Changes in Albuminuria But Not GFR are Associated with Early Changes in Kidney Structure in Type 2 Diabetes.
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ABSTRACT:
SUBMITTER: Looker HC
PROVIDER: S-EPMC6551789 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
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Project description:Higher levels of albuminuria associate with increased risk for adverse outcomes independent of estimated GFR (eGFR), but whether albuminuria also associates with concurrent complications specific to chronic kidney disease (CKD) is unknown. Here, we assessed the association of spot albumin-to-creatinine ratio with anemia, acidosis, hyperphosphatemia, hypoalbuminemia, hyperparathyroidism, and hypertension among 30,528 adult participants in NHANES 1988-1994 and 1999-2006. After multivariable adjustment including eGFR, higher albumin-to-creatinine ratios associated with anemia, acidosis, hypoalbuminemia, hyperparathyroidism, and hypertension but only weakly associated with acidosis and anemia. Furthermore, the associations between albumin-to-creatinine ratio and both anemia and acidosis were not consistent across eGFR strata. Higher albumin-to-creatinine ratio levels did not associate with hyperphosphatemia. Lower eGFR associated with higher prevalence ratios for all complications, and these associations were stronger than those observed for the albumin-to-creatinine ratio; after multivariable adjustment, however, the associations between eGFR and both hypoalbuminemia and hypertension were NS. In conclusion, albuminuria and eGFR differentially associate with complications of CKD.
| S-EPMC3279937 | biostudies-literature
Project description:BACKGROUND:Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain. STUDY DESIGN:Meta-analysis of cohort studies. SETTING & POPULATION:8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts. SELECTION CRITERIA FOR STUDIES:Cohorts participating in the CKD Prognosis Consortium. PREDICTORS:Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions. OUTCOME:Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results. RESULTS:During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension. LIMITATIONS:AKI identified by diagnostic code. CONCLUSIONS:Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.
| S-EPMC4594211 | biostudies-literature
Project description:Estimation of GFR from serum concentrations of creatinine and cystatin C has been refined using cross-sectional data from large numbers of people. However, the ability of the improved estimating equations to identify changes in GFR within individuals over time has not been rigorously evaluated, particularly within the normal range of GFR. In cross-sectional and longitudinal analyses of 1441 participants in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study with type 1 diabetes, we compared GFR estimated from creatinine (eGFR(Cr)), cystatin C (eGFR(Cys)), or both (eGFR(Cr+Cys)) with iothalamate GFR (iGFR), including changes in each over time. Mean (SD) iGFR was 122.7 (21.0) ml/min per 1.73 m(2). In cross-sectional analyses, eGFR(Cr+Cys) estimated iGFR with the highest correlation (r=0.48 versus 0.39-0.42), precision, and accuracy. In longitudinal analyses, change in eGFR(Cr+Cys) best estimated change in iGFR; however, differences between estimates were small, and no estimate accurately classified change in iGFR. Over a median 23 years of follow-up, mean rate of change in eGFR was similar across estimates of eGFR(Cr), eGFR(Cys), and eGFR(Cr+Cys) (-1.37, -1.11, and -1.29 ml/min per 1.73 m(2) per year, respectively). Associations of BP and hemoglobin A1c with change in eGFR were strongest for eGFR(Cys) and eGFR(Cr+Cys). Together, these results suggest that the addition of cystatin C to creatinine to estimate GFR may improve identification of the causes and consequences of GFR loss in type 1 diabetes, but may not meaningfully improve the tracking of GFR in clinical care.
| S-EPMC3968500 | biostudies-literature
Project description:ObjectivesNeutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid binding protein (L-FABP) are emerging as excellent biomarkers in the urine and plasma for the early prediction of acute and chronic kidney injury. The aims of this prospective study were to determine the role of albuminuria, and that of serum and urine levels of NGAL and L-FABP as predictors of a decline in the glomerular filtration rate (GFR) in patients with type 2 diabetes.MethodsA longitudinal cohort study with one hundred forty type 2 diabetic patients was conducted. Serum and urine levels of NGAL and L-FABP, and the urine albumin excretion rate were determined. The correlation between the kidney injury biomarkers and rate of GFR decline was analyzed.ResultsThe eGFR of study subjects decreased significantly as the study progressed (86.4±31.1 vs. 74.4±27.3 ml/min/1.73 m(2), P<0.001), and the urine albumin excretion rate increased significantly (264.9±1060.3 vs. 557.7±2092.5 mg/day, P = 0.009). The baseline urine albumin excretion rate and serum L-FABP level were significantly correlated with baseline eGFR (P<0.05). The results of regression analysis for the correlations between the rate of eGFR change and the baseline levels of NGAL and L-FABP, and the urine albumin excretion rate showed that only the urine albumin excretion rate was significantly correlated with the rate of eGFR change (standardized coefficients: -0.378; t: -4.298; P<0.001).ConclusionsTubular markers, such as NGAL and L-FABP, may not be predictive factors associated with GFR decline in type 2 diabetic patients.
