| 1. |
- Axelsson, Matthias, et al.
(författare)
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Long and Short-Term Effects of Hypothermic Machine Perfusion vs. Cold Storage on Transplanted Kidneys from Expanded Criteria Donors-A Matched Comparison Study
- 2023
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Ingår i: JOURNAL OF CLINICAL MEDICINE. - 2077-0383. ; 12:17
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermic machine perfusion (HMP) has been shown to reduce delayed graft function (DGF)-rates in kidneys from expanded criteria donors (ECD) and may increase graft survival compared with static cold storage (SCS). This single-center, retrospective observational study aimed to evaluate this effect. The primary endpoint was the DGF-rate, defined as the use of dialysis in the first postoperative week, excluding the first 24 h. The main secondary endpoint was graft survival at 5 years. Recipients of ECD-kidneys between 2013 and 2021 with =2 grafts were included (n = 438). The SCS-kidneys were marginal-matched by propensity score to the HMP-group for donor age, cold ischemia time, and graft number. Multivariable adjusted analysis for confounders in the unmatched cohort and caliper-based ID-matching constituted sensitivity analyses. HMP showed a trend to lower DGF-rate in the marginal-matched comparison (9.2% vs. 16.1%, p = 0.063). This was strengthened by a significant benefit observed for HMP in both the sensitivity analyses: an adjusted OR of 0.45 (95% CI: 0.24; 0.84; p = 0.012) in the multivariable analysis and DGF-rate of 8.7% vs. 17.4% (p = 0.024) after ID-matching. The 5-year graft survival rate was >90% in both groups, with no benefit using HMP (HR = 0.79; 95% CI:0.39-1.16; p = 0.52). Our results suggest that HMP may be effective in decreasing DGF-rates, however, without any significant benefit in graft survival.
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| 2. |
- Baid-Agrawal, Seema, 1966, et al.
(författare)
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Weekend versus weekday transplant surgery and outcomes after kidney transplantation in the USA: a retrospective national database analysis
- 2016
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether kidney transplants performed during a weekend had worse outcomes than those performed during weekdays. Participants: 136 715 adult recipients of deceased donor single organ kidney transplants in the USA between 4/1994 and 9/2010. Main outcome measures: The primary outcomes were patient survival and death-censored and overall allograft survival. Secondary outcomes included initial length of hospital stay after transplantation, delayed allograft function, acute rejection within the first year of transplant, and patient and allograft survival at 1 month and at 1 year after transplantation. Cox proportional hazards models were used to evaluate the impact of weekend kidney transplant surgery on primary and secondary outcomes, adjusting for multiple covariates. Results: Among the 136 715 kidney recipients, 72.5% underwent transplantation during a regular weekday (Monday-Friday) and 27.5% during a weekend (Saturday-Sunday). No significant association was noted between weekend transplant status and patient survival, death-censored allograft survival or overall allograft survival in the adjusted analyses (HR 1.01 (95% CI 0.92 to 1.04), 1.012 (95% CI 0.99 to 1.034), 1.012 (95% CI 0.984 to 1.04), respectively). In addition, no significant association was noted between weekend transplant status and the secondary outcomes of patient and graft survival at 1 month and 1 year, delayed allograft function or acute rejection within the first year. Results remained consistent across all definitions of weekend status. Conclusions: The outcomes for deceased donor kidney transplantation in the USA are not affected by the day of surgery. The operationalisation of deceased donor kidney transplantation may provide a model for other surgeries or emergency procedures that occur over the weekend, and may help reduce length of hospital stay and improve outcomes.
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| 3. |
- Dannewitz, B., et al.
(författare)
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Status of periodontal health in German patients suffering from chronic kidney disease-Data from the GCKD study
- 2020
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Ingår i: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 47:1, s. 19-29
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Tidskriftsartikel (refereegranskat)abstract
- Aim To assess the prevalence and severity of periodontitis in patients with moderate chronic kidney disease (CKD) and comparing the results with the self-reported periodontitis awareness of the study subjects. Material and methods The periodontal status of 270 patients with moderate CKD randomly selected from a cohort of 5,217 subjects participating in the prospective observational German Chronic Kidney Disease (GCKD) project was analysed by recording bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL). Furthermore, the awareness of the study subjects of their periodontal conditions was evaluated by a self-reported questionnaire. Results 24.4% of the CKD study patients showed no or only mild signs of periodontal disease, 47.6% displayed moderate and 27% severe periodontitis. Questionnaire data revealed that 62.3% of the study subjects with severe periodontitis were not aware of the presence of the disease, 44.4% denied having received any systematic periodontal therapy so far, although 50% of them indicated to visit their dentist regularly for professional tooth cleanings. Conclusion While the clinical study data confirm an increased prevalence of periodontitis in CKD patients, their self-reported awareness of periodontitis was low.
