Background. This report describes data collected by the Czech Registry of Renal Biopsies (CRRB). Methods. Twenty-eight centres provided data on all biopsies of native kidneys performed in the Czech ...Republic (population 10.3 million) over the period 1994–2000. Data on serum creatinine concentration (sCr), 24 h proteinuria, haematuria, serum albumin level, arterial hypertension, diabetes mellitus, histological diagnosis and complications after renal biopsy were collected. Results. Altogether 4004 biopsies in 3874 patients were performed (males 57.9%, children ≤15 years 17.7%, elderly >60 years 14.3%). Microhaematuria was present in 65.9%, macrohaematuria in 9.2%, nephrotic proteinuria (≥3.5 g/24 h) in 39.3%, and low-grade proteinuria (<3.5 g/24 h) in 41.4%. Among adults, hypertension was present in 45.2%, mild renal insufficiency in 23% (sCr 111–200 µmol/l) and advanced renal insufficiency in 13.7% (sCr 201–400), while 11.5% of patients had sCr >400 µmol/l. The most frequent renal diseases were primary (59.8%) and secondary (25.4%) glomerulonephritis (GN). Tubulointerstitial nephritis (TIN) was observed in 4.4% and hypertensive nephroangiosclerosis in 3.4%. The samples were non-diagnostic in 4.6%. Among primary GNs, the most frequent diagnoses were: IgA nephropathy (IgAN) 34.5%, minimal change disease (MCD) 12.4%, non-IgA mesangioproliferative GN (MesGN) 11.3%, focal segmental glomerulosclerosis (FSGS) 10.8% and membranous GN (MGN) 9.3%. Among secondary GNs, systemic lupus erythematosus (SLE) represented 23.0%, necrotizing vasculitis (NV) 15.5%, Henoch–Schönlein purpura 5.7%, thin basement membrane glomerulopathy (TBN) 19.3%, Alport syndrome 6.9%, renal amyloidosis 9.9% and myeloma kidney 2.9%. Among children, the most common were IgAN (19.2%), MCD (17.6%) and TBM glomerulopathy (12.3%), while among the elderly the most common were MGN (11.0%), NV (10.7%) and amyloidosis (9.6%). The most common in patients with nephrotic proteinuria were MCD (50.5%) among children, but IgAN (24.6%) in adults aged 16–60 years and MGN (16.8%) among the elderly. IgAN (21.3%) and FSGS (8.3%) were the most common diagnoses among patients with mild renal insufficiency, but TIN (11.6%) and NV (11.3%) were the most common in more advanced renal insufficiency. Since 1999, diabetic patients represented 12.2% of adults, with mean proteinuria 8.9 g/24 h; diabetic glomerulosclerosis was found in 42.4% (with microhaematuria present in 66%) and non-diabetic renal diseases in 47.5% (IgAN in 17.5%, MGN and NAS in 11.1% and NV in 9.5%). The mean annual incidence (per million population) was: primary GN 32.4, secondary GN 13.8, IgAN 11.2, MCD 4.0, MesGN 3.7, FSGS 3.5, SLE 3.2, MGN 3.0, TBM 2.7, TIN 2.4 and NV 2.1. Ultrasound needle guidance was used in 56%, preferably in children (79%). The frequency of serious complications (gross haematuria, symptomatic haematoma, blood transfusion) remained at 3%. Conclusion. The CRRB provides important data on the epidemiology of GN based on a whole country population.
Pregnancy complicated by CKD is currently not fully understood topic. Outcome of pregnancy in patients with CKD is related to impaired glomerular filtration rate and the degree of proteinuria. In our ...study we evaluated the association of serum creatinine level and proteinuria with both maternal and fetal outcomes in the cohort of 84 pregnant patients with CKD. In CKD group we confirmed negative correlation of highest serum creatinine level in pregnancy to fetal weight (p value < 0.001) and gestation period (p value < 0.001). Likewise, negative correlation of preconception serum creatinine to fetal weight (p value < 0.001) and gestation period (p value 0.002). Negative correlation of proteinuria to gestation period (p value < 0.001) and fetal weight (p value < 0.001) was also demonstrated. CKD is serious risk factor for pregnancy outcome. Proteinuria and serum creatinine level should be examined before pregnancy and regularly monitored during pregnancy. Higher serum creatinine levels and higher proteinuria predispose to shorter gestation period and lower birth weight of the neonate.
