BACKGROUND: Kidney involvement is common in anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) and the prognosis is determined by the severity of kidney damage. This study focused on long-term kidney outcomes, defining possible risk factors and comparing the performance of three different histological classifications to predict outcomes for patients with AAV. METHODS: The dataset included 848 patients with newly diagnosed AAV who participated in seven randomized controlled trials (RCTs) (1995-2012). Follow-up information was obtained from questionnaires sent to the principal investigators of the original RCTs. RESULTS: The cumulative incidence of end-stage kidney disease (ESKD) at 5 and 10 years was 17% and 22%, respectively. Patients who developed ESKD had reduced patient survival compared with those with preserved kidney function (hazard ratio 2.8, P < .001). Comparing patients with AAV and kidney involvement with a matched general population, patients with AAV had poor survival outcomes, even in early stages of chronic kidney disease. The main cause of death was infection followed by cardiovascular disease in patients developing ESKD and malignancy in those who did not. Some 34% of patients with initial need for dialysis recovered kidney function after treatment. Thirty-five out of 175 in need of kidney replacement therapy (KRT) during follow-up received a kidney transplant with good outcome; there was 86% patient survival at 10 years.In the subcohort of 214 patients with available kidney biopsies, three scoring systems were tested: the Berden classification, the Renal Risk Score and the Mayo Clinic Score. The scores highlighted the importance of normal glomeruli and severe glomerulosclerosis on kidney survival (P < .001 and P = .001, respectively). The Renal Risk Score demonstrated a moderate prediction of kidney survival (area under the curve 0.79; standard error 0.03, 95% confidence interval 0.71-0.83). CONCLUSIONS: Early diagnosis of AAV is extremely important. Even milder forms of kidney involvement have an impact on the prognosis. Patients in need of KRT had the lowest survival rates, but kidney transplantation has shown favorable outcomes for eligible AAV patients. The three histologic scoring systems were all identified as independent prognostic factors for kidney outcome.
- MeSH
- ANCA-asociované vaskulitidy * komplikace mortalita terapie MeSH
- chronické selhání ledvin * mortalita terapie etiologie MeSH
- dospělí MeSH
- hodnoty glomerulární filtrace MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- následné studie MeSH
- prognóza MeSH
- rizikové faktory MeSH
- senioři MeSH
- vyšetření funkce ledvin MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Výskyt monoklonální gamapatie (MG) stoupá s věkem. U jedinců starších 80 let můžeme diagnostikovat přítomnost monoklonálního imunoglobulinu až v 10 % případů. Nejen maligní onemocnění typu mnohočetného myelomu, ale i benigní formy jako MGUS (monoklonální gamapatie nejistého významu) mohou vést k postižení ledvin. Nejvíce ledviny poškozují lehké řetězce imunoglobulinů, protože ty se v důsledku své molekulové hmotnosti volně filtrují do moči. Detekce přítomnosti monoklonálního imunoglobulinu se opírá zejména o kombinaci imunofixační elektroforézy séra (IELFO) a moči a o stanovení volných lehkých řetězců kappa a lambda a jejich poměru (κ/λ) v séru. Kombinace těchto testů s 99% senzitivitou odhalí přítomnost monoklonálního imunoglobulinu. Poškození ledvin u MG může být způsobeno přímou depozicí monoklonálního imunoglobulinu v glomerulech (např. AL amyloidóza, nemoc z ukládání lehkých řetězců imunoglobulinů) či tubulech (v distálním tubulu jako myelomová ledvina nebo v proximálním tubulu jako Fanconiho syndrom či proximální tubulopatie). Typickým močovým nálezem u těchto chorob bývá velká proteinurie až nefrotický syndrom. Akutní poškození ledvin (AKI) lze očekávat zejména při zvýšení koncentrace volných lehkých řetězců v séru nad 500 mg/l. Pro stanovení přesné diagnózy, a tím i zahájení správné léčby, je klíčové provedení renální biopsie. Léčba těchto typů poškození ledvin zahrnuje stejné léčebné režimy, které se používají v léčbě mnohočetného myelomu, včetně inhibitorů proteasomu či daratumumabu.
