Urinary Albumin-to-creatinine Ratio Research Articles

Urinary Biomarkers of Tubular Health and Risk for Kidney Function Decline or Mortality in Diabetes

Introduction: Diabetes is a leading cause of end-stage kidney disease (ESKD). Biomarkers of tubular health may prognosticate chronic kidney disease (CKD) progression beyond estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Methods: We examined associations of five urinary biomarkers of tubular injury and repair (NGAL, KIM-1, IL-18, MCP-1, YKL-40) with kidney function decline (first occurrence of a decrease in eGFR ≥30 mL/min/1.73 m2 if randomization eGFR ≥60 or ≥50% if randomization eGFR <60; ESKD) and all-cause mortality among 1,135 VA NEPHRON-D trial participants with baseline UACR ≥300 mg/g and available urine samples. Covariates included age, sex, race, BMI, systolic BP, HbA1c, treatment arm, eGFR, and UACR. In a subset of participants with 12-month samples (n = 712), we evaluated associations of KIM-1, MCP-1, and YKL-40 change (from baseline to 12 months) with eGFR decline (from 12 months onward). Results: At baseline, mean age was 65 years, mean eGFR was 56 mL/min/1.73 m2, and median UACR was 840 mg/g. Over a median of 2.2 years, 13% experienced kidney function decline and 9% died. In fully adjusted models, the highest versus lowest quartiles of MCP-1 and YKL-40 were associated with 2.18- and 1.76-fold higher risks of kidney function decline, respectively. One-year changes in KIM-1, MCP-1, and YKL-40 were not associated with subsequent eGFR decline. Higher baseline levels of NGAL, IL-18, MCP-1, and YKL-40 levels (per 2-fold higher) were independently associated with 10–40% higher risk of mortality. Conclusion: Among Veterans with diabetes and CKD, urinary biomarkers of tubular health were associated with kidney function decline and mortality.

Causal Effects of Specific Gut Microbiota on Chronic Kidney Diseases and Renal Function-A Two-Sample Mendelian Randomization Study.

Targeting the gut microbiota may become a new therapeutic to prevent and delay the progression of chronic kidney disease (CKD). Nonetheless, the causal relationship between specific intestinal flora and CKD is still unclear. To identify genetically predicted microbiota, we used summary data from genome-wide association studies on gut microbiota in 18340 participants from 24 cohorts. Furthermore, we genetically predicted the causal relationship between 211 gut microbiotas and six phenotypes (outcomes) (CKD, estimated glomerular filtration rate (eGFR), urine albumin to creatinine ratio (UACR), dialysis, rapid progress to CKD, and rapid decline of eGFR). Four Mendelian randomization (MR) methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used to investigate the casual relationship between gut microbiotas and various outcomes. The result of IVW was deemed as the primary result. Then, Cochrane's Q test, MR-Egger, and MR-PRESSO Global test were used to detect heterogeneity and pleiotropy. The leave-one method was used for testing the stability of MR results and Bonferroni-corrected was used to test the strength of the causal relationship between exposure and outcome. Through the MR analysis of 211 microbiotas and six clinical phenotypes, a total of 36 intestinal microflora were found to be associated with various outcomes. Among them, Class Bacteroidia (=-0.005, 95% CI: -0.001 to -0.008, p = 0.002) has a strong causality with lower eGFR after the Bonferroni-corrected test, whereas phylum Actinobacteria (OR = 1.0009, 95%CI: 1.0003-1.0015, p = 0.0024) has a strong causal relationship with dialysis. The Cochrane's Q test reveals that there is no significant heterogeneity between various single nucleotide polymorphisms. In addition, no significant level of pleiotropy was found according to MR-Egger and MR-PRESSO Global tests. Through the two-sample MR analysis, we identified the specific intestinal flora that has a causal relationship with the incidence and progression of CKD at the level of gene prediction, which may provide helpful biomarkers for early disease diagnosis and potential therapeutic targets for CKD.

Neck-to-height ratio is positively associated with diabetic kidney disease in Chinese patients with type 2 diabetes mellitus.

