Association between serum uric acid and renal outcome in patients with biopsy-confirmed diabetic nephropathy.
Ontology highlight
ABSTRACT: Objective
To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN).Methods
A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least 1 year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group: 286.02 ± 46.66 μmol/L (n = 98); Q2 group: 358.23 ± 14.03 μmol/L (n = 99); Q3 group: 405.50 ± 14.59 μmol/L (n = 98) and Q4 group: 499.14 ± 56.97μmol/L (n = 98). Renal outcome was defined by progression to end-stage renal disease (ESRD). Kaplan-Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes.Results
During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%). No significant difference between SUA level and the risk of progression of DN (P = 0.747) was shown in the Kaplan-Meier survival analysis. In multivariable-adjusted model, hazard ratios for developing ESRD were 1.364 (0.621-2.992; P = 0.439), 1.518 (0.768-3.002; P = 0.230) and 1.411 (0.706-2.821; P = 0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 (P = 0.652).Conclusions
No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improving ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.
SUBMITTER: Zou Y
PROVIDER: S-EPMC8558902 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:This study was performed to develop and validate a predictive model for the risk of end-stage renal disease (ESRD) inpatients with diabetic nephropathy (DN) confirmed by renal biopsy. We conducted a retrospective study with 968 patients with T2DM who underwentrenal biopsy for the pathological confirmation of DNat the First Affiliated Hospital of Zhengzhou University from February 2012 to January 2015; the patients were followed until December 2018. The outcome was defined as a fatal or nonfatal ESRD event (peritoneal dialysis or hemodialysis for ESRD, renal transplantation, or death due to chronic renal failure or ESRD). The dataset was randomly split into development (75%) and validation (25%) cohorts. We used stepwise multivariablelogistic regression to identify baseline predictors for model development. The model's performance in the two cohorts, including discrimination and calibration, was evaluated by the C-statistic and the P value of the Hosmer-Lemeshow test. During the 3-year follow-up period, there were 225 outcome events (47.1%) during follow-up. Outcomes occurred in 187 patients (52.2%) in the derivation cohort and 38 patients (31.7%) in the validation cohort. The variables selected in the final multivariable logistic regression after backward selection were pathological grade, Log Urinary Albumin-to-creatinine ratio (Log ACR), cystatin C, estimated glomerular filtration rate (eGFR) and B-type natriuretic peptide (BNP). 4 prediction models were created in a derivation cohort of 478 patients: a clinical model that included cystatin C, eGFR, BNP, Log ACR; a clinical-pathological model and a clinical-medication model, respectively, also contained pathological grade and renin-angiotensin system blocker (RASB) use; and a full model that also contained the pathological grade, RASB use and age. Compared with the clinical model, the clinical-pathological model and the full model had better C statistics (0.865 and 0.866, respectively, vs. 0.864) in the derivation cohort and better C statistics (0.876 and 0.875, respectively, vs. 0.870) in the validation cohort. Among the four models, the clinical-pathological model had the lowest AIC of 332.53 and the best P value of 0.909 of the Hosmer-Lemeshow test. We constructed a nomogram which was a simple calculator to predict the risk ratio of progression to ESRD for patients with DN within 3 years. The clinical-pathological model using routinely available clinical measurements was shown to be accurate and validated method for predicting disease progression in patients with DN. The risk model can be used in clinical practice to improve the quality of risk management and early intervention.
| S-EPMC7020820 | biostudies-literature
Project description:Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.
