T2DM/CKD genetic risk scores and the progression of diabetic kidney disease in T2DM subjects.

This study aimed at understanding the predictive potential of genetic risk scores (GRS) for diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM) and Major Cardiovascular Events (MCVE) and All-Cause Mortality (ACM) as secondary outcomes. We evaluated 30 T2DM and CKD GWAS-derived single nucleotide polymorphisms (SNPs) and their association with clinical outcomes in a central European cohort (n = 400 patients). Our univariate Cox analysis revealed significant associations of age, duration of diabetes, diastolic blood pressure, total cholesterol and eGFR with progression of DKD (all P < 0.05). However, no single SNP was conclusively associated with progression to DKD, with only CERS2 and SHROOM3 approaching statistical significance. While a single SNP was associated with MCVE - WSF1 (P = 0.029), several variants were associated with ACM - specifically CANCAS1, CERS2 and C9 (all P < 0.02). Our GRS did not outperform classical clinical factors in predicting progression to DKD, MCVE or ACM. More precisely, we observed an increase only in the area under the curve (AUC) in the model combining genetic and clinical factors compared to the clinical model alone, with values of 0.582 (95 % CI 0.487-0.676) and 0.645 (95 % CI 0.556-0.735), respectively. However, this difference did not reach statistical significance (P = 0.06). This study highlights the complexity of genetic predictors and their interplay with clinical factors in DKD progression. Despite the promise of personalised medicine through genetic markers, our findings suggest that current clinical factors remain paramount in the prediction of DKD. In conclusion, our results indicate that GWAS-derived GRSs for T2DM and CKD do not offer improved predictive ability over traditional clinical factors in the studied Czech T2DM population.

Atypical form of Goodpasture's disease.

Goodpasture's disease and anti-glomerular basement membrane nephritis (anti-GBM nephritis) are rare autoimmune small vessel vasculitis predominantly affecting young men. Goodpasture's disease plays an important part in differential diagnosis of pulmonary - renal syndrome. The evidence of circulating autoantibodies, a typical histological appearance of the kidney biopsy with finding of the crescent glomerulonephritis and clinical presentation of nephritic syndrome play an important role in diagnosis. Our case report describes a case of a young male with anti-GBM nephritis that presents as rapidly progressive glomerulonephritis (RPGN) with progression to dialysis-dependent renal failure. The atypical sign of the case was development of nephrotic syndrome with volume-dependent hypertension. The case was complicated by heparin-induced thrombocytopenia. During combined immunosuppressive therapy with plasmapheresis, the condition of the patient has stabilized. However, renal function did not recover. This previously fatal disease has nowadays a very good survival rate because of immunosuppresion therapy, plasmapheresis and hemodialysis.

Primary cilia and hypoxia-associated signaling in developmental odontogenic cysts in relation to autosomal dominant polycystic kidney disease - A novel insight.

Developmental cysts are pathological epithelial-lined cavities arising in various organs as a result of systemic or hereditary diseases. Molecular mechanisms involved in the formation of developmental odontogenic cysts (OCs) are not fully understood yet; the cystogenesis of renal cysts originating from the autosomal dominant polycystic kidney disease (ADPKD) has been, however, explored in much greater detail. This narrative review aimed i) to summarize molecular and cellular processes involved in the formation and growth of developmental OCs, especially dentigerous cysts (DCs) and odontogenic keratocysts (OKCs), ii) to find if there are any similarities in their cystogenesis to ADPKD cysts, and, based on that, iii) to suggest potential factors, candidate molecules, and mechanisms that could be involved in the DC formation, thus proposing further research directions. Here we suggest a possible association of developmental OCs with primary cilia disruption and with hypoxia, which have been previously linked with cyst formation in ADPKD patients. This is illustrated on the imagery of tissues from an ADPKD patient (renal cyst) and from developmental OCs, supporting the similarities in cell proliferation, apoptosis, and primary cilia distribution in DC/OKC/ADPKD tissues. Based on all that, we propose a novel hypothesis of OCs formation suggesting a crucial role of mutations associated with the signaling pathways of primary cilia (in particular, Sonic Hedgehog). These can lead to excessive proliferation and formation of cell agglomerates, which is followed by hypoxia-driven apoptosis in the centers of such agglomerates (controlled by molecules such as Hypoxia-inducible factor-1 alpha), leading to cavity formation and, finally, the OCs development. Based on this, we propose future perspectives in the investigation of OC pathogenesis.