Genetic studies of hereditary forms of NS have led to the identification of proteins playing a crucial role in slit-diaphragm signalling, regulation of actin cytoskeleton dynamics, maintenance of podocyte integrity and cell-matrix interactions.
Hence, our work reveals a novel role of VCR in regulating actin fiber assembly and provides first evidence on the therapeutic mechanism of VCR on nephrotic syndrome.
Olfm-1 and myocilin are markedly induced in podocytes during PAN nephrosis and appear to be involved in the processes that govern the reorganization of the actin cytoskeleton during podocyte repair.
Ongoing studies in many laboratories are aiming at an understanding of the dynamic relationship between SD proteins, the actin cytoskeleton, and the dynamics of FP structure in nephrotic syndrome and FSGS.
The melanocortin-1 receptor (MC1R) in podocytes has been suggested as the mediator of the ACTH renoprotective effect in patients with nephrotic syndrome with the mechanism of action beeing stabilization of the podocyte actin cytoskeleton.
Synaptopodin is an actin-associated protein essential for the integrity of the podocyte actin cytoskeleton because synaptopodin-deficient mice display impaired recovery from protamine sulfate-induced foot process effacement and lipopolysaccharide-induced nephrotic syndrome.
The role of the cytoskeleton has been revealed by the development of proteinuria/NS in patients with ACTN4 mutation and the occurrence of early and severe NS in alpha-actinin-4-deficient mice.
Associations with various genes (NPHS1, ACTN4, NPHS2, WT-1) and linkage to several chromosomal regions (such as 19q13, 11q21, 11q24) have been reported in patients with familial NS/FSGS.
FSGS1 may have widely variable clinical and pathological phenotypes and therefore should be considered in young children with full-blown and rapidly progressing nephrotic syndrome.
This study shows that an adolescent/adult form of recessive FSGS maps to a locus on chromosome 1q25-31, which overlaps with a region previously identified as harboring a locus for an early childhood onset recessive form of nephrotic syndrome (SRN1).
In this study, the angiotensinogen -235T allele was found to be related with steroid resistance, renal dysfunction and progression of ESRD in nephrotic syndrome.
AGT-M235T genotype was associated with the presence of nephrotic syndrome (p < 0.05), correlated to the number of antihypertensive drugs agents taken (p < 0.01) and influenced the rate of deterioration of renal function (p < 0.05).
The NS-associated changes in intestinal, but not renal, K<sup>+</sup> handling responded to suppression of corticosterone, whereas angiotensin II type 1 receptor and MR blockers and amiloride had no effect on urine K<sup>+</sup> excretion during NS.
There were no statistically significant differences for the C allele of AT1R or the T allele of AGT genes between the children with nephrotic syndrome and control group, but on the other hand statistically significant differences were detected for D allele of ACE gene.