The incidence of monoclonal gammopathy (MG) increases with age. In individuals over 80 years of age, we can diagnose the presence of monoclonal immunoglobulin (MIg) in up to 10 % of cases. Not only malignant diseases such as multiple myeloma (MM), but also benign forms such as MGUS (monoclonal gammopathy of undetermined significance) can lead to renal involvement. The light chains of immunoglobulins (LC) are the most damaging to the kidneys, as they are freely filtered into the urine due to their molecular weight. Detection of MIg relies mainly on a combination of immunofixation electrophoresis of serum (IELFO) and urine and determination of free light chains (FLC) of kappa and lambda and their ratio (κ/λ) in serum. The combination of these tests will detect the presence of MIg with 99 % sensitivity. Renal damage in MG may be caused by direct deposition of MIg in the glomeruli (e.g. AL amyloidosis, LC deposition disease) or tubules (in the distal tubule as a myeloma kidney or in the proximal tubule as Fanconi syndrome or proximal tubulopathy). Typical urinary findings in these diseases are moderate or severe proteinuria or nephrotic syndrome. Acute kidney injury (AKI) can be expected especially when serum FLC is >500 mg/l. Renal biopsy is crucial to establish an accurate diagnosis and thus initiate the correct treatment. Treatment of these types of renal damage involves the same treatment regimens used in the treatment of MM, including proteasome inhibitors or daratumumab.
- MeSH
- amyloidóza etiologie komplikace MeSH
- chronické selhání ledvin * etiologie MeSH
- dialýza ledvin metody MeSH
- imunoglobuliny škodlivé účinky MeSH
- lidé MeSH
- mnohočetný myelom * komplikace MeSH
- monoklonální gamapatie nejasného významu * etiologie komplikace MeSH
- plazmaferéza metody MeSH
- Check Tag
- lidé MeSH
BACKGROUND: VAVASC study (Validation of Arterio Venous Access Stage Classification) is a multicentre, international, prospective study. The study aims to validate the AVAS classification, which is a classification system describing vascular status of patients indicated for creation of arteriovenous access on the upper limb. METHODS: Observational, prospective, multicentre, international study starting in March 2021. Participant recruitment has commenced. Basic demographic data, risk factors and vascular mapping parameters are collected via an online platform. The outcome measures are class of AVAS, predicted arteriovenous access, final arteriovenous access that has been created and a functionality of the arteriovenous access. Predictive models will be used for statistical analysis. CURRENT STATUS: A total of 140 patients from 4 centres in Great Britain, Czech Republic, Brazil and Slovakia are already included and undergoing evaluation. CONCLUSIONS: The study is registered in the Clinical trials registry (NCT04796558), https://register.clinicaltrials.gov/. Study is still open for collaboration with other centres that can register via www.vavasc.com.
- MeSH
- arteriovenózní zkrat * škodlivé účinky metody MeSH
- chronické selhání ledvin * etiologie MeSH
- dialýza ledvin metody MeSH
- horní končetina krevní zásobení MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- pozorovací studie jako téma MeSH
- prospektivní studie MeSH
- průchodnost cév MeSH
- výsledek terapie MeSH
- výzkumný projekt MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
- MeSH
- bortezomib aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- chronické selhání ledvin etiologie terapie MeSH
- cyklofosfamid aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- dexamethason aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- dialýza ledvin metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- paraproteinemie * diagnóza komplikace terapie MeSH
- proteinurie etiologie MeSH
- renální insuficience diagnóza etiologie terapie MeSH
- senioři MeSH
- transplantace kostní dřeně metody škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- roxadustat,
- MeSH
- anemie * diagnóza etiologie farmakoterapie MeSH
- chronické selhání ledvin etiologie komplikace MeSH
- erytropoéza účinky léků MeSH
- hepcidiny MeSH
- hypoxie etiologie farmakoterapie MeSH
- inhibitory prolylhydroxylas * klasifikace terapeutické užití MeSH
- klinická studie jako téma MeSH
- transkripční faktory MeSH
- Publikační typ
- přehledy MeSH
Updated guidelines on the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were released in 2021 by the American College of Rheumatology jointly with the Vasculitis Foundation and, subsequently, in 2022 by the European Alliance of Associations for Rheumatology. In addition, in 2021, the Kidney Disease: Improving Global Outcomes had released updated recommendations on the treatment of AAV with glomerulonephritis (AAV-GN). Kidney involvement is particularly relevant in microscopic polyangiitis and granulomatosis with polyangiitis, but is less frequent in eosinophilic granulomatosis with polyangiitis. The management of AAV-GN has been a focus for drug development and change over the past 10 years. Avoidance of progression to end-stage kidney disease (ESKD) or kidney failure is one of the main unmet needs in the management of AAV, with ESKD having a major impact on morbidity, health costs and mortality risk. Relevant changes in AAV-GN management are related to remission-induction treatment of patients with severe kidney disease, the use of glucocorticoids and avacopan, and remission-maintenance treatment. All the documents provide guidance in accordance with the evidence-based standard of care available at the time of their release. With our work we aim to (i) show the progress made and identify the differences between guidelines and recommendations, (ii) discuss the supporting rationale for those, and (iii) identify gaps in knowledge that could benefit from additional research and should be revised in subsequent updates.
