Glucose and Blood Pressure-Dependent Pathways-The Progression of Diabetic Kidney Disease.
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ABSTRACT:
SUBMITTER: Patel DM
PROVIDER: S-EPMC7139394 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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Glucose and Blood Pressure-Dependent Pathways-The Progression of Diabetic Kidney Disease.
Patel Devang M DM Bose Madhura M Cooper Mark E ME
International journal of molecular sciences 20200323 6
The major clinical associations with the progression of diabetic kidney disease (DKD) are glycemic control and systemic hypertension. Recent studies have continued to emphasize vasoactive hormone pathways including aldosterone and endothelin which suggest a key role for vasoconstrictor pathways in promoting renal damage in diabetes. The role of glucose per se remains difficult to define in DKD but appears to involve key intermediates including reactive oxygen species (ROS) and dicarbonyls such a ...[more]
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Project description:AimsWe determined the influence of age on the effects of glucose and blood pressure control on diabetic kidney disease in patients with type 2 diabetes.MethodsA total of 721 patients with type 2 diabetes, aged 41-85 years and with an estimated glomerular filtration rate (eGFR) ≥30 mL/ [min · 1.73 m(2)], were enrolled in this study between August 2001 and December 2002. All participants were followed up at our clinics until December 31, 2010. Primary outcomes were the development of end-stage renal disease (ESRD) and all-cause mortality. Secondary outcomes were the development of clinical albuminuria and a severe decline in eGFR.ResultsDuring the follow-up period (median: 8.3 years), 27 (3.7%) patients developed ESRD, 130 (18.0%) patients died without developing ESRD, and 16 (2.2%) patients died after developing ESRD. Mortality rate increased with age, but the incidence rate of ESRD did not. Poor glucose and blood pressure control was associated with the development of clinical albuminuria and with a severe decline in eGFR in younger patients with diabetes, but not in older patients. The development of severe decline in eGFR and ESRD was significantly lower in the middle tertile of blood pressure (i.e., SBP of 128-141 mm Hg) in older patients.ConclusionsAdequate glucose and blood pressure control did not reduce the risk of ESRD; however, it may have delayed the onset of clinical albuminuria as well as eGFR decline in younger patients with type 2 diabetes.
| S-EPMC4124170 | biostudies-literature
Project description:AimThe renoprotective effect of sodium-glucose cotransporter 2 inhibitors is thought to be due, at least in part, to a decrease in blood pressure. The aim of this study was to determine the renal effects of these inhibitors in low blood pressure patients and the dependence of such effect on blood pressure management status.MethodsThe subjects of this retrospective study were 740 patients with type 2 diabetes mellitus and chronic kidney disease who had been managed at the clinical facilities of the Kanagawa Physicians Association. Data on blood pressure management status and urinary albumin-creatinine ratio were analyzed before and after treatment.ResultsChanges in the logarithmic value of urinary albumin-creatinine ratio in 327 patients with blood pressure < 130/80 mmHg at the initiation of treatment and in 413 patients with BP above 130/80 mmHg were -0.13 ± 1.05 and -0.24 ± 0.97, respectively. However, there was no significant difference between the two groups by analysis of covariance models after adjustment of the logarithmic value of urinary albumin-creatinine ratio at initiation of treatment. Changes in the logarithmic value of urinary albumin-creatinine ratio in patients with mean blood pressure of <102 mmHg (n = 537) and those with ≥102 mmHg (n = 203) at the time of the survey were -0.25 ± 1.02 and -0.03 ± 0.97, respectively, and the difference was significant in analysis of covariance models even after adjustment for the logarithmic value of urinary albumin-creatinine ratio at initiation of treatment (p < 0.001).ConclusionOur results confirmed that blood pressure management status after treatment with SGLT2 inhibitors influences the extent of change in urinary albumin-creatinine ratio. Stricter blood pressure management is needed to allow the renoprotective effects of sodium-glucose cotransporter 2 inhibitors.
