in the routine analysis of renal biopsies in cases of podocytopathies when the lesion (sclerosis) is not sampled.
Nephrotic syndrome (NS) in children comprises a diverse group of diseases, including podocytopathies of genetic causes with early onset or developed idiopathically. Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are the main idiopathic podocytopathies reaching the pediatric age group . They have a similar clinical presentation generally with nephrotic syndrome, due to the effacement of foot processes and alteration in proteins of the slit diaphragm (SD). In the early stages of the disease, MCD and FSGS show great similarity , however, they seem to have different development mechanisms . There are controversies among researchers, as some believe they are the same disease at different evolutionary stages and others believe they are distinct diseases. However, in some cases, due to the sample representativeness of a renal biopsy, the findings may suggest MCD, but the biopsy performed in another occasion would show typical characteristics of FSGS [4, 5].
The relationship between MCD and FSGS is controversial, as there are still doubts whether they represent distinct diseases or if they are only at different evolutionary stages. The morphological diagnosis of these two podocytopathies is a challenge for the nephropathologist, especially when biopsies do not contain adequate number of glomeruli and / or segmental sclerosis is not sampled. In this way, establishing specific biomarkers to differentiate these entities is of paramount importance.