BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. METHODS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. RESULTS: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. CONCLUSIONS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

• MeSH
• biopsie MeSH
• dítě MeSH
• dospělí MeSH
• hodnoty glomerulární filtrace MeSH
• IgA nefropatie * komplikace   farmakoterapie   patologie   MeSH
• IgA vaskulitida * komplikace   farmakoterapie   patologie   MeSH
• ledviny patologie   MeSH
• lidé MeSH
• mladiství MeSH
• nefritida * komplikace   MeSH
• proteinurie etiologie   MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• IgA nefropatie * farmakoterapie   MeSH
• imunoglobulin A MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunoglobulin A MeSH

BACKGROUND: Tolvaptan slows expansion of kidney volume and kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD). Progression during childhood could be treated before irreversible kidney damage occurs, but trial data are lacking. We evaluated the safety and efficacy of tolvaptan in children/adolescents with ADPKD. METHODS: This was the 1-year, randomized, double-blind, portion of a phase 3b, two-part trial being conducted at 20 academic pediatric nephrology centers. Key eligibility criteria were ADPKD and eGFR ≥60 ml/min per 1.73 m2. Participants aged 12-17 years were the target group (group 1, enrollment goal n≥60); participants aged 4-11 years could additionally enroll (group 2, anticipated enrollment approximately 40). Treatments were tolvaptan or placebo titrated by body weight and tolerability. Coprimary end points, change from baseline in spot urine osmolality and specific gravity at week 1, assessed inhibition of antidiuretic hormone activity. The key secondary end point was change in height-adjusted total kidney volume (htTKV) to month 12 in group 1. Additional end points were safety/tolerability and quality of life. Statistical comparisons were exploratory and post hoc. RESULTS: Among the 91 randomized (group 1, n=66; group 2, n=25), least squares (LS) mean reduction (±SEM) in spot urine osmolality at week 1 was greater with tolvaptan (-390 [28] mOsm/kg) than placebo (-90 [29] mOsm/kg; P<0.001), as was LS mean reduction in specific gravity (-0.009 [0.001] versus -0.002 [0.001]; P<0.001). In group 1, the 12-month htTKV increase was 2.6% with tolvaptan and 5.8% with placebo (P>0.05). For tolvaptan and placebo, respectively, 65% and 16% of subjects experienced aquaretic adverse events, and 2% and 0% experienced hypernatremia. There were no elevated transaminases or drug-induced liver injuries. Four participants discontinued tolvaptan, and three discontinued placebo. Quality-of-life assessments remained stable. CONCLUSIONS: Tolvaptan exhibited pharmacodynamic activity in pediatric ADPKD. Aquaretic effects were manageable, with few discontinuations. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease) NCT02964273.

• MeSH
• antagonisté antidiuretického hormonu škodlivé účinky   MeSH
• benzazepiny škodlivé účinky   MeSH
• dítě MeSH
• dospělí MeSH
• kvalita života MeSH
• ledviny MeSH
• lidé MeSH
• mladiství MeSH
• polycystické ledviny autozomálně dominantní * MeSH
• tolvaptan škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté antidiuretického hormonu MeSH
• benzazepiny MeSH
• tolvaptan MeSH

• Klíčová slova
• ANCA, glomerulonephritis, rituximab,
• MeSH
• ANCA-asociované vaskulitidy * farmakoterapie   komplikace   MeSH
• glomerulonefritida * komplikace   MeSH
• křehký senior MeSH
• ledviny MeSH
• lidé MeSH
• protilátky proti cytoplazmě neutrofilů MeSH
• rituximab terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protilátky proti cytoplazmě neutrofilů MeSH
• rituximab MeSH

Long-term peritoneal dialysis is associated with alterations in peritoneal function, like the development of high small solute transfer rates and impaired ultrafiltration. Also, morphologic changes can develop, the most prominent being loss of mesothelium, vasculopathy, and interstitial fibrosis. Current research suggests peritoneal inflammation as the driving force for these alterations. In this review, the available evidence for inflammation is examined and a new hypothesis is put forward consisting of high glucose-induced pseudohypoxia. Hypoxia of cells is characterized by a high (oxidized-reduced nicotinamide dinucleotide ratio) NADH-NAD+ ratio in their cytosol. Pseudohypoxia is similar but occurs when excessive amounts of glucose are metabolized, as is the case for peritoneal interstitial cells in peritoneal dialysis. The glucose-induced high NADH-NAD+ ratio upregulates the hypoxia-inducible factor-1 gene, which stimulates not only the glucose transporter-1 gene but also many profibrotic genes like TGFβ, vascular endothelial growth factor, plasminogen activator inhibitor-1, and connective tissue growth factor, all known to be involved in the development of peritoneal fibrosis. This review discusses the causes and consequences of pseudohypoxia in peritoneal dialysis and the available options for treatment and prevention. Reducing peritoneal exposure to the excessively high dialysate glucose load is the cornerstone to avoid the pseudohypoxia-induced alterations. This can partly be done by the use of icodextrin or by combinations of low molecular mass osmotic agents, all in a low dose. The addition of alanyl-glutamine to the dialysis solution needs further clinical investigation.

