Early reduction in albuminuria is associated with a steeper 'dip' in initial estimated glomerular filtration rate but favourable long-term kidney outcomes in people with diabetes receiving sodium-glucose cotransporter-2 inhibitors.

AIM: To assess if early change in albuminuria was linked to an initial change in estimated glomerular filtration rate (eGFR) and long-term kidney outcomes in people with type 2 diabetes (T2D) receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors. METHODS: Using a medical database from a multicentre healthcare institute in Taiwan, we retrospectively enrolled 8310 people receiving SGLT2 inhibitors from 1 June 2016 to 31 December 2021. We compared the risks of initial eGFR decline, major adverse renal events (MARE; >50% eGFR reduction or development of end-stage kidney disease), major adverse cardiovascular events (MACE), or hospitalization for heart failure (HHF) using a Cox proportional hazards model. RESULTS: In all, 36.8% (n = 3062) experienced a >30% decrease, 21.0% (n = 1743) experienced a 0%-30% decrease, 14.4% (n = 1199) experienced a 0%-30% increase, and 27.7% (n = 2306) experienced a >30% increase in urine albumin-to-creatine ratio (UACR) after 3 months of SGLT2 inhibitor treatment. Greater acute eGFR decline at 3 months correlated with greater UACR reduction: -3.6 ± 10.9, -2.0 ± 9.5, -1.1 ± 8.6, and -0.3 ± 9.7 mL/min/1.73 m2 for the respective UACR change groups (p < 0.001). Over a median of 29.0 months, >30% UACR decline was associated with a higher risk of >30% initial eGFR decline (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.61-4.47]), a lower risk of MARE (HR 0.66, 95% CI 0.48-0.89), and a comparable risk of MACE or HHF after multivariate adjustment (p < 0.05). The nonlinear analysis showed early UACR decline was linked to a lower risk of MARE but a higher risk of initial steep eGFR decline of >30%. CONCLUSION: Physicians should be vigilant for the potential adverse effects of abrupt eGFR dipping associated with a profound reduction in UACR, despite the favourable long-term kidney outcomes in the population with T2D receiving SGLT2 inhibitor treatment.

Elevated urine albumin-to-creatinine ratio increases the risk of new-onset heart failure in patients with type 2 diabetes.

BACKGROUND: Although albuminuria has been linked to heart failure in the general population, the relationship between urine albumin-to-creatinine ratio (uACR) and heart failure in type 2 diabetes patients is not well understood. We aimed to investigate the relationship between uACR and new-onset heart failure (HF) in type 2 diabetics. METHODS: We included 9287 Chinese participants with type 2 diabetes (T2D) but no heart failure (HF) who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (< 3 mg/mmol), microalbuminuria (3-30 mg/mmol), and macroalbuminuria (≥ 30 mg/mmol). The relationship between uACR and new-onset HF was studied using Cox proportional hazard models and restricted cubic spline. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to see if incorporating uACR into existing models could improve performance. RESULTS: 216 new-onset HF cases (2.33%) were recorded after a median follow-up of 4.05 years. When compared to normal uACR, elevated uACR was associated with a progressively increased risk of new-onset HF, ranging from microalbuminuria (adjusted HR, 2.21; 95% CI 1.59-3.06) to macroalbuminuria (adjusted HR, 6.02; 95% CI 4.11-8.80), and 1 standard deviation (SD) in ln (uACR) (adjusted HR, 1.89; 95% CI 1.68-2.13). The results were consistent across sex, estimated glomerular filtration rate, systolic blood pressure, and glycosylated hemoglobin subgroups. The addition of uACR to established HF risk models improved the HF risk prediction efficacy. CONCLUSIONS: Increasing uACR, even below the normal range, is an independent risk factor for new-onset HF in a type 2 diabetic population. Furthermore, uACR may improve HF risk prediction in community-based T2D patients.

The Value of a Cystatin C-based Estimated Glomerular Filtration Rate for Cardiovascular Assessment in a General Japanese Population: Results From the Iwate Tohoku Medical Megabank Project.