The aim of this study was to investigate the associations of neck circumference (NC) and neck-to-height (NHR) with diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM). A total of 2,615 patients with prevalent T2DM were enrolled. NHR was calculated through NC (cm) divided by height (cm), and prevalent DKD was defined as the urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g or the estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 in the absence of other primary kidney diseases. The levels of NC and NHR were higher in DKD patients compared with non-DKD patients (38.22 vs. 37.71, P = 0.003; 0.232 vs. 0.227, P < 0.001, respectively). After full adjustments, individuals at the highest tertile of NHR had higher odds of DKD than those at the lowest tertile (multivariate-adjusted OR = 1.63, 95% CI: 1.22, 2.18), but this association was not pronounced with NC (multivariate-adjusted OR = 1.24, 95% CI: 0.87, 1.76). Individuals at the highest tertile of NHR had lower eGFR (β = -4.64, 95% CI: -6.55, -2.74) and higher UACR levels (β = 0.27, 95% CI: 0.10, 0.45) than those at the lowest tertile. The adverse association between NHR and prevalent DKD remained statistically significant among most of the subgroups analyzed and no interaction effects were observed. The increase in NHR was adversely and independently associated with DKD in this Chinese T2DM population.

The association of thyroid parameters with markers of chronic kidney disease in euthyroid patients with type 2 diabetes.

This study was established to explore the association of thyroid parameters including thyroid hormone and thyroid sensitivity indices with chronic kidney disease (CKD) in euthyroid patients with type 2 diabetes (T2D). CKD markers were defined by estimated glomerular filtration rate (eGFR) based on serum creatinine (Scr) (eGFRcr), eGFR based on cystatin C (cys C) (eGFRcys), and urinary albumin-to-creatinine ratio (UACR). Thyroid parameters, including triiodothyronine (FT3), free thyroxin (FT4), thyroid-stimulating hormone (TSH), FT3/FT4 ratio, TSH index (TSHI), and thyrotroph T4 resistance index (TT4RI), were measured. The prevalence rates of CKD defined by eGFRcys, eGFRcr, and UACR was 19.9%, 14.1%, and 50.6%, respectively. The eGFRcys and eGFRcr levels increased with increasing FT3 and FT3/FT4 tertiles, while the UACR levels increased with decreasing FT3 tertiles. Spearman's analysis demonstrated that FT3 and FT3/FT4 were positively associated with eGFRcys and eGFRcr, and negatively associated with UACR. In logistic regression analyses, compared with the lowest FT3 tertile (≤4.12 pmol/L), the adjusted ORs for CKD (eGFRcys <60 mL/min/1.73 m2) in the middle FT3 tertile (4.12-4.74 pmol/L) and higher FT3 tertile (>4.74 pmol/L) were 0.248 and 0.153, respectively, but prominent associations of thyroid parameters with eGRFcr <60 mL/min/1.73 m2 and UACR were not observed after adjustment. Linear regression analysis demonstrated that eGFRcys was more strongly associated with FT3 than eGFRcr or UACR in the adjusted model. Among euthyroid patients with T2D, FT3 in the normal range was the independent factor most strongly related to CKD. Additionally, eGFRcys rather than eGFRcr or UACR was the CKD marker most associated with FT3.

Serum VEGF as a predictive marker of glycemic control and diabetic nephropathy in Chinese older adults with type 2 diabetes mellitus.

Recent researches have demonstrated good correlation between vascular endothelial growth factor (VEGF) and diabetic nephropathy (DN); however, this relationship seems less clear-cut when VEGF was measured in blood samples. We tended to explore the possible association between serum VEGF and glycemic control and diabetic nephropathy severity in Chinese older adults with type 2 diabetes mellitus (T2DM). This study retrospectively enrolled 595 older T2DM adults at random. Participants were clinically grouped across the urine albumin-to-creatinine ratio (UACR) and the HbA1c tertiles by genders. Linear regressions were performed for the correlation of VEGF with HbA1c and UACR and binary logistic regressions for the odds of DN after adjusting for confounders. The receiver operating characteristic (ROC) curves were conducted for the predictive value of VEGF for DN. Both males and females with DN exhibited higher VEGF levels than non-DN (P < 0.001). Furthermore, a positive correlation of VEGF with UACR and HbA1c was presented regardless of adjusting confounding factors (P < 0.001). Serum VEGF level and fasting plasma glucose (FPG) were independent risk factors of DN in older adults of both genders (P < 0.05), while the risk prediction of DN by HbA1c only reflected in female patients (P < 0.05). The ROC curve of VEGF for DN had the area under curve (AUC) of 0.819 for males and 0.793 for females, indicating the clinical value of serum VEGF as a predictive biomarker. Serum VEGF was strongly associated with UACR and HbA1c in both genders, and could be regarded as a predictive biomarker for glycemic control and diabetic nephropathy in older adults with T2DM.

Kidney damage on fertility and pregnancy: A Mendelian randomization.

