Frail hypertensive older adults with prediabetes and chronic kidney disease: insights on organ damage and cognitive performance - preliminary results from the CARYATID study.

BACKGROUND: Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR). METHODS: We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min. RESULTS: 237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable. CONCLUSIONS: Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD.

Association between albuminuria and retinal microvascular parameters measured with swept-source optical coherence tomography angiography in patients with diabetic retinopathy.

PURPOSE: To evaluate the relationship between urine albumin excretion (UAE) and retinal microvascular parameters assessed using swept-source optical coherence tomography angiography (SS-OCTA) in patients with diabetic retinopathy (DR). METHODS: This retrospective cross-sectional study included 180 patients with diabetes and 50 age-matched controls. Patients with diabetes were grouped according to the five-stage DR severity, combined with the presence of albuminuria. All subjects underwent 12×12mm2 field SS-OCTA. The foveal avascular zone metrics, vessel density, and capillary nonperfusion area (NPA) were quantified using a semi-automatic software algorithm on three different rectangular fields (3×3 mm2, 6×6 mm2, and 10×10 mm2). The correlations between albuminuria and the four OCTA parameters were analyzed. RESULTS: A total of 105 subjects had normal UAE, and 75 subjects had albuminuria. Of the 102 subjects whose DR severity was higher than mild non-proliferative DR (NPDR), capillary NPA on the 3×3 mm2, 6×6 mm2, and 10×10 mm2 fields was significantly larger in the albuminuria group. None of the OCTA parameters were significantly different between the two groups in subjects with mild NPDR or without DR. Multiple logistic regression analysis showed that an increase in NPA in the 6×6 mm2 and 10×10 mm2 fields was a significant risk factor for the presence of albuminuria (odds ratio = 1.92 and 1.35). CONCLUSION: An increase in capillary NPA was independently associated with albuminuria in patients with clinically significant DR levels. SS-OCTA imaging can be a useful marker for the early detection of diabetic nephropathy.

Association between short-term blood pressure variability and target organ damage in non-dialysis patients with chronic kidney disease.

BACKGROUND: It is unclear whether short-term blood pressure variability (BPV) is associated with target organ damage in patients with non-dialysis chronic kidney disease (CKD). METHODS: A cross-sectional, single-center study was conducted among 3442 non-dialysis CKD patients hospitalized in the department of Nephrology of the Fifth Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2022 and collected the demographic, laboratory, clinic blood pressure, ambulatory blood pressure data, and short-term BPV assessed by the weighted standard deviation (wSD) derived from ambulatory blood pressure monitoring (ABPM). Multivariate logistic analyses were used to evaluate the independent effects between short-term BPV and subclinical target organ damage, including left ventricular hypertrophy (LVH), abnormal carotid intima-media thickness (CIMT), low estimated glomerular filtration rate (eGFR), and albuminuria. RESULTS: The average age of the participants was 47.53 ± 14.06 years and 56% of participants were male. The baseline eGFR was 69 mL/min/1.73 m2. Based on the tertile distribution of wSD according to equal numbers, patients were divided into three categories with T1(< 9.66 mmHg), T2(9.66-12.23 mmHg), and T3(> 12.23 mmHg) of SBPV; T1(< 8.17 mmHg), T2(8.17-9.93 mmHg), and T3(> 9.93 mmHg) of DBPV. The participants with the higher wSD group had a higher prevalence of target organ damage than their counterparts (P-trend < 0.05). An increasing trend in short-term variability was present with advancing CKD stages (P-trend < 0.001). Multivariate logistic analyses results showed that the odds ratio (OR) of SBP wSD was (1.07 [1.03,1.11], P < 0.001) for LVH, (1.04 [1.01,1.07, P = 0.029) for abnormal CIMT, (1.05 [1.02,1.08], P = 0.002) for low eGFR, and (1.06 [1.02,1.09], P = 0.002) for albuminuria; The OR of DBP wSD was (1.07 [1.02,1.12], P = 0.005) for LVH, (1.05 [1.01,1.09], P = 0.028) for abnormal CIMT, (1.05 [1.01,1.09], P = 0.022) for low eGFR, and (1.05 [1.01,1.10], P = 0.025) for albuminuria when adjusted for confounding factors and mean BP. CONCLUSIONS: In conclusion, short-term BPV is associated with target organ damage, and irresponsible of average blood pressure levels, in Chinese non-dialysis CKD participants.