- MeSH
- ANCA-asociované vaskulitidy * komplikace farmakoterapie MeSH
- chronické selhání ledvin * etiologie terapie MeSH
- Churgův-Straussové syndrom * MeSH
- glomerulonefritida * farmakoterapie MeSH
- granulomatóza s polyangiitidou * terapie MeSH
- lidé MeSH
- mikroskopická polyangiitida * terapie MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
RATIONALE & OBJECTIVE: There is a dearth of data characterizing patients receiving kidney replacement therapy (KRT) for kidney failure due to systemic lupus erythematosus (SLE) and their clinical outcomes. The aim of this study was to describe trends in incidence and prevalence of KRT among these patients as well as to compare their outcomes versus those of patients treated with KRT for diseases other than SLE. STUDY DESIGN: Retrospective cohort study based on kidney registry data. SETTING & PARTICIPANTS: Patients recorded in 14 registries of patients receiving KRT that provided data to the European Renal Association Registry between 1992 and 2016. PREDICTOR: SLE as cause of kidney failure. OUTCOMES: Incidence and prevalence of KRT, patient survival while receiving KRT, patient and graft survival after kidney transplant, and specific causes of death. ANALYTICAL APPROACH: Kaplan-Meier methods and Cox regression models were fit to compare patient survival between the SLE and non-SLE groups, overall KRT, dialysis, and patient and graft survival after kidney transplant. RESULTS: In total, 1,826 patients commenced KRT for kidney failure due to SLE, representing an incidence of 0.80 per million population (pmp) per year. The incidence remained stable during the study period (annual percent change, 0.1% [95% CI, -0.6% to 0.8%]). Patient survival among patients with SLE receiving KRT was similar to survival in the comparator group (hazard ratio [HR], 1.11 [95% CI, 0.99-1.23]). After kidney transplant, the risk of death was greater among patients with SLE than among patients in the comparator group (HR, 1.25 [95% CI, 1.02-1.53]), whereas the risk of all-cause graft failure was similar (HR, 1.09 [95% CI, 0.95-1.27]). Ten-year patient overall survival during KRT and patient and graft survival after kidney transplant improved over the study period (HRs of 0.71 [95% CI, 0.56-0.91], 0.43 [95% CI, 0.27-0.69], and 0.60 [95% CI, 0.43-0.84], respectively). Patients with SLE receiving KRT were significantly more likely to die of infections (24.8%) than patients in the comparator group (16.9%; P < 0.001). LIMITATIONS: No data were available on extrarenal manifestations of SLE, drug treatments, comorbidities, kidney transplant characteristics, or relapses of SLE. CONCLUSIONS: The prognosis of patients with SLE receiving KRT has improved over time. Survival of patients with SLE who required KRT was similar compared with patients who required KRT for other causes of kidney failure. Survival following kidney transplants was worse among patients with SLE.
- MeSH
- chronické selhání ledvin * epidemiologie etiologie terapie MeSH
- incidence MeSH
- lidé MeSH
- náhrada funkce ledvin metody MeSH
- nefritida při lupus erythematodes * MeSH
- registrace MeSH
- renální insuficience * komplikace MeSH
- retrospektivní studie MeSH
- systémový lupus erythematodes * komplikace epidemiologie terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pacienti s chronickým onemocněním ledvin nejsou často pro minimální obtíže včas podchyceni ani praktickým lékařem ani odborným lékařem a přicházejí k léčbě nahrazující funkci ledvin nepřipraveni a pozdě. Nemají informace o možnostech léčby, včetně preemptivní transplantace ledvin a nemají vytvořený trvalý dialyzační přístup. Tento fakt pak zvyšuje riziko úmrtí a morbiditu pacientů po zařazení do dialyzačního programu. Preventivní vyšetření, jako je kontrola krevního tlaku, biochemické vyšetření séra, vyšetření moči a vyšetření glomerulární filtrace by umožnilo záchyt těchto pacientů praktickými a odbornými lékaři a včasné předání nemocných nefrologům.