| S-EPMC10972048 | biostudies-literature
Project description:Background and objectivesThe aim of the study was to examine the associations of uric acid (UA) in blood and urine with subclinical renal damage (SRD) and its progression in a Chinese cohort.Methods1) 2342 participants from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine the relationships between serum and urinary UA and the risk of SRD. 2) A total of 266 participants were recruited from the same cohort in 2013, and followed up in 2017. Longitudinal analysis was used to determine the relationships of serum and urinary UA with progression of SRD, which was defined as urinary albumin-to-creatinine ratio (uACR) progression or estimated glomerular filtration rate (eGFR) decline.ResultsIn cross-sectional analysis, higher levels of uACR were associated with higher levels of serum uric acid (SUA) and urinary uric acid/creatinine ratio (uUA/Cre). Lower eGFR was associated with higher levels of SUA and fractional excretion of uric acid (FEUA) but lower uUA/Cre levels in all subjects. In addition, the multivariate-adjusted odds ratios for SRD compared with non-SRD were 3.574 (2.255-5.664) for uUA/Cre. Increasing uUA/Cre levels were associated with higher risk of SRD. In longitudinal analysis, 4-year changes of uUA/Cre and SUA were significantly associated with eGFR decline.ConclusionsThis study suggested that urinary UA excretion was significantly associated with the risk of SRD in Chinese adults. Furthermore, 4-year changes of serum and urinary UA were associated with SRD progression. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of decreased renal function in otherwise healthy subjects.
| S-EPMC6857911 | biostudies-literature
Project description:Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UE(UA)) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UE(UA), suggesting that SUA decreased as a result of the increase in the UE(UA). The increase in UE(UA) was correlated with an increase in urinary D-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UE(UA) is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and D-glucose. It was observed that the efflux of [(14) C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm D-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [(14) C]UA by oocytes was cis-inhibited by 100 mm D-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UE(UA) could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose.
| S-EPMC4223977 | biostudies-literature
Project description:PurposeTo investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD) using contrast-enhanced ultrasound (CEUS) method.Materials and methods79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA) group and a high SUA group. Contrast-enhanced ultrasound (CEUS) was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis.ResultsNormal controls (NCs) had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P < 0.05). DKD patients with low urinary uric acid (UUA) excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P < 0.05).ConclusionHyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.
| S-EPMC4464846 | biostudies-literature
Project description:Diabetic nephropathy (DN) is one of the major complications of diabetes and contributes significantly towards end-stage renal disease. Previous studies have identified the gene encoding carnosinase (CN-1) as a predisposing factor for DN. Despite this fact, the relationship of the level of serum CN-1 and the progression of DN remains uninvestigated. Thus, the proposed study focused on clarifying the relationship among serum CN-1, indicators of renal function and tissue injury, and the progression of DN. A total of 14 patients with minimal changes disease (MCD) and 37 patients with DN were enrolled in the study. Additionally, 20 healthy volunteers were recruited as control. Further, DN patients were classified according to urinary albumin excretion rate into two groups: DN with microalbuminuria (n = 11) and DN with macroalbuminuria (n = 26). Clinical indicators including urinary protein components, serum carnosine concentration, serum CN-1 concentration and activity, and renal biopsy tissue injury indexes were included for analyzation. The serum CN-1 concentration and activity were observed to be the highest, but the serum carnosine concentration was the lowest in DN macroalbuminuria group. Moreover, within DN group, the concentration of serum CN-1 was positively correlated with uric acid (UA, r = 0.376, p = 0.026) and serum creatinine (SCr, r = 0.399, p = 0.018) and negatively correlated with serum albumin (Alb, r = - 0.348, p = 0.041) and estimated glomerular filtration rate (eGRF, r = - 0.432, p = 0.010). Furthermore, the concentration of serum CN-1 was discovered to be positively correlated with indicators including 24-h urinary protein-creatinine ratio (24 h-U-PRO/CRE, r = 0.528, p = 0.001), urinary albumin-to-creatinine ratio (Alb/CRE, r = 0.671, p = 0.000), urinary transferrin (TRF, r = 0.658, p = 0.000), retinol-binding protein (RBP, r = 0.523, p = 0.001), N-acetyl-glycosaminidase (NAG, r = 0.381, p = 0.024), immunoglobulin G (IgG, r = 0.522, p = 0.001), cystatin C (Cys-C, r = 0.539, p = 0.001), beta-2-microglobulin (β2-MG, r = 0.437, p = 0.009), and alpha-1-macroglobulin (α1-MG, r = 0.480, p = 0.004). Besides, in DN with macroalbuminuria group, serum CN-1 also showed a positive correlation with indicators of fibrosis, oxidative stress, and renal tubular injury. Taken together, our data suggested that the level of CN-1 was increased as clinical DN progressed. Thus, the level of serum CN-1 might be an important character during the occurrence and progression of DN. Our study will contribute significantly to future studies focused on dissecting the underlying mechanism of DN.