| S-EPMC3551928 | biostudies-literature
Project description:Rationale & objectiveChronic kidney disease (CKD) is associated with impaired physical performance. However, the association between albuminuria, a marker of vascular endothelial dysfunction, and physical performance has not been fully characterized. We hypothesized that estimated glomerular filtration rate (eGFR) and albuminuria would be independently associated with physical performance.Study designCross-sectional analysis.Setting & participantsA total of 571 adults with and without CKD.PredictorsCreatinine-based eGFR (eGFRCr) and cystatin C-based eGFR (eGFRCysC) and urine albumin to creatinine ratio (UACR).OutcomeShort Physical Performance Battery (SPPB).Analytical approachUnivariate and multivariable logistic regression models were used to examine associations of eGFR and UACR with impaired physical performance.ResultsOf the 571 participants (mean age, 69.3 years), 157 (27.5%) had eGFRCr (mL/min/1.73m2) <30, 276 (48.3%) had eGFRCr 30-<60, and 138 (24.2%) had eGFRCr ≥60; 303 (55.3%) participants had eGFRcysC <30, 141 (25.7%) had eGFRcysC 30-<60, and 104 (19.0%) had eGFRcysC ≥60. Impaired physical performance was observed in 222 (38.9%) participants. Separate univariate analyses showed that lower eGFRCr, lower eGFRCysC, and higher UACR were associated with higher odds of impaired physical performance. In the adjusted model with eGFRCr or eGFRCysC, UACR, and covariates, UACR retained a statistically significant association with impaired physical performance (adjusted odds ratio [OR], 2.04; 95% confidence interval [CI], 1.21-3.47 for UACR from 30-300 mg/g vs <30 mg/g and adjusted OR, 1.93; 95% CI, 1.01-3.69 for UACR >300 mg/g vs <30 mg/g), but eGFRCr and eGFRCysC did not.LimitationsCross-sectional analysis, estimated rather than measured GFR.ConclusionsOnly UACR was associated with worse physical performance in the fully adjusted model, suggesting that vascular endothelial function and inflammation may be important mechanisms of decreased physical function. Similar results were found using eGFRCr or eGFRCysC, suggesting that confounding based on muscle mass does not explain the lack of an association between eGFRCr and physical performance.
| S-EPMC9523089 | biostudies-literature
Project description:BackgroundRapid glomerular filtration rate (GFR) decline (>3 mL/min/1.73 m(2)) is an increasingly recognized high-risk diabetic nephropathy (DN) phenotype in Type 1 diabetes. Rapid GFR decline is a recognized predictor of impaired GFR (<60 mL/min/1.73 m(2)). However, the association between rapid GFR decline and renal hyperfiltration is not well described in Type 1 diabetes. We hypothesized that renal hyperfiltration (estimated glomerular filtration rate, eGFR ≥ 120 mL/min/1.73 m(2)) would predict rapid GFR decline over 6 years and that rapid GFR decline would predict impaired GFR at 6 years in adults with Type 1 diabetes.MethodsGFR was calculated by chronic kidney disease epidemiology (CKD-EPI) creatinine in 646 adults with Type 1 diabetes in the coronary artery calcification in Type 1 diabetes study. Logistic multivariable models were employed to investigate the relationships between renal hyperfiltration and rapid GFR decline, and rapid GFR decline and incident impaired GFR over 6 years.ResultsRenal hyperfiltration predicted greater odds of rapid GFR decline over 6 years [odds ratio (OR): 5.00, 95% confidence interval (CI): 3.03-8.25, P < 0.0001] adjusting for hemoglobin A1c (HbA1c), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), sex, duration, log of albumin/creatinine ratio and estimated insulin sensitivity. Furthermore, rapid GFR decline predicted greater odds of incident impaired eGFR (OR: 15.99, 95% CI 2.34-114.37, P = 0.006) in a similarly adjusted model. Sensitivity analyses with GFR calculated by CKD-EPI combined creatinine and cystatin C, and renal hyperfiltration defined as ≥135 mL/min/1.73 m(2) yielded similar results.ConclusionsIn adults with Type 1 diabetes, rapid GFR decline over 6 years was associated with baseline renal hyperfiltration and incident GFR impairment. These observations may suggest an intermediate and predictive role of rapid GFR decline in the progression of DN.