Low fertility and adverse pregnancy outcomes are commonly observed in women with chronic kidney disease (CKD). However, a causal relationship between low fertility and adverse pregnancy outcomes with CKD remains unclear. Besides, whether mild kidney dysfunction can affect fertility and pregnancy still needs exploration. Hence, this study aimed to investigate the causal effect of kidney damage on fertility and pregnancy using Mendelian randomization (MR). We first used two-sample MR to examine the effects of kidney damage on fertility and pregnancy. Next, we introduced the Bayesian model averaging MR analysis to detect major causal relationships and render the results robust. The genetic instruments and outcome data were derived from various large genome-wide association studies. Adverse pregnancy outcomes: Our analyses supported a suggestive causal effect of CKD and estimated glomerular filtration rate (eGFR) rapid on stillbirth, with CKD having an odds ratio (OR) of 1.020 [95% confidence interval (CI) 1.002 to 1.038] and eGFR rapid having an OR of 1.026 (95% CI 1.004-1.048). We also discovered a suggestive causal effect of eGFR on spontaneous abortion, with an OR of 2.63 (95% CI 1.269 to 5.450). Moreover, increased urinary albumin-to-creatinine ratio (UACR) was regarded as a potential risk factor for pre-eclampsia (OR = 1.936; 95% CI 1.065 to 3.517) and gestational hypertension (OR = 1.700; 95% CI 1.002 to 2.886). Fertility assessment: The results indicated that eGFR and UACR had a suggestive causal relationship with the anti-Müllerian hormone level (eGFR beta: 1.004; UACR beta: 0.405). Our study used MR to demonstrate a suggestive causal relationship between kidney damage and fertility and pregnancy. We reported that mild kidney dysfunction might be a risk factor for reduced fertility and adverse pregnancy outcomes. Dynamic renal detection may help preserve fertility and reduce the risk of pregnancy loss.

Copeptin is associated with microalbuminuria and renal function in the general Japanese population.

An association between copeptin (precursor molecule of arginine vasopressin) and markers for renal function has been reported, but data on the Japanese population has been limited. In this study, we investigated whether elevated copeptin levels are associated with microalbuminuria and renal dysfunction in the general Japanese population. A total of 1,262 participants (842 female and 420 male) were enrolled. Multiple regression analysis was performed to assess the association of copeptin levels (logarithm) with estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR) after adjusting for age, BMI, and lifestyle variables. Odds ratios (ORs) and 95% confidence intervals were calculated using logistic regression methods in which chronic kidney disease (CKD) was the dependent variable. The copeptin levels differed significantly with sex, but were not found to be related to age or the span of time from preceding meal to blood sampling. In female participants, copeptin level was negatively correlated with eGFR (beta = -0.100, p-value = 0.006) and positively correlated with UACR (beta = 0.099, p-value = 0.003). In male participants, a negative correlation (beta = -0.140, p-value = 0.008) was observed for eGFR. In both females and males, those with high copeptin levels had more than double the ORs of CKD (OR = 2.1-2.9) adjusted for CKD-related factors. The present study found elevated copeptin levels to be associated with renal function loss in the Japanese population and microalbuminuria in female. Moreover, it was evident that high copeptin levels are associated with CKD. These results suggest that copeptin could be considered a marker of renal function.

Correlation between muscle mass reduction and serum uric acid and urinary albumin in middle-aged and elderly type 2 diabetes men

This cross-sectional study correlated the muscle mass reduction with serum uric acid and urinary albumin in middle-aged and elderly men having type 2 diabetes. The study subjects were 288 middle-aged and elderly male patients with type 2 diabetes (T2DM) admitted to our hospital. They were divided into sarcopenia (n = 95) and non-sarcopenia (n = 193) groups based on whether diagnosed with sarcopenia or not. The relevant clinical information of patients was collected. Single factor analysis and multiple factor regression analysis were employed to explore the influencing factors of sarcopenia. A binary logistic regression analysis model was established for the sarcopenia probability in middle-aged and elderly men with T2DM. Hosmer and Lemeshow test evaluated the Goodness of fit of probability model. ROC (Receiver Operating Characteristic) curve was drawn by SPSS and the predictive value of prediction model was evaluated. The univariate analysis depicted that the patients in sarcopenia group compared to those in non-sarcopenia were older with lower BMI (Body Mass Index), lower UA (Uric Acid) and higher CRP (C-reactive Protein). The differences were statistically significant (p &lt; 0.05). The binary logistic regression analysis exhibited that the age and UACR (Urine Albumin-to-Creatinine Ratio) were the risk factors, while BMI and UA were the protective factors for sarcopenia in middle-aged and elderly men with T2DM. For middle-aged and elderly male patients with T2DM, age and UACR were the risk factors, and BMI and UA were the protective factors for sarcopenia. The changes in above-stated indicators of patients with T2DM should be clinically monitored, and early and active intervention be given to high-risk groups for minimizing the sarcopenia occurrence.

PS-BPB06-3: EXAMINATION OF THE EFFECTIVENESS OF DIABETIC NEPHROPATHY TREATMENT TARGETING CHREBP ACTIVITY

Introduction: Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD), and is characterized by elevated urinary albumin to creatinine ratio (UACR) and serum creatinine, and decreased glomerular filtration rate. Anti hypertensive agents are used for DN treatment, however, the effects of these drugs are insufficient, and the establishment of more effective treatment methods is desired. Carbohydrate responsive element binding protein (ChREBP) is one of the factors reported to be involved in the onset and progression of DN. Furthermore, whole body ablation of ChREBP suggested that the progression of DN was suppressed in the rodent model. On the other hand, the effectiveness of pharmaceutical ChREBP suppression is unclear, thus, we performed administration experiment to DN model mice using ChREBP activity inhibitor and examined the effects of pharmaceutical ChREBP activity suppression on renal function of diabetic mice. Results: First, we established high-throughput screening system capable of detecting ChREBP activity and performed screening of Tohoku university compound library. The result compound, D-532, was ChREBP activity specific inhibitor without cell toxicity. D-532 directly binds to DNA-binding domain of ChREBP, and inhibits the transcriptional activity. We next performed administration experiment using type 1 DN model mice. D-532 treatment group showed an improvement tendency of the low body weight compared with that of vehicle treatment group, while it had no effect on blood glucose level. About renal functions, both of UACR and serum creatinine were significantly lower in D-532 treatment group. Importantly, renal tissues such as glomeruli and renal tubules were preserved in D-532 treatment group compared with in vehicle treatment group. In vivo as well, D-532 suppressed ChREBP target genes mRNA expression, and RNA-sequence analysis with mice renal cortex RNA at the end of D-532 administration experiment indicated that D-532 suppressed excessive oxidative stress through the ChREBP activation under diabetes. Conclusion: These results indicate that ChREBP suppression is effective on DN rodent model, and ChREBP activity inhibitor D-532 may have potential as a new treatment for DN in the future.

Impact of magnesium supplementation on clinical outcome and disease progression of patients with diabetic nephropathy: a prospective randomized trial.

Magnesium (Mg) deficiency is closely linked with proteinuria. To assess the impact of oral Mg citrate supplementation on the clinical outcome of diabetic nephropathy (DN) patients. This was a prospective, randomized, controlled, open-label study. Sixty DN patients were recruited from Nephrology and Endocrinology departments, Ain Shams University Hospitals, Cairo, Egypt. Patients were assigned by stratified randomization based on their Mg status, to either Mg citrate group, (n = 30), who received the standard regimen + oral Mg citrate 2.25 g/day or Control group, (n = 30), who received the standard regimen only. The primary endpoint was a change in urinary albumin to creatinine ratio (UACR) after 12 weeks. Secondary outcomes were insulin resistance, glycemic control, lipid profile, serum osteocalcin, quality of life (QoL) and Mg tolerability. Out of a total of 60 patients enrolled, only 54 patients (26 in Mg citrate group and 28 in the control group) completed the study. Groups were comparable at baseline. The UACR median percent reduction was significantly higher in the Mg citrate group (-6.87%) versus (-0.9%) in the Control group, p = 0.001. After 12 weeks, the estimated glomerular filtration rate significantly improved in the Mg citrate group versus Control group (p = 0.001). Comparable change was observed in glycemic indices. Lipid profile significantly improved in the Mg citrate group versus Control group (p = 0.001). Serum osteocalcin levels significantly declined in the Mg citrate group (p = 0.001) versus control group. Regarding QoL, the total score and all domains significantly improved in the Mg citrate group compared to control. The Mg supplement was tolerable with only mild reported side effects that required no intervention. Oral Mg citrate supplementation improved microalbuminuria in DN patients. It also had favorable effects on serum osteocalcin, lipid profile and QoL with no reported major side effects. ClinicalTrials.gov identifier: NCT03824379.