BACKGROUND: Epidemiological studies have shown that high circulating cystatin C is associated with a risk of cardiovascular disease (CVD) independent of creatinine-based renal function measurements. The present study investigated the comparison between the cystatin C-based estimated glomerular filtration rate (GFRcys) and creatinine-based GFR (GFRcr) to determine whether these measurements are associated with CV biomarkers and elevated CVD risk in a general Japanese population. METHODS: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture (n = 29,375). Chronic kidney disease (CKD) was estimated using the GFRcys, GFRcr and the urine albumin-to-creatinine ratio (UACR). RESULTS: The prevalence of CKD in the participants was found to be higher based on the GFRcr than the GFRcys. Multiple variable analyses after adjusting for baseline characteristics showed that high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with the GFRcys. The area under the receiver operating characteristic (AUROC) curve for identifying individuals with a high Suita score was higher for the GFRcys (AUROC = 0.68) than it was for the GFRcr (AUROC = 0.64, P < 0.001). The GFRcys provided reclassification improvement for the CVD risk prediction model by the GFRcr (net reclassification improvement = 0.341; integrated discrimination improvement = 0.018, respectively, P < 0.001). CONCLUSIONS: The GFRcys is more closely associated with CV biomarkers, including hs-cTnT and NT-proBNP levels, and a high Suita score than the GFRcr, and it provides additional value in the assessment of CVD risk using GFRcr.

Relationship between Clinical Features of Diabetic Retinopathy and Systemic Factors in Patients with Newly Diagnosed Type II Diabetes Mellitus.

BACKGROUND: We investigated the relationship between clinical features of diabetic retinopathy (DR) and systemic factors in patients with newly diagnosed type II diabetes mellitus (T2DM). METHODS: Retrospective review of newly diagnosed T2DM-patients who underwent complete ophthalmic examinations at the time of T2DM diagnosis were conducted. We reviewed DM related systemic factor data and investigated systemic factors related to the presence of DR at T2DM diagnosis. In DR patients, the relationship between DR severity and systemic factors was analyzed. RESULTS: Of 380 patients, forty (10.53%) patients had DR at the initial ophthalmologic examination. Glycated hemoglobin (HbA1C), fasting plasma glucose (FPG), urine albumin to creatinine ratio (UACR), and urine microalbumin level were significantly higher in DR patients than in patients without DR. In the multivariate logistic regression analysis, high HbA1C was a significant risk factor for the presence of DR at new T2DM diagnosis (odds ratio, 2.372; P < 0.001). HbA1C, FPG, UACR, and urine microalbumin level showed significantly positive correlations with DR severity . CONCLUSION: In patients with newly diagnosed T2DM, 10.53% have DR at initial ophthalmologic examination and high HbA1C, FPG, UACR and urine microalbumin levels. These factors are significantly positively correlated with DR severity. Therefore, more careful fundus examination is needed for newly diagnosed T2DM patients with high HbA1C, FPG, UACR, and urine microalbumin levels.

Increased Spot Urine Albumin-to-Creatinine Ratio and Stroke Incidence: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to clarify the association between an increased spot urine albumin-to-creatinine ratio (UACR) and the risk of stroke. METHODS: We performed a systematic review and meta-analysis of cohort studies, case-control studies, and ancillary data randomized controlled trials (RCTs), which were treated as cohorts in this study, and estimated the association between albuminuria, as measured with the UACR, and the risk of stroke. We performed a comprehensive search of PubMed, Embase, and the Cochrane Library and conducted a systematic review and cumulative meta-analysis of cohort studies with a cross-sectional with prospective design in which stroke incidence was reported and the baseline UACR was measured. Ancillary data from RCTs were also included as part of the cohort study. We studied the characteristics of the participants, quality scores and risk ratios (RR, with confidence intervals, CI) of stroke associated with normal and high UACRs, and we synthesized the data via a meta-analysis. RESULTS: Twelve eligible studies including a total of 32,888 participants and 3,944 cases of stroke were identified. A high UACR (>30 mg/mmol) increased the risk of stroke by 1.67 times (RR: 1.67, 95% CI: 1.49-1.86, P<0.001 I2 = 26%). The results were not different between Asian and non-Asian patients (RR: 1.64, 95% CI: 1.41-1.91, P<0.001, I2 = 23% compared with RR: 1.67, 95% CI: 1.50-1.85, P<0. 00, I2 = 39%) or between subgroups classified by old age (RR: 1.61, 95% CI: 1.39-1.88, P<0.001, I2 = 34% compared with RR: 1.68, 95% CI: 1.52-1.87, P<0.001, I2 = 13%). A sensitivity analysis did not significantly change the results. CONCLUSION: The incidence of stroke increased significantly in the high UACR group compared with the normal UACR group. The UACR could be a clinical addition for the early indication of high-risk stroke patients.