• Klíčová slova
• connective tissue growth factor, glucose exposure, inflammation, peritoneal dialysis, peritoneal membrane alterations, plasminogen activator inhibitor-1, pseudohypoxia, vascular endothelial growth factor,
• MeSH
• dialyzační roztoky škodlivé účinky   metabolismus   MeSH
• glukosa škodlivé účinky   metabolismus   MeSH
• hypoxie MeSH
• lidé MeSH
• NAD * metabolismus   MeSH
• peritoneální dialýza * škodlivé účinky   MeSH
• peritoneum metabolismus   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• dialyzační roztoky MeSH
• glukosa MeSH
• NAD * MeSH
• vaskulární endoteliální růstový faktor A MeSH

Genetic testing for pathogenic COL4A3-5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate genetic testing for persistent hematuria, even when a heterozygous pathogenic COL4A3 or COL4A4 is suspected, and cascade testing of their first-degree family members because of their risk of impaired kidney function. The experts recommend too that COL4A3 or COL4A4 heterozygotes do not act as kidney donors. Testing for variants in the COL4A3-COL4A5 genes should also be performed for persistent proteinuria and steroid-resistant nephrotic syndrome due to suspected inherited FSGS and for familial IgA glomerulonephritis and kidney failure of unknown cause.

• Klíčová slova
• Alport syndrome, COL4A3, COL4A4, COL4A5, FSGS, collagen IV, digenic Alport syndrome, genetic testing, kidney cysts, thin basement membrane nephropathy,
• MeSH
• autoantigeny genetika   MeSH
• dědičná nefritida diagnóza   genetika   terapie   MeSH
• genetické testování normy   MeSH
• kolagen typu IV genetika   MeSH
• lidé MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoantigeny MeSH
• COL4A5 protein, human MeSH Prohlížeč
• kolagen typu IV MeSH
• type IV collagen alpha3 chain MeSH Prohlížeč

BACKGROUND AND OBJECTIVES: The median kidney transplant half-life is 10-15 years. Because of the scarcity of donor organs and immunologic sensitization of candidates for retransplantation, there is a need for quantitative information on if and when a second transplantation is no longer associated with a lower risk of mortality compared with waitlisted patients treated by dialysis. Therefore, we investigated the association of time on waiting list with patient survival in patients who received a second transplantation versus remaining on the waiting list. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective study using target trial emulation, we analyzed data of 2346 patients from the Austrian Dialysis and Transplant Registry and Eurotransplant with a failed first graft, aged over 18 years, and waitlisted for a second kidney transplantation in Austria during the years 1980-2019. The differences in restricted mean survival time and hazard ratios for all-cause mortality comparing the treatment strategies "retransplant" versus "remain waitlisted with maintenance dialysis" are reported for different waiting times after first graft loss. RESULTS: Second kidney transplantation showed a longer restricted mean survival time at 10 years of follow-up compared with remaining on the waiting list (5.8 life months gained; 95% confidence interval, 0.9 to 11.1). This survival difference was diminished in patients with longer waiting time after loss of the first allograft; restricted mean survival time differences at 10 years were 8.0 (95% confidence interval, 1.9 to 14.0) and 0.1 life months gained (95% confidence interval, -14.3 to 15.2) for patients with waiting time for retransplantation of <1 and 8 years, respectively. CONCLUSIONS: Second kidney transplant is associated with patient survival compared with remaining waitlisted and treatment by dialysis, but the survival difference diminishes with longer waiting time.