Association between diabetic kidney disease and low muscle mass in patients with type 2 diabetes: a cross-sectional study

This study included 1241 inpatients with type 2 diabetes mellitus(T2DM) at the First Affiliated Hospital of Chongqing Medical University, China, from October 2013 to October 2018 to investigate the relationship between diabetic kidney disease and low muscle mass. The body composition of patients was measured with dual-energy X-ray-absorptiometry. Social history, medical history, and Clinical indexes were all collected to analyze. In the results, this study found: (1) The percentage of low muscle mass in the population with diabetic complications and cardiovascular and cerebrovascular diseases was far more than the diabetic patients without those; (2) Urinary albumin-to-creatinine ratio (UACR) in patients with low muscle mass was significantly higher than that observed in the cases without [23.3(5.80, 193.35) vs. 16.45(4.80, 76.73), P=0.01], and the prevalence of low muscle mass was positively correlated with stratified UACR (Cramer’s V=0.086, P for Cramer’s V=0.011); (3) Diabetic kidney disease was one of the independent risk factors for low muscle mass in patients with T2DM. [OR=1.64(1.05, 2.55), P=0.02].

PS-P15-8: EFFICACY AND SAFETY OF ESAXERENONE IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES AND RECEIVING SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS (EAGLE-DH STUDY)

Objective: Hypertensive patients with type 2 diabetes mellitus (T2DM) who respond inadequately to antihypertensive therapy are at high risk for cardiorenal events and require effective treatment options. Clinical trials have shown that esaxerenone, a non-steroidal mineralocorticoid receptor blocker, has favorable antihypertensive and renoprotective effects in hypertensive patients with various characteristics including T2DM and albuminuria. However, clinical evidence is lacking regarding the concomitant use of esaxerenone and sodium-glucose cotransporter 2 (SGLT2) inhibitors in hypertensive patients with T2DM. The study aimed to evaluate the efficacy and safety of esaxerenone and SGLT2 inhibitor combination therapy in Japanese hypertensive patients with T2DM who had an inadequate response to blood pressure (BP)-lowering treatment with renin angiotensin system (RAS) inhibitor or calcium channel blocker (CCB) monotherapy or combined therapy. Design and method: EAGLE-DH (jRCTs031200273) was a multicenter, open-label, interventional study in hypertensive patients (age, ≧ 20 years) with T2DM. Inclusion criteria were previous use of antihypertensive therapy (a RAS inhibitor, CCB, or RAS inhibitor plus CCB) and oral hypoglycemic drugs (a SGLT2 inhibitor with or without one or two other oral hypoglycemic drugs) for ≧ 12 weeks; morning home systolic BP (SBP) 125 to &lt; 160 mmHg and/or diastolic BP (DBP) 75 to &lt; 100 mmHg; and eGFRcreat ≧ 30 mL/min/1.73m2 at baseline. Over the 24-week study period, esaxerenone dose was started at 1.25 or 2.5 mg/day, and based on the individual patient's condition, the dose could be titrated at weeks 4 and 8 to a maximum of 5 mg/day. The primary endpoints were change in morning home BP from baseline to weeks 12 and 24. Secondary endpoints included change in bedtime home BP and office BP, proportion of patients achieving target SBP/DBP (home, &lt; 125/75 mmHg; office, &lt; 130/80 mmHg), change in urine albumin-to-creatinine ratio (UACR), and safety variables including adverse events, eGFR, and serum potassium. Results: The study population comprised 93 patients. Baseline characteristics were mean age, 66.3 years; male, 68.8%; mean morning home SBP/DBP, 136.4/82.3 mmHg; mean UACR 145.3 mg/g creatinine; one RAS inhibitor use, 33.3%; one CCB inhibitor use, 19.4%; RAS inhibitor plus CCB, 47.3%; mean HbA1c 6.8%; mean serum potassium, 4.2 mEq/L; and mean eGFRcreat 66.8 mL/min/1.73m2. Efficacy and safety results will be presented at the conference. Conclusions: EAGLE-DH will provide the first evidence from clinical practice for the efficacy of esaxerenone plus SGLT2 inhibitor in reducing morning/bedtime home and office BP with improving albuminuria as well as for its safety profile in Japanese hypertensive patients with T2DM.

Single spot albumin to creatinine ratio as an independent predictor of 12 years follow-up mortality in acute coronary syndromes without ST-segment elevation.

