Open Access Open Badges Research article

Mechanism of cystogenesis in nephrotic kidneys: a histopathological study

Marijan Saraga1, Katarina Vukojević2, Vjekoslav Krželj1, Zvonimir Puretić3, Ivana Bočina4, Merica Glavina Durdov5, Stefanie Weber6, Bernd Dworniczak7, Danica Galešić Ljubanović8 and Mirna Saraga-Babić2*

Author Affiliations

1 Department of Paediatrics, University Hospital in Split, Split, Croatia

2 Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia

3 Department of Dialysis, University Hospital Centre Zagreb, Zagreb, Croatia

4 Department of Biology, University of Split, Split, Croatia

5 Department of Pathology, University Hospital in Split, Split, Croatia

6 Division of Pediatric Nephrology, University Children’s Hospital Essen, Essen, Germany

7 Department of Human Genetics, University Münster, Münster, Germany

8 Department of Pathology, University Hospital in Zagreb, Zagreb, Croatia

For all author emails, please log on.

BMC Nephrology 2014, 15:3  doi:10.1186/1471-2369-15-3

Published: 8 January 2014



Nephrotic syndrome (NS) is pathological condition characterized by heavy proteinuria. Our study investigates hypothesis that change in cell proliferation of proximal tubules influences primary cilia structure and function and promotes cystogenesis in congenital nephrotic syndrome of the Finnish type (CNF) and focal segmental glomerulosclerosis (FSGS).


CNF kidneys were analyzed genetically. Proliferation (Ki-67), apoptosis (caspase-3), and primary cilia (α-tubulin) length and structure were analyzed immunohistochemically and ultrastructurally in healthy, CNF and FSGS kidneys. Cyst diameters were measured and correlated with proliferation index.


Proximal tubules cells of healthy kidneys did not proliferate. In nephrotic kidneys, tubules with apparently normal diameter covered by cuboidal/columnar epithelium (PTNC) contained 81.54% of proliferating cells in CNF and 36.18% in FSGS, while cysts covered with columnar epithelium (CC) contained 37.52% of proliferating cells in CNF and 45.23% in FSGS. The largest cysts, covered with squamous epithelium (CS) had 11.54% of proliferating cells in CNF and 13.76% in FSGS. Increase in cysts diameter correlated with changes in proliferation index, tubular cells shape, primary cilia formation and appearance of apoptotic cells.


We present a novel histopathological data on the structure and possible changes in function of tubular cell in NS kidneys during cystogenesis. We suggest existence of common principles of cystogenesis in CNF and FSGS kidneys, including serious disturbances of tubular cells proliferation and apoptosis, and faulty primary cilia signaling leading to deterioration of proteinuria in NS kidneys.

Nephrotic kidney; Cystogenesis; CNF; FSGS; Cell proliferation; Primary cilia; Apoptosis