| S-EPMC6875192 | biostudies-literature
Project description:ObjectiveIn patients with type 2 diabetes and diabetic kidney disease (DKD), explore the relationship between estimated glomerular filtration rate decline (eGFR-d) and simultaneously assessed vascular risk markers including office, ambulatory or central blood pressure, pulse pressure, carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (IMT) and renal resistive indexes (RRI).Research design and methodsAt baseline, vascular risk markers were measured in addition to the routine clinical workup. The eGFR-d was based on 2000-2019 creatinine values. Parameters were compared by eGFR-d quartiles. Regression models of eGFR-d and vascular markers were assessed.ResultsIn total, 135 patients were included. Mean age was 63.8 ± 10.8y, baseline eGFR 60.2 ± 26.4 ml/min/1.73 m2 and urine albumin-creatinine ratio (ACR) 49 ± 108 mg/mmol. Mean eGFR-d was based on 43 ± 39 creatinine values within a time span of 7.0 ± 1.9y. The average yearly eGFR decline was -1.8 ± 3.0 ml/min/1.73 m2 ranging from -5.8 ± 2.3 in the first quartile to +1.4 ± 1.7 in the fourth quartile. Mean 24 h systolic (SBP) and diastolic (DBP) blood pressure were 126 ± 17 and 74 ± 9 mmHg. Mean PWV was 11.8 ± 2.8 m/s, RRI 0.76 ± 0.07 and IMT 0.77 ± 0.21 mm. SBP and pulse pressure correlated with eGFR-d but not DBP. 24 h SBP stood out as a stronger predictor of eGFR-d than office or central SBP. PWV and RRI correlated with eGFR decline in univariate, but not multivariate regression models including 24 SBP and ACR.ConclusionsIn this study, eGFR decline was highly variable in patients with type 2 diabetes and DKD. Twenty-four hour SBP provided an added value to the routine measurement of ACR in predicting eGFR decline, whereas PWV and RRI did not.
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Project description:AimsArterial stiffness increases with both advancing age and chronic kidney disease (CKD) and may contribute to kidney function decline, but evidence is inconsistent. We hypothesized that greater baseline arterial stiffness (assessed as pulse pressure (PP) and carotid-femoral pulse-wave velocity CFPWV)) was independently associated with kidney disease progression over the follow-up period (3.8 years) in the Systolic Blood Pressure Intervention Trial (SPRINT).Materials and methods8,815 SPRINT participants were included in the analysis of PP. 592 adults who participated in a SPRINT ancillary study that measured CFPWV were included in subgroup analyses. Cox proportional hazards analysis was used to examine the association between PP and time to kidney disease progression endpoints: (A) incident estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 in non-CKD participants at baseline; (B) 50% decline in eGFR, initiation of dialysis, or transplant in those with baseline CKD. Mixed model analyses examined the association of baseline PP/CFPWV with follow-up eGFR.Results and conclusionMean ± SD age was 68 ± 10 years, baseline PP was 62 ± 14 mmHg, and CFPWV was 10.8 ± 2.7 m/s. In the fully adjusted model, PP ? median was associated with an increased hazard of kidney disease progression endpoints (HR: 1.93 (1.43 - 2.61)). The association remained significant in individuals without (2.05 (1.47 - 2.87)) but not with baseline CKD (1.28 (0.55 - 2.65)). In fully adjusted models, higher baseline PP associated with eGFR decline (p < 0.0001 (all, CKD, non-CKD)), but baseline CFPWV did not. Among older adults at high risk for cardiovascular events, baseline PP was associated with kidney disease progression.
| S-EPMC7814777 | biostudies-literature
Project description:ImportanceOptimal blood pressure (BP) management in children with chronic kidney disease (CKD) slows progression to end-stage renal disease. Studies often base progression risk on a single baseline BP measurement, which may underestimate risk.ObjectiveTo determine whether time-varying BP measurements are associated with a higher risk of progression of CKD than baseline BP measurements.Design, setting, and participantsThe ongoing longitudinal, prospective cohort study Chronic Kidney Disease in Children (CKID) recruited children from January 19, 2005, through March 19, 2014, from pediatric nephrology centers across North America, with data collected at annual study visits. Participants included children aged 1 to 16 years with a diagnosis of CKD and a glomerular filtration rate (GFR) of 30 to 90 mL/min/1.73 m2. Data were analyzed from February 11, 2005, through February 13, 2018.ExposuresOffice BP measurement classified as less than 50th percentile, 50th to less than 90th percentile, or at least 90th percentile. Blood pressure categories were treated as time fixed (baseline) or time varying (updated at each visit) in models.Main outcomes and measuresA composite renal outcome (50% GFR reduction from baseline, estimated GFR less than 15 mL/min/1.73 m2, or dialysis or transplant). Pooled logistic models using inverse probability weighting estimated the hazard odds ratio (HOR) of the composite outcome associated with each BP category stratified by CKD diagnosis.ResultsA total of 844 children (524 [62.1%] male; median age, 11 [interquartile range, 8-15] years; 151 [17.9%] black; 580 [68.7%] with nonglomerular CKD; and 264 [31.3%] with