| S-EPMC4838003 | biostudies-literature
Project description:Background and objectivesWhether combining changes in eGFR and urine albumin-to-creatinine ratio (UACR) is more strongly associated with outcomes compared with either change alone is unknown.Design, setting, participants, & measurementsWe analyzed 8766 patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation Observational (ADVANCE-ON) study. Changes in eGFR and UACR (baseline to 2 years) were defined as ?40% decrease, minor change, and ?40% increase. The primary outcome was the composite of major macrovascular (nonfatal or fatal myocardial infarction, nonfatal or fatal stroke, or cardiovascular death), major kidney events (requirement for kidney replacement therapy or kidney death), and all-cause mortality.ResultsOver a median of 7.7 years of follow-up, 2191 primary outcomes were recorded. Strong linear associations between eGFR and UACR changes and subsequent risk of the outcome were observed. For eGFR, the hazard ratios were 1.58 (95% confidence interval [95% CI], 1.27 to 1.95) for a decrease ?40% and 0.82 for an increase ?40% (95% CI, 0.64 to 1.04) compared with minor change. For UACR, the hazard ratios were 0.96 (95% CI, 0.85 to 1.07) for a decrease ?40% and 1.32 (95% CI, 1.19 to 1.46) for ?40% increase compared with minor change. Compared with dual minor changes, both an eGFR decrease ?40% and a UACR increase ?40% had 2.31 (95% CI, 1.67 to 3.18) times the risk of the outcome, with evidence of interaction between the two markers.ConclusionsClinically meaningful decreases in eGFR and increases in UACR over 2 years, independently and in combination, were significantly associated with higher risk of major clinical outcomes.
| S-EPMC6556720 | biostudies-literature
Project description:IntroductionMarkers of oxidative stress increase with age and are prevalent with chronic kidney disease. However, the role of oxidative stress markers as predictors for kidney function decline in the general population is unclear.MethodsWe investigated whether a baseline urinary excretion of oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG]) and oxidative RNA damage (8-oxo-7,8-dihydroguanosine [8-oxoGuo]) was associated with the age-related glomerular filtration rate (GFR) decline or incident low-grade albuminuria during a median of 5.6 years of follow-up. In the Renal Iohexol Clearance Survey in the Sixth Tromsø Study, we measured GFR using iohexol clearance in 1591 participants without renal disease, diabetes, or cardiovascular disease. Low-grade albuminuria was defined as an albumin-creatinine ratio >1.13 mg/mmol.ResultsThe mean (SD) annual GFR change was -0.84 (2.00) ml/min per 1.73 m2 per year. In linear mixed models, urinary 8-oxodG and 8-oxoGuo levels were not associated with the GFR change rate. In a multivariable adjusted logistic regression model, a baseline urinary 8-oxoGuo in the highest quartile was associated with an increased risk of low-grade albuminuria at follow-up (odds ratio: 2.64; 95% confidence interval: 1.50-4.65). When the highest quartile of urinary 8-oxoGuo was added to the baseline model, the area under the receiver operating characteristics curve for predicting low-grade albuminuria at follow-up improved from 0.67 to 0.71 (P = 0.002).ConclusionOxidative stress measured as urinary 8-oxoGuo excretion was independently associated with incident low-grade albuminuria, but neither 8-oxoGuo nor 8-oxodG predicted an accelerated age-related GFR decline in a cohort representative of the middle-aged general population during almost 6 years of follow-up.