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| 4. |
- Ekberg, Jana, 1964, et al.
(författare)
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A Randomized Controlled Trial on Safety of Steroid Avoidance in Immunologically Low-Risk Kidney Transplant Recipients
- 2022
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 7:2, s. 259-269
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Steroid-based immunosuppression after transplantation increases the risk of post-transplant diabetes mellitus (PTDM), with adverse effects on patient and graft survival. In the SAILOR study, we investigated the safety and efficacy of complete steroid avoidance in immunologically low-risk kidney recipients without diabetes on the current standard-of-care maintenance regimen with tacrolimus/mycophenolate mofetil (MMF). Methods: In this 2-year, multicenter, open-label trial, a total of 222 patients were randomized to receive either steroid avoidance protocol (tacrolimus/MMF/antithymocyte globulin [ATG] induction [n = 113]) or steroid maintenance protocol (tacrolimus/MMF/prednisolone/basiliximab-induction [n = 109]). Results: At 1 year, no significant differences were found between steroid avoidance and steroid maintenance arms in the incidence of PTDM, the primary end point (12.4% vs. 18.3%, respectively, P = 0.30, CI: 16.3–4.4), or in overall biopsy-proven rejections (15% vs. 13.8%, respectively, P = 0.85). At 2 years, the composite end point of freedom from acute rejection, graft loss, and death (81% vs. 85%, respectively, P = 0.4), kidney function, or adverse events was comparable between the 2 arms. Moreover, 63.9% of the patients in the steroid avoidance arm remained free from steroids at 2 years. Conclusion: The SAILOR study provides further evidence for the feasibility, safety, and efficacy of early steroid-free treatment at 2 years in immunologically low-risk kidney recipients with tacrolimus/MMF maintenance regimen. © 2021 International Society of Nephrology
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| 5. |
- Ekberg, Jana, 1964, et al.
(författare)
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Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort
- 2023
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Ingår i: TRANSPLANTATION DIRECT. - 2373-8731. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Background.Chronic kidney disease is common after non-renal solid organ transplantation, mainly secondary to calcineurin inhibitors toxicity. Uterus transplantation (UTx) is an innovative treatment for women with absolute uterine factor infertility. UTx is exclusive because it is transient with the absence of lifelong immunosuppression and is performed in young healthy participants. Therefore, UTx provides a unique setting for evaluating the effect of time-limited calcineurin inhibitors treatment on recipients' kidney function.Methods.In the first UTx cohort worldwide, we studied kidney function using estimated glomerular filtration rate (eGFR) in 7 women over a median follow-up of 121 (119-126) mo.Results.Median eGFR (mL/min/1.73 m2) of the cohort was 113 at UTx, which declined to 74 during month 3, 71 at months 10-12, 76 at hysterectomy (HE), and 83 at last follow-up. Median duration of tacrolimus exposure was 52 (22-83) mo, and median trough levels (mu g/L) were 10 during month 3 and 5.8 at HE. Between UTx and month 3, decline in kidney function was observed in all 7 participants with a median eGFR slope for the whole cohort of -24 mL/min/1.73 m2, which declined further by -4 mL/min/1.73 m2 until months 10-12. Thereafter, eGFR slope improved in 3 participants, remained stable in 3, and worsened in 1 until HE/tacrolimus discontinuation, after which it improved in 2. Eventually, between UTx and last follow-up, 4 of 7 participants had a decline in their eGFR, the median annual eGFR slope being negative at -1.9 mL/min/1.73 m2/y for the whole group.Conclusions.Kidney function declined in all recipients early after UTx followed by a persistent long-term decrease in majority, despite transplantectomy and discontinuation of immunosuppression. Thus, UTx may incur an increased risk of chronic kidney disease even in this young and healthy population, highlighting the importance of close surveillance of kidney function and minimization of tacrolimus exposure.