glomerular CKD) with complete baseline data and median follow-up of 4 (interquartile range, 2-6) years were included. One hundred ninety-six participants with nonglomerular diagnoses (33.8%) and 99 with glomerular diagnoses (37.5%) reached the composite outcome. Baseline systolic BP in at least the 90th percentile was associated with a higher risk of the composite outcome (HOR for nonglomerular disease, 1.58 [95% CI, 1.07-2.32]; HOR for glomerular disease, 2.85 [95% CI, 1.64-4.94]) compared with baseline systolic BP in less than the 50th percentile. Time-fixed estimates were substantially lower compared with time-varying systolic BP percentile categories (HOR among those with nonglomerular CKD, 3.75 [95% CI, 2.53-5.57]; HOR among those with glomerular diagnoses, 5.96 [95% CI, 3.37-10.54]) comparing those at or above the 90th percentile vs below the 50th percentile. Adjusted models (adjusted for proteinuria and use of antihypertensives) attenuated the risk in nonglomerular CKD (adjusted HOR for baseline measurement, 1.52 [95% CI, 0.98-2.36]; adjusted HOR for time-varying measurement, 2.25 [95% CI, 1.36-3.72]) and in glomerular CKD (adjusted HOR for baseline, 0.97 [95% CI, 0.39-2.36]; adjusted HOR for time-varying measurement, 1.41 [95% CI, 0.65-3.03]). Similar results were observed for diastolic BP.Conclusions and relevanceAmong children with nonglomerular CKD included in this study, elevated time-varying BP measurements were associated with a greater risk of CKD progression compared with baseline BP measurement. This finding suggests that previous studies using only baseline BP likely underestimated the association between BP and CKD progression.
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Project description:Diabetic kidney disease (DKD) progresses at different rates among patients with type 2 diabetes mellitus (T2D). Early identification of patients with a higher risk of DKD progression is essential to improve prognosis. Epigenetic modifications, particularly DNA methylation, have been independently implicated in T2D and chronic kidney disease. The current study aimed to determine changes in blood DNA methylation that reflects and predicts DKD progression. C57BL/6 mice were fed a high-fat diet (HFD) from weaning and subclassified into two groups, HFD-1 and HFD-2, according to urinary kidney injury marker KIM-1/creatinine ratios (low vs. high) and histological abnormalities (mild-moderate vs. advanced). DNA methylation profiles were determined by reduced representative bisulfide sequencing (RRBS). Our results confirmed early and established DKD at week 9 and week 32, respectively. At week 32, advanced kidney injury was associated with dysregulation of methylation and demethylation enzymes in the kidney. Blood RRBS revealed 579 and 203 differentially methylated sites (DMS) between HFD-1 and HFD-2 animals at week 32 and week 9, respectively, among which 11 were common. The DMS in blood and kidney at week 32 were both related to organ development, neurogenesis, cell junction, and Wnt signalling, while the DMS in blood at week 9 suggested a specific enrichment of kidney development processes. In conclusion, our data strongly support the implication of early blood DNA methylation modifications and DKD progression in T2D that could be used to improve the disease's prognostication.
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Project description:The target blood pressure (BP) value is unclear for diabetic kidney disease (DKD). Therefore, we aimed to evaluate the effect of strict BP control or 'on treatment' BP on clinical outcomes in patients with DKD. A post-hoc analysis of the prespecified secondary outcomes of the FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial, a randomized multicenter double-blind phase III trial. Eligible patients were aged ≥ 19 years with DKD. We assigned 341 participants with DKD to BP control strategy (standard-systolic BP [SBP] < 140 mmHg versus strict-SBP < 130 mmHg). The outcome was the occurrence of cardiovascular events and renal events. Separate analyses were performed to compared the risk of outcome according to achieved average BP levels. A total of 341 participants were included in the analysis. Over a median follow-up of 2.8 years, cardiovascular/renal events were observed in 25 (7.3%) participants. Mean (SD) SBPs in the standard and strict BP control group were 140.2 (11.6) and 140.2 (11.9) mmHg, respectively. The strict BP control group did not show significantly reduced risk of cardiovascular/renal events (HR 1.32; 95% CI 0.60-2.92]). In the post-hoc analyses using achieved BP, achieved average SBP of 130-139 mmHg resulted in reduced risk of cardiovascular/renal events (HR 0.15; 95% CI 0.03-0.67) compared to achieved average SBP ≥ 140 mmHg, whereas further reduction in achieved average SBP < 130 mmHg did not impart additional benefits. In patients with DKD, targeting a SBP of less than 130 mmHg, as compared with less than 140 mmHg, did not reduce the rate of a composite of cardiovascular and renal events. Achieved SBP of 130-139 mmHg was associated with a decreased risk for the primary outcome in patients with DKD. ClinicalTirals.gov Identifier: NCT02620306, registered December 3, 2015. ( https://clinicaltrials.gov/study/NCT02620306 ).
