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  • 1
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    Focus on Microalbuminuria to Improve Cardiac and Renal Protection
    S. Karger AG ; 2009
    In:  Nephron Clinical Practice Vol. 111, No. 3 ( 2009-2-12), p. c204-c211
    Details
    In: Nephron Clinical Practice, S. Karger AG, Vol. 111, No. 3 ( 2009-2-12), p. c204-c211
    Abstract: With the recent attention to diagnose earlier stages of chronic kidney diseases (CKD), most attention focuses on screening for an impaired estimated glomerular filtration rate (eGFR), i.e. CKD stages 3–5. Less attention is given to the impact of the urinary leakage of albumin. Its presence is not taken into account in the definition of stages 3–5, but only required to diagnose stages 1 and 2. As in stages 1 and 2 CKD, eGFR is not or only modestly impaired, these stages are generally considered to have a relatively better prognosis. In this review, we will show evidence that screening for albuminuria may be of great benefit, not only as an argument to start treatment to prevent progressive renal function loss, but also to prevent cardiovascular events.
    Type of Medium: Online Resource
    ISSN: 1660-2110
    URL: Article
    DOI: 10.1159/000201568
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2009
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  • 2
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    Rapid Progression of Autosomal Dominant Polycystic Kidney Disease: Urinary Biomarkers as Predictors
    S. Karger AG ; 2019
    In:  American Journal of Nephrology Vol. 50, No. 5 ( 2019), p. 375-385
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 50, No. 5 ( 2019), p. 375-385
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Markers currently used to predict the likelihood of rapid disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) are expensive and time consuming to assess and often have limited sensitivity. New, easy-to-measure markers are therefore needed that alone or in combination with conventional risk markers can predict the rate of disease progression. In the present study, we investigated the ability of tubular damage and inflammation markers to predict kidney function decline. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 At baseline, albumin, immunoglobulin G, kidney injury molecule 1, β2 microglobulin (β2MG), heart-type fatty acid-binding protein, neutrophil gelatinase-associated lipocalin, and monocyte chemotactic protein-1 ­(MCP-1) were measured in 24-h urine samples of patients participating in a study investigating the therapeutic efficacy of lanreotide in ADPKD. Individual change in estimated glomerular filtration rate (eGFR) during follow-up was calculated using mixed-model analysis taking into account 13 ­eGFRs (chronic kidney disease EPIdemiology) per patient. Logistic regression analysis was used to select urinary biomarkers that had the best association with rapidly progressive disease. The predictive value of these selected urinary biomarkers was compared to other risk scores using C-statistics. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Included were 302 patients of whom 53.3% were female, with an average age of 48 ± 7 years, eGFR of 52 ± 12 mL/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 , and a height-adjusted total kidney volume (htTKV) of 1,082 (736–1,669) mL/m. At baseline, all urinary damage and inflammation markers were associated with baseline eGFR, also after adjustment for age, sex and baseline htTKV. For longitudinal analyses only patients randomized to standard care were considered ( 〈 i 〉 n 〈 /i 〉 = 152). A stepwise backward analysis revealed that β2MG and MCP-1 showed the strongest association with rapidly progressive disease. A urinary biomarker score was created by summing the ranking of tertiles of β2MG and MCP-1 excretion. The predictive value of this urinary biomarker score was higher compared to that of the Mayo htTKV classification (area under the curve [AUC] 0.73 [0.64–0.82] vs. 0.61 [0.51–0.71], 〈 i 〉 p 〈 /i 〉 = 0.04) and comparable to that of the predicting renal outcomes in ­ADPKD score (AUC 0.73 [0.64–0.82] vs. 0.65 [0.55–0.75] , 〈 i 〉 p 〈 /i 〉 = 0.18). In a second independent cohort with better kidney function, similar results were found for the urinary biomarker score. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Measurement of urinary β2MG and MCP-1 excretion allows selection of ADPKD patients with rapidly progressive disease, with a predictive value comparable to or even higher than that of TKV or 〈 i 〉 PKD 〈 /i 〉 mutation. Easy and inexpensive to measure urinary markers therefore hold promise to help predict prognosis in ADPKD.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000502999
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2019
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  • 3
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    The Association of Combined Total Kidney and Liver Volume with Pain and Gastrointestinal Symptoms in Patients with Later Stage Autosomal Dominant Polycystic Kidney Disease
    S. Karger AG ; 2017
    In:  American Journal of Nephrology Vol. 46, No. 3 ( 2017), p. 239-248
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 46, No. 3 ( 2017), p. 239-248