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| 6. |
- Heindel, J., et al.
(författare)
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Association Between Dietary Patterns and Kidney Function in Patients With Chronic Kidney Disease: A Cross-Sectional Analysis of the German Chronic Kidney Disease Study
- 2020
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Ingår i: Journal of renal nutrition. - : Elsevier BV. - 1051-2276. ; 30:4, s. 296-304
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Tidskriftsartikel (refereegranskat)abstract
- Objective In the general population, “healthy” dietary patterns are associated with improved health outcomes, but data on associations between observance of specific dietary patterns and kidney function in patients with chronic kidney disease (CKD) are sparse. Methods Dietary intake was evaluated using food frequency questionnaires in patients with moderately severe CKD under nephrology care enrolled into the observational multicenter German CKD study. The Dietary Approaches to Stop Hypertension (DASH) diet score, Mediterranean diet score, and German Food Pyramid Index (GFPI) were calculated and their association with estimated glomerular filtration rate (eGFR) and albuminuria was assessed by multivariable linear regression analysis, adjusted for gender, age, body mass index, energy intake, smoking status, alcohol intake, education, high-density lipoprotein-cholesterol (HDL- cholesterol), low-density lipoprotein-cholesterol (LDL-cholesterol), hypertension, and diabetes mellitus. Results A total of 2,813 patients (41% women; age 60.1 ± 11.6 years) were included in the analysis. High DASH diet score and GFPI were associated with lower systolic blood pressure and lower intake of antihypertensive medication, higher HDL, and lower uric acid levels. Mediterranean-style diet was associated with lower prevalence of diabetes mellitus. Higher DASH and Mediterranean diet scores were associated with higher eGFR (β-coefficient = 1.226, P < .001; β-coefficient = 0.932, P = .007, respectively). In contrast, GFPI was not associated with eGFR. For the individual components of the dietary patterns, higher intake of nuts and legumes, cereals, fish, and polyunsaturated fats was associated with higher eGFR and higher intake of dairy, composed of low- and whole-fat dairy, was associated with lower eGFR. No association was found between dietary patterns and albuminuria. Conclusion Higher observance of the DASH or Mediterranean diet, but not German food pyramid recommendations, was associated with higher eGFR among patients with CKD. Improving dietary habits may offer an opportunity to better control comorbidities and kidney function decline in patients with CKD.
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| 7. |
- Kaesler, N., et al.
(författare)
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Low adherence to CKD-specific dietary recommendations associates with impaired kidney function, dyslipidemia, and inflammation
- 2021
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 75, s. 1389-1397
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Tidskriftsartikel (refereegranskat)abstract
- Background/Objectives A diet following chronic kidney disease (CKD)-specific recommendations is considered essential for optimal management of patients with CKD. However, data on the adherence to these recommendations and its implications for health-relevant biomarkers are lacking. The objectives were to estimate adherence to CKD-specific dietary recommendations, to identify characteristics and lifestyle variables associated with poor adherence, and to investigate the relationship of adherence with biomarkers. Methods In this cross-sectional analysis, average dietary intake was estimated in 3193 participants with moderately severe CKD enrolled into the observational multicenter German CKD study using a food frequency questionnaire. A CKD diet score was developed to assess adherence to CKD-specific dietary recommendations based on intake of sodium, potassium, fiber, protein, sugar, and cholesterol. The associations of dietary adherence with characteristics, lifestyle variables, and biomarker levels were determined. Results Logistic regression analysis revealed younger age, higher body mass index, male gender, lower educational attainment, various lifestyle variables (cigarette smoking, infrequent alcohol consumption, low physical activity), and lower estimated glomerular filtrate rate associated with lower adherence to dietary recommendations. Low adherence to dietary recommendations was further associated with dyslipidemia, higher uric acid, and C-reactive protein levels. Associations between low dietary adherence and biomarkers were mostly driven by low intake of fiber and potassium, and high intake of sugar and cholesterol. Conclusions This study revealed differential characteristics and biomarkers associated with lower adherence to CKD-specific dietary recommendations. Promotion of CKD-specific dietary recommendations may help to mitigate the adverse prognosis in CKD patients.