Screening for chronic kidney disease in Canadian indigenous peoples is cost-effective.

Canadian indigenous (First Nations) have rates of kidney failure that are 2- to 4-fold higher than the non-indigenous general Canadian population. As such, a strategy of targeted screening and treatment for CKD may be cost-effective in this population. Our objective was to assess the cost utility of screening and subsequent treatment for CKD in rural Canadian indigenous adults by both estimated glomerular filtration rate and the urine albumin-to-creatinine ratio. A decision analytic Markov model was constructed comparing the screening and treatment strategy to usual care. Primary outcomes were presented as incremental cost-effectiveness ratios (ICERs) presented as a cost per quality-adjusted life-year (QALY). Screening for CKD was associated with an ICER of $23,700/QALY in comparison to usual care. Restricting the model to screening in communities accessed only by air travel (CKD prevalence 34.4%), this ratio fell to $7,790/QALY. In road accessible communities (CKD prevalence 17.6%) the ICER was $52,480/QALY. The model was robust to changes in influential variables when tested in univariate sensitivity analyses. Probabilistic sensitivity analysis found 72% of simulations to be cost-effective at a $50,000/QALY threshold and 93% of simulations to be cost-effective at a $100,000/QALY threshold. Thus, targeted screening and treatment for CKD using point-of-care testing equipment in rural Canadian indigenous populations is cost-effective, particularly in remote air access-only communities with the highest risk of CKD and kidney failure. Evaluation of targeted screening initiatives with cluster randomized controlled trials and integration of screening into routine clinical visits in communities with the highest risk is recommended.

Risk factors for CKD progression in Japanese patients: findings from the Chronic Kidney Disease Japan Cohort (CKD-JAC) study.

BACKGROUND: Chronic kidney disease (CKD) eventually progresses to end-stage renal disease (ESRD). However, risk factors associated with CKD progression have not been well characterized in Japanese patients with CKD who are less affected with coronary disease than Westerners. METHODS: A large-scale, multicenter, prospective, cohort study was conducted in patients with CKD and under nephrology care, who met the eligibility criteria [Japanese; age 20-75 years; and estimated glomerular filtration rate (eGFR): 10-59 mL/min/1.73 m2]. The primary endpoint was a composite of time to a 50 % decline in eGFR from baseline or time to the initiation of renal replacement therapy (RRT). The secondary endpoints were the rate of decline in eGFR from baseline, time to a 50 % decline in eGFR from baseline, time to the initiation of RRT, and time to doubling of serum creatinine (Cre) concentration. RESULTS: 2966 patients (female, 38.9 %; age, 60. 3 ± 11.6 years) were enrolled. The incidence of the primary endpoint increased significantly (P < 0.0001) in concert with CKD stage at baseline. The multivariate Cox proportional hazards models revealed that elevated systolic blood pressure (SBP) [hazard ratio (HR) 1.203, 95 % confidence interval (CI) 1.099-1.318)] and increased albumin-to-creatinine ratio (UACR ≥ 1000 mg/g Cre; HR: 4.523; 95 % CI 3.098-6.604) at baseline were significantly associated (P < 0.0001, respectively) with the primary endpoint. CONCLUSIONS: Elevated SBP and increased UACR were risk factors that were significantly associated with CKD progression to ESRD in Japanese patients under nephrology care. UMIN clinical trial registry number: UMIN000020038.

Association of estimated glomerular filtration rate and urine albumin-to-creatinine ratio with incidence of cardiovascular diseases and mortality in chinese patients with type 2 diabetes mellitus - a population-based retrospective cohort study.