Rituximab is being increasingly prescribed for the treatment of autoimmune glomerular diseases. While it is highly effective for some diseases, the response is less predictable for others, which may ...be due to differing requirements in terms of the dosing according to the disease type and variations concerning exposure to the drug.
We compiled novel rituximab dosing schedules according to pharmacokinetic analysis of data gathered from rituximab treated patients in a tertiary referral nephrology centre between May 2020 and June 2023. The population-pharmacokinetic analysis was based on the rituximab dosing, the patients’ characteristics, rituximab levels and anti-rituximab antibodies.
The analysis, which was based on data from 185 patients, clearly highlighted differing rituximab dosing requirements for patients with ANCA associated vasculitis and minimal change disease compared to those with membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This corresponded to the good treatment response of the first two diseases and the unreliable efficacy for the others. The model predicts the rituximab pharmacokinetics with high degree of accuracy when body weight, proteinuria, type of glomerulonephritis, treatment length and anti-rituximab antibodies formation are used as covariates. We proposed a dosing schedule with shortened dosing intervals for difficult-to-treat diagnoses with high proteinuria.
In order to ensure reliable and comparable exposure of rituximab with respect to the full range of glomerular diseases, the dosing schedule should be adjusted for membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This is largely, but not solely, due to the enhanced level of unselective proteinuria in these diseases.
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•A population pharmacokinetic model was constructed for rituximab based on real data.•Rituximab elimination is faster in lupus nephritis, FSGS and MN than in AAV and MCD.•Proteinuria and the formation of ADA significantly enhance rituximab elimination.•The clearance (CL) of rituximab decreases with the treatment duration.•The dosing interval must be shortened for selected patients to overcome fast CL.
Acute tubulointerstitial nephritis (ATIN) is a well-recognized cause of acute kidney injury (AKI) due to the tubulointerstitial inflammation. The aim of this study was to explore the clinical ...features, outcomes, and responses to corticosteroid treatment in patients with ATIN.
Patients with biopsy-proven ATIN, who were diagnosed between 1994 and 2016 at the Department of Nephrology, Charles University, First Faculty of Medicine, and General University Hospital in Prague, were included in the study. Patient demographics, the aetiological and clinical features, the treatment given, and the outcome at 1 year of follow-up were extracted from patient records.
A total of 103 ATIN patients were analysed, of which 68 had been treated with corticosteroids. There was no significant difference in the median serum creatinine 280 (169-569) µmol/L in the conservatively managed group versus 374 (249-558) µmol/L in the corticosteroid-treated group, p = 0.18, and dependence on dialysis treatment at baseline at the time of biopsy (10.3 vs. 8.6%). During the 1 year of follow-up, those ATIN patients who had been treated with corticosteroids did better and showed greater improvement in kidney function, determined as serum creatinine difference from baseline and from 1 month over 1-year period (p = 0.001).
This single-centre retrospective cohort study supports the beneficial role of the administration of corticosteroid therapy in the management of ATIN.
