Browsing by Author "Steubl, Dominik"

Now showing 1 - 4 of 4
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    Empagliflozin and incidence of events consistent with acute kidney injury: Pooled safety analysis in >15 000 individuals
    (Wiley, 2022) Agarwal, Rajiv; Hauske, Sibylle Jenny; Wheeler, David C.; Doi, Kent; Elsaesser, Amelie; Ritter, Ivana; Steubl, Dominik; Wanner, Christoph; Medicine, School of Medicine
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    Hypothesis: Potential Utility of Serum and Urine Uromodulin Measurement in Kidney Transplant Recipients?
    (Lippincott, Williams & Wilkins, 2017-10-06) Bostom, Andrew G.; Steubl, Dominik; Friedman, Allon N.; Medicine, School of Medicine
    Seventy years after its discovery, studies of the myriad properties, and potential disease associations of uromodulin are now burgeoning. Although normative ranges for serum/plasma uromodulin concentrations were established over 30 years ago, their external validation occurred only in very recent, larger studies. As tubular function indices, serum and urinary uromodulin may be more sensitive indicators of kidney graft dysfunction undetected by glomerular filtration markers, or proteinuria. Moreover, 2 sizable, just published longitudinal reports revealed that lower serum uromodulin levels were associated with cardiovascular disease (CVD) outcomes, total mortality, and infectious disease deaths, in patients with known or suspected coronary heart disease. Preliminary longitudinal studies have reported that reduced levels of plasma or serum uromodulin were linked to progression to end-stage renal disease in chronic kidney disease patients, and graft failure in kidney transplant recipients (KTRs). Conflicting data on the associations, or lack thereof, between lower urinary uromodulin concentrations and accelerated loss of renal function, or renal failure, in nontransplant chronic kidney disease patients, are perhaps due, in part, to analytical limitations in determining urine uromodulin. Potential longitudinal associations between serum and urinary uromodulin concentrations, and CVD outcomes, graft failure, and all-cause mortality, await validation in large, diverse cohorts of chronic KTRs. Taking advantage of an efficient case-cohort design scheme, we demonstrate how the completed FAVORIT clinical trial cohort might be ideally suited to evaluate these associations. Using available case-cohort sample data, statistical power simulations are provided to detect relative risk estimates of 1.50 for CVD (n = 309 events), 1.56 for graft failure (n = 223 events) or 1.50 for death from any cause (n = 320 events), comparing values below the median, to values equal to or above the median for serum uromodulin values. Edifying data such as these would advance our understanding of the hypothetical utility of uromodulin measurement in KTRs considerably.
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    Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation—A Prospective Cohort Study
    (MDPI, 2021-06-11) Kemmner, Stephan; Holzmann-Littig, Christopher; Sandberger, Helene; Bachmann, Quirin; Haberfellner, Flora; Torrez, Carlos; Schmaderer, Christoph; Heemann, Uwe; Renders, Lutz; Assfalg, Volker; El-Achkar, Tarek M.; Garimella, Pranav S.; Scherberich, Jürgen; Steubl, Dominik; Medicine, School of Medicine
    Delayed graft function (DGF) following kidney transplantation is associated with increased risk of graft failure, but biomarkers to predict DGF are scarce. We evaluated serum uromodulin (sUMOD), a potential marker for tubular integrity with immunomodulatory capacities, in kidney transplant recipients and its association with DGF. We included 239 kidney transplant recipients and measured sUMOD pretransplant and on postoperative Day 1 (POD1) as independent variables. The primary outcome was DGF, defined as need for dialysis within one week after transplantation. In total, 64 patients (27%) experienced DGF. In multivariable logistic regression analysis adjusting for recipient, donor and transplant associated risk factors each 10 ng/mL higher pretransplant sUMOD was associated with 47% lower odds for DGF (odds ratio (OR) 0.53, 95% confidence interval (95%-CI) 0.30–0.82). When categorizing pretransplant sUMOD into quartiles, the quartile with the lowest values had 4.4-fold higher odds for DGF compared to the highest quartile (OR 4.41, 95%-CI 1.54–13.93). Adding pretransplant sUMOD to a model containing established risk factors for DGF in multivariable receiver-operating-characteristics (ROC) curve analysis, the area-under-the-curve improved from 0.786 [95%-CI 0.723–0.848] to 0.813 [95%-CI 0.755–0.871, p = 0.05]. SUMOD on POD1 was not associated with DGF. In conclusion, higher pretransplant sUMOD was independently associated with lower odds for DGF, potentially serving as a non-invasive marker to stratify patients according to their risk for developing DGF early in the setting of kidney transplantation.
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    Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials
    (American Diabetes Association, 2022) Tuttle, Katherine R.; Levin, Adeera; Nangaku, Masaomi; Kadowaki, Takashi; Agarwal, Rajiv; Hauske, Sibylle J.; Elsäßer, Amelie; Ritter, Ivana; Steubl, Dominik; Wanner, Christoph; Wheeler, David C.; Medicine, School of Medicine
    Objective: To assess the safety of empagliflozin in patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD) (category G3-4) enrolled in clinical trials. Research design and methods: This analysis pooled data from 19 randomized, placebo-controlled, phase 1-4 clinical trials and 1 randomized, placebo-controlled extension study in which patients received empagliflozin 10 mg or 25 mg daily. Time to first occurrence of adverse events (AEs) was evaluated using Kaplan-Meier analysis and multivariable Cox regression models. Results: Among a total of 15,081 patients who received at least one study drug dose, 1,522, 722, and 123 were classified as having G3A, G3B, and G4 CKD, respectively, at baseline. Demographic and clinical characteristics were similar between treatment groups across CKD categories. Rates of serious AEs, AEs leading to discontinuation, and events of special interest (including lower limb amputations and acute renal failure [ARF]) were also similar between empagliflozin and placebo across CKD subgroups. In adjusted Cox regression analyses, risks for volume depletion and ARF were similar for empagliflozin and placebo in the combined group with CKD categories G3B and G4 and the G3A group. Notably lower risks were observed in both groups for hyperkalemia (hazard ratio 0.59 [95% CI 0.37-0.96, P = 0.0323] and 0.48 [0.26-0.91, P = 0.0243], respectively) and edema (0.47 [0.33-0.68, P < 0.0001] and 0.44 [0.28-0.68, P = 0.0002], respectively). Conclusions: Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of hyperkalemia and edema.