BACKGROUND: Estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) are renal markers associated with risks of cardiovascular diseases (CVD) and all-cause mortality in diabetic patients. This study aims to quantify such risks in Chinese diabetic patients based on eGFR and UACR. METHODS: This was a territory-wide retrospective cohort study on primary care diabetic patients with documented eGFR and UACR but without baseline CVD in 2008/2009. They were followed up till 2013 on CVD events and mortality. Associations between eGFR/UACR and incidence of CVD/mortality were evaluated by multivariable Cox proportional models adjusted with socio-demographic and clinical characteristics. RESULTS: The data of 66,311 patients who had valid baseline eGFR and UACR values were analysed. The risks of CVD events and mortality increased exponentially with the decrease in eGFR, with a hazard ratio (HR) increasing from 1.63 to 4.55 for CVD, and from 1.70 to 9.49 for mortality, associated with Stage 3 to 5 CKD, compared to Stage 1 CKD. UACR showed a positive linear association with CVD events and mortality. Microalbuminuria was associated with a HR of 1.58 and 2.08 for CVD and mortality in male (1.48 and 1.79 for female), respectively, compared to no microalbuminuria. Male patients with UACR 1-1.4 mg/mmol and eGFR ≥90 ml/min/1.73 m2 (60-89 ml/min/1.73 m2) had a HR of 1.25 (1.43) for CVD. Female patients with UACR 2.5-3.4 mg/ml and eGFR ≥90 ml/min/1.73 m2 (60-89 ml/min/1.73 m2) had a HR of 1.45 (1.65) for CVD. CONCLUSIONS: Risks of CVD events and mortality increased exponentially with eGFR drop, while UACR showed positive predictive linear relationships, and the risks started even in high-normal albuminuria. UACR-based HR was further modified according to eGFR level, with risk progressed with CKD stage. Combining eGFR and UACR level was more accurate in predicting risk of CVD/mortality. The findings call for more aggressive screening and intervention of microalbuminuria in diabetic patients.

The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Sodium glucose cotransporter 2 (SGLT2) inhibition lowers HbA1c, systolic BP (SBP) and weight in patients with type 2 diabetes and reduces renal hyperfiltration associated with type 1 diabetes, suggesting decreased intraglomerular hypertension. As lowering HbA1c, SBP, weight and intraglomerular pressure is associated with anti-albuminuric effects in diabetes, we hypothesised that SGLT2 inhibition would reduce the urine albumin-to-creatinine ratio (UACR) to a clinically meaningful extent. METHODS: We examined the effect of the SGLT2 inhibitor empagliflozin on UACR by pooling data from patients with type 2 diabetes and prevalent microalbuminuria (UACR = 30-300 mg/g; n = 636) or macroalbuminuria (UACR > 300 mg/g; n = 215) who participated in one of five phase III randomised clinical trials. Primary assessment was defined as percentage change in geometric mean UACR from baseline to week 24. RESULTS: After controlling for clinical confounders including baseline log-transformed UACR, HbA1c, SBP and estimated GFR (according to the Modification of Diet in Renal Disease [MDRD] formula), treatment with empagliflozin significantly reduced UACR in patients with microalbuminuria (-32% vs placebo; p < 0.001) or macroalbuminuria (-41% vs placebo; p < 0.001). Intriguingly, in regression models, most of the UACR-lowering effect with empagliflozin was not explained by SGLT2 inhibition-related improvements in HbA1c, SBP or weight. CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes and either micro- or macroalbuminuria, empagliflozin reduced UACR by a clinically meaningful amount. This effect was largely independent of the known metabolic or systemic haemodynamic effects of this drug class. Our results further support a direct renal effect of SGLT2 inhibitors. Prospective studies are needed to explore the potential of this intervention to alter the course of kidney disease in high-risk patients with diabetes. TRIAL REGISTRATION: Clinicaltrials.gov NCT01177813 (study 1); NCT01159600 (study 2); NCT01159600 (study 3); NCT01210001 (study 4); and NCT01164501 (study 5).

Comparison between urine albumin-to-creatinine ratio and urine protein dipstick testing for prevalence and ability to predict the risk for chronic kidney disease in the general population (Iwate-KENCO study): a prospective community-based cohort study.

