Association of Serum Tsukushi Levels with Urinary Albumin-Creatinine Ratio in Type 2 Diabetes Patients.

Objective: Tsukushi is a newly identified hepatokine. Recent studies have shown that it relates to diabetes, lipid metabolism and fibrosis, but there is currently no investigation about whether Tsukushi is associated with diabetic kidney disease. Therefore, this study aimed to investigate the relationship between Tsukushi and diabetic kidney disease by characterizing Tsukushi levels in healthy subjects and type 2 diabetes with urinary albumin-creatinine ratio. Methods: Serum Tsukushi level was quantified by enzyme-linked immunosorbent assay in 167 normoalbuminuria, 80 microalbuminuria, and 31 macroalbuminuria patients with type 2 diabetes as compared with 53 healthy subjects. The correlation analysis was used to investigate the relationship between urinary albumin-creatinine ratio or Tsukushi level and other metabolic parameters. Multiple linear regression and logistic regression analysis were used to analyze the independent factors for urinary albumin-creatinine ratio and estimated glomerular filtration rate. Results: The Tsukushi level in the macroalbuminuria group was significantly higher than that in the normoalbuminuria or the microalbuminuria group. Multiple linear regression showed that the significantly independent factors for UACR included high Tsukushi quartile, systolic blood pressure, creatinine, homeostasis model assessment of insulin resistance, low 2-h post-oral glucose tolerance test c-peptide and female. Logistic regression demonstrated that the odds ratio of Tsukushi for glomerular filtration rate ≤90(mL/min/1.73m2) was 1.636 (95% CI 1.091-2.452, P=0.017). Conclusion: The circulating Tsukushi increased in type 2 diabetes patients with albuminuria and was associated with urinary albumin-creatinine ratio, implying that Tsukushi may be involved in the pathogenesis of diabetic kidney disease, which deserves future studies.

Retrospective analysis of the effect of SGLT-2 inhibitors on renal function in patients with type 2 diabetes in the real world.

Introduction: The protective effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on the kidneys has been widely recognized. However, limited research has reported the changes in estimated glomerular filtration rate (eGFR) of real-world patients with type 2 diabetes mellitus (T2DM) over time after administration of SGLT-2 inhibitors. This study aimed to reflect the trend of eGFR changes over time in T2DM patients having different baseline eGFR after SGLT-2 inhibitors administration in the real world. Methods: A single-center retrospective study was performed in a tertiary public hospital in Beijing, China. In total, 998 outpatients with T2DM who initiated SGLT-2 inhibitors treatment were included in the study. The changes in eGFR, urinary albumin/creatinine ratio (UACR), and glycolipid metabolism indicators were analyzed during the 18-month follow-up period. Results: The eGFR levels significantly decreased to their lowest point (-3.04 mL/min/1.73 m2) in the first 3 months after initiation of SGLT-2 inhibitors treatment, however, gradually returned to the baseline level after 1 year. Compared to the subgroup with eGFR >90 mL/min/1.73 m2, improvements in renal function were more significant in patients with T2DM from the 60 < eGFR ≤90 mL/min/1.73 m2 and eGFR ≤60 mL/min/1.73 m2 subgroups after treatment with SGLT-2 inhibitors. Similarly, SGLT-2 inhibitors reduced the UACR in patients with diabetic nephropathy. Conclusion: This study further confirmed the real-world long-term protective effect of SGLT-2 inhibitors on the kidneys of patients with T2DM, which is not related to baseline renal function and blood glucose.

Tadalafil versus pentoxifylline in the management of diabetic kidney disease: a randomized clinical trial.