Increasing obstructive sleep apnea risk is associated with albuminuria in Korean adults: cross-sectional analysis.

Several studies have shown an association between albuminuria and obstructive sleep apnea (OSA). However, studies on the relationship between the STOP-BANG questionnaire that can screen for OSA and microalbuminuria are still insufficient. Therefore, this study attempted to clarify the relationship between microalbuminuria and OSA risk using the STOP-BANG questionnaire in Korean adults. A total of 7478 participants (3289 men and 4189 women) aged over 40 were enrolled in the Korean National Health and Nutrition Examination Survey from 2019 to 2020. STOP-BANG questionnaire to screen OSA was obtained from subjects. The urinary albumin/creatinine ratio (ACR) and proteinuria were measured via a single dipstick to evaluate renal function. The high OSA risk group had a higher mean ACR value than the low OSA risk group (36.8 ± 172.2 vs 17.7 ± 82.5; P < 0.001). The proportion of subjects with values of 30 ≤ ACR < 300 mg/g (11.9% vs 6.1%; P < 0.001) and ACR > 300 mg/g (2.1% vs 0.7%; P < 0.001) was significantly higher in high OSA risk group. Multivariate logistic regression results confirmed that microalbuminuria (OR 1.279, 95% confidence interval (CI) 1.068-1.532, P = 0.008) was significantly correlated with high OSA risk. In addition, significant correlation with high OSA risk was also found in macroalbuminuria (OR 1.684, 95% CI 1.073-2.530, P = 0.022) and proteinuria (OR 1.355, 95% CI 1.030-1.783, P = 0.030). We confirmed a significant correlation between high OSA risk and albuminuria/proteinuria in Korean adults. Therefore, renal function evaluation is required in high OSA risk patients, and OSA diagnosis through PSG test and treatment is necessary.

Association of domain-specific physical activity with albuminuria among prediabetes and diabetes: a large cross-sectional study.

BACKGROUND: Albuminuria, the presence of excess of protein in urine, is a well-known risk factor for early kidney damage among diabetic/prediabetic patients. There is a complex interaction between physical activity (PA) and albuminuria. However, the relationship of specific-domain PA and albuminuria remained obscure. METHODS: Albuminuria was defined as urinary albumin/creatinine ratio (ACR) > 30 mg/g. PA was self-reported by participants and classified into transportation-related PA (TPA), occupation-related PA (OPA), and leisure-time PA (LTPA). Weighted logistic regression was conducted to compute the odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) was used to evaluate the dose-response of PA domains with the risk of albuminuria. RESULTS: A total of 6739 diabetic/prediabetic patients (mean age: 56.52 ± 0.29 years) were enrolled in our study, including 3181 (47.20%) females and 3558 (52.80%) males. Of them, 1578 (23.42%) were identified with albuminuria, and 5161(76.58%) were without albuminuria. Diabetic/prediabetic patients who adhered the PA guidelines for total PA had a 22% decreased risk of albuminuria (OR = 0.78, 95%CI 0.64-0.95), and those met the PA guidelines for LTPA had a 28% decreased of albuminuria (OR = 0.72, 95%CI 0.57-0.92). However, OPA and TPA were both not associated with decreased risk of albuminuria. RCS showed linear relationship between the risk of albuminuria with LTPA. CONCLUSIONS: Meeting the PA guideline for LTPA, but not OPA and TPA, was inversely related to the risk of albuminuria among diabetic/prediabetic patients. Additionally, achieving more than 300 min/week of LTPA conferred the positive effects in reducing albuminuria among diabetic/prediabetic patients.

Risk factors for lower renal compensation after nephrectomy: an analysis of living kidney donors in an Amazonian cohort.

INTRODUCTION: Living donor kidney transplantation is considered the ideal renal replacement therapy because it has a lower complication rate and allows an efficient response to the high demand for grafts in the healthcare system. Careful selection and adequate monitoring of donors is a key element in transplantation. Individuals at greater risk of developing kidney dysfunction after nephrectomy must be identified. OBJECTIVE: To identify risk factors associated with a renal compensation rate (CR) below 70% 12 months after nephrectomy. METHODS: This observational retrospective longitudinal study included living kidney donors followed up at the Lower Amazon Regional Hospital between 2016 and 2022. Data related to sociodemographic variables, comorbid conditions and kidney function parameters were collected. RESULTS: The study enrolled 32 patients. Fourteen (43.75%) had a CR < 70% 12 months after kidney donation. Logistic regression found obesity (Odds Ratio [95%CI]: 10.6 [1.7-65.2]), albuminuria (Odds Ratio [95%CI]: 2.41 [1.2-4.84]) and proteinuria (Odds Ratio [95%CI]: 1.14 [1.03-1.25]) as risk factors. Glomerular filtration rate was a protective factor (Odds Ratio [95% CI]: 0.92 [0.85-0.99]). CONCLUSION: Obesity, albuminuria and proteinuria adversely affected short-term renal compensation rate. Further studies are needed to uncover the prognostic implications tied to these risk factors. Our findings also supported the need for careful individualized assessment of potential donors and closer monitoring of individuals at higher risk.