BACKGROUND: This study compared the combination of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) vs. eGFR and urine protein reagent strip testing to determine chronic kidney disease (CKD) prevalence, and each method's ability to predict the risk for cardiovascular events in the general Japanese population. METHODS: Baseline data including eGFR, UACR, and urine dipstick tests were obtained from the general population (n = 22 975). Dipstick test results (negative, trace, positive) were allocated to three levels of UACR (<30, 30-300, >300), respectively. In accordance with Kidney Disease Improving Global Outcomes CKD prognosis heat mapping, the cohort was classified into four risk grades (green: grade 1; yellow: grade 2; orange: grade 3, red: grade 4) based on baseline eGFR and UACR levels or dipstick tests. RESULTS: During the mean follow-up period of 5.6 years, 708 new onset cardiovascular events were recorded. For CKD identified by eGFR and dipstick testing (dipstick test ≥ trace and eGFR <60 mL/min/1.73 m(2)), the incidence of CKD was found to be 9 % in the general population. In comparison to non-CKD (grade 1), although cardiovascular risk was significantly higher in risk grades ≥3 (relative risk (RR) = 1.70; 95 % CI: 1.28-2.26), risk predictive ability was not significant in risk grade 2 (RR = 1.20; 95 % CI: 0.95-1.52). When CKD was defined by eGFR and UACR (UACR ≥30 mg/g Cr and eGFR <60 mL/min/1.73 m(2)), prevalence was found to be 29 %. Predictive ability in risk grade 2 (RR = 1.41; 95 % CI: 1.19-1.66) and risk grade ≥3 (RR = 1.76; 95 % CI: 1.37-2.28) were both significantly greater than for non-CKD. Reclassification analysis showed a significant improvement in risk predictive abilities when CKD risk grading was based on UACR rather than on dipstick testing in this population (p < 0.001). CONCLUSIONS: Although prevalence of CKD was higher when detected by UACR rather than urine dipstick testing, the predictive ability for cardiovascular events from UACR-based risk grading was superior to that of dipstick-based risk grading in the general population.

Transient albuminuria in the setting of short-term severe hyperglycemia in type 1 diabetes.

In a cohort of 1817 children with type 1 diabetes (T1D), short-term hyperglycemia was associated with transient albuminuria (11 % during new-onset T1D without diabetic ketoacidosis (DKA), 12 % during/after DKA, 6 % during routine screening). Our findings have implications regarding future risk of diabetic kidney disease and further investigation is needed.

Association between consumption of flavonol and its subclasses and chronic kidney disease in US adults: an analysis based on National Health and Nutrition Examination Survey data from 2007-2008, 2009-2010, and 2017-2018.

Background: There is little research on the relationship between flavonol consumption and chronic kidney disease (CKD). This study aimed to examine the link between flavonol consumption and the risk of CKD among US adults, using data from the 2007-2008, 2009-2010 and 2017-2018 National Health and Nutrition Examination Survey (NHANES). Methods: A cross-sectional approach was used, drawing on data from three NHANES cycles. The flavonol consumption of the participants in this study was assessed using a 48 h dietary recall interview. CKD was diagnosed based on an estimated glomerular filtration rate below 60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio of 30 mg/g or higher. Results: Compared to the lowest quartile of flavonol intake (Q1), the odds ratios for CKD were 0.598 (95% CI: 0.349, 1.023) for the second quartile (Q2), 0.679 (95% CI: 0.404, 1.142) for the third quartile (Q3), and 0.628 (95% CI: 0.395, 0.998) for the fourth quartile (Q4), with a p value for trend significance of 0.190. In addition, there was a significant trend in CKD risk with isorhamnetin intake, with the odds ratios for CKD decreasing to 0.860 (95% CI: 0.546, 1.354) in the second quartile, 0.778 (95% CI: 0.515, 1.177) in the third quartile, and 0.637 (95% CI: 0.515, 1.177) in the fourth quartile (p for trend = 0.013). Conclusion: Our analysis of the NHANES data spanning 2007-2008, 2009-2010, and 2017-2018 suggests that high consumption of dietary flavonol, especially isorhamnetin, might be linked to a lower risk of CKD in US adults. These findings offer new avenues for exploring strategies for managing CKD.

An elevated urinary albumin-to-creatinine ratio increases the risk of incident cardia-cerebrovascular disease in individuals with type 2 diabetes.

AIMS: We aimed to explore the associations between urine albumin-to-creatinine ratio (uACR) and cardia-cerebrovascular disease (CVD) in Chinese population with type 2 diabetes(T2D). METHODS: We included 8975 participants with T2D but free of prevalent CVD (including myocardial infarction, ischemic and hemorrhagic stroke) at baseline from Kailuan study who were assessed with uACR between 2014 and 2016. The participants were divided into three groups based on their baseline uACR: normal (< 3 mg/mmol), microalbuminuria (3-30 mg/mmol), and macroalbuminuria (≥ 30 mg/mmol). Cox regression models and restricted cubic spline were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CVD. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to see if incorporating uACR into existing models could improve performance. RESULTS: During a median follow-up of 4.05 years, 560 participants developed first CVD event (6.24%). After adjustment for potential confounders, participants with microalbuminuria had higher risks of CVD compared with normal uACR, with HRs of 1.57(95% CI 1.04-2.37) for myocardial infarction, 1.24(95% CI 1.00-1.54) for ischemic stroke,1.62(95% CI 0.73-3.61) for hemorrhagic stroke, and 1.30(95% CI 1.07-1.57) for total CVD. The risks gradually attenuated with uACR increase, with HRs of 2.86(95% CI 1.63-5.00) for myocardial infarction, 2.46(95% CI 1.83-3.30) for ischemic stroke, 4.69(95% CI 1.72-12.78) for hemorrhagic stroke, and 2.42(95% CI 1.85-3.15) for total CVD in macroalbuminuria. The addition of uACR to established CVD risk models improved the CVD risk prediction efficacy. CONCLUSIONS: Increasing uACR, even below the normal range, is an independent risk factor for new-onset CVD in T2D population. Furthermore, uACR could improve the risk prediction for CVD among community based T2D patients.