AIMS: To investigate the efficacy and safety of tadalafil (TAD) versus pentoxifylline (PTX) in the management of diabetic kidney disease (DKD). Some animal studies and clinical trials reported that tadalafil and pentoxifylline have a reducing effect on different blood glucose parameters and lipid profiles which contribute to progress the patients with diabetes mellitus (DM) to DKD. METHODS: From February 2022 to March 2023, 90 patients with type 2 DM and DKD (micro-albuminuria) were enrolled in this randomized-controlled study. The patients were randomized into three equal groups: control group, TAD group, and PTX group. The three groups received traditional blood glucose lowering therapy + ramipril 10 mg PO. The TAD group also received tadalafil 20 mg PO every other day. The PTX group also received pentoxifylline 400 mg PO twice daily. RESULTS: Both TAD and PTX groups produced statistically significant improvement in the primary outcomes by a significant reduction in Urinary albumin/creatinine ratio (UACR) which was pronounced by a reduction percentage of-47.47%, -53.73% respectively. In addition to a significant decrease in Hemoglobin A1C (HbA1c) (mmol/mol), Fasting blood glucose (FBG), 2-h postprandial blood glucose (2-h PPG) (p < 0.001). Only the PTX group showed a significant increase in Cr Cl and a significant decrease in S. Cr (p < 0.001). Only the TAD group showed a significant increase in high-density lipoprotein-cholesterol (HDL-C) (p < 0.001), while the PTX group showed a significant decrease in low-density lipoprotein-cholesterol (LDL-C) (p-value 0.011), and triglyceride (p-value 0.002). Both TAD and PTX groups showed a decrease in tumor necrosis factor-α (TNF-α) which was significant only in the PTX group (p < 0.001). There was a significant increase in malondialdehyde (MDA) (p < 0.001), and an increase in urinary neutrophil gelatinase-associated Lipocalin (uNGAL) (p-value 0.850, 0.014 respectively) which was significant only in the PTX group. CONCLUSIONS: The use of tadalafil or pentoxifylline may serve as an effective adjuvant therapy for patients with diabetic kidney disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05487755, July 25, 2022.

The effect of PAP on UACR and metabolic indexes in patients with MS and OSAHS.

PURPOSE: To investigate the effects of positive airway pressure (PAP) device on urinary albumin to creatinine ratio (UACR) and metabolic indexes in patients with metabolic syndrome (MS) and obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: This study is a retrospective cohort study. Grouped according to whether to use PAP treatment, there were 25 cases in the PAP group and 44 cases in the no OSAHS treatment group. The PAP group received positive airway pressure device and routine treatment of MS. The no OSAHS treatment group received routine treatment of OSAHS and MS. The treatment period is 3 months. RESULTS: 1. The PAP group demonstrated significant reductions in Body Mass Index (BMI), Waist circumference (WC), Neck circumference (NC), Visceral fat area (VFA), Fasting C peptide (FCP), high-sensitivity C-reactive protein (hs-CRP), and UACR compared to the no OSAHS treatment group, with significant differences (P all <0.05). Among them, the UACR in the PAP group decreased significantly (from 86.05(52.55,131.61)mg/g to 16.76(8.70,25.12)mg/g, P<0.001). 2. Linear regression analysis using the decrease in UACR values as the dependent variable demonstrated a positive linear relationship with the decrease in BMI, VFA, fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR). Furthermore, multiple linear regression analysis indicated that the decrease in VFA (B=0.537 [95% confidence interval, 0.084 to 0.989]; P = 0.021) and HOMA-IR (B=1.000 [95% confidence interval, 0.082 to 1.917]; P = 0.033) values independently correlated with decrease in UACR values. CONCLUSIONS: PAP treatment can reduce UACR in patients with MS and OSAHS, and has the effect of improving metabolic disorders. The decrease of UACR in patients may be related to the decrease of visceral fat and the improvement of insulin resistance.

Association of the longitudinal trajectory of urinary albumin/creatinine ratio in diabetic patients with adverse cardiac event risk: a retrospective cohort study.