Background: Up to date there is no evidence of the association between microalbuminuria, measured as single spot urine albumin to creatinine ratio (ACR), with very long-term mortality in patients with non-ST segment Elevation Acute Coronary Syndromes (NSTE-ACS). Aim: To evaluate the association between admission ACR and very long-term all-cause mortality in an unselected cohort of NSTE-ACS patients. Methods: A prospective cohort study was conducted, including patients with NSTE- ACS admitted in the Intensive Care Unit. The ACR was determined in spontaneous urine samples during the first 24 hours after admission and analyzed by immunoturbidimetry. The primary endpoint was all-cause mortality during the follow-up. Actuarial survival curves were compared by log rank test and a logistical Cox regression analysis was performed to identify variables independently associated with mortality in the follow-up. Statistics were calculated using the IBM Statistics program SPSS version 26. Results: 600 patients were analyzed. The overall average ACR value was 7 mg/gr (95% CI 4-26). 76% had normoalbuminuria (ACR 0-30 mg/gr), 22% had microalbuminuria (ACR 30-300 mg/gr), and 1.5% had macroalbuminuria (ACR &gt; 300 mg/gr). The median and interquartile range of follow-up was 12 years (95% IC 11-14). The average IAC among those who met the primary endpoint was 59.15 mg/gr (95% CI 52-66) and among the survivors, 27.66 mg/gr (95 % CI 63-77), p 0,003. ACR terciles were defined by 33th and 66th percentiles: tercile 1: patients with IAC of 0 to 4 mg/gr, tercile 2: IAC from 4 to 17 mg/g and tercile 3 values greater than 17mg/gr. Strong associations were observed between ACR with age, hypertension, stroke and history of COPD, previous use of angiotensin II converter/blocking enzyme inhibitors, systolic blood pressure at admission, ST segment deviation, left ventricle ejection fraction and elevation of serum Troponin T and CPK MB. All cause-mortality during the follow-up was 14% (CI 95% 11-17). Elevation of ACR was significantly associated with long term mortality risk: log rank test chi square: 133.936, p = 0.0001. By multivariate Cox regression analysis adjusted by age, gender, diabetes, hypertension, serum creatinine, troponin T elevation, ST segment deviation, previous AMI, prior use of aspirin, statins and percutaneous coronary intervention after hospitalization, the ACR was independently associated with a 12-year follow-up mortality: OR 13 (95% IC 5-35; p 0.0001). Conclusion: Single spot urine ACR at admission is a strong predictor of 12-year follow- up mortality in an unselected cohort of patients with NSTE-ACS.

Urinary orosomucoid is associated with diastolic dysfunction and carotid arteriopathy in the general population. Cross-sectional data from the Tromsø study

Objectives. Urinary albumin excretion is a risk marker for cardiovascular disease (CVD). Studies suggest that urinary orosomucoid may be a more sensitive marker of general endothelial dysfunction than albuminuria. The aim of this population-based cross-sectional study was to examine the associations between urinary orosomucoid to creatinine ratio (UOCR), urinary albumin to creatinine ratio (UACR) and subclinical CVD. Design. From the Tromsø Study (2007/2008), we included all men and women who had measurements of urinary orosomucoid (n = 7181). Among these, 6963 were examined with ultrasound of the right carotid artery and 2245 with echocardiography. We assessed the associations between urinary markers and subclinical CVD measured as intima media thickness of the carotid artery, presence and area of carotid plaque and diastolic dysfunction (DD). UOCR and UACR were dichotomized as upper quartile versus the three lowest. Results. High UOCR, adjusted for UACR, age, cardiovascular risk factors and kidney function, was associated with presence of DD in men (OR: 3.18, 95% CI [1.27, 7.95], p = .013), and presence of plaque (OR: 1.20, 95% CI [1.01, 1.44], p = .038) and intima media thickness in women (OR: 1.34, 95% CI [1.09, 1.65], p = .005). Analyses showed no significant interaction between sex and UOCR for any endpoints. UACR was not significantly associated with DD, but the associations with intima media thickness and plaque were of magnitudes comparable to those observed for UOCR. Conclusions. UOCR was positively associated with subclinical CVD. We need prospective studies to confirm whether UOCR is a clinically useful biomarker and to study possible sex differences.

