scholarly journals P1000URINE MYO-INOSITOL AS A NOVEL PROGNOSTIC BIOMARKER FOR DIABETIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chun Soo Lim ◽  
Soie Kwon ◽  
Jung Pyo Lee

Abstract Background and Aims Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESRD). Metabolomics has been increasingly applied to identify the cause of CKD, as it can present epigenetics and suggest corresponding treatment options. Only a few metabolomics studies were conducted in DKD patients, and the results are inconclusive. We investigated the association between urine metabolites and renal disease progression and mortality in DKD, using 800 MHz NMR spectroscopy based targeted metabolomics profiling. Method Prospectively stored urine samples from consecutive patients with DKD stage 1 to 5 (n=208) and their healthy controls (n=26) were analyzed. Cross-sectional associations were evaluated between eGFR or urine protein creatinine ratio (UPCR) and 26 urinary metabolites. Multivariable adjusted Cox models were conducted for the risk prediction of ESRD and mortality. The receiver-operating characteristic (ROC) analyses were used to assess the additive effect of each metabolite to predict the progression to ESRD. Results ESRD occurred in 103 (44.0%) patients and 65 (27.8%) deaths occurred during median 4.5 years (IQR, 2.06–6.58) follow-up period. The median fold change in 9 metabolites (glucose, mannose, myo-inositol, glycerol, lactate, fumarate, creatine, taurine and choline) in patient group revealed a trend corresponding to DKD stages. Linear regression showed that myo-inositol had a strongest association with eGFR. The relationship between the competitive metabolites and outcomes (ESRD and mortality) was investigated by multivariate Cox models after adjusting for the baseline covariates. Of these, 4 metabolites (myo-inositol, glycerol, fumarate, oxoisocaproate) had predictive values for ESRD, and among them, only myo-inositol retained predictive significance in mortality (adjusted HR 1.004, 95% confidence interval 1.002-1.006, P < 0.001). At ROC analysis, urinary myo-inositol had additive effect to serum creatinine concentration and UPCR in the prediction for ESRD progression (NRI = 2.9%, P = 0.03; IDI = 35.1%, P = 0.02). Conclusion These results suggest that myo-inositol can be a predictive biomarker for the risk of ESRD progression and mortality in DKD. Further studies are needed to elucidate the pathophysiological roles of myo-inositol in DKD.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Randa I. Farah ◽  
Mohammed Q. Al-Sabbagh ◽  
Munther S. Momani ◽  
Asma Albtoosh ◽  
Majd Arabiat ◽  
...  

Abstract Aim Diabetic kidney disease (DKD) is a major long-term complication of diabetes mellitus (DM). Given the paucity of data on DKD in Jordan, we aimed to evaluate the prevalence, characteristics and correlates of DKD in Jordanian patients with type 2 DM. Methods This cross-sectional study included 1398 adult patients with type 2 DM who sought medical advice in the endocrinology clinic between March and September 2019. Demographic, clinical and laboratory data were reviewed. DKD was defined as reduced eGFR, and/or albuminuria. Three regression models were constructed to identify factors associated with CKD stages, albuminuria and DKD. Results Overall, 701 (50.14%) patients had DKD, with a median age of 59.71 ± 11.36  years. Older age, high triglycerides, and low high-density lipoprotein were associated with DKD (multivariable odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01–1.03, p < 0.01; OR: 1.1, 95% CI: 1.01–1.2; and OR: 0.98, 95% CI: 0.97–0.99, p < 0.01 respectively). Metformin and renin-angiotensin system blockers were negatively associated with albuminuria and chronic kidney disease stages (p < 0.01). Conclusion Our study demonstrated that approximately one half of patients with type 2 DM had DKD. Further studies are necessary to understand this high prevalence and the underlying factors. Future research are needed to assess implementing targeted community-based intervention.


2021 ◽  
Vol 18 (1) ◽  
pp. 147916412199252
Author(s):  
Yuwei Yang ◽  
Peng Xu ◽  
Yan Liu ◽  
Xiaohong Chen ◽  
Yiyang He ◽  
...  