Objective: The baseline urinary albumin/creatinine ratio (uACR) has been proven to be significantly associated with the risk of major adverse cardiac events (MACE). However, data on the association between the longitudinal trajectory patterns of uACR, changes in glycated hemoglobin A1c (HbA1c), and the subsequent risk of MACE in patients with diabetes are sparse. Methods: This is a retrospective cohort study including 601 patients with type 2 diabetes mellitus (T2DM; uACR < 300 mg/g) admitted to The First Hospital of Shanxi Medical University and The Second Hospital of Shanxi Medical University from January 2015 to December 2018. The uACR index was calculated as urinary albumin (in milligrams)/creatinine (in grams), and latent mixed modeling was used to identify the longitudinal trajectory of uACR during the exposure period (2016-2020). The deadline for follow-up was December 31, 2021. The primary outcome was the MACE [a composite outcome of cardiogenic death, hospitalization related to heart failure (HHF), non-fatal acute myocardial infarction, non-fatal stroke, and acute renal injury/dialysis indications]. The Kaplan-Meier survival analysis curve was used to compare the risk of MACE among four groups, while univariate and multivariate Cox proportional hazards models were employed to calculate the hazard ratio (HR) and 95% confidence interval (CI) for MACE risk among different uACR or HbA1c trajectory groups. The predictive performance of the model, both before and after the inclusion of changes in the uACR and HbA1c, was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). Results: Four distinct uACR trajectories were identified, namely, the low-stable group (uACR = 5.2-38.3 mg/g, n = 112), the moderate-stable group (uACR = 40.4-78.6 mg/g, n = 229), the high-stable group (uACR = 86.1-153.7 mg/g, n = 178), and the elevated-increasing group (uACR = 54.8-289.4 mg/g, n = 82). In addition, five distinct HbA1c trajectories were also identified: the low-stable group (HbA1c = 5.5%-6.8%, n = 113), the moderate-stable group (HbA1c = 6.0%-7.9%, n = 169), the moderate-decreasing group (HbA1c = 7.4%-6.1%, n = 67), the high-stable group (HbA1c = 7.7%-8.9%, n = 158), and the elevated-increasing group (HbA1c = 8.4%-10.3%, n = 94). Compared with the low-stable uACR group, patients in the high-stable and elevated-increasing uACR groups were more likely to be older, current smokers, and have a longer DM course, higher levels of 2-h plasma glucose (PG), HbA1c, N-terminal pro-B-type natriuretic peptide (NT-proBNP), uACR, and left ventricular mass index (LVMI), while featuring a higher prevalence of hypertension and a lower proportion of ß-receptor blocker treatment (p < 0.05). During a median follow-up of 45 months (range, 24-57 months), 118 cases (19.6%) of MACE were identified, including 10 cases (1.7%) of cardiogenic death, 31 cases (5.2%) of HHF, 35 cases (5.8%) of non-fatal acute myocardial infarction (AMI), 18 cases (3.0%) of non-fatal stroke, and 24 cases (4.0%) of acute renal failure/dialysis. The Kaplan-Meier survival curve showed that, compared with that in the low-stable uACR group, the incidence of MACE in the high-stable (HR = 1.337, 95% CI = 1.083-1.652, p = 0.007) and elevated-increasing (HR = 1.648, 95% CI = 1.139-2.387, p = 0.009) uACR groups significantly increased. Similar results were observed for HHF, non-fatal AMI, and acute renal injury/dialysis indications (p < 0.05). The multivariate Cox proportional hazards models indicated that, after adjusting for potential confounders, the HRs for the risk of MACE were 1.145 (p = 0.132), 1.337 (p = 0.007), and 1.648 (p = 0.009) in the moderate-stable, high-stable, and elevated-increasing uACR groups, respectively. In addition, the HRs for the risk of MACE were 1.203 (p = 0.028), 0.872 (p = 0.024), 1.562 (p = 0.033), and 2.218 (p = 0.002) in the moderate-stable, moderate-decreasing, high-stable, and elevated-increasing groups, respectively. The ROC curve showed that, after adding uACR, HbA1c, or both, the AUCs were 0.773, 0.792, and 0.826, which all signified statistically significant improvements (p = 0.021, 0.035, and 0.019, respectively). Conclusion: A long-term elevated uACR is associated with a significantly increased risk of MACE in patients with diabetes. This study implies that regular monitoring of uACR could be helpful in identifying diabetic patients with a higher risk of MACE.

Using nephropathy as an outcome to determine the HbA1c diagnostic threshold for type 2 diabetes.

OBJECTIVE: The hemoglobin A1c (HbA1c) diagnostic threshold for type 2 diabetes (T2D) of 6.5 % (48 mmol/mol) was based on the prevalence of retinopathy found in populations not known to have T2D. It is unclear if nephropathy has a similar HbA1c threshold, partly because it is a rarer complication of early diabetes. This cohort study investigated a very high diabetes prevalence population to determine if a better diagnostic HbA1c value can be established for predicting nephropathy rather than retinopathy in subjects without T2D. METHODS: The urine albumin:creatinine ratios (UACRs) of 2920 healthy individuals from the Qatar Biobank who had an HbA1c ≥ 5.6 %. were studied. Nephropathy was defined as a UACR≥30 mg/g and its prediction by HbA1c was assessed using cut-points ranging from 5.7 to 7.0 % to dichotomize high from low HbA1c. RESULTS: Although there was a significant trend for an increased prevalence of abnormal UACR as the HbA1c threshold increased (p < 0.01), significance was due mostly to subjects with HbA1c ≥ 7.0 % (53 mmol/mol). The odds ratios for abnormal UACR were similar over the 5.7-6.9 % HbA1c threshold range, with a narrow odds ratio range of 1.2-1.6. Utilizing area-under-receiver-operating characteristic curves, no HbA1c threshold <7.0 % was identified as the best predictor of nephropathy. CONCLUSION: Even in a population with a high prevalence of known and unknown diabetes, no HbA1c threshold <7.0 % could be found predicting an increased prevalence of nephropathy. This means there is not a requirement to change the existing retinopathy-based HbA1c threshold of 6.5 % to also accommodate diabetes nephropathy risk.