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| 8. |
- Kumar, V., et al.
(författare)
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The Indian Chronic Kidney Disease (ICKD) study: baseline characteristics
- 2022
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 15:1, s. 60-69
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Tidskriftsartikel (refereegranskat)abstract
- Background. Chronic kidney disease (CKD) is an important cause of morbidity and mortality worldwide. There is a lack of information on epidemiology and progression of CKD in low-middle income countries. The Indian Chronic Kidney Disease (ICKD) study aims to identify factors that associate with CKD progression, and development of kidney failure and cardiovascular disease (CVD) in Indian patients with CKD. Methods. ICKD study is prospective, multicentric cohort study enrolling patients with estimated glomerular filtration rate (eGFR) 15-60 mL/min/1.73m(2), or >60 mL/min/1.73m(2) with proteinuria. Clinical details and biological samples are collected at annual visits. We analysed the baseline characteristics including socio-demographic details, risk factors, disease characteristics and laboratory measurements. In addition, we compared characteristics between urban and rural participants. Results. A total of 4056 patients have been enrolled up to 31 March 2020. The mean +/- SD age was 50.3 +/- 11.8 years, 67.2% were males, two-thirds of patients lived in rural areas and the median eGFR was 40 mL/min/1.73m(2). About 87% were hypertensive, 37% had diabetes, 22% had CVD, 6.7% had past history of acute kidney injury and 23% reported prior use of alternative drugs. Diabetic kidney disease, chronic interstitial nephritis (CIN) and CKD-cause unknown (CKDu) were the leading causes. Rural participants had more occupational exposure and tobacco use but lower educational status and income. CIN and unknown categories were leading causes in rural participants. Conclusions. The ICKD study is the only large cohort study of patients with mild-to-moderate CKD in a lower middle income country. Baseline characteristics of study population reveal differences as compared with other cohorts from high-income countries.
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| 9. |
- Larsson, P., et al.
(författare)
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Difficult-to-Treat Rejections in Kidney Transplant Recipients: Our Experience with Everolimus-Based Quadruple Maintenance Therapy
- 2023
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Ingår i: Journal of Clinical Medicine. - 2077-0383. ; 12:20
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Tidskriftsartikel (refereegranskat)abstract
- All chronic and treatment-resistant acute rejections are "difficult-to-treat" and lead to progressive loss of graft function in kidney transplant recipients (KTR), as no effective treatment exists for such rejections to date. We review our experience with a novel strategy to treat such rejections by adding everolimus as a "rescue" to conventional triple maintenance therapy with prednisolone, mycophenolate mofetil and calcineurin inhibitor. We retrospectively analysed data in 28 KTR who received everolimus-based quadruple therapy at our institution for biopsy-proven chronic active T cell-mediated or antibody-mediated rejection (n = 19) or treatment-resistant acute rejections (n = 9) between 2011-2017. The primary outcome was 5-year death-censored graft survival. Main secondary outcomes were response to treatment defined by stable or improved graft function, 5-year patient survival and discontinuation rate of treatment. The Kaplan-Meier estimate for 5-year death-censored graft survival was 79% in all patients, 90% for patients with chronic active T cell-mediated rejections, 78% for chronic active antibody-mediated rejection and 67% for acute rejections. Response to treatment was achieved in 43% and 5-year patient survival was 94%. Treatment was stopped in 12 (43%) patients due to adverse events. Everolimus-based maintenance quadruple therapy, despite high rate of everolimus discontinuation due to adverse events, may be a valid approach in a subset of kidney transplant recipients with such difficult-to-treat rejections, which otherwise would lead to a high rate of graft loss.
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| 10. |
- Makvandi, Kianoush, et al.