Aim: Atherosclerosis involves vascular endothelial damage and lipid metabolism disorder, which is closely related to the occurrence and development of diabetic kidney disease (DKD). However, studies on non-high albuminuria DKD (NHADKD) with an albumin to creatinine ratio (ACR) <30 mg/g are rare. This study is to investigate the relationship between atherogenic factors and the occurrence of NHADKD. Methods: Serum lipid indicators, lipoprotein-associated phospholipase A2 (Lip-PLA2) and homocysteine levels were measured in 1116 subjects to analyze their relationship with NHADKD. Results: Among all subjects, Lip-PLA2 had the closest but relatively weak correlation with ACR ( r = 0.297, p < 0.001) and only homocysteine was moderately correlated with eGFR ( r = −0.465, p < 0.001). However, in patients with NHADKD, these atherosclerotic factors were weakly correlated or uncorrelated with eGFR (max. | r| = 0.247). Stratified risk analysis showed that when ACR was <10 mg/g, homocysteine [OR = 6.97(4.07–11.95)], total cholesterol (total-Chol) [OR = 6.04(3.03–12.04)], and high-density lipoprotein cholesterol (HDL-Chol) [OR = 5.09(2.99–8.64)] were risk factors for NHADKD. There was no significant difference of OR between these three factors ( Z = 0.430–1.044, all p > 0.05). When ACR was ⩾10mg/g, homocysteine [OR = 17.26(9.67–30.82)] and total-Chol [OR = 5.63(2.95–10.76)] were risk factors for NHADKD, and ORhomocysteine was significantly higher than ORtotal-Chol ( Z = 3.023, p < 0.05). Conclusions: The occurrence of NHADKD may be related to the levels of homocysteine, total-Chol, HDL-Chol, and Lip-PLA2 in blood. Among them, homocysteine may be most closely related to NHADKD.


Author(s):  
Tetsuo Shoji ◽  
Hisako Fujii ◽  
Katsuhito Mori ◽  
Shinya Nakatani ◽  
Yuki Nagata ◽  
...  

Abstract Background Previous studies reported mixed results regarding the contributions of cardiovascular disease (CVD) and blood pressure to cognitive impairment in chronic kidney disease. Methods This was a cross-sectional study in 1213 patients on maintenance hemodialysis from 17 dialysis units in Japan. The main exposures were prior CVD and blood pressure components including systolic (SBP) and diastolic pressure (DBP). The outcome was low cognitive function evaluated with the Modified Mini-Mental State examination (3MS) with a cut-off level of 3MS &lt; 80. Results The median age was 67 years, median duration of dialysis was 71 months, 37% were women, 39% had diabetic kidney disease, and 36% had any pre-existing CVD. Median (interquartile range) of 3MS score was 91 (82 to 97), and 240 patients (20%) had 3MS &lt; 80. Logistic regression analysis showed that 3MS &lt; 80 was associated with the presence of any prior CVD, particularly prior stroke. 3MS &lt; 80 was associated with lower DBP but not with SBP. When patients were stratified by the presence of prior stroke, lower DBP, higher age, and lower education level were factors associated with 3MS &lt; 80 in both subgroups. In the subgroup of patients without prior stroke, diabetic kidney disease was an additional factor associated with 3MS &lt; 80. CVDs other than stroke were not associated with 3MS in either subgroup. Conclusions Prior stroke and lower DBP were associated with 3MS &lt; 80 in hemodialysis patients. These findings support the hypothesis that these vascular factors contribute to low cognitive performance in patients undergoing hemodialysis.


2018 ◽  
Vol 7 (2) ◽  
pp. 98-103
Author(s):  
Sindou Sanogo ◽  
Serge Didier Konan ◽  
Kouamé Hubert Yao ◽  
Emma Kouassi ◽  
Séry Patrick Diopoh ◽  
...  