A cross-sectional study investigating the relationship between urinary albumin creatinine ratio and abdominal aortic calcification in adults.

Introduction: The presence of abdominal aortic calcification (AAC) is strongly linked to the development of atherosclerosis and the incidence of morbidity and mortality related to cardiovascular diseases (CVD). Urinary albumin creatinine ratio (UACR) was found related with the increased risk of CVD. The aim of this study is to explore the relationship between the UACR and severe AAC (SAAC). Methods and Results: This study included a total of 2,379 individuals aged over 40 years, and their information was obtained from the National Health and Nutrition Examination Survey conducted (NHANES) in 2013-2014. The measurement of AAC was conducted through dual-energy x-ray absorptiometry and assessed using the Kauppila scoring system. SAAC was characterized by a Kauppila score of 6 or higher. Multivariate regression models were used to analyze the relationship between UACR level and SAAC, with covariate adjustment. In the completely adapted model, the top third subgroup exhibits increased likelihood of SAAC (odds ratio 1.50; 95%CI: 0.98, 2.29; p = 0.030) in contrast to the bottom third subgroup. The subgroup analyses revealed a more pronounced correlation among the older participants (p-value for interaction = 0.013). Discussion: In the United States, SAAC was more likely to occur in adults who had a higher probability of UACR. The use of UACR has the potential to be a valuable method for forecasting the likelihood of SAAC.

Low Levels of Metrnl are Linked to the Deterioration of Diabetic Kidney Disease.

Objective: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Metrnl is a secreted protein that plays an important role in kidney disease. The aim of this study was to investigate DKD-related factors and the correlation between serum Metrnl levels and the severity of DKD. Methods: Ninety-six type 2 diabetes mellitus (T2DM) patients and 45 DKD patients were included in the study. A range of parameters were measured simultaneously, including waist-to-hip ratio (WHR), body mass index (BMI), urinary albumin/creatinine ratio (UACR), monocyte-lymphocyte ratio (MLR), albumin/globulin (A/G), liver and kidney function, blood lipid profile, islet function, and others. Subsequently, the related factors and predictive significance of DKD were identified. The correlation between the relevant factors of DKD and serum Metrnl levels with DKD was evaluated. Results: The duration of the disease (OR: 1.12, 95% CI: 1.01-1.24, P=0.031), hypertension (OR: 4.86, 95% CI: 1.16-20.49, P=0.031), fasting blood glucose (OR: 1.23, 95% CI: 1.03-1.48, P=0.025), WHR (OR: 2.53, 95% CI: 1.03-6.22, P=0.044), and MLR (OR: 1.91, 95% CI: 1.18-3.08, P=0.008) are independent risk factors for DKD (P < 0.05). Conversely, A/G (OR: 0.13, 95% CI: 0.02-0.76, P=0.024) and Metrnl (OR: 0.99, 95% CI: 0.98-1.00, P=0.001) have been identified as protective factors against DKD. Furthermore, the level of Metrnl was negatively correlated with the severity of DKD (rs=-0.447, P<0.001). The area under receiver operating characteristic (ROC) curves for the diagnostic accuracy of Metrnl for DKD is 0.765 (95% CI: 0.686-0.844). Conclusion: The duration of the disease, hypertension, fasting blood glucose, WHR, and MLR are major risk factors for DKD. Metrnl and A/G are protective factors for DKD. Serum Metrnl concentrations are inversely correlated with DKD severity.

The Correlation Between Glycation Gap and Renal Complications in Patients with Type 2 Diabetes Mellitus.

Purpose: The aim of this study was to investigate the correlations between the glycation gap (GG) and renal complications such as urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus patients. Materials and Methods: A cross-sectional study was conducted on 104 individuals (52 males and 52 females), aged 36-93 years old. Fasting blood glucose (FBG), HbA1c, and serum fructosamine were measured simultaneously. GG was calculated as the difference between the measured and fructosamine-based predicted HbA1c levels (FHbA1c). Results: There was a moderately positive correlation between HbA1c and fructosamine concentration (r = 0.488; p < 0.001). GG was positively correlated with UACR (r = 0.3275; p = 0.0007), negatively correlated with eGFR (r = -0.3400; p = 0.0004). HbA1c was positively correlated with UACR (r = 0.2437; p = 0.0127) but not correlated with eGFR (r = -0.444; p = 0.6542). Fructosamine has a positive correlation with eGFR (r = 0.2426; p = 0.0131) but not with UACR (r = -0.1021; p = 0.3025). Conclusion: GG was positively correlated with UACR and inversely correlated with eGFR in type 2 Diabetes mellitus patients. This suggests that GG is a valuable index for predicting kidney complications due to diabetes.