(författare)
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Multiparametric magnetic resonance imaging allows non-invasive functional and structural evaluation of diabetic kidney disease
- 2022
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 15:7, s. 1387-1402
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Tidskriftsartikel (refereegranskat)abstract
- Background We sought to develop a novel non-contrast multiparametric MRI (mpMRI) protocol employing several complementary techniques in a single scan session for a comprehensive functional and structural evaluation of diabetic kidney disease (DKD). Methods In the cross-sectional part of this prospective observational study, 38 subjects ages 18-79 years with type 2 diabetes and DKD [estimated glomerular filtration rate (eGFR) 15-60 mL/min/1.73 m(2)] and 20 age- and gender-matched healthy volunteers (HVs) underwent mpMRI. Repeat mpMRI was performed on 23 DKD subjects and 10 HVs. By measured GFR (mGFR), 2 DKD subjects had GFR stage G2, 16 stage G3 and 20 stage G4/G5. A wide range of MRI biomarkers associated with kidney haemodynamics, oxygenation and macro/microstructure were evaluated. Their optimal sensitivity, specificity and repeatability to differentiate diabetic versus healthy kidneys and categorize various stages of disease as well as their correlation with mGFR/albuminuria was assessed. Results Several MRI biomarkers differentiated diabetic from healthy kidneys and distinct GFR stages (G3 versus G4/G5); mean arterial flow (MAF) was the strongest predictor (sensitivity 0.94 and 1.0, specificity 1.00 and 0.69; P = .04 and .004, respectively). Parameters significantly correlating with mGFR were specific measures of kidney haemodynamics, oxygenation, microstructure and macrostructure, with MAF being the strongest univariate predictor (r = 0.92; P < .0001). Conclusions A comprehensive and repeatable non-contrast mpMRI protocol was developed that, as a single, non-invasive tool, allows functional and structural assessment of DKD, which has the potential to provide valuable insights into underlying pathophysiology, disease progression and analysis of efficacy/mode of action of therapeutic interventions in DKD.
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| 11. |
- Modi, G. K., et al.
(författare)
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Nonmedical Factors and Health-Related Quality of Life in CKD in India
- 2020
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Ingår i: Clinical Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1555-9041 .- 1555-905X. ; 15:2, s. 191-199
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectivesPatient-reported outcomes have gained prominence in the management of chronic noncommunicable diseases. Measurement of health-related quality of life is being increasingly incorporated into medical decision making and health care delivery processes.Design, setting, participants, & measurementsThe Indian Chronic Kidney Disease Study is a prospective cohort of participants with mild to moderate CKD. Baseline health-related quality of life scores, determined by the standardized Kidney Disease Quality of Life 36 item instrument, are presented for the inception cohort (n=2919). Scores are presented on five subscales: mental component summary, physical component summary, burden, effect of kidney disease, and symptom and problems; each is scored 0?100. The associations of socioeconomic and clinical parameters with the five subscale scores and lower quality of life (defined as subscale score <1 SD of the sample mean) were examined. The main socioeconomic factors studied were sex, education, occupation, and income. The key medical factors studied were age, eGFR, diabetes, hypertension, and albuminuria.ResultsThe mean (SD) subscale scores were physical component summary score, 43?9; mental component summary score, 48?10; burden, 61?33; effects, 87?13; and symptoms, 90?20. Among the socioeconomic variables, women, lower education, and lower income were negatively associated with reduced scores across all subscales. For instance, the respective ?-coefficients (SD) for association with the physical component summary subscale were ?2.6 (?3.4 to ?1.8), ?1.5 (?2.2 to ?0.7), and ?1.6 (?2.7 to ?0.5). Medical factors had inconsistent or no association with subscale scores. The quality of life scores also displayed regional variations.ConclusionsIn this first of its kind analysis from India, predominantly socioeconomic factors were associated with quality of life scores in patients with CKD.
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| 12. |
- Muche, M., et al.