| S-EPMC8128792 | biostudies-literature
Project description:Multiterritorial atherosclerosis has dramatically increased annual risk of adverse cardiovascular events than atherosclerotic disease with single-artery affected. Serum uric acid (SUA) is an important predictor of stroke and atherosclerosis; however, which is supported by few direct evidence based on cohort studies. A prospective cohort study including 2644 North Chinese adults aged ≥40 years was performed in 2010-2012 to investigate the association between SUA and multiterritorial vascular stenosis. Hyperuricaemia was defined as SUA levels >6 and >7 mg/dL for males and females, respectively. All participants underwent twice transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS) and peripheral arterial disease (PAD) was determined by ankle-brachial index (ABI) on January 2010 and January 2012 based on regular health check-ups. The cumulative incidence of vascular stenosis was significantly higher in subjects with hyperuricaemia than in those without hyperuricaemia (54.1% vs. 34.7%, P < 0.001). The adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for new on-set vascular stenosis due to hyperuricaemia and a 1-mg/dL change in SUA level were 1.75 (1.32-2.31) and 1.29 (1.21-1.38), respectively. Furthermore, in the gender-stratified analysis, the association between SUA levels and ICAS was statistically significant in males (OR: 2.02; 95% CI: 1.18-3.46), but not females (OR: 0.85, 95% CI: 0.41-1.76, P for interaction: 0.026).
| S-EPMC6652300 | biostudies-literature
Project description:BackgroundWhether there is an association between serum uric acid (SUA) level and risk of mortality in the general population remains unclear. Based on the China National Survey of Chronic Kidney Disease linked to mortality data, a population-based cohort study was performed to investigate the association between SUA level and all-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality in China.MethodsThe survival status of participants in the cross-sectional survey was identified from January 1, 2006 to December 31, 2017. Only 33,268 individuals with complete SUA data among the 47,204 participants were included in the analysis. We determined the rates of all-cause mortality, CVD mortality, and cancer mortality. We used Cox proportional hazards regression models to evaluate the effect of the SUA level on mortality.ResultsDuring a total of 297,538.4 person-years of follow-up, 1282 deaths occurred. In the Cox proportional hazards regression model, the rate of all-cause mortality, CVD mortality, and cancer mortality had a U-shaped association with SUA levels only in men, whereas no significant associations were detected in women. For all-cause mortality in men, the multivariable-adjusted hazard ratios (HRs) in the first, second, and fourth quartiles compared with the third quartile were 1.31 (95% confidence interval [CI] 1.04-1.67), 1.17 (95% CI 0.92-1.47), and 1.55 (95% CI 1.24-1.93), respectively. For CVD mortality, the corresponding HRs were 1.47 (95% CI 1.00-2.18), 1.17 (95% CI 0.79-1.75), and 1.67 (95% CI 1.16-2.43), respectively. For the cancer mortality rate, only a marginally significant association was detected in the fourth quartile compared with the third quartile with an HR of 1.43 (95% CI 0.99-2.08).ConclusionsThe association between SUA and mortality differed by sex. We demonstrated a U-shaped association with SUA levels for all-cause and CVD mortalities among men in China.