Influence of Medication Compliance of Type 2 Diabetes Chronic Disease Management Patients in Two Communities of Kunming on Disease Control / 昆明医科大学学报

Objective To analyze the influence of medication compliance of chronic type 2 diabetes management patients on disease control in two communities in Kunming.Methods A total of 138 patients with type 2 diabetes who were included in chronic disease management in Guandu and Xiaobanqiao communities of Kunming were selected from December 2021 to September 2022.Basic information collection and HbAlc and other related tests were improved.A questionnaire survey of 8-item Morisliy medication adherence scale(MMAS-8)was conducted to analyze the levels of HbAlc and other indexes of three groups with high(group A),medium(group B),and low(group C)adherence,and to conduct statistical analysis.Results Group A accounted for 22.5%,group B for 44.9%,and group C for 32.6%.There were significance differences in urinary albumin creatinine ratio(UACR),HbA1c and blood creatinine among the three groups(P<0.05).The levels of UACR,HbAlc and serum creatinine in group A were lower than those in group B and group C,and there was a negative correlation between UACR,HbAlc and serum creatinine and medication compliance rate(P<0.05).Conclusion In the Guandu Community and Xiaobanqiao community of Kunming,only 22.5%of patients with chronic type 2 diabetes had high medication compliance.The higher the compliance,the lower the level of UACR,HbAlc and serum creatinine,there is a correlation between the two,suggesting that medication compliance should be regarded as one of the key points in the management of chronic diabetes mellitus in the community,and the intervention of patients'medication compliance should be strengthened.

Risk factors of abnormal urinary albumin/creatinine ratio in people with obesity / 中华内分泌代谢杂志

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.

Enhanced trimethylamine metabolism and gut dysbiosis in type 2 diabetes mellitus with microalbumin.

Background: Abnormal gut microbiota and blood trimethylamine-N-oxide (TMAO) metabolome have been reported in patients with type 2 diabetes mellitus (T2DM) and advanced diabetic nephropathy. This study aimed to investigate the gut microbiota profiles and a group of targeted urine metabolic characteristics in T2DM patients with or without microalbuminuria, to determine the correlation between the gut microbiota composition, trimethylamine (TMA) metabolism, and the clinical features during progression of diabetic kidney disease (DKD). Methods: This study included 26 T2DM patients with microalbuminuria (Micro), 26 T2DM patients with normoalbuminuria (Normo), and 15 healthy controls (HC). Urine and Fecal samples were detected using ultra performance liquid chromatography tandem mass spectrometry and 16S ribosomal DNA gene sequencing, respectively. Results: The TMAO/TMA ratio decreased gradually during the HC-Normo-Micro transition. The levels of TMA, choline and betaine were significantly different between the HC group and the T2DM patients belonging to both Normo and Micro groups. At the operational taxonomic unit (OTU) level, the gut microflora diversity was significantly reduced in the Micro groups compared to the HC groups and the Normo groups. Taxonomic analyses revealed significant consumption in the relative abundances of eight bacterial genera and significant enrichment of two bacterial genera during the HC-Normo-Micro transition. Furthermore, the relative abundances of six bacterial genera, namely, Ruminococcus_1, [Eubacterium]_ruminantium_group, Roseburia, Faecalibacterium, Fusicatenibacter and Coprococcus_3 exhibited significant differences, and were associated with elevated urinary albumin creatinine ratio (UACR), TMAO/TMA, TMA and its precursors in the Micro group compared with the other groups. Conclusion: The imbalance of gut microbiota has occurred in patients with early-stage DKD, and the consumption of short-chain fatty acid-producing bacteria were associated with the accumulation of TMA and UACR.

Potential application of Klotho as a prognostic biomarker for patients with diabetic kidney disease: a meta-analysis of clinical studies.