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 There is an ongoing debate if and how kidney and liver volume are associated with pain and gastrointestinal (GI) symptoms in autosomal dominant polycystic kidney disease (ADPKD) patients. Since both kidney and liver volume could interact, we investigated whether combined total kidney and liver volume had stronger associations with ADPKD-related pain and GI symptoms than the volumes of the organs separately. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We used baseline data from the DIPAK-1 study, which included ADPKD patients with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 . MR imaging was performed to measure height-adjusted total kidney volume (hTKV), height-adjusted total liver volume (hTLV) and the combination of both (height-adjusted total kidney liver volume [hTKLV]). 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Three hundred nine ADPKD patients were included with a mean age of 48 ± 7 years, 53% female, eGFR 50 ± 11 mL/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 and median hTKV, hTLV and hTKLV of 1,095 (758-1,669), 1,173 (994-1,523) and 2,496 (1,972-3,352) mL/m, respectively. ADPKD-related pain and GI symptoms were present in, respectively, 27.5 and 61.2% of patients. Gender was no effect modifier in the association between kidney and/or liver volume, and symptom burden, indicating that all models could be tested in the overall study population. hTKLV and hTLV were significantly associated with pain and GI symptoms, whereas hTKV was not. Model testing revealed that the associations of pain and GI symptoms with hTKLV were significantly stronger than with hTKV ( 〈 i 〉 p 〈 /i 〉 = 0.04 and 〈 i 〉 p 〈 /i 〉 = 0.04, respectively) but not when compared to hTLV ( 〈 i 〉 p 〈 /i 〉 = 0.2 and 〈 i 〉 p 〈 /i 〉 = 0.5, respectively). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 This study indicates that combined kidney and liver volume was associated with the presence and severity of pain and GI symptoms in ADPKD, with a more prominent role for hTLV than for hTKV.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000479436
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
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  • 4
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    Dialysis Hypotension: A Role for Inadequate Increase in Arginine Vasopressin Levels? A Systematic Literature Review and Meta-Analysis
    S. Karger AG ; 2014
    In:  American Journal of Nephrology Vol. 39, No. 2 ( 2014), p. 100-109
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 39, No. 2 ( 2014), p. 100-109
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Intradialytic hypotension is a common complication of hemodialysis (HD). Some studies have suggested that inadequate arginine vasopressin (AVP) increase could play a role in the pathogenesis of intradialytic hypotension. However, AVP levels during HD and its relation to hypotension has never been systematically studied. 〈 b 〉 〈 i 〉 Summary: 〈 /i 〉 〈 /b 〉 PubMed and Embase were searched (1970-2013, search terms ‘vasopressin' and ‘hemodialysis') for studies reporting on AVP levels during standard HD or other dialysis techniques. Observational studies reporting on AVP levels pre- and postdialysis were additionally included in a meta-analysis. Thirty-seven studies were included in the systematic literature review, of which 26 studies were eligible for meta-analysis. The main findings were that pretreatment AVP levels were higher in dialysis patients compared with healthy controls (6.4 ± 3.5 vs. 2.5 ± 1.3 pg/ml, p = 0.003) and that plasma AVP levels showed little or no increase during HD (from 7.0 ± 4.9 to 8.8 ± 9.3, p = 0.433) 〈 i 〉 . 〈 /i 〉 Significant heterogeneity was found between studies. Meta-regression analysis revealed no significant associations between AVP and patient or study characteristics. Studies on other dialysis techniques showed mixed results regarding the AVP course. The eight studies that addressed the relation between intradialytic hypotension and AVP also showed inconsistent results. 〈 b 〉 〈 i 〉 Key Messages: 〈 /i 〉 〈 /b 〉 Plasma AVP levels are higher in dialysis patients compared with healthy controls, but show little or no increase during HD. The lack of a rise in AVP levels during HD may be pathophysiologically involved in the onset of intradialytic hypotension, but firm conclusions are not possible from our review of the literature.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000358203
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2014
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  • 5
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    Rationale and Design of a Clinical Trial Investigating Tolvaptan Safety and Efficacy in Autosomal Dominant Polycystic Kidney Disease
    S. Karger AG ; 2017
    In:  American Journal of Nephrology Vol. 45, No. 3 ( 2017), p. 257-266
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 45, No. 3 ( 2017), p. 257-266
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 In TEMPO 3:4, the vasopressin V2-receptor antagonist tolvaptan slowed kidney growth and function decline in autosomal dominant polycystic kidney disease (ADPKD) patients with relatively preserved kidney function. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Prospective, phase 3b, multi-center, randomized-withdrawal, placebo-controlled, double-blind trial of tolvaptan in ADPKD patients with late stage 2 to early stage 4 chronic kidney disease (CKD). The primary endpoint was estimated glomerular filtration rate (eGFR) change from pre-treatment baseline to post-treatment follow-up. Secondary endpoints included annualized eGFR slope, incidence of ADPKD complications, and overall and hepatic safety profiles. Participants were 18-55 year-old ADPKD patients with baseline eGFR ≥25 and ≤65 mL/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 or 56-65 year-old with eGFR ≥25 and ≤44 mL/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 and evidence of eGFR decline 〉 2.0 mL/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 per year. Daily split doses of tolvaptan were titrated to tolerance (30/15, 45/15, 60/30, or 90/30 mg) and maintained for 12 months, after an 8-week pre-randomization period to screen out subjects unable to tolerate at least 60/30 mg for 3 weeks. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Of 1,495 subjects who entered the tolvaptan titration period, 125 (8.4%) discontinued the study before randomization. One thousand three hundred seventy subjects (684 tolvaptan, 686 placebo) from 213 centers across 21 countries were randomized. Baseline demographics were well balanced across treatment arms. Information collected during the study included eGFR, survey scores (PKD history and outcome), adverse events, vital signs, hematology, urinalysis, and serum chemistry tests. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy (REPRISE) determines whether tolvaptan administered over 1 year exhibits disease-modifying properties in ADPKD patients with late stage 2 to early stage 4 CKD, which provides an important therapeutic advancement for this difficult-to-treat disease.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000456087
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
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  • 6
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    Effect of Vasopressin on the Hypothalamic-Pituitary-Adrenal Axis in ADPKD Patients during V2 Receptor Antagonism
    S. Karger AG ; 2020
    In:  American Journal of Nephrology Vol. 51, No. 11 ( 2020), p. 861-870
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 51, No. 11 ( 2020), p. 861-870
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Patients with autosomal dominant polycystic kidney disease (ADPKD) are treated with a vasopressin V2 receptor antagonist (V2RA) to slow disease progression. This drug increases vasopressin considerably in these patients with already elevated baseline levels. Vasopressin is known to stimulate the hypothalamic-pituitary-adrenal (HPA) axis through V1 and V3 receptor activation. It is unknown whether this increase in vasopressin during V2RA treatment affects glucocorticoid production. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Twenty-seven ADPKD patients were studied on and off treatment with a V2RA and compared to age- and sex-matched healthy controls and IgA nephropathy patients, the latter also matched for kidney function. Vasopressin was measured by its surrogate copeptin. Twenty-four-hour urinary excretions of cortisol, cortisone, tetrahydrocortisone, tetrahydrocortisol, allotetrahydrocortisol, and the total glucocorticoid pool were measured. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 At baseline, ADPKD patients demonstrated a higher copeptin concentration in comparison with healthy controls, while urinary excretion of cortisol and cortisone was lower (medians of 0.23 vs. 0.34 μmol/24 h, 〈 i 〉 p 〈 /i 〉 = 0.007, and 0.29 vs. 0.53 μmol/24 h, 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001, respectively). There were no differences in cortisol and cortisone excretion compared to IgA nephropathy patients. Cortisol, cortisone, and total glucocorticoid excretions correlated with kidney function ( 〈 i 〉 R 〈 /i 〉 = 0.37, 0.58, and 0.19, respectively; all 〈 i 〉 p 〈 /i 〉 & #x3c; 0.05). Despite that V2RA treatment resulted in a 3-fold increase in copeptin, only cortisone excretion increased (median of 0.44 vs. baseline 0.29 μmol/24 h, 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001), whereas no changes in cortisol or total glucocorticoid excretion were observed. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Increased concentration of vasopressin in ADPKD patients at baseline and during V2RA treatment does not result in activation of the HPA axis. The impaired glucocorticoid production in these patients is related to their degree of kidney function impairment.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000511000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
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  • 7
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    Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci
    S. Karger AG ; 2019
    In:  American Journal of Nephrology Vol. 49, No. 3 ( 2019), p. 193-202
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 49, No. 3 ( 2019), p. 193-202
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Serum urea level is a heritable trait, commonly used as a diagnostic marker for kidney function. Genome-wide association studies (GWAS) in East-Asian populations identified a number of genetic loci related to serum urea, however there is a paucity of data for European populations. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We performed a two-stage meta-analysis of GWASs on serum urea in 13,312 participants, with independent replication in 7,379 participants of European ancestry. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We identified 6 genome-wide significant single nucleotide polymorphisms (SNPs) in or near 6 loci, of which 2 were novel ( 〈 i 〉 POU2AF1 〈 /i 〉 and 〈 i 〉 ADAMTS9-AS2 〈 /i 〉 ). Replication of East-Asian and Scottish data provided evidence for an additional 8 loci. SNPs tag regions previously associated with anthropometric traits, serum magnesium, and urinary albumin-to-creatinine ratio, as well as expression quantitative trait loci for genes preferentially expressed in kidney and gastro-intestinal tissues. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Our findings provide insights into the genetic underpinnings of urea metabolism, with potential relevance to kidney function.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000496930
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2019