• Klíčová slova
• kidney transplantation, patient survival, restricted mean survival time, second kidney transplantation, target trial emulation, waiting lists,
• MeSH
• časové faktory MeSH
• chronické selhání ledvin mortalita   chirurgie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• opakovaná terapie statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• seznamy čekatelů * MeSH
• transplantace ledvin statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND AND OBJECTIVES: People with kidney failure typically receive KRT in the form of dialysis or transplantation. However, studies have suggested that not all patients with kidney failure are best suited for KRT. Additionally, KRT is costly and not always accessible in resource-restricted settings. Conservative kidney management is an alternate kidney failure therapy that focuses on symptom management, psychologic health, spiritual care, and family and social support. Despite the importance of conservative kidney management in kidney failure care, several barriers exist that affect its uptake and quality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Global Kidney Health Atlas is an ongoing initiative of the International Society of Nephrology that aims to monitor and evaluate the status of global kidney care worldwide. This study reports on findings from the 2018 Global Kidney Health Atlas survey, specifically addressing the availability, accessibility, and quality of conservative kidney management. RESULTS: Respondents from 160 countries completed the survey, and 154 answered questions pertaining to conservative kidney management. Of these, 124 (81%) stated that conservative kidney management was available. Accessibility was low worldwide, particularly in low-income countries. Less than half of countries utilized multidisciplinary teams (46%); utilized shared decision making (32%); or provided psychologic, cultural, or spiritual support (36%). One-quarter provided relevant health care providers with training on conservative kidney management delivery. CONCLUSIONS: Overall, conservative kidney management is available in most countries; however, it is not optimally accessible or of the highest quality.

• Klíčová slova
• capacity, conservative kidney management, global health, kidney failure, survey,
• MeSH
• chronické selhání ledvin terapie   MeSH
• dostupnost zdravotnických služeb statistika a číselné údaje   MeSH
• internacionalita MeSH
• konzervativní terapie * normy   MeSH
• kvalita zdravotní péče * MeSH
• lidé MeSH
• náboženství MeSH
• průzkumy a dotazníky MeSH
• rozvojové země statistika a číselné údaje   MeSH
• sdílené rozhodování MeSH
• sociální opora MeSH
• týmová péče o pacienty statistika a číselné údaje   MeSH
• vyspělé země statistika a číselné údaje   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• ANCA, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Antineutrophil Cytoplasmic, vasculitis,
• MeSH
• azathioprin terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• granulomatóza s polyangiitidou komplikace   farmakoterapie   MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé MeSH
• mikroskopická polyangiitida komplikace   farmakoterapie   MeSH
• myeloblastin imunologie   MeSH
• nemoci ledvin etiologie   patofyziologie   MeSH
• peroxidasa imunologie   MeSH
• protilátky proti cytoplazmě neutrofilů * MeSH
• recidiva MeSH
• rituximab terapeutické užití   MeSH
• udržovací chemoterapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azathioprin MeSH
• cyklofosfamid MeSH
• imunosupresiva MeSH
• MPO protein, human MeSH Prohlížeč
• myeloblastin MeSH
• peroxidasa MeSH
• protilátky proti cytoplazmě neutrofilů * MeSH
• rituximab MeSH

BACKGROUND AND OBJECTIVES: The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A validation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score. RESULTS: The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P<0.001). Kidney failure at 10-year follow-up was 14% in the crescentic class versus 20% in the mixed class (P=0.98). In the meta-analysis, no significant difference in kidney failure was also observed when crescentic class was compared with mixed class (relative risk, 1.15; 95% confidence interval, 0.94 to 1.41). When we applied the ANCA kidney risk score to our cohort, kidney survival at 3 years was 100%, 96%, and 77% in the low-, medium-, and high-risk groups, respectively (P<0.001). These survival percentages are higher compared with the percentages in the original study. CONCLUSIONS: The crescentic and mixed classes seem to have a similar prognosis, also after adjusting for differences in patient populations, treatment, and interobserver agreement. However, at this stage, we are not inclined to merge the crescentic and mixed classes because the reported confidence intervals do not exclude important differences in prognosis and because an important histopathologic distinction would be lost.

• Klíčová slova
• ANCA, Antibodies, Antineutrophil Cytoplasmic, Biopsy, Cohort Studies, Confidence Intervals, Observer Variation, Prognosis, Renal Insufficiency, glomerulonephritis, kidney biopsy,
• MeSH
• biopsie MeSH
• časové faktory MeSH
• glomerulonefritida * klasifikace   komplikace   imunologie   patologie   MeSH
• ledviny * imunologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• progrese nemoci MeSH
• protilátky proti cytoplazmě neutrofilů * imunologie   MeSH
• renální insuficience * diagnóza   etiologie   MeSH
• reprodukovatelnost výsledků MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• validační studie MeSH
• Názvy látek
• protilátky proti cytoplazmě neutrofilů * MeSH