Background: Diabetic kidney disease (DKD) is a serious diabetic complication and the performance of serum Klotho in DKD's prognostic evaluation is controversial. Objective: To assess the association of serum Klotho with adverse kidney and non-kidney clinical outcomes in patients with DKD. Design: Clinical studies regarding the relationship of serum Klotho with DKD were included. Study quality was assessed using the Newcastle-Ottawa scale. Subgroup and sensitive analyses were performed to search for the source of heterogeneity. Data sources and methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane library databases up to 27 September 2022. The associations of Klotho with albuminuria, such as the urinary albumin creatinine ratio (UACR), kidney outcomes such as persistent albuminuria, estimated glomerular filtration rate decline, and non-kidney outcomes such as diabetic retinopathy, cardiovascular morbidity, and mortality, were evaluated. The indicators, such as the correlation coefficient (r), odds ratio (OR), relative risk, and hazard ratio, were retrieved or calculated from the eligible studies. Results: In all, 17 studies involving 5682 participants fulfilled the inclusion criteria and were included in this meta-analysis. There was no significant association of serum Klotho with UACR in DKD patients [summary r, -0.28 (-0.55, 0.04)] with high heterogeneity. By contrast, a strong association was observed regarding serum Klotho with kidney outcomes [pooled OR, 1.60 (1.15, 2.23)], non-kidney outcomes [pooled OR, 2.78 (2.11, 3.66)], or combined kidney and non-kidney outcomes [pooled OR, 1.96 (1.45, 2.65)] with moderate heterogeneity. Subgroup analysis indicated that age, study design, and the estimated glomerular filtration rate may be the sources of heterogeneity. Conclusion: A decreased serum Klotho level is possibly associated with an increased risk of developing kidney and non-kidney clinical outcomes in DKD patients; thus, Klotho may be a possible biomarker to predict DKD clinical outcomes. Additional studies are needed to clarify and validate Klotho's prognostic value.

Biochemical Markers of Early Renal Dysfunction in Patients with ß-thalassemia Major: A Systematic Review and Meta-analysis.

BACKGROUND: Early diagnosis of renal dysfunction in ß-thalassemia major (ß- TM) may help take specific measures to delay irreversible damage and renal failure. Therefore, the present meta-analysis aimed to compare biochemical markers of premature renal dysfunction between ß-TM and healthy subjects and identify renal issues' prevalence in patients with ß-TM. METHODS: We searched PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Medline, Scopus, Web of Science, ScienceDirect, ProQuest, Google Scholar, and State Inpatient Databases (SIDs) without any language constraints for all relevant articles published up to April 2019. RESULTS: Out of 1458 articles published up to April 2019, 24 case-control and 22 crosssectional studies were investigated. The investigated levels of serum phosphorus, uric acid (UA), cystatin C, and ferritin were significantly different between ß-TM patients and controls. The albumin/creatinine ratio (ACR), N-acetyl-ß-D-glucosaminidase/creatinine (NAG/Cr) ratio, urinary and serum ß2 microglobulin (ß2MG), and serum ferritin levels were significantly higher in ß-TM patients than in healthy individuals. However, glomerular filtration rate, creatinine clearance, and pretransfusion hemoglobin indicated a significantly lower rate. The general prevalence of renal glomerular and/or tubular defects in patients with ß-TM was 50.22%. CONCLUSION: Urinary NAG, ß2MG, ACR, and Scys-C may be early markers of renal dysfunction in patients with ß-thalassemia major. An observation of elevated levels of these markers despite normal levels of other markers of renal dysfunction may indicate primary, subclinical injury to the renal tubules and glomeruli.

Association of high-normal albuminuria and vascular aging: Hanzhong adolescent hypertension study.

Normoalbuminuria has recently been associated with increased cardiovascular risk, and vascular aging is proposed as the early manifestation of cardiovascular disease. Here, the authors aimed to examine the association of high-normal albuminuria and vascular aging in a Chinese cohort. From our previously established cohort, 1942 participants with estimated glomerular filtration rate ≥60 mL/min/1.73 m2 or urinary albumin-creatinine ratio (UACR) <30 mg/g were enrolled. Brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s and/or carotid intima-media thickness (CIMT) ≥0.9 mm were used as indicators of vascular aging. Multivariate regression and receiving operating characteristic curve analysis were performed to examine the relationship between continuous and categorical UACR with vascular aging. We found an average UACR value of 8.08 (5.45-12.52) mg/g in this study. BaPWV and CIMT demonstrated positive correlations with lg-UACR (p < .05). High-normal albuminuria (10-29 mg/g) was significantly associated with the presence of vascular aging after adjusting for multiple cardiovascular confounders (OR = 1.540, 95% CI = 1.203-1.972, p = .001). In addition, a lg-UACR cutoff point of 0.918 lg(mg/g) (equal to UACR of 8.285 mg/g) was significantly associated with the presence of vascular aging and its components for all participants and those without hypertension or diabetes and without medication (p < .05). Briefly, high-normal albuminuria was significantly associated with vascular aging in this sample of Chinese adults. These findings implied the warning of elevated UACR even within normal range in clinical practice and the importance of UACR screening in normoalbuminuria for early detection and prevention of cardiovascular disease in otherwise healthy participants.

