👤 von Holtum D

to evaluate the expression of profibrotic markers TGF-1, MMP-9 and FGFR in the epithelium of proximal renal tubules in patients with urolithiasis depending on the composition of the nodule, as well as on the degree of decrease in the glomerular filtration rate (GFR). complex examination of 17 patients with urolithiasis was carried out. Cockcroft-Gault formula for determining the glomerular filtration rate was used to estimate renal function, according to the results of which all patients were divided into 3 groups depending on the stage of GFR. Percutaneous nephrolithotripsy (PNLT) was performed according to the standard technique using laser treatment. The physical and chemical composition of the nodule was determined by polarization microscopy. All patients underwent morphological and morphometric study of nephrobiopsy specimens obtained at creation of puncture passage during PNLT in patients with nephrolithiasis. Immunohistochemical study was performed using profibrotic marker Anti-TGF beta 1 antibody (1:500, Abcam, UK), Anti-MMP-9 antibody (1:500, Abcam, UK), Anti-FGFR-1 1:50, Abcam, UK). Analysis of the results of morphological study revealed a correlation only between morphological manifestations of CPN progression and expression of profibrotic marker TGF-. The increase in TGF- expression is accompanied by more pronounced atrophic changes in the epithelium of proximal renal tubules, which indicates the triggering of tubulointerstitial fibrosis mechanisms and the role of this marker in the progression of chronic kidney disease in patients with urolithiasis. Show less

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene. Show less