(författare)
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Low prevalence of occult hepatitis B virus infection in chronic haemodialysis and kidney transplant patients
- 2019
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Ingår i: Liver International. - : Wiley. - 1478-3223. ; 39:2, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- Background Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver in HBsAg-negative patients. We investigated the prevalence of OBI in large chronic haemodialysis (CHD) and kidney transplant recipients (KTxR) cohorts, including determination of HBV DNA in peripheral blood mononuclear cells (PBMCs). Methods HBV DNA was determined in both serum and PBMCs in 417 CHD patients, 417 KTxR, 20 HBsAg-positive non-CHD non-KTx patients (positive controls) and 40 HBsAg-negative healthy subjects (negative controls). Results Chronic haemodialysis group: two of 376 patients were HBsAg-positive. The 374 HBsAg-negative patients tested negative for HBV DNA in both serum and PBMCs. KTxR group: 14 of 417 patients were HBsAg-positive. One of 403 HBsAg-negative patients tested positive for HBV DNA in serum but not in PBMCs. Positive controls: six of 20 patients were under antiviral therapy and had negative HBV DNA in both serum and PBMCs. In 11 of 14 remaining patients, HBV DNA was detected in serum and in both serum and PBMCs in 3 patients. Negative controls: All 34 patients were anti-HBc-negative and HBV DNA-negative in both serum and PBMCs. In the long term, the only case of anti-HBc-negative OBI lost anti-HBs 5 years after inclusion in the study and showed HBV reactivation with HBsAg re-seroconversion. Conclusions We found nil prevalence of OBI in CHD patients and a very low prevalence (<1%) in KTxR suggesting that routine screening for HBV DNA is not required in CHD population in our region. However, in KTxR, pretransplant screening with HBV DNA should be considered. Testing for HBV DNA in PBMCs does not seem to be of additional value.
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| 13. |
- Prasad, N., et al.
(författare)
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Prescription Practices in Patients With Mild to Moderate CKD in India
- 2021
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 6:9, s. 2455-2462
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Patients with chronic kidney disease (CKD) require multiple medications. There is no information on prescription patterns or the use of evidence-based therapies for management of CKD from low-middle-income countries. Using baseline data from the Indian CKD (ICKD) cohort, we describe the drug prescription practices in patients with mild to moderate CKD. Methods: The ICKD study is a prospective, observational cohort study of mild to moderate kidney disease across 11 centers in India. We analyzed all the prescriptions captured at enrollment in the ICKD study. Drugs were categorized into 11 different groups. We provide descriptive data on prescription details and evaluate the appropriateness of medication use. Results: Complete prescription data were available in 3966 out of 4056 (97.8%) subjects enrolled in the ICKD database. Most patients had stage 3 CKD, 24.9% had diabetic kidney disease, 87% had hypertension, and 25.5% had moderate to severe proteinuria. Renin-angiotensin-aldosterone system blockers were prescribed in less than half (47.9%) and in 58.8% of patients with proteinuric CKD. Metformin was prescribed in 25.7% of diabetic subjects with CKD. Only 40.4% of patients were taking statins; 31.1% and 2.8% subjects with anemia were receiving iron and erythropoiesis-stimulating agents, respectively. Conclusion: This study highlights the missed opportunities for improving outcomes through appropriate prescriptions of drugs in patients with CKD. There is need for dissemination of evidence-based guidelines and institution of sustainable implementation practices for improving the overall health of patients with CKD. © 2021 International Society of Nephrology
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| 14. |
- Prasad, N., et al.
(författare)
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Renin-angiotensin blocker use is associated with improved cardiovascular mortality in Indian patients with mild-moderate chronic kidney disease-findings from the ICKD study
- 2022
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionAngiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are the antihypertensive drug class of choice in patients with chronic kidney disease (CKD). Head-to-head comparisons of the renal or non-renal outcomes between ACEI/ARB users and nonusers have not been conducted in all population groups. We examined the renal and cardiovascular outcomes in users and nonusers enrolled in the Indian Chronic Kidney Disease (ICKD) Study. MethodsA total of 4,056 patients with mild-moderate CKD were studied. Patients were categorized as ACEI/ARB users or nonusers. Major adverse kidney events [ESKD (end stage kidney disease), >= 50% decline in eGFR and kidney death], all-cause mortality, and cardiovascular mortality were analyzed over a median follow-up period of 2.64 (1.40, 3.89) years between the two groups. ResultsOut of a total of 4,056 patients, 3,487 (87%) were hypertensive. The adjusted sub-hazard ratio (SHR) and 95 % CI for ACEI /ARB users was 0.85 (0.71, 1.02) for MAKE, 0.80 (0.64, 0.99) for a 50% decline in eGFR, and 0.72 (0.58, 0.90) for ESKD. For cardiovascular mortality, ACEI/ARB users were at lower risk (SHR = 0.55, 95% CI: 0.34, 0.88). Diuretic users were at increased risk of all-cause mortality (HR = 1.95, 95% CI: 1.50, 2.53) and cardiovascular mortality (adjusted SHR = 1.73, 95% CI: 1.09, 2.73). There was non-significant association between the use of other antihypertensives and any of the end points. DiscussionACEI/ARB use is associated with slower rate of decline in eGFR in those with CKD stage 1-3. ACEI/ARB users had a significantly lower risk of renal outcomes, and cardiovascular mortality.