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  • 8
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    Improving Renoprotective Therapy by Targeting the Body Sodium Balance
    S. Karger AG ; 2021
    In:  American Journal of Nephrology Vol. 52, No. 5 ( 2021), p. 351-353
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 52, No. 5 ( 2021), p. 351-353
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000515811
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
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  • 9
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    The Need for Routine Native Nephrectomy in the Workup for Kidney Transplantation in Autosomal Dominant Polycystic Kidney Disease Patients
    S. Karger AG ; 2023
    In:  Urologia Internationalis Vol. 107, No. 2 ( 2023), p. 148-156
    Details
    In: Urologia Internationalis, S. Karger AG, Vol. 107, No. 2 ( 2023), p. 148-156
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 There is no consensus if nor when a native nephrectomy should be performed in the workup for kidney transplantation in ADPKD patients. In our PKD Expertise Center, a restrictive approach is pursued in which nephrectomy is performed only in patients with severe complaints, i.e., in case of serious volume-related complaints, lack of space for the allograft, recurrent cyst infections, persistent cyst bleedings, or chronic refractory pain. We analyzed in a retrospective cohort study whether this approach is justified. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 All ADPKD patients who received kidney transplantation between January 2000 and January 2019 were reviewed. Patients were subdivided into three groups: no nephrectomy (no-Nx), nephrectomy performed before (pre-Tx), or after kidney transplantation (post-Tx). Simultaneous nephrectomy together with transplantation were not performed in our center. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 391 patients (54 ± 9 years, 55% male) were included. The majority of patients did not undergo a nephrectomy ( 〈 i 〉 n 〈 /i 〉 = 257, 65.7%). A nephrectomy was performed pre-Tx in 114 patients (29.2%). After Tx, nephrectomy was performed in only 30 patients (7.7%, median 4.4 years post-Tx). Surgery-related complication rates did not differ between both groups (38.3% pre-Tx vs. 27.0% post-Tx, 〈 i 〉 p 〈 /i 〉 = 0.2), nor were there any differences in 10-year patient survival (74.4% pre-Tx vs. 80.7% post-Tx vs. 67.6% no-Nx, 〈 i 〉 p 〈 /i 〉 = 0.4), as well as in 10-year death-censored graft survival (84.4% pre-Tx vs. 85.5% post-Tx vs. 90.0% no-Nx, 〈 i 〉 p 〈 /i 〉 = 0.9). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 This study indicates that with a restrictive nephrectomy policy in the workup for kidney transplantation, only a part of ADPKD patients need a native nephrectomy.
    Type of Medium: Online Resource
    ISSN: 0042-1138 , 1423-0399
    URL: Article
    DOI: 10.1159/000525575
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
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  • 10
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    Rationale, Design, and Baseline Characteristics of ARTS-DN: A Randomized Study to Assess the Safety and Efficacy of Finerenone in Patients with Type 2 Diabetes Mellitus and a Clinical Diagnosis of Diabetic Nephropathy
    S. Karger AG ; 2014
    In:  American Journal of Nephrology Vol. 40, No. 6 ( 2014), p. 572-581
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 40, No. 6 ( 2014), p. 572-581
    Abstract: 〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 Finerenone decreases albuminuria in patients having heart failure with reduced ejection fraction and mild-to-moderate (stage 2-3) chronic kidney disease. The MinerAlocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN; NCT01874431) is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b study. ARTS-DN investigated whether the mineralocorticoid receptor antagonist finerenone reduces albuminuria without causing major alterations in serum potassium levels in patients with type 2 diabetes mellitus and a clinical diagnosis of DN who were receiving a renin-angiotensin-system (RAS) inhibitor. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Patients were randomized to oral finerenone 1.25-20 mg or placebo once daily. The primary objectives were to assess the ratio of the urinary albumin-to-creatinine ratio at day 90 to that at baseline in patients receiving finerenone, and to compare it with that in the placebo group. Additional exploratory analyses included evaluating changes from baseline in serum potassium levels, efficacy and safety biomarkers, and health-related quality of life. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Of 1,501 patients screened, 821 (the sample population) received at least one dose of finerenone/placebo. Baseline characteristics included: male, 77.8%; white, 84.2%; very high albuminuria (formerly macroalbuminuria), 38.4%; high albuminuria (formerly microalbuminuria), 60.3%; median (range) estimated glomerular filtration rate, 66.3 (24.5-130.7) ml/min/1.73 m 〈 sup 〉 2 〈 /sup 〉 ; and systolic blood pressure (mean ± standard deviation), 138.1 ± 14.4 mm Hg. There was a history of cardiovascular disease in 39.6%, diabetic neuropathy in 20.0%, and diabetic retinopathy in 19.9% of patients. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 ARTS-DN is the first phase 2b trial of finerenone in combination with a RAS inhibitor in patients with type 2 diabetes mellitus and a clinical diagnosis of DN.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000371497
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2014
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