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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.

In patients with advanced cirrhosis with ascites disorders of water and electrolyte metabolism are often present and they are associated with changes in acid-base balance. These changes can be very complicated, their diagnosis and treatment difficult. Dilutional hyponatremia is the most common disorder. Hyponatremia in these patients is associated with increased morbidity and mortality before and after liver transplantation. Other common disorders include hyperchloremic acidosis, hypokalemia, metabolic alkalosis, lactic acidosis, respiratory alkalosis. If renal impairment occurs (for example hepatorenal syndrome), metabolic acidosis and retention of acid metabolites may develop. The pathogenesis of these conditions applies primarily hemodynamic changes. Activation of renin-angiotensin-aldosterone system and non-osmotic stimulation of antidiuretic hormone trigger serious changes in water and natrium-chloride metabolism. This activation is clinically expressed like oedema, ascites, hydrothorax, low to zero natrium concentration in urine and increased urinary osmolality, which is higher than serum osmolality. In practice, the evaluation can be significantly modified by the ongoing diuretic therapy. Closer monitoring of water and electrolyte metabolism together with acid-base balance in patients with ascitic liver cirrhosis is important, not only in terms of diagnosis but especially in terms of therapy.

Introduction: Prevalence of a positive testing for microalbuminuria (MA) in patients with diabetes mellitus in the Czech Republic is not described in the available literature. The data is important with regard to monitoring effectiveness of the comprehensive therapy for diabetes mellitus, from the prognostic and pharmacoeconomic perspective.The aim of the study was to assess the prevalence of presence of microalbuminuria or proteinuria (PU) in randomly chosen patients with diabetes mellitus aged up to 65 years in a cross-cutting study. The secondary aim was to assess the distribution of eGFR (estimated glomerular filtration) in the same population., Methodology: 2 024 patients with diabetes aged up to 65 years were examined within the project. The median of diabetes duration was 6.0 years, the BMI median was 30.7 kg/m2, the creatinine median 74.9 µmol/l, the median of HbA1c 5.45 %, the blood pressure median 132/80 mm Hg. 1 888 patients had type 2 diabetes (DM2T)., Results: 19.96 % of the examined patients tested positive for MA (24.24 % of them with type 1 diabetes - DM1T, 19.16 % DM2T). 11.36 % tested positive for PU (17.78 % DM1T, 10.21 % DM2T). Glomerular filtration was established through calculation (MDRD), with a normal value identified in 44.7 %, a mild decrease (eGFR 1.0-1.49 ml/s) in 46.7 %, medium (eGFR 0,5-0,99 ml/s) in 7.7 %, and a severe decrease (eGFR < 0.5 ml/s) identified in 0.7 %, hemodialysis in 0.2 %. The median of diabetes duration in MA-negative patients was 5 years, in MA-positive patients 7 years and in patients with proteinuria 11 years. Regarding patients with eGFR between 0.5-0.99 ml/s/1.73 m2, 63.23 % of them tested negative for MA and 71.62 % for PU, regarding those with eGFR in the range of 0.25-0.49 ml/s/1,73 m2, 15.38 % tested negative for MA and 7.69 % were PU-negative., Conclusion: The IDN-Micro project shows high prevalence of positive MA and PU findings in individuals with diabetes mellitus younger than 65. For a significant proportion of individuals, the most likely cause of the decrease in eGFR is other than hyperglycemia. It is apparent that examination of serum concentrations of creatinine and evaluation of eGFR is also necessary for relatively younger patients with diabetes.Key words: diabetes mellitus - eGFR - microalbuminuria.

Changes to the overall volume of body water and acid base equilibrium can be reflected in the values of differences and ratios relating to serum concentrations of natrium and chlorides. Both these quantities can be used for patients with hyponatremia in the hyponatremia differential diagnosis. This paper presents a case study which is an example of the clinical use of differences in and ratios of serum concentrations of natrium and chlorides when monitoring effectiveness of the therapy.Key words: acid base equilibrium - depletion hyponatremia - differential diagnosis of hyponatremia - dilution hyponatremia.

Unlabelled: The differential diagnosis of hyponatremia is often difficult. This most frequently occurring disorder of the water and electrolyte metabolism is frequently connected with deviations relating to the acid-base balance (ABB). This survey analyzes the relationship between the changes of the volume of body fluids and ABB and infers to what extent the analysis of combinations of the two disorders can support the differential diagnosis of different forms of hyponatremia (differentiation between the dilution vs. depletion forms). The changes of the total water volume (CTV) and ABB may be presented at the same time in the values of the difference and ratio between serum concentrations of natrium and chlorides (SNa+ - SCl-; SNa+/SCl-). The changes of these quantities are analyzed in the models of pathologies connected through hyponatremia and ABB related deviations: (i) retention of solute-free water (hyponatremia associated with dilution acidosis); (ii) retention Na+ in combination with water retention (hyponatremia associated with dilution and hyperchloremic acidosis); (iii) depletion Na+ combined with water depletion (depletion hyponatremia combined with hypochloremic alkalosis), and (iv) combination of dilution and depletion (hyponatremia which may be associated with different ABB related deviations). This survey specifies the extent to which the applied models are consistent with the existing clinical findings and experience. The examinations SNa+ - SCl- and SNa+/SCl- rely only on routinely used laboratory test methods. Monitoring of these quantities may contribute to continuous assessment of the effect of a chosen therapy., Key Words: acid-base balance - depletion hyponatremia - differential diagnosis of hyponatremia - dilution hyponatremia - hyponatremia - retention of solute-free water - body fluid volumes.