Kidney and liver fat accumulation: from imaging to clinical consequences.

BACKGROUND: Recent studies indicate that accumulation of adipose tissue in various organs such as liver and kidney may contribute to the pathophysiology of metabolic syndrome. We aim to investigate the association between kidney and liver adipose tissue accumulation, assessed by the magnetic resonance imaging (MRI) proton density fat fraction technique, along with its relation to clinical and biochemical parameters. METHODS: We included 51 volunteers with phenotypical features of metabolic syndrome (mean age = 34 years, mean body-mass index = 26.4 kg/m2) in our study in which liver and kidney adipose tissue accumulation was assessed via MRI-proton density fat fraction along with multiple other clinical and biochemical parameters such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio, serum lipid profile, liver function tests and body-mass index (BMI). RESULTS: Our results from the univariate linear regression analysis indicate that both the kidney and liver scores were positively correlated with markers such as BMI, urine albumin-to-creatinine ratio, triglycerides (p < 0.001) and negatively correlated with eGFR (p < 0.05). In multivariate analysis, urine albumin-to-creatinine ratio (p < 0.05), triglycerides (p < 0.01), eGFR (p < 0.05) and BMI (p < 0.001) were found to be independently associated with kidney and liver fat accumulation, respectively (R2 = 0.64; R2 = 0.89). There was also a positive correlation between kidney and liver fat accumulation. CONCLUSION: We have found a significant association between adipose tissue accumulation in liver and kidney and the parameters of metabolic syndrome. Moreover, the presence of a strong association between kidney and liver fat accumulation and kidney function parameters such as urine albumin-to-creatinine ratio and eGFR may be an indicator of the clinical significance of parenchymal fat accumulation.

Investigating Interleukin-6 Levels in Type 2 Diabetes Mellitus Patients With and Without Diabetic Nephropathy.

BACKGROUND AND OBJECTIVE: Diabetic nephropathy (DN), a severe complication affecting 40% of diabetic individuals, is a leading cause of chronic kidney disease (CKD). It involves a progressive increase in urinary albumin and a decline in the glomerular filtration rate. Early detection and intervention are crucial to preventing CKD progression. The current marker, albuminuria, measured as the urine albumin-to-creatinine ratio (UACR), has limitations, highlighting the need for alternative biomarkers. Researchers have linked the proinflammatory cytokine interleukin-6 (IL-6) to the progression of DN, observing elevated levels in DN patients compared to those without DN. IL-6 also regulates glucose metabolism, promoting insulin effectiveness and secretion. Inflammation and glucose control are two things that IL-6 does. This makes it a promising biomarker and therapeutic target for DN and type 2 diabetes mellitus (T2DM). This study focuses on IL-6 levels in T2DM patients with and without DN. METHODS AND MATERIALS: From September 2022 to June 2024, the Department of General Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pune, conducted an observational cross-sectional comparative study on 80 T2DM patients, with 40 in group A (cases = T2DM patients with DN) and 40 in group B (controls = T2DM patients without DN). The study included patients with T2DM between the ages of 40 and 80. The study excludes conditions such as diabetic ketoacidosis, patients with end-stage renal disease, and conditions that increase IL-6, such as COVID-19. The study excluded autoimmune conditions with elevated IL-6, such as rheumatoid arthritis, systemic lupus erythematous, ankylosing spondylitis, psoriasis, and Crohn's disease. We obtained ethical approval and written consent from participants. RESULTS: In the current study, 61 patients (76.2%) were 60 years old or younger, while 19 patients (23.8%) were older than 60 years. Among the participants, 38 were females (47.5%) and 42 were males (52.5%). The case group, which consisted of 40 T2DM patients with DN, had a mean glycated hemoglobin (HbA1c) of 7.1700 ± 0.71044. In contrast, the control group, comprising 40 T2DM patients without DN, had a mean HbA1c of 6.8650 ± 0.57179. This difference was statistically significant, with a p value of 0.038. Additionally, the mean UACR in the case group was 134.34 ± 95.56, significantly higher than the control group's mean UACR of 22.32 ± 9.90. This difference was highly significant, with a p value of 0.001. Furthermore, the case group exhibited elevated mean IL-6 levels of 15.48 ± 4.27 compared to the control group's 7.02 ± 2.46, which is also highly significant, reflected by a p value of 0.001. CONCLUSION: As the concentration of IL-6 rises in diabetic patients with nephropathy, this study suggests that IL-6 may have an effect on the development of DN. This cytokine is necessary for both the initiation and progression of the condition. Using IL-6 as a supportive diagnostic test could help rule out other potential causes of DN in T2DM. Moreover, this marker does not require invasive procedures, and early measurement may help reduce mortality and morbidity.