Association of urinary albumin-to-creatinine ratio with lipid abnormalities and glycemic control in patients with type 2 diabetes mellitus.

Introduction: While proteinuria aggravates dyslipidemia in diabetic patients, dyslipidemia further worsens proteinuria via inflammatory cytokines-mediated glomerular damage. Urinary albumin creatinine ratio (ACR) is an easy and reliable method of detecting proteinuria. This study aims to determine the association of ACR with lipid abnormalities and glycemic control in the Nepalese population. Methods: This was a cross-sectional study conducted among 201 diabetes patients visiting the outpatient department of internal medicine. Based on ACR values, patients were categorized as nonalbuminuric (less than 300 µg/mg) or albuminuric (more than 300 µg/mg). An unpaired t-test was used to compare the mean of various lipoproteins in these two categories. Binary logistic regression was used to check the association of ACR with sociodemographic factors (age, sex, and education), hypertension, and glycated hemoglobin. Results: Albuminuric patients had higher mean cholesterol (192.8±53.5 vs. 184.2± 37.6; P=0.209), triglyceride (194.9±97.8 vs. 164.4±73.7; P=0.017) and low-density lipoprotein (99.9±38.4 vs. 90.0±27.4; P=0.034) but lower high-density lipoprotein (53.9±18.5 vs. 61.3±19.9; P=0.008) compared to nonalbuminuric patients. There was a significant difference in mean HbA1c values across albuminuria and nonalbuminuria groups (7.1±1.1 vs. 6.7±0.8; OR: 1.4, 95% CI=1.1-1.9, P=0.030). Conclusions: Urine ACR of more than 30 mg/gram was associated with higher triglyceride and low-density lipoprotein levels and lower high-density lipoprotein levels. The HbA1c level strongly correlates with the development of albuminuria.

Association between urinary C-megalin levels and progressive kidney dysfunction: a cohort study based on the diabetes distress and care registry at Tenri (DDCRT 24).

AIMS: The aim of this cohort study was to evaluate the association between urinary levels of C-megalin, a full-length form of megalin, and kidney dysfunction progression and its dependence on the urinary albumin-creatinine ratio (UACR) in individuals with diabetes. METHODS: We enrolled 1,547 individuals with diabetes who visited the ambulatory clinic at Tenri Hospital, a regional tertiary-care hospital in Tenri City, Nara Prefecture, Japan, with an estimated glomerular filtration (eGFR) of ≥ 30 mL/min/1.73 m2. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox proportional hazard models to examine the association between urinary C-megalin levels and eGFR decline by ≥ 40% from baseline. RESULTS: Urinary C-megalin level was not associated with ≥ 40% eGFR decline in an age-, sex-, eGFR-, systolic blood pressure-, hemoglobin-, and UACR-adjusted model in the 1,547 patients enrolled in the study. However, urinary C-megalin levels were associated with a ≥ 40% decline in eGFR when accounting for the relationship between urinary C-megalin levels and UACR in the model. This association was UACR-dependent. CONCLUSIONS: High urinary C-megalin levels were associated with progressive kidney dysfunction in individuals with diabetes, and this association was attenuated by high UACRs.

Vitamin D status and biomarkers of renal graft function after kidney transplantation: a longitudinal study / Estado de la vitamina D y biomarcadores de función del injerto renal después del trasplante de riñón: un estudio longitudinal

Introduction: Low 25-hydroxyvitamin D [25(OH)D] levels occur after kidney transplantation (KTx), and can be associated with increase the risk of graft loss. This longitudinal study aimed to evaluate the vitamin D status and association with biomarkers of the renal graft function after KTx. Methods: this longitudinal study included 42 patients evaluated at baseline, 3 and 6 months after KTx. Biodemographic, clinical, and biochemical parameters such as 25(OH)D and parathyroid hormone (PTH), and biomarkers of renal graft function, such as creatinine, estimated glomerular filtration rate (eGFR), and albumin/creatinine ratio (ACR), were assessed. Sun exposure was also evaluated. Patients were categorized according to their 25(OH)D levels. Results: at baseline, 25(OH)D levels < 30 ng/mL were found in 43 % patients, and 38 % of these patients failed to improve their 25(OH)D levels by 6 months after KTx. Low 25(OH)D levels occurred regardless of sun exposure. Further, 44 % patients developed albuminuria at 6 months. An increased ACR was observed in patients with 25(OH)D levels < 30 ng/mL (p = 0.002) compared to that in patients with 25(OH)D > 30 ng/mL. Additionally, 25(OH)D levels were negatively correlated with ACR at 6 months post-KTx (r = -0.444; p = 0.003). Twelve (28.6 %) patients with 25(OH)D levels < 30 ng/mL showed no eGFR recovery until 6 months after KTx. Conclusion: low vitamin D levels and increased albuminuria were observed at 6 months after KTx, even in a region with high sun exposure. The association between vitamin D status and biomarkers of renal graft function after KTx should be explored in further studies. (AU)