| S-EPMC5976868 | biostudies-literature
Project description:BackgroundDiabetic nephropathy is a growing clinical problem, and the cause for >40% of incident ESRD cases. Unfortunately, few modifiable risk factors are known. The objective is to examine if albuminuria and history of diabetic nephropathy (DN) in a sibling are associated with early DN progression or mortality.MethodsIn this longitudinal study of adults >18 yrs with diabetes monitored for up to 9 yrs (mean 4.6?±?1.7 yrs), 435 subjects at high risk (DN family history) and 400 at low risk (diabetes >10 yrs, normoalbuminuria, no DN family history) for DN progression were evaluated for rate of eGFR change using the linear mixed effects model and progression to ESRD. All-cause mortality was evaluated by Kaplan-Meier analyses while controlling for baseline covariates in a Cox proportional hazards model. Covariates included baseline eGFR, age, gender, race, diabetes duration, blood pressure, hemoglobin A1c and urine albumin:creatinine ratio. Propensity score matching was used to identify high and low risk group pairs with balanced covariates. Sensitivity analyses were employed to test for residual confounding.ResultsMean baseline eGFR was 74 ml/min/1.73 m2 (86% of cohort >60 ml/min/1.73 m2). Thirty high risk and no low risk subjects developed ESRD. eGFR decline was significantly greater in high compared to low risk subjects. After controlling for confounders, change in eGFR remained significantly different between groups, suggesting that DN family history independently regulates GFR progression. Mortality was also significantly greater in high versus low risk subjects, but after controlling for baseline covariates, no significant difference was observed between groups, indicating that factors other than DN family history more strongly affect mortality. Analyses of the matched pairs confirmed change in eGFR and mortality findings. Sensitivity analyses demonstrated that the eGFR results were not due to residual confounding by unmeasured covariates of a moderate effect size in the propensity matching.ConclusionsDiabetic subjects with albuminuria and family history of DN are vulnerable for early GFR decline, whereas subjects with diabetes for longer than 10 years, normoalbuminuria and negative family history, experience slower eGFR decline, and are extremely unlikely to require dialysis. Although we would not recommend that patients with low risk characteristics be neglected, scarce resources would be more sensibly devoted to vulnerable patients, such as the high risk cases in our study, and preferably prior to the onset of albuminuria or GFR decline.
| S-EPMC3703258 | biostudies-literature
Project description:BACKGROUND:Children with type 1 diabetes (T1D) are at higher risk of early adult-onset cardiovascular disease. We assessed cardiovascular structure and function in adolescents with T1D compared with healthy controls and the relationships between peripheral vascular function and myocardial parameters. METHODS AND RESULTS:199 T1D [14.4 ± 1.6 years, diabetes duration 6.2 (2.0-12.8) years] and 178 controls (14.4 ± 2.1 years) completed endothelial function by flow mediated vasodilatation (FMD), arterial stiffness using pulse wave velocity (PWV) along with M-mode, pulse wave and tissue Doppler, and myocardial deformation echocardiographic imaging. Systolic (113 ± 10 vs. 110 ± 9 mmHg; p = 0.0005) and diastolic (62 ± 7 vs. 58 ± 7 mmHg; p < 0.0001) blood pressures, carotid femoral PWV and endothelial dysfunction measurements were increased in T1D compared with controls. Systolic and diastolic left ventricular dimensions and function by M-mode and pulse wave Doppler assessment were not significantly different. Mitral valve lateral e' (17.6 ± 2.6 vs. 18.6 ± 2.6 cm/s; p < 0.001) and a' (5.4 ± 1.1 vs. 5.9 ± 1.1 cm/s; p < 0.001) myocardial velocities were decreased and E/e' (7.3 ± 1.2 vs. 6.7 ± 1.3; p = 0.0003) increased in T1D. Left ventricular mid circumferential strain (-20.4 ± 2.3 vs. -19.5 ± 1.7 %; p < 0.001) was higher, whereas global longitudinal strain was lower (-19.0 ± 1.9 vs. -19.8 ± 1.5 % p < 0.001) in T1D. CONCLUSIONS:Adolescents with T1D exhibit early changes in blood pressure, peripheral vascular function and left ventricular myocardial deformation indices with a shift from longitudinal to circumferential shortening. Longitudinal follow-up of these changes in ongoing prospective trials may allow detection of those most at risk for cardiovascular abnormalities including hypertension that could preferentially benefit from early therapeutic interventions.
| S-EPMC4754808 | biostudies-literature