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| 15. |
- Schultheiss, U. T., et al.
(författare)
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Thyroid function, renal events and mortality in chronic kidney disease patients: the German Chronic Kidney Disease study
- 2021
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 14:3, s. 959-968
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Tidskriftsartikel (refereegranskat)abstract
- Background. Hypothyroidism and low free triiodothyronine (FT3) syndrome [low FT3 levels with normal thyroid-stimulating hormone (TSH)] have been associated with reduced kidney function cross-sectionally in chronic kidney disease (CKD) patients with severely reduced estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Results on the prospective effects of impaired thyroid function on renal events and mortality for patients with severely reduced eGFR or from population-based cohorts are conflicting. Here we evaluated the association between thyroid and kidney function with eGFR (cross-sectionally) as well as renal events and mortality (prospectively) in a large, prospective cohort of CKD patients with mild to moderately reduced kidney function. Methods. Thyroid markers were measured among CKD patients from the German Chronic Kidney Disease study. Incident renal endpoints (combined ESKD, acute kidney injury and renal death) and all-cause mortality were abstracted from hospital records and death certificates. Time to first event analysis of complete data from baseline to the 4-year follow-up (median follow-up time 4.04years) of 4600 patients was conducted. Multivariable linear regression and Cox proportional hazards models were fitted for single and combined continuous thyroid markers [TSH, free thyroxine (FT4), FT3] and thyroid status. Results. Cross-sectionally, the presence of low-FT3 syndrome showed a significant inverse association with eGFR and continuous FT3 levels alone showed a significant positive association with eGFR; in combination with FT4 and TSH, FT3 levels also showed a positive association and FT4 levels showed a negative association with eGFR. Prospectively, higher FT4 and lower FT3 levels were significantly associated with a higher risk of all-cause mortality (N-events=297). Per picomole per litre higher FT3 levels the risk of reaching the composite renal endpoint was 0.73-fold lower (95% confidence interval 0.65-0.82; N-events=615). Compared with euthyroid patients, patients with low-FT3 syndrome had a 2.2-fold higher risk and patients with hypothyroidism had a 1.6-fold higher risk of experiencing the composite renal endpoint. Conclusions. Patients with mild to moderate CKD suffering from thyroid function abnormalities are at an increased risk of adverse renal events and all-cause mortality over time.
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| 16. |
- Sekula, P., et al.
(författare)
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Urine 6-Bromotryptophan: Associations with Genetic Variants and Incident End-Stage Kidney Disease
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Higher serum 6-bromotryptophan has been associated with lower risk of chronic kidney disease (CKD) progression, implicating mechanisms beyond renal clearance. We studied genetic determinants of urine 6-bromotryptophan and its association with CKD risk factors and incident end-stage kidney disease (ESKD) in 4,843 participants of the German Chronic Kidney Disease (GCKD) study. 6-bromotryptophan was measured from urine samples using mass spectrometry. Patients with higher levels of urine 6-bromotryptophan had higher baseline estimated glomerular filtration rate (eGFR, p<0.001). A genome-wide association study of urine 6-bromotryptophan identified two significant loci possibly related to its tubular reabsorption, SLC6A19, and its production, ERO1A, which was also associated with serum 6-bromotryptophan in an independent study. The association between urine 6-bromotryptophan and time to ESKD was assessed using Cox regression. There were 216 ESKD events after four years of follow-up. Compared with patients with undetectable levels, higher 6-bromotryptophan levels were associated with lower risk of ESKD in models unadjusted and adjusted for ESKD risk factors other than eGFR (= median level: HR 0.50, 95% CI 0.34 to 0.74). Upon adjustment for baseline eGFR, this association became attenuated, suggesting that urine 6-bromotryptophan may represent a correlated marker of kidney health.
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| 17. |
- Streichart, Lillian, 1983, et al.