| S-EPMC11293031 | biostudies-literature
Project description:Non-dipping nocturnal blood pressure (BP) pattern is a predictor of the future decline of renal function; however, it is unclear whether it is still a risk for chronic kidney disease (CKD) patients with normal BP. To solve this question, a retrospective cohort study was conducted, and 1107 CKD patients who underwent ambulatory blood pressure monitoring (ABPM) were enrolled. We divided patients into 4 groups based on their nocturnal BP dipping pattern (dipper or non-dipper) and average 24-hour BP (hypertension or normotension). The cumulative incidence of composite renal outcomes, including a 40% reduction in eGFR, the induction of renal-replacement therapy, or death from renal causes, was analyzed. Overall, 86.1% of participants were non-dippers and 48.2% of them were normotensive. During the median follow-up period of 4.72 years, the incidence of renal composite outcomes was highest in hypertensive non-dipper patients, and was similar between normotensive dipper and non-dipper patients. Multivariate regression analysis revealed that the 24-hour systolic BP, amount of urinary protein, and hemoglobin values were associated with the incidence of renal outcomes. In conclusion, our ABPM-based analysis revealed that a non-dipping BP pattern with normotension does not predict the future incidence of composite renal outcomes in CKD patients.
| S-EPMC6917780 | biostudies-literature
Project description:Background It is unclear whether short-term blood pressure variability is associated with renal outcomes in patients with chronic kidney disease. Methods and Results This study analyzed data from participants in the C-STRIDE (Chinese Cohort Study of Chronic Kidney Disease) who had chronic kidney disease stages 1 to 4. Short-term blood pressure variability was measured by calculating the weighted SD (w-SD) of systolic blood pressure (SBP). Renal outcomes were defined as dialysis initiation and/or transplantation. Risk factors associated with w-SD of SBP were evaluated by linear regression. Associations of short-term SBP variability with renal outcomes were evaluated by Cox regression. In total, 1421 patients with chronic kidney disease were included in this study (mean age, 49.4±13.6 years; 56.2% men; estimated glomerular filtration rate, 50.5±29.3 mL/min per 1.73 m2; proteinuria, 0.9 [0.3-2.0] g/d). Mean w-SD of SBP was 12.6±4.4 mm Hg. w-SD of SBP was independently associated with older age, 24-hour SBP, blood pressure circadian pattern, and angiotensin II receptor blocker treatment. During a median follow-up of 4.9 years, 237 patients developed renal outcomes (37.01 per 1000 patient-years). The incidence rate increased across the quartiles of w-SD (log-rank P=0.005). w-SD of SBP was associated with an increased risk of renal outcomes, both as a continuous variable (hazard ratio [HR], 1.47; 95% CI, 1.09-1.99) and as a categorical variable (quartile 4 versus quartile 1: HR, 1.60; 95% CI, 1.08-2.36), independent of 24-hour SBP, daytime SBP, and nighttime SBP. Conclusions Short-term SBP was independently associated with the risk of dialysis initiation and/or transplantation in patients with chronic kidney disease.
| S-EPMC7429039 | biostudies-literature
Project description:BackgroundWomen are reported to have a lower incidence of renal replacement therapy, despite a higher prevalence of chronic kidney disease (CKD).AimTo analyze diabetic kidney disease (DKD) progression in men and women.MethodsProspective cohort: n = 261, 35% women, new consecutive nephrology DKD referrals.ResultsWomen smoked less and better complied with the dietary phosphate and sodium restrictions. Despite a less frequent nephrology referral, women had lower baseline albuminuria. Over a 30 ± 10-month follow-up, albuminuria decreased in women and the estimated glomerular filtration rate (eGFR) loss was slower than in men. However, the percentage of rapid progressors was similar in both sexes. The best multivariate model predicting rapid progression in men (area under curve (AUC) = 0.92) and women differed. Albuminuria and fractional excretion of phosphate (FEphosphate) were part of the men multivariable model, but not of women. The AUC for the prediction of rapid progression by albuminuria was higher in men than in women, and the albuminuria cut-off points also differed. In women, there was a higher percentage of rapid progressors who had baseline physiological albuminuria.ConclusionsFemale DKD differs from male DKD: albuminuria was milder and better responsive to therapy, the loss of eGFR was slower and the predictors of rapid progression differed from men: albuminuria was a better predictor in men than in women. Lifestyle factors may contribute to the differences.
| S-EPMC7356286 | biostudies-literature