Risk Factors for Diabetic Nephropathy among Newly Detected Type 2 Diabetic Patients Attending a Tertiary Care Hospital of Bangladesh

Background: Patients with type 2 diabetes mellitus may present with different macro- and micro-vascular complications including diabetic nephropathy. This study was designed to evaluate the risk factors for diabetic nephropathy among newly detected type 2 diabetic patients. Methods: This case-control study was done at BIRDEM General Hospital, Dhaka, Bangladesh from January to September 2017. Adult (³18 years), type 2 diabetic patients, who were detected as diabetic for the first time, within the previous three months and who tested, at least, 2 urine samples for urine albumin to creatinine ratio (UACR), at least 6 weeks apart, were consecutively enrolled for the study. Pregnant ladies, patients with diagnosed kidney disease, patients having features of glomerulonephritis and systemic diseases like vasculitis and systemic lupus erythematosus, history of recent fever, urinary tract infection and menstruation were excluded. Patients having UACR ³30 mg/g in at least 2 (out of 3, if tested) samples were taken as cases and those with UACR &lt; 30 mg/g were controls. Data were analyzed by statistical package for social sciences (SPSS) version 20. Results: Total patients were 224 with female predominance (150, 67%). Fifty one (22.8%) patients had diabetic nephropathy (microalbuminuria = 47 and overt proteinuria = 4). Multivariate regression analysis revealed that, hypertension [odds ratio (OR) = 3.71; 95% CI 1.23 to 4.31, p = 0.003], smoking (OR = 3.27; 95% CI 2.91 to 4.79, p = 0.003), family history of diabetes (OR = 2.31; 95% CI 1.84 to 3.14, p = 0.005) and diabetic nephropathy (OR = 3.34; 95% CI 2.40 to 4.97, p = 0.001), dyslipidaemia (OR = 2.31; 95% CI 1.98 to 3.91, p = 0.023), increased body mass index (BMI) (OR = 2.11; 95% CI 1.54 to 4.87, p = 0.001 and high glycated haemoglobin (HbA1c) (OR 3.21; 95% CI 1.71 to 5.97, p = 0.034) were significant risk factors for diabetic nephropathy. Conclusion: One in every five type 2 diabetic patients had diabetic nephropathy during diabetes diagnosis and most patients had microalbuminuria. Hypertension, dyslipidaemia, smoking, family history of diabetes and diabetic nephropathy, increased BMI and high HbA1c were significant risk factors for diabetic nephropathy among newly detected type 2 diabetic patients. J Bangladesh Coll Phys Surg 2023; 41: 15-21

Comparative evaluation of clinical outcomes of dapagliflozin and empagliflozin in type-2 diabetes mellitus.

Sodium-glucose transporter 2 (SGLT-2) inhibitors provide additional benefits besides glycemic control. This study aims to compare the clinical outcomes of dapagliflozin and empagliflozin. This retrospective study evaluated data retrieved from medical records of patients who were under follow-up with the diagnosis of type 2 diabetes mellitus (T2DM) and were started on dapagliflozin or empagliflozin treatment between January 1, 2017, and June 1, 2020. Demographic features, comorbidities, clinical features, duration of diabetes, baseline, and follow-up laboratory test results were recorded. The significance level was set at p < 0.05. This study comprised 342 patients who are on the treatment with dapagliflozin (n = 228) or empagliflozin (n = 114). The glycosylated hemoglobin a1c (HBA1C) level was significantly decreased in both the dapagliflozin (8.18-7.59, p < 0.001) and empagliflozin (8.35-7.58, p < 0.001) groups. The urine albumin-to-creatinine ratio (ACR) was also decreased in both groups. A decrease in urine ACR was observed independent of using a renin-angiotensin-aldosterone system (RAAS) blocker both in the whole group and in patients with diabetic nephropathy. The time to addition of a new anti-diabetic agent to the treatment was shorter in the dapagliflozin group (14.4months vs 17.7months, p = 0.041, respectively). Dapagliflozin and empagliflozin are the drugs to choose for renoprotection in diabetics independent of the use of a RAAS blocker. Even the time to addition of a new anti-diabetic agent is longer in the empagliflozin group, head-to-head comparative trials are needed to asess the potential differences in this regard.

Intraperitoneally Delivered Umbilical Cord Lining Mesenchymal Stromal Cells Improve Survival and Kidney Function in Murine Lupus via Myeloid Pathway Targeting