[Kidney diseases in type 2 diabetes mellitus : Overview and implementation of guidelines, position papers and practical recommendations for diagnostics and monitoring]. / Nierenerkrankungen bei Diabetes mellitus Typ 2 : Überblick und Implementierung der Leitlinien, Positionspapiere und Praxisempfehlungen zur Diagnostik und Überwachung.

BACKGROUND: National and international medical societies have published guidelines and recommendations pertaining to the diagnostics and monitoring of chronic kidney disease in patients with type 2 diabetes mellitus. Consistency and implementation in daily clinical practice are rarely reported. OBJECTIVE: This article provides an overview on recommendations as a reflection of the global state of the art and assesses the implementation in daily practice in Germany, which was collected via a representative questionnaire. MATERIAL AND METHODS: The current guidelines were compared with respect to the consistency of parameters, frequency of testing and recommendations for nephrological referrals. The results were then compared with the survey responses to estimate the level of their implementation in daily practice in Germany. RESULTS: According to the recommendations the estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (UACR) should be tested at least once per year in all patients with type 2 diabetes. In cases of more severe kidney impairment (above Kidney Disease:Improving Global Outcomes, KDIGO, stage 3b with eGFR < 45 ml/min/1,73 m2) or albuminuria (from stage A2), more frequent measurements and nephrological referrals are recommended; however, different threshold values and frequencies are recommended. The responses from the questionnaires indicate that eGFR is tested annually in 96.5% of all cases and albuminuria is tested in 77.2% of cases. An eGRF triggered referral to a nephrologist is implemented by 19.6% of all nonnephrological practitioners, albuminuria triggered referrals are implemented in the majority of cases. CONCLUSION: Measurement of eGFR is the established standard in Germany. Potential improvement was found in albumin measurement, the frequency of testing and the time point for nephrological consultation. All guidelines emphasize the benefits of interdisciplinary cooperation.

Cardiovascular Risk Factor Control in 70- to 95-Year-Old Individuals: Cross-Sectional Results from the Population-Based AugUR Study.

Cardiovascular risk factors such as high glucose, LDL-cholesterol, blood pressure, and impaired kidney function are particularly frequent in old-aged individuals. However, population-based data on the extent of cardiovascular risk factor control in the old-aged population is limited. AugUR is a cohort of the mobile "70+"-year-old population of/near Regensburg, recruited via population registries. We conducted cross-sectional analyses assessing the proportion of AugUR participants with LDL-cholesterol, HbA1c, or blood pressure beyond recommended levels and their association with impaired creatinine- and cystatin-based estimated glomerular filtration rate (eGFR, <60 mL/min/1.73 m2) or urine albumin-creatinine ratio (UACR, ≥30 mg/g). Among 2215 AugUR participants, 74.7% were taking lipid-, glucose-, blood-pressure-lowering, or diuretic medication. High LDL-cholesterol at ≥116 mg/dL was observed for 76.1% (51.1% among those with prior cardiovascular events). We found HbA1c ≥ 7.0% for 6.3%, and high or low systolic blood pressure for 6.8% or 26.5%, respectively (≥160, <120 mmHg). Logistic regression revealed (i) high HbA1c levels associated with increased risk for impaired kidney function among those untreated, (ii) high blood pressure with increased UACR, and (iii) low blood pressure with impaired eGFR, which was confined to individuals taking diuretics. Our results provide important insights into cardiovascular risk factor control in individuals aged 70-95 years, which are understudied in most population-based studies.

