Epidemiology of Uromodulin-Associated Kidney Disease – Results from a Nation-Wide Survey

BACKGROUND/AIMS: Uromodulin-associated kidney disease (UAKD) is caused by uromodulin mutations and leads to end-stage renal disease. Our objective was to examine the epidemiology of UAKD. METHODS: Data from all UAKD families in Austria were collected. Patients included in the Austrian Dialysis and Transplantation Registry (OEDTR) with unclear diagnoses or genetic diseases were asked whether they had (1) a family history of kidney disease or (2) had suffered from gout. Patients with gout and autosomal dominant renal disease underwent mutational analysis. Kaplan-Meier and Cox analysis was employed to estimate time to renal failure. RESULTS: Of the 6,210 patients in the OEDTR, 541 were approached with a questionnaire; 353 patients answered the questionnaire. Nineteen of them gave two affirmative answers. In 7 patients, an autosomal dominant renal disease was found; in 1 patient a UMOD mutation was identified. One family was diagnosed through increased awareness as a consequence of the study. At present, 14 UAKD patients from 5 families are living in Austria (1.67 cases per million), and 6 of them require renal replacement therapy (0.73 per 1,000 patients). Progression to renal failure was significantly associated with UMOD genotype. CONCLUSION: UAKD patients can be identified by a simple questionnaire. UMOD genotype may affect disease progression

Efficacy of eculizumab in a patient with immunoadsorption- dependent catastrophic antiphospholipid syndrome: A case report

Catastrophic antiphospholipid syndrome (CAPS) is a rare but devastating complication in patients with antiphospholipid syndrome (APS) with a high morbidity and mortality. We describe a case of a 30-year old female patient with immunoglobulin A (IgA) deficiency who underwent splenectomy because of idiopathic thrombocytopenic thrombocytopenia. Subsequently, an APS and finally systemic lupus erythematosus was diagnosed. After an uncomplicated pregnancy that was terminated by cesarean section, the patient developed severe CAPS with cerebral, myocardial, renal, and pulmonary involvement. Because of IgA deficiency, standard therapy consisting of plasmapheresis and intravenous immunoglobulins in addition to steroids was not tolerated. After 8 sessions of immunoadsorption (IAS), massive pulmonary hemorrhage was controlled but relapsed twice whenever IAS was terminated. As other immunosuppressive agents were considered dangerous because of the risk of infections in the face of severe hypogammaglobulinemia, we administered eculizumab, an inhibitor of the terminal complement pathway, which led to a persistent control of her disease. Interestingly, eculizumab therapy was associatedwith a further decline of complement C3 and C4 serumlevels. The patient developed a subsequent flare of her systemic lupus erythematosus, potentially indicating that complement inhibition by eculizumab is not effective in preventing lupus flares. Taken together, we describe a unique case of life-threatening and difficult-to-treat CAPS with a good clinical response after terminal complement complex inhibition with eculizumab. Further controlled trials are necessary to investigate the value of eculizumab in patients with CAPS

The Association of Mid-Regional Pro-Adrenomedullin and Mid-Regional Pro-Atrial Natriuretic Peptide with Mortality in an Incident Dialysis Cohort

High levels of the plasma peptides mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) are associated with clinical outcomes in the general population. Data in patients with chronic kidney disease are sparse. We therefore investigated the association of MR-proANP and MR-proADM levels with all-cause and cardiovascular (CV) mortality, CV events and peripheral arterial disease in 201 incident dialysis patients of the INVOR-Study prospectively followed for a period of up to more than 7 years. The overall mortality rate was 43%, thereof 43% due to CV events. Both baseline MR-proANP and MR-proADM were associated with higher risk of all-cause (HR = 1.44, p = 0.001 and HR = 1.32, p = 0.002, respectively) and CV mortality (HR = 1.75, p<0.001 and HR = 1.41, p = 0.007, respectively) after adjustment for age, sex, previous CV events, diabetes mellitus and time-dependent type of renal replacement therapy. We then stratified patients in high risk (both peptides in the upper tertile), intermediate risk (only one of the two peptides in the upper tertile) and low risk (none in the upper tertile). Although demographic, clinical and laboratory variables were similar among the intermediate and high risk group, to be with both parameters in the upper tertile was associated with a 3-fold higher risk for all-cause (HR = 2.87, p<0.001) and CV mortality (HR = 3.58, p = 0.001). In summary, among incident dialysis patients MR-proANP and MR-proADM were shown to be associated with all-cause and CV mortality, with the highest risk when both parameters were in the upper tertiles

Association of HbA1c values with mortality and cardiovascular events in O

Abstract Background: Improved glycemic control reduces complications in patients with diabetes mellitus (DM). However, it is discussed controversially whether patients with diabetes mellitus and end-stage renal disease benefit from strict glycemic control

Association of HbA1c Values with Mortality and Cardiovascular Events in Diabetic Dialysis Patients. The INVOR Study and Review of the Literature

BACKGROUND: Improved glycemic control reduces complications in patients with diabetes mellitus (DM). However, it is discussed controversially whether patients with diabetes mellitus and end-stage renal disease benefit from strict glycemic control. METHODS: We followed 78 patients with DM initiating dialysis treatment of the region of Vorarlberg in a prospective cohort study applying a time-dependent Cox regression analysis using all measured laboratory values for up to more than seven years. This resulted in 880 HbA(1c) measurements (with one measurement every 3.16 patient months on average) during the entire observation period. Non-linear P-splines were used to allow flexible modeling of the association with mortality and cardiovascular disease (CVD) events. RESULTS: We observed a decreased mortality risk with increasing HbA(1c) values (HR = 0.72 per 1% increase, p = 0.024). Adjustment for age and sex and additional adjustment for other CVD risk factors only slightly attenuated the association (HR = 0.71, p = 0.044). A non-linear P-spline showed that the association did not follow a fully linear pattern with a highly significant non-linear component (p = 0.001) with an increased risk of all-cause mortality for HbA(1c) values up to 6-7%. Causes of death were associated with HbA(1c) values. The risk for CVD events, however, increased with increasing HbA(1c) values (HR = 1.24 per 1% increase, p = 0.048) but vanished after extended adjustments. CONCLUSIONS: This study considered the entire information collected on HbA(1c) over a period of more than seven years. Besides the methodological advantages our data indicate a significant inverse association between HbA(1c) levels and all-cause mortality. However, for CVD events no significant association could be found

The Risk of Severe Infections Following Rituximab Administration in Patients With Autoimmune Kidney Diseases: Austrian ABCDE Registry Analysis.

OBJECTIVE: To characterize the incidence, type, and risk factors of severe infections (SI) in patients with autoimmune kidney diseases treated with rituximab (RTX). METHODS: We conducted a multicenter retrospective cohort study of adult patients with immune-related kidney diseases treated with at least one course of RTX between 2015 and 2019. As a part of the ABCDE Registry, detailed data on RTX application and SI were collected. SI were defined by Common Terminology Criteria for Adverse Events v5.0 as infectious complications grade 3 and above. Patients were dichotomized between "nephrotic" and "nephritic" indications. The primary outcome was the incidence of SI within 12 months after the first RTX application. RESULTS: A total of 144 patients were included. Twenty-five patients (17.4%) presented with SI, mostly within the first 3 months after RTX administration. Most patients in the nephritic group had ANCA-associated vasculitis, while membranous nephropathy was the leading entity in the nephrotic group. Respiratory infections were the leading SI (n= 10, 40%), followed by urinary tract (n=3, 12%) and gastrointestinal infections (n=2, 8%). On multivariable analysis, body mass index (BMI, 24.6 kg/m2versus 26.9 kg/m2, HR: 0.88; 95%CI: 0.79-0.99; p=0.039) and baseline creatinine (HR: 1.25; 95%CI: 1.04-1.49; p=0.017) were significantly associated with SI. All patients in the nephritic group (n=19; 100%) who experienced a SI received oral glucocorticoid (GC) treatment at the time of infection. Hypogammaglobulinemia was frequent (58.5%) but not associated with SI. CONCLUSIONS: After RTX administration, impaired kidney function and lower BMI are independent risk factors for SI. Patients with nephritic glomerular diseases having concomitant GC treatment might be at higher risk of developing SI

Genetic and Clinical Predictors of Age of ESKD in Individuals With Autosomal Dominant Tubulointerstitial Kidney Disease Due to UMOD Mutations

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Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

Acute Kidney Injury Treated with Dialysis outside the Intensive Care Unit: A Retrospective Observational Single-Center Study.

The number of patients suffering from acute kidney injury requiring dialysis (AKI-D) is increasing. Whereas causes and outcome of AKI-D in the intensive care unit (ICU) are described extensively, few data exist about AKI-D patients treated outside the ICU. Aim of this study was to identify the causes of AKI-D, determine in-depth the comorbid conditions and outcome of this particular patient group and identify possibilities for its prevention.We retrospectively studied all AKI-D patients treated outside the ICU in a single nephrology referral center between January 2010 and June 2015. Data on comorbid conditions, renal function and drug therapy prior to AKI-D, and possible causal events were collected. Patients were grouped into those with renal hypoperfusion as the predominant cause of AKI-D (hemodynamic group) and those with other causes (non-hemodynamic group).During 66 months 128 patients (57% male, mean age 69.3 years) were treated. AKI-D was community-acquired in 70.3%. The most frequent comorbidities were hypertension (62.5%), chronic kidney disease (CKD) (58.9%), coronary artery disease (CAD) (46.1%), diabetes (35.9%) and heart failure (34.1%). Most patients were prescribed diuretics (61.7%) and inhibitors of the renin-angiotensin-aldosterone system (RASI) (57.8%); 46.1% had a combination of both. In the 88 patients with hemodynamic AKI-D (68.8%) the most frequent initiating events were diarrhea (39.8%), infections (17.0%) and acute heart failure (13.6%). In the 40 patients with non-hemodynamic AKI-D (31.2%) interstitial nephritis (n = 15) was the prominent diagnosis. Patients with hemodynamic AKI-D were older (72.6 vs. 62.1 years, p = 0.001), suffered more often from CKD (68.2% vs. 33.3%, p = 0.003), CAD (54.5% vs. 27.5%, p = 0.004) and diabetes (42.0% vs. 22.5%, p = 0.033), and were more frequently on diuretics (75.0% vs. 32.5%, p<0.001), RASI (67.0% vs. 37.5%, p = 0.002) or their combination (58.0% vs. 20.0%, p<0.001). Twenty-two (17.2%) patients died and 27 (21.1%) patients died or developed end-stage renal disease.AKI-D treated outside the ICU is most often caused by renal hypoperfusion. It predominantly afflicts elderly patients with one or more comorbid conditions, who are treated with diuretics and RASI and have an acute illness leading to volume depletion. Early discontinuation of these drugs may be a successful strategy to avoid AKI-D in vulnerable patients