To determine the therapeutic efficacy of human umbilical cord lining mesenchymal stromal cells (CL-MSCs) (US Patent number 9,737,568) in lupus-prone MRL/lpr (Faslpr) mice and elucidate its working mechanisms. A total of 4 doses of (20-25) × 106 cells/kg of CL-MSCs was given to 16-week-old female Faslpr mice by intraperitoneal injection. Three subsequent doses were given on 17 weeks, 18 weeks, and 22 weeks, respectively. Six-week-old Faslpr mice were used as disease pre-onset controls. Mice were monitored for 10 weeks. Mouse kidney function was evaluated by examining complement component 3 (C3) deposition, urinary albumin-to-creatinine ratio (ACR), and lupus nephritis (LN) activity and chronicity. Working mechanisms were elucidated by flow cytometry, Luminex/ELISA (detection of anti-dsDNA and isotype antibodies), and RNA sequencing. CL-MSCs improved mice survival and kidney function by reducing LN activity and chronicity and lymphocyte infiltration over 10 weeks. CL-MSCs also reduced urinary ACR, renal complement C3 deposition, anti-dsDNA, and isotype antibodies that include IgA, IgG1, IgG2a, IgG2b, and IgM. Immune and cytokine profiling demonstrated that CL-MSCs dampened inflammation by suppressing splenic neutrophils and monocytes/macrophages, reducing plasma IL-6, IL-12, and CXCL1 and stabilizing plasma interferon-γ and TNF-α. RNA sequencing further showed that CL-MSCs mediated immunomodulation via concerted action of pro-proinflammatory cytokine-induced chemokines and production of nitric oxide in macrophages. CL-MSCs may provide a novel myeloid (neutrophils and monocytes/macrophages)-targeting therapy for SLE.

Circulating Fibroblast Growth Factor-23 Levels Can Predict Rapid Kidney Function Decline in a Healthy Population: A Community-Based Study

Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study. A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD-a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD. The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD. Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population.

Nontraditional Risk Factors for Progression Through Chronic Kidney Disease Risk Categories: The Coronary Artery Risk Development in Young Adults Study

BackgroundThere may be nontraditional pathways of chronic kidney disease (CKD) progression that are complementary to classical pathways. Therefore, we aimed to examine nontraditional risk factors for incident CKD and its progression. MethodsWe used the generally healthy population (n = 4382) starting at age 27-41 years in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, which is an observational longitudinal study. Nontraditional risk factors included forced vital capacity, inflammation, serum urate, and serum carotenoids. CKD risk category was classified using the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) measured in 1995-1996 and repeated every 5 years for 20 years: No CKD, low risk, moderate risk, high risk, and very high risk. ResultsAt baseline, 84.8% had no CKD (eGFR ≥60 mL/min/1.73 m2 and UACR <10 mg/g), 10.3% were in the low risk (eGFR ≥60 and UACR 10-29), and 4.9% had CKD (eGFR <60 and/or UACR ≥ 30). Nontraditional risk factors were significantly associated with the progression of CKD to higher categories. Hazard ratios per standard deviation of the predictor for incident CKD and its progression from the No CKD and low and moderate risk into CKD were inverse for forced vital capacity and serum carotenoids and positive for serum urate, GlycA, and C-reactive protein, the first 3 even after adjustment for conventional risk factors. ConclusionSeveral nontraditional markers were significantly associated with an increased risk of progression to higher CKD categories in generally healthy young to middle-aged adults.

Elevated serum uric acid is not an independent risk factor for the occurrence of Type 2 diabetic kidney disease in Chinese populations

Previous studies suggested that increased serum uric acid (SUA) level is an independent risk factor for albuminuria in Type 2 diabetes (T2D) patients. However, the association between SUA and onset of Type 2 DKD (T2DKD) remained to be clarified. This was a cross-sectional clinical study in which 1210 Chinese T2D patients were enrolled. According to the urine albumin-to-creatinine ratio (UACR), the cohort was divided into normal-albuminuria (UACR < 30 mg/g), micro-albuminuria (UACR 30-300 mg/g) and macro-albuminuria (UACR > 300 mg/g). The micro- and macro-albuminuria groups were combined into albuminuria category. Results showed that T2D patients with macro-albuminuria have significantly higher SUA than the other 2 groups (P < .001). In the binary logistic regression model, the subjects with SUA higher than 420 μmol/L were associated with a 2-fold increase in the odds of albuminuria (odds ratio = 2.024, 95% confidence interval: 1.232-3.325, P = .005), as compared with those with SUA lower than 300 μmol/L. Moreover, the multinomial regression analysis revealed that the subjects with SUA higher than 420 μmol/L had about 3-fold increase in the odds of macro-albuminuria (odds ratio = 3.758, 95% confidence interval: 2.051-6.885, P < .001), as compared with those with SUA lower than 300 μmol/L. However, SUA was not significantly associated with the presence of micro-albuminuria. Although the SUAwas not independently risk factor for micro-albuminuria, it was closely correlated with the development of macro-albuminuria in Chinese T2DKD patients. Elevated SUA may be useful for predicting the occurrence of macro-albuminuria but not onset of micro-albuminuria at the early stage of T2DKD.