Fatty liver index is an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes: an 11-year observational study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), identified by the Fatty Liver Index (FLI), is associated with increased mortality and cardiovascular (CV) outcomes. Whether this also applies to type 1 diabetes (T1D) has not been yet reported. METHODS: We prospectively observed 774 subjects with type 1 diabetes (males 52%, 30.3 ± 11.1 years old, diabetes duration (DD) 18.5 ± 11.6 years, HbA1c 7.8 ± 1.2%) to assess the associations between FLI (based on BMI, waist circumference, gamma-glutamyl transferase and triglycerides) and all-cause death and first CV events. RESULTS: Over a median 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 individuals with retrievable incidence data. At baseline, FLI was < 30 in 515 subjects (66.5%), 30-59 in 169 (21.8%), and ≥ 60 in 90 (11.6%). Mortality increased steeply with FLI: 3.9, 10.1, 22.2% (p < 0.0001). In unadjusted Cox analysis, compared to FLI < 30, risk of death increased in FLI 30-59 (HR 2.85, 95% CI 1.49-5.45, p = 0.002) and FLI ≥ 60 (6.07, 3.27-11.29, p < 0.0001). Adjusting for Steno Type 1 Risk Engine (ST1-RE; based on age, sex, DD, systolic BP, LDL cholesterol, HbA1c, albuminuria, eGFR, smoking and exercise), HR was 1.52 (0.78-2.97) for FLI 30-59 and 3.04 (1.59-5.82, p = 0.001) for FLI ≥ 60. Inclusion of prior CV events slightly modified HRs. FLI impact was confirmed upon adjustment for EURODIAB Risk Engine (EURO-RE; based on age, HbA1c, waist-to-hip ratio, albuminuria and HDL cholesterol): FLI 30-59: HR 1.24, 0.62-2.48; FLI ≥ 60: 2.54, 1.30-4.95, p = 0.007), even after inclusion of prior CVD. CV events incidence increased with FLI: 3.5, 10.5, 17.2% (p < 0.0001). In unadjusted Cox, HR was 3.24 (1.65-6.34, p = 0.001) for FLI 30-59 and 5.41 (2.70-10.83, p < 0.0001) for FLI ≥ 60. After adjustment for ST1-RE or EURO-RE, FLI ≥ 60 remained statistically associated with risk of incident CV events, with trivial modification with prior CVD inclusion. CONCLUSIONS: This observational prospective study shows that FLI is associated with higher all-cause mortality and increased risk of incident CV events in type 1 diabetes.

Age- and gender-adjusted estimated glomerular filtration rate definition reveals hyperfiltration as a risk factor for renal function deterioration in type 2 diabetes.

AIM: To assess the role of hyperfiltration for diabetic kidney disease (DKD) progression. MATERIALS AND METHODS: A retrospective observational cohort study enrolled type 2 diabetes (T2D) patients with an initial estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m2 or higher. Patients were categorized into two groups: hyperfiltration (eGFR exceeding the age- and gender-specific 95th percentile values from a prior national cohort study) and normofiltration. Rapid DKD progression was defined as an eGFR decline of more than 5 mL/min/1.73m2/year. We used a linear mixed effect model and Cox regression with time-varying covariate model to compare eGFR changes and identify factors associated with rapid DKD progression. RESULTS: Of the enrolled 7563 T2D patients, 7.2% had hyperfiltration. The hyperfiltration group exhibited a higher rate of eGFR decline compared with the normofiltration group (-2.0 ± 0.9 vs. -1.1 ± 0.9 mL/min/1.73m2/year; P < .001). During an average follow-up period of 4.65 ± 3.86 years, 24.7% of patients with hyperfiltration experienced rapid DKD progression, compared with 15.7% of patients with normofiltration (P < .001). Cox regression analyses identified that initial hyperfiltration was a significant determinant of rapid DKD progression, with a hazard ratio of 1.66 (95% confidence interval: 1.41-1.95; P < .001). When combined with albuminuria, the risk of progression was further compounded (hazard ratio 1.76-3.11, all P < .001). CONCLUSIONS: In addition to using the current Kidney Disease: Improving Global Outcomes CGA classification system, considering glomerular hyperfiltration status can improve the accuracy of predicting DKD progression.