Introduction: Diabetes mellitus is a disease whose prevalence has been steadily increasing worldwide. Objectives: To evaluate the prevalence of diabetic kidney disease and to identify the associated factors in type 2 diabetic patients. Material and Methods: This was a descriptive and analytical cross-sectional study. The study was conducted over a period from January to June 2016, among patients with type 2 diabetes, followed up at the Division of Diabetology of the University Hospital of Treichville, Abidjan. Results: Of 154 included patients, diabetic nephropathy (DN) was observed in 40 cases (25.9% prevalence). We observed a female predominance (sex ratio; 0.17) and the mean age of 57.7 ± 11 years. Based on the K/DOQI guidelines, half of our patients had stage 3 kidney disease. Complications such as diabetic retinopathy (100%), hypertension (HT) (75%), dyslipidemia (45%) and obesity (30%) were found. Factors such as female sex (P = 0.001; OR [95% CI] = 4.76 [1.85-12.19]), a range 55-65 years old (P = 0.010; OR [95% CI] = 2.64 [1.26-5.53]), obesity (P = 0.012; OR [95% CI] = 3.06 [1.27-7.36]), hypertension (P = 0.0001; OR [95% CI] = 4.77 [2.12-10.71]) and HbA1c <7% (P = 0.002; OR [94% CI] = 3.42 [1.57-7.44]) were associated with nephropathy by multivariate analysis. Conclusion: the prevalence of diabetic kidney disease is high in our study. The associated factors are non-modifiable such as female gender and age, but also modifiable such as obesity and hypertension.


2020 ◽  
Vol 8 (1) ◽  
pp. e000902 ◽  
Author(s):  
Yui Yoshida ◽  
Kosuke Kashiwabara ◽  
Yosuke Hirakawa ◽  
Tetsuhiro Tanaka ◽  
Shinsuke Noso ◽  
...  

ObjectiveGlomerular filtration rate (GFR) decreases without or prior to the development of albuminuria in many patients with diabetes. Therefore, albuminuria and/or a low GFR in patients with diabetes is referred to as diabetic kidney disease (DKD). A certain proportion of patients with diabetes show a rapid progressive decline in renal function in a unidirectional manner and are termed early decliners. This study aimed to elucidate the prevalence of DKD and early decliners and clarify their risk factors.Research design and methodsThis combination cross-sectional and cohort study included 2385 patients with diabetes from 15 hospitals. We defined DKD as a urinary albumin to creatinine ratio (ACR) ≥30 mg/gCr and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². We classified patients into four groups based on the presence or absence of albuminuria and a decrease in eGFR to reveal the risk factors for DKD. We also performed a trajectory analysis and specified the prevalence and risk factors of early decliners with sequential eGFR data of 1955 patients in five facilities.ResultsOf our cohort, 52% had DKD. Above all, 12% with a low eGFR but no albuminuria had no traditional risk factors, such as elevated glycated hemoglobin, elevated blood pressure, or diabetic retinopathy in contrast to patients with albuminuria but normal eGFR. Additionally, 14% of our patients were early decliners. Older age, higher basal eGFR, higher ACR, and higher systolic blood pressure were significantly associated with early decliners.ConclusionsThe prevalence of DKD in this cohort was larger than ever reported. By testing eGFR yearly and identifying risk factors in the early phase of diabetes, we can identify patients at high risk of developing end-stage renal disease.


2019 ◽  
Vol 10 ◽  
pp. 204201881989111
Author(s):  
Yongzhang Qin ◽  
Shuang Zhang ◽  
Xiaofang Shen ◽  
Shunming Zhang ◽  
Jingyu Wang ◽  
...  

Background: The aim of this study was to evaluate the diagnostic value of six urinary biomarkers for prediction of diabetic kidney disease (DKD). Methods: The cross-sectional study recruited 1053 hospitalized patients with type 2 diabetes mellitus (T2DM), who were categorized into the diabetes mellitus (DM) with normoalbuminuria (NA) group ( n = 753) and DKD group ( n = 300) according to 24-h urinary albumin excretion rate (24-h UAE). Data on the levels of six studied urinary biomarkers [transferrin (TF), immunoglobulin G (IgG), retinol-binding protein (RBP), β-galactosidase (GAL), N-acetyl-beta-glucosaminidase (NAG), and β2-microglobulin (β2MG)] were obtained. The propensity score matching (PSM) method was applied to eliminate the influences of confounding variables. Results: Patients with DKD had higher levels of all six urinary biomarkers. All indicators demonstrated significantly increased risk of DKD, except for GAL and β2MG. Single RBP yielded the greatest area under the curve (AUC) value of 0.920 compared with the other five markers, followed by TF (0.867) and IgG (0.867). However, GAL, NAG, and β2MG were shown to have a weak prognostic ability. The diagnostic values of the different combinations were not superior to the single RBP. Conclusions: RBP, TF, and IgG could be used as reliable or good predictors of DKD. The combined use of these biomarkers did not improve DKD detection.


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