Chronic kidney disease patients often present late for dialysis due to minimal clinical symptoms, which are frequently undiscovered by both general practitioners and specialists. They have no information about renal replacement therapy, including preemptive kidney transplantation and do not have a permanent dialysis access. This fact increases the morbidity and mortality of those patients. Common preventive examinations such as blood pressure measurement, serum biochemistry, urinalysis, and glomerular filtration tests, might help with earlier diagnosis of these patients by others specialities and timely referral to nephrologist.
- MeSH
- algoritmy MeSH
- analýza moči MeSH
- chronické selhání ledvin diagnóza etiologie klasifikace patologie prevence a kontrola terapie MeSH
- hematurie diagnóza MeSH
- hodnoty glomerulární filtrace fyziologie MeSH
- ledviny * fyziologie MeSH
- lidé MeSH
- proteinurie diagnóza klasifikace MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
We have developed an artificial neural network prediction model for end-stage kidney disease (ESKD) in patients with primary immunoglobulin A nephropathy (IgAN) using a retrospective cohort of 948 patients with IgAN. Our tool is based on a two-step procedure of a classifier model that predicts ESKD, and a regression model that predicts development of ESKD over time. The classifier model showed a performance value of 0.82 (area under the receiver operating characteristic curve) in patients with a follow-up of five years, which improved to 0.89 at the ten-year follow-up. Both models had a higher recall rate, which indicated the practicality of the tool. The regression model showed a mean absolute error of 1.78 years and a root mean square error of 2.15 years. Testing in an independent cohort of 167patients with IgAN found successful results for 91% of the patients. Comparison of our system with other mathematical models showed the highest discriminant Harrell C index at five- and ten-years follow-up (81% and 86%, respectively), paralleling the lowest Akaike information criterion values (355.01 and 269.56, respectively). Moreover, our system was the best calibrated model indicating that the predicted and observed outcome probabilities did not significantly differ. Finally, the dynamic discrimination indexes of our artificial neural network, expressed as the weighted average of time-dependent areas under the curve calculated at one and two years, were 0.80 and 0.79, respectively. Similar results were observed over a 25-year follow-up period. Thus, our tool identified individuals who were at a high risk of developing ESKD due to IgAN and predicted the time-to-event endpoint. Accurate prediction is an important step toward introduction of a therapeutic strategy for improving clinical outcomes.
CONTEXT: Fabry disease is a rare X-linked genetic disease due to pathogenic variants in the GLA gene. Classic Fabry disease is characterized by glycosphingolipids accumulation in all organs including the kidney, resulting in end-stage renal disease in a subset of male patients. Fabry disease should therefore be considered in the differential diagnosis of patients with unexplained end-stage renal disease. OBJECTIVE: We performed a prospective screening study in Western France to determine the prevalence of Fabry disease in a large population of dialyzed and transplanted patients. PATIENTS AND METHODS: Patients meeting the inclusion criteria (males, 18-70 years with end-stage renal disease of unknown or vascular origin) were selected from the REIN® registry and the CRISTAL® database. Screening on filter papers was performed after patient consent was obtained during either a dialysis session or a transplantation follow-up visit. RESULTS: One thousand five hundred and sixty-one end-stage renal disease male patients were screened and 819 consented (dialysis: n=242; transplant: n=577). One single patient was found with decreased alpha-galactosidase levels <25%. GLA sequencing identified the p.Phe113Leu variant in favor of an unknown superimposed kidney disease responsible for end-stage renal disease since this GLA pathogenic variant is associated with a later-onset cardiac form of Fabry disease with minimal kidney involvement. Family cascade genotyping revealed a previously undiagnosed affected brother. CONCLUSION: The prevalence of Fabry disease in end-stage renal disease patients was 0.12%, questioning the efficacy of this screening strategy with respect to the low prevalence. However, beside the benefit for the patient and his family, the increased awareness of Fabry disease among participating nephrologists may be of interest for future patients.