(författare)
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Tocilizumab in chronic active antibody-mediated rejection: rationale and protocol of an in-progress randomized controlled open-label multi-center trial (INTERCEPT study)
- 2024
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Ingår i: TRIALS. - : BioMed Central (BMC). - 1745-6215. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR. However, it has not been systematically investigated so far underscoring the need for randomized controlled studies in this area.MethodsThe INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05.The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection.MethodsThe INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05.The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection.DiscussionNo effective treatment exists for caAMR at present. Based on the hypothesis that inhibition of IL-6 receptor by tocilizumab will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR, therewith slowing the decline in graft function in the long-term.
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| 18. |
- Söfteland, John M., 1977, et al.
(författare)
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Longevity of anti-spike and anti-nucleocapsid antibodies after COVID-19 in solid organ transplant recipients compared to immunocompetent controls.
- 2022
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Ingår i: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. - : Elsevier BV. - 1600-6143. ; 22:4, s. 1245-1252
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Tidskriftsartikel (refereegranskat)abstract
- Solid organ transplant recipients (SOTRs) are on lifelong immunosuppression, which may interfere with adaptive immunity to COVID-19. The data on dynamics and duration of antibody response in SOTRs are limited. This longitudinal study examined the longevity of both anti-spike (S)- and anti-nucleocapsid (N)-specific IgG-antibodies after COVID-19 in SOTRs compared to matched immunocompetent persons. SOTRs (n=65) were matched with controls (n=65) for COVID-19 disease severity, age, and sex in order of priority. Serum-IgG-antibodies against N- and S-antigens of SARS-CoV-2 were analyzed. At 1 and 9 months after COVID-19, anti-S-IgG detectability decreased from 91% to 82% in SOTRs versus 100% to 95% in controls, whereas the anti-N-IgG decreased from 63% to 29% in SOTRs versus 89% to 46% in controls. A matched paired analysis showed SOTRs having significantly lower levels of anti-N-IgG at all time points (1-month P=0.007, 3-months P<0.001, 6-months P=0.019 and 9-months P=0.021) but not anti-S-IgG at any time points. A mixed-model analysis confirmed these findings except for anti-S-IgG at one month (p=0.005) and identified severity score as the most important predictor of antibody response. SOTRs mount comparable S-specific, but not N-specific, antibody responses to SARS-CoV-2 infection compared to immunocompetent controls.
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| 19. |
- Winitzki, D., et al.
(författare)
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Educational Attainment Is Associated With Kidney and Cardiovascular Outcomes in the German CKD (GCKD) Cohort
- 2022
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 7:5, s. 1004-1015
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Prospective data on impact of educational attainment on prognosis in patients with chronic kidney disease (CKD) are scarce. We investigated the association between educational attainment and all-cause mortality, major adverse cardiovascular (CV) events (MACEs), kidney failure requiring dialysis, and CKD etiology. Methods: Participants (N = 5095, aged 18–74 years) of the ongoing multicenter German Chronic Kidney Disease (GCKD) cohort, enrolled on the basis of an estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min (stages G3, A1–A3) or overt proteinuria (stages G1–G2, A3), were divided into 3 categories according to their educational attainment and were followed for 6.5 years. Results: Participants with low educational attainment (vs. high) had a higher risk for mortality (hazard ratio [HR] 1.48, 95% CI: 1.16–1.90), MACE (HR 1.37, 95% CI: 1.02–1.83), and kidney failure (HR 1.54, 95% CI: 1.15–2.05). Mediators between low educational attainment and mortality were smoking, CV disease (CVD) at baseline, low income, higher body mass index, and higher serum levels of CRP, high-density lipoprotein cholesterol, uric acid, NGAL, BAP, NT-proBNP, OPN, H-FABP, and urea. Low educational attainment was positively associated with diabetic nephropathy (odds ratio [OR] 1.65, 95% CI: 1.36–2.0) and CKD subsequent to acute kidney injury (OR 1.56, 95% CI: 1.03–2.35), but negatively associated with IgA nephropathy (OR 0.68, 95% CI: 0.52–0.90). Conclusion: Low educational attainment is associated with adverse outcomes and CKD etiology. Lifestyle habits and biomarkers mediate associations between low educational attainment and mortality. Recognition of the role of educational attainment and the associated health-relevant risk factors is important to optimize the care of patients with CKD and improve prognosis. © 2022 International Society of Nephrology
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