| S-EPMC8439999 | biostudies-literature
Project description:AimsHyperuricemia has attracted increasing attention. However, limited concern has been paid to the potential dangers of lowering serum uric acid (SUA). We observed lower levels of SUA in patients with COVID-19. Therefore, we aim to explore whether patients with COVID-19 had SUA lower than normal and the relationship of SUA and the severity of COVID-19.MethodsThis was a case-control study based on 91 cases with COVID-19 and 273 age- and sex-matched healthy control subjects. We first compared SUA levels and uric acid/creatinine (UA/Cr) ratio between patients with COVID-19 and the healthy controls. Then, we examined the association of SUA levels and UA/Cr ratios with COVID-19 severity in COVID-19 cases only, defined according to the fifth edition of China's Diagnosis and Treatment Guidelines of COVID-19.ResultsSUA levels in patients with COVID-19 were 2.59% lower, UA/Cr ratios 6.06% lower at admission compared with healthy controls. In sex stratified analysis, levels of SUA and UA/Cr were lower in male patients with COVID-19 while only level of SUA was lower in female patients with COVID-19. Moreover, SUA and UA/Cr values were 4.27 and 8.23% lower in the severe group than that in the moderate group among male COVID-19 patients. Bivariate and partial correlations analysis showed negative correlations between SUA or UA/Cr ratio and COVID-19 after adjusting for age, sex, BMI and eGFR. A multiple linear regression analysis showed that SARS-CoV-2 infection and male sex were independent risk factors associated with lower SUA levels. Male patients with COVID-19 accompanied by low SUA levels had higher risk of developing severe symptoms than those with high SUA levels (incidence rate ratio: 4.05; 95% CI:1.11, 14.72) at admission. Comparing SUA and UA/Cr ratio at three time points (admission, discharge, and follow-up), we found that male patients experienced severe symptoms had lower SUA and UA/Cr ratio levels comparing to moderate patients, but no significant difference between three time points. On the contrary, female patients had lower SUA and UA/Cr ratio at discharge than those at admission, but no significant difference of SUA and UA/Cr ratio between moderate and severe group.ConclusionPatients with COVID-19 had SUA and UA/Cr values lower than normal at admission. Male COVID-19 patients with low SUA levels had a significantly higher crude risk of developing severe symptoms than those with high SUA levels. During disease aggravation, the level of SUA gradually decreased until discharge. At the follow-up exam, the level of SUA was similar to the levels at admission.
| S-EPMC8106517 | biostudies-literature
Project description:Background and aimsMetabolic Syndrome (Mets) and increased serum uric acid (SUA), are well known renal risk predictors and often coexist in patients with type 2 diabetes (T2D). Whether they independently contribute to the onset of CKD is at present unclear.Methods and resultsWithin the AMD Annals database we identified patients with T2D and normal renal function and urine albumin excretion at baseline and regular follow-up visits during a 4-year period. Blood pressure, BMI, HDL, triglycerides, and SUA were available in 14,267 patients. The association between Mets and/or hyperuricemia (HU, top fifth gender specific quintile) and the occurrence of renal outcomes were evaluated.ResultsAt baseline 59% of patients (n = 8,408) showed Mets and 18% (n = 2,584) HU. Over the 4-year follow-up, 14% (n = 1,990) developed low eGFR (i.e. below 60 mL/min/1.73 m2), and 26% (n = 3,740) albuminuria. After adjustment for confounders, BP≥130/85, low HDL, triglycerides ≥150 and HU were independently related to the development of low eGFR (1.57, P<0.001; 1.13, P = 0.056; 1.18, P = 0.008; 1.26, P = 0.001) and of albuminuria (1.35, P<0.001; 1.18, P = 0.001; 1.15, P = 0.002; 1.24, P = 0.001), respectively. The incidence of low eGFR was higher in patients with HU independent of the presence or absence of Mets (21%, OR 1.30, p = 0.009 and 20%, 1.57, p<0.000 respectively), while albuminuria occurred more frequently in those with Mets and HU (32%, OR 1.25, p = 0.005) as compared to the reference group.ConclusionsHU and Mets are independent predictors of CKD and its individual components in patients with T2D.
| S-EPMC5396926 | biostudies-literature