Introducción: los bajos niveles de 25-hidroxivitamina D [25(OH)D] ocurren después del procedimiento de trasplante de riñón (KTx) y pueden estar asociados con un aumento del riesgo de pérdida del injerto. Este estudio longitudinal tuvo como objetivo evaluar el estado de la vitamina D y la asociación con los biomarcadores de función del injerto renal después del KTx. Métodos: este estudio longitudinal incluyó a 42 pacientes que fueron evaluados al inicio del estudio, y 3 y 6 meses después del KTx. Se evaluaron los parámetros biodemográficos, clínicos y bioquímicos, como 25(OH)D y hormona paratiroidea (PTH), y los biomarcadores de función del injerto renal, como creatinina, tasa de filtración glomerular estimada (eGFR) y relación albúmina/creatinina (ACR). También se evaluó la exposición al sol. Los pacientes se clasificaron según sus niveles de 25(OH)D. Resultados: al inicio del estudio se encontraron niveles de 25(OH)D < 30 ng/ml en el 43 % de los pacientes, mientras que el 38 % de estos pacientes no lograron mejorar sus niveles de 25(OH)D a los 6 meses después del KTx. También se produjeron niveles bajos de 25(OH)D independientemente de la exposición al sol. Asimismo, el 44 % de los pacientes desarrollaron albuminuria a los 6 meses. Se observó un aumento de la ACR en los pacientes con niveles de 25(OH)D < 30 ng/mL (p = 0,002) en comparación con los pacientes con 25(OH)D > 30 ng/mL. Además,los niveles de 25(OH)D se correlacionaron negativamente con la ACR a los 6 meses después del KTx (r = -0,444; p = 0,003). Doce (28,6 %) pacientes con niveles de 25(OH)D < 30 ng/ml no mostraron recuperación de la TFGe hasta 6 meses después del KTx. Conclusión: se observaron niveles bajos de vitamina D y un aumento de la albuminuria a los 6 meses después del KTx, incluso en una región con alta exposición solar. La asociación entre el estado de la vitamina D y los biomarcadores de función del injerto renal después del KTx debeexplorarse en estudios adicionales. (AU)

Correlation of Mid-Trimester Spot Urinary Albumin: Creatinine Ratio With the Adverse Pregnancy Outcome.

Background Urinary albumin creatinine ratio (ACR) is a known method of measurement of microalbuminuria. Microalbuminuria may be an early marker of endothelial dysfunction which can lead to various complications during the course of pregnancy. The objective of our study was to evaluate the correlation of mid-trimester spot urinary ACR with the pregnancy outcome. Material and methods We performed a prospective cohort study in the department of Obstetrics & Gynaecology, All India Institute of Medical Sciences, Bhopal, for a period of one year. We studied 130 antenatal women between 14 and 28 weeks of gestation after obtaining written informed consent. The patients with ongoing urinary tract infection (UTI), pre-existing hypertension, or diabetes were excluded. Urinary samples were examined for spot ACR, and the women were followed until delivery. Primary maternal outcomes were development of gestational hypertension, pre-eclampsia, gestational diabetes mellitus (GDM), and preterm labour. Neonatal outcome was assessed in terms of birth weight, the APGAR (Appearance, Pulse, Grimace, Activity, Respiration) scores, and neonatal intensive care unit (NICU) admission. Results  In our study, mean urinary ACR was 19.07±12.94 mcg/mg and median urinary ACR (IQR) was 18 (9.43-25.25) mcg/mg. Prevalence of microalbuminuria in our study was 19.2%. It was observed that urinary ACR level was significantly higher in women with maternal complications like GDM, gestational hypertension, preeclampsia, and preterm labour. Also, mean urinary ACR of women who developed preeclampsia was higher (37.53±31.85) compared to women who developed gestational hypertension (27.40±9.71). Urinary ACR level was significantly higher in babies with low APGAR scores and in babies who needed NICU admission (p value < 0.05). The sensitivity and specificity of spot urinary ACR to predict GDM and preeclampsia were found to be good as calculated from the receiver operating curve. Conclusion We found definite correlation of higher values of mid-trimester urinary ACR with the adverse pregnancy outcome.