Unlabelled: The case report shows a surprising presentation of pulmonary granulomatosis with polyangiitis (GPA) through symptoms of diabetes insipidus (DI) with granulomatous infiltration of the pituitary gland. The pituitary hormonal dysfunction as a result of granulomatosis of the pituitary gland is rare. Several studies have demonstrated that the incidence of the pituitary dysfunction reaches approx. 1 % of the patients with GPA. However it is mostly presented in patients with the disease already diagnosed. The patient described by us had no clinical expressions of GPA in the respiratory tract. He presented with polyuria and polydipsia. It was not until a more detailed examination of these symptoms was performed that a focal lung disease was detected and diagnosed as GPA., Key Words: diabetes insipidus - granulomatosis with polyangiitis - granulomatous infiltration of the pituitary gland - pituitary hormonal dysfunction.

Introduction: Moderate to medium decrease in glomerular filtration (GFR) in individuals with chronic kidney disease (CKD) does not need to be associated with hyperphosphatemia due to an adaptive decrease in tubular reabsorption of phosphates (TRPi) in residual nephrons. The clinical assessment of this function is performed based on the measurement of fractional phosphate excretion (FEPi), which is a quantity specifying the proportion of the filtered amount of phosphates which is excreted in the urine. This quantity may provide useful information about the involvement of kidneys in phosphate homeostasis of the internal environment. This study focuses on the comparison of a kr(FEPi) value examined based on a ratio of a phosphate clearance (CPi) and a creatinine clearance (CKr) marked kr(FEPi), and a value calculated based on a ratio of CPi and an exactly measured GFR as an inulin clearance (Cin), marked as in(FEPi).The goal of comparing the two methods of examining FEPi was to establish to what extent it is possible to evaluate the degree of inhibition of tubular phosphate transport in residual nephrons based on a simple examination of kr(FEPi) ., Methodology: The examination of in(FEPi) and kr(FEPi) was carried out for 53 patients with CKD. The values of the examined quantities were as follows: SKr 199±45 µmol/l; SPi 1.41±0.29 mmol/l; CKr 0,95±0.36 ml/s/1.73 m2; Cin 0.71±0.25 ml/s/1.73 m2. For the purpose of comparison a cohort of 18 healthy volunteers was examined., Results: For individuals with CKD an average value of kr(FEPi) equalled 29.1±10.9% and in(FEPi) 52.4±4.3%. The values of in(FEPi) were higher than kr(FEPi) (p<0.001) for all patients, although an average CPi value for patients with CKD did not significantly differ from the control cohort (0.22 vs 0.21 ml/s/1.73 m2). The values of in(FEPi) increased proportionally to SKr values and at higher values SKr (>300 µmol/l) they gradually approached 100% (indicating the complete inhibition of tubular reabsorption of phosphates in residual nephrons). The values of in(FEPi) were higher in all patients with CKD than kr(FEPi) as expected, likely because the value CKr decreases at a slower rate than Cin (GFR) in individuals with CKD as a result of increased tubular secretion of creatinine in residual nephrons., Conclusion: The results of this study support the assumption that, provided the values of kr(FEPi) which are easily measurable in clinical practice have reached 50-60%, almost complete inhibition of tubular reabsorption of phosphates in residual nephrons must be assumed and no favourable effect of phosphatonins on renal phosphate excretion can be expected. When looking for new possibilities of inhibition of tubular phosphate reabsorption, potential adverse effects of phosphatonins on organs must be considered.

Tubular transport of sodium (TNa+) and chloride (TCl-) is decreased in patients with chronic kidney disease. The decrease of TCl- is relatively lower than that of TNa+. These changes of tubular transport of Na+ and Cl- participate on the development of acid base disturbance in patients with chronic kidney disease and with their glomerular filtration rate lower than 0.5 ml/s/1.73 m2.

The urine colour change is an important clinical sign associated with patological process not only in the urinary tract. Apart from the commonest urine colour modifications due to metabolites of haemoglobin, myoglobin and bilirubin one may come accross with some less frequent changes. The violet urine coloration is very rare but represents the important clinical finding that is known as purple urine bag syndrome. The change of colour is made by indirubin and indigo. It is connected all the time with urine tract infection. In our presentation we describe a case where this sign was the only presentation of clinically important bacteriuria. Consequently antibiotic treatment could be given early before possible sepsis evolution.