Background/Aims: The aim of our study was to retrospectively analyse data of 520 Czech patients with IgA nephropathy (IgAN) and to specify the risk factors affecting renal survival of IgAN patients. ...Methods: Cox proportional hazards regression model was used to evaluate the effects of different variables on renal survival during a median follow up of six years. McNemar´s test was used to analyse the progression of renal function according to Bartosik´s formula. Results: In our retrospective analysis of 520 Czech IgAN patients Cox proportional hazards regression model with five variables hypertension, sex, GFR, proteinuria, age was used. Significant regression coefficient was found for GFR, hypertension and proteinuria. Using stepwise algorithm GFR (OR = 3.09), hypertension (OR = 2.09) and proteinuria (OR = 1.97) were found as the most important factors for renal survival in our group of IgAN patients. Among patients with CKD 3 we found significantly better renal survival in patients with proteinuria < 1g/day compared to patients with higher proteinuria. We did not find the significant difference between predicted progression of renal function due to Bartosik´s formula and real progression of renal parametres assessed by GFR at the end of the follow up in our group of IgAN patients. Conclusion: Our retrospective study of 520 Czech IgAN patients confirmed GFR, hypertension and proteinuria as the most important factors affecting the prognosis of IgAN patients. We validated Toronto Bartosik´s formula to predict prognosis of IgAN patients.
Anakinra has been increasingly used in off-label indications as well as dosing and mode of administration in a variety of inflammatory conditions. We aimed to review our clinical practice and compare ...treatment outcomes with published data.
Clinical data from electronic records were retrospectively reviewed for patients treated with anakinra over the past 6 years for autoinflammatory diseases (AID).
From 47 eligible patients (27 female patients), 32 were children. Macrophage activation syndrome (MAS) was the indication for anakinra therapy in 42.6% of patients. Systemic juvenile idiopathic arthritis (SJIA) was the most common underlying diagnosis (19/47) followed by the spectrum of AID. Off-label use was noted in 38.3% patients. Recommended dose was exceeded in 21 children (mean induction dose 5.1, highest dose 29.4 mg/kg/day) and two adults; five patients were treated intravenously. The mean treatment duration for SJIA was 1.4 years, that for AID was 2.2 years, and that for patients with higher anakinra dose was 9.7 (19.3) months. The mean follow-up duration was 2.7 (1.7) years. Treatment was effective in the majority of SJIA and cryopyrinopathy patients as well as those with MAS. Anakinra was well-tolerated without any major adverse effects even in patients with long-term administration of higher than recommended doses including two infants treated with a dose of over 20 mg/kg/day.
Our results support early use of anakinra in the individually tailored dosing. In patients with hyperinflammation, anakinra may be lifesaving and may even allow for corticosteroid avoidance. Further studies are needed in order to set up generally accepted response parameters and define condition-specific optimal dosing regimen.
Muckle-Wells syndrome (MWS) represents a moderate phenotype of cryopyrinopathies. Sensorineural hearing loss and AA amyloidosis belong to the most severe manifestations of uncontrolled disease. ...Simultaneous discovery of MWS in four generations of one large kindred has enabled us to document natural evolution of untreated disease and their response to targeted therapy.
A retrospective case study, clinical assessment at the time of diagnosis and 2-year prospective follow-up using standardized disease assessments were combined.
Collaborative effort of primary care physicians and pediatric and adult specialists led to identification of 11 individuals with MWS within one family. Presence of p.Ala441Val mutation was confirmed. The mildest phenotype of young children suffering with recurrent rash surprised by normal blood tests and absence of fevers. Young adults all presented with fevers, rash, conjunctivitis, and arthralgia/arthritis with raised inflammatory markers. Two patients aged over 50 years suffered with hearing loss and AA amyloidosis. IL-1 blockade induced disease remission in all individuals while hearing mildly improved or remained stable in affected patients as did renal function in one surviving individual with amyloidosis.
We have shown that severity of MWS symptoms gradually increased with age toward distinct generation-specific phenotypes. A uniform trajectory of disease evolution has encouraged us to postpone institution of IL-1 blockade in affected oligosymptomatic children. This report illustrates importance of close interdisciplinary collaboration.
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
. In this study, we analyzed the spectrum of
variants and their associated phenotype in Czech adult FSGS patients.
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
gene. The histological classification of FSGS followed the Columbia classification.
We detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic
variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of
-positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated
-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
in Central European FSGS populations. The phenotype of the p.Val290Met
-associated FSGS demonstrated a later onset and a much milder course of the disease compared to other
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.
We identified the most prevalent pathogenic variant, p.Val290Met, in the
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
-associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment.
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