Hepatitis C virus antibody seropositivity is associated with albuminuria but not peripheral artery disease in patients with type 2 diabetes.

Hepatitis C virus (HCV) infection is prevalent in patients with type 2 diabetes mellitus (DM). We aimed to investigate whether HCV antibody (Ab) seropositivity is associated with diabetic micro- and macro-vascular diseases. In this hospital-based cross-sectional study, we retrospectively collected data from patients who participated in the diabetes pay-for-performance program and underwent HCV Ab screening in the annual comprehensive assessment between January 2021 and March 2022. We examined the relationships of HCV Ab seropositivity with the spot urinary albumin-to-creatinine ratio (UACR) and ankle-brachial index (ABI) in patients aged ≥ 50 years with type 2 DM. A total of 1758 patients were enrolled, and 85 (4.83%) of the enrolled patients had HCV Ab seropositivity. Multivariable regression analyses revealed that albuminuria showed a dose-dependent association with HCV Ab seropositivity (UACR [30-299 mg/g]: odds ratio [OR] = 1.463, 95% confidence interval [CI] 0.872‒2.456); UACR [≥ 300 mg/g]: OR = 2.300, 95% CI 1.160‒4.562; P for trend = 0.015) when compared with normal albuminuria (UACR < 30 mg/g). However, the proportion of patients with peripheral arterial disease, defined as an ABI ≤ 0.9, was not significantly different between the groups with and without HCV Ab seropositivity (3.5% vs. 3.9%, P = 0.999). In conclusion, severely increased albuminuria, but not the ABI, showed a significant association with HCV Ab seropositivity in patients aged ≥ 50 years with type 2 DM.

Dapagliflozin and Blood Pressure in Patients with Chronic Kidney Disease and Albuminuria.

BACKGROUND AND AIMS: Sodium-glucose cotransporter 2 inhibitors decrease blood pressure in patients with type 2 diabetes, but the consistency and magnitude of blood pressure lowering with dapagliflozin in patients with chronic kidney disease (CKD) is unknown. We conducted a prespecified analysis of the DAPA-CKD trial to investigate the effect of dapagliflozin on systolic blood pressure (SBP) in patients with CKD, with and without type 2 diabetes. METHODS: A total of 4304 adults with baseline estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g were randomized to either dapagliflozin 10 mg or placebo once daily; median follow-up was 2.4 years. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or death from a kidney or cardiovascular cause. Change in SBP was a prespecified outcome. RESULTS: Baseline mean (SD) SBP was 137.1 mmHg (17.4). By Week 2, dapagliflozin compared to placebo reduced SBP by 3.6 mmHg (95% CI 2.8-4.4 mmHg), an effect maintained over the duration of the trial (2.9 mmHg, 2.3-3.6 mmHg). Time-averaged reductions in SBP were 3.2 mmHg (2.5-4.0 mmHg) in patients with diabetes and 2.3 mmHg (1.2-3.4 mmHg) in patients without diabetes. The time-averaged effect of dapagliflozin on diastolic blood pressure (DBP) was 1.0 mmHg (0.6-1.4 mmHg); 0.8 mmHg (0.4-1.3 mmHg) in patients with diabetes and 1.4 mmHg (0.7-2.1 mmHg) in patients without diabetes. Benefits of dapagliflozin on the primary composite and secondary endpoints were evident across the spectrum of baseline SBP and DBP. CONCLUSION: In patients with CKD and albuminuria, randomization to dapagliflozin was associated with modest reductions in systolic and diastolic BP.

Dynapenia and sarcopenia: association with the diagnosis, duration and complication of type 2 diabetes mellitus in ELSA-Brasil.

Sarcopenia (the loss of muscle mass, strength and skeletal muscle function) increases mortality and the risk of hospitalization in the older population. Although it is known that older adults with type 2 diabetes mellitus (T2DM) have a higher risk of dynapenia and sarcopenia, few studies have investