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Background: Genetic focal segmental glomerulosclerosis (FSGS) is caused by pathogenic variants in a broad spectrum of genes that have a variable representation based on subjects' ethnicity and/or age. The most frequently mutated autosomal recessive gene in FSGS is NPHS2 . In this study, we analyzed the spectrum of NPHS2 variants and their associated phenotype in Czech adult FSGS patients., Methods: A representative cohort of 234 adult patients with FSGS, derived from 225 families originating from all regions of Czechia, was analyzed by massively parallel sequencing. In this study, we focused on the comprehensive analysis of the NPHS2 gene. The histological classification of FSGS followed the Columbia classification., Results: We detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic NPHS2 variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of NPHS2 -positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated NPHS2 -associated FSGS patients was 50% (6/12), and Haplotype analysis predicted its origin to be a result of a founder effect. There is an identical V290M-related haplotype on all V290M alleles spanning a 0,7 Mb region flanking NPHS2 in Central European FSGS populations. The phenotype of the p.Val290Met NPHS2 -associated FSGS demonstrated a later onset and a much milder course of the disease compared to other NPHS2 pathogenic variants associated with FSGS. The mean age of the FSGS diagnosis based on kidney biopsy evaluation was 31.2 ± 7.46 years. In 50% of all cases, the initial disease manifestation of proteinuria occurred only in adulthood, with 83% of these cases not presenting with edemas. One-third (33%) of the studied subjects progressed to ESRD (2 out of 6) at the mean age of 35.0 ± 2.82 years., Conclusions: We identified the most prevalent pathogenic variant, p.Val290Met, in the NPHS2 gene among Czech adult FSGS patients, which has arisen due to a founder effect in Central Europe. The documented milder course of the disease associated with this variant leads to the underdiagnosis in childhood. We established the histopathological features of the NPHS2 -associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment., Competing Interests: MP was employed by Biopticka Laboratory. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Thomasová, Zelinová, Libik, Geryk, Votýpka, Rajnochová Bloudíčková, Krejčí, Reiterová, Jančová, Machová, Kollárová, Rychík, Havrda, Horáčková, Putzová, Šafránek, Kollár and Macek.)

Objective: Respiratory alkalosis (RA) and dilutional hyperchloremic acidosis (DHA) are the most common acid-base balance (ABB) disorders in patients with liver cirrhosis. The aims of this study were to clarify whether RA develops in relation to DHA via respiratory compensation of metabolic acidosis and whether spironolactone in combination with low-dose furosemide - diuretics known to ameliorate DHA - positively affects RA in liver cirrhosis patients., Materials and Methods: 59 patients with advanced cirrhosis were divided into two groups. Group D consisted of individuals (urine sodium concentration (U Na+ ) > 20 mmol/L) who responded to combination therapy consisting of spironolactone and low-dose furosemide. The non-D group consisted of individuals (U Na+ ≤ 20 mmol/L) who either did not respond to the treatment or who were not administered it. In both groups, we examined serum and urine concentrations of electrolytes and ABB parameters, including S Na+ -S Cl- and S Na+ /S Cl- values., Results: In group D, we found a statistically significant relationship between pCO 2 and S HCO3- : r = 0.756 (p < 0.001) and between pCO 2 and S Na+ -S Cl- : r = 0.522 (p = 0.001). Neither S alb nor the corrected anion gap were associated with changes in S HCO3- or pCO 2 values. Although S HCO3- values were normal, abnormal pCO 2 values were observed in one third of group D patients. Based on multivariable analysis, S HCO3- proved to be a statistically significant influencing factor on pCO 2 values., Conclusion: DHA contributes to the development of RA in individuals with liver cirrhosis. Reducing DHA by means of effective diuretic therapy comprising spironolactone and furosemide has a beneficial effect on RA in such patients.