Identification of Patients With Elevated Urine Albumin-to-Creatinine Ratio Levels in a Type 2 Diabetes Mellitus Cohort Based on Data Submitted by Patients via a Smartphone App (SMART-Finder): Protocol for an Observational Study.

BACKGROUND: Despite effective treatment options, chronic kidney disease (CKD) has become a major cause of mortality worldwide due to the ever-increasing number of patients with type 2 diabetes mellitus (T2DM). Guideline-compliant, at least, annual screening of patients with T2DM is crucial to prevent renal disease progression. However, data on the prevalence of CKD in patients with T2DM and on screening frequency are limited. SMART-Finder is the first study to exclusively use data provided directly by patients via an adherence app to collect information on the prevalence of CKD, risk factors, disease management, and quality of life of patients with T2DM in Germany. OBJECTIVE: The primary objective of this study is to determine the proportion of patients with T2DM and an elevated urine albumin-to-creatinine ratio (UACR; albumin-to-creatinine ratio stage A2 and A3) at baseline and after 12 (±3) months. Secondary objectives include the proportion of patients who remain in or switch to another albumin-to-creatinine ratio classification category after 12 months, information on quality of life, disease awareness, and adherence rates, as well as the proportion of patients without any UACR-screening data. Recruitment occurs via push notification among MyTherapy app users with T2DM. METHODS: This is a single-arm, retrospective/prospective, observational, digital, patient-centered cohort study, with recruitment and data documentation via a health app. Required routine laboratory data are provided by treating physicians to their patients for data entry. The study population includes adult patients with T2DM documenting their data in the MyTherapy app using their own smartphone or tablet. Study participants are provided with a specifically developed electronic case report form containing questions on demographic and general data, quality of life, disease awareness, and laboratory values including estimated glomerular filtration rate, UACR, hemoglobin 1Ac, and blood pressure. Apart from demographic and general data, all data are collected at baseline and 12 months after the last UACR assessment. An automatically generated push notification reminds participants of the second data entry. The extracted and pseudonymized data are analyzed descriptively. RESULTS: The enrollment period for this study started in February 2023 and shall end after 12 months or after the enrollment of 5000 patients. An interim analysis is planned 3 months after the inclusion of the first patient and the final analysis after 12 months of follow-up. CONCLUSIONS: Overall, the study will contribute to minimizing the existing data gap on the prevalence of CKD in patients with T2DM in Germany, provide important insights into the current disease management of patients with T2DM in everyday clinical practice in Germany, and support guideline-based care for the participating patients. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44996.

Early diagnosis of chronic kidney disease in patients with diabetes in France: multidisciplinary expert opinion, prevention value and practical recommendations.

Diabetes is the leading cause of end-stage kidney disease (ESKD), accounting for approximately 50% of patients starting dialysis. However, the management of these patients at the stage of chronic kidney disease (CKD) remains poor, with fragmented care pathways among healthcare professionals (HCPs). Diagnosis of CKD and most of its complications is based on laboratory evidence. This article provides an overview of critical laboratory evidence of CKD and their limitations, such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), Kidney Failure Risk Equation (KFRE), and serum potassium. eGFR is estimated using the CKD-EPI 2009 formula, more relevant in Europe, from the calibrated dosage of plasma creatinine. The estimation formula and the diagnostic thresholds have been the subject of recent controversies. Recent guidelines emphasized the combined equation using both creatinine and cystatin for improved estimation of GFR. UACR on a spot urine sample is a simple method that replaces the collection of 24-hour urine. Albuminuria is the preferred test because of increased sensitivity but proteinuria may be appropriate in some settings as an alternative or in addition to albuminuria testing. KFRE is a new tool to estimate the risk of progression to ESKD. This score is now well validated and may improve the nephrology referral strategy. Plasma or serum potassium is an important parameter to monitor in patients with CKD, especially those on renin-angiotensin-aldosterone system (RAAS) inhibitors or diuretics. Pre-analytical conditions are essential to exclude factitious hyperkalemia. The current concept is to correct hyperkalemia using pharmacological approaches, resins or diuretics to be able to maintain RAAS blockers at the recommended dose and discontinue them at last resort. This paper also suggests expert recommendations to optimize the healthcare pathway and the roles and interactions of the HCPs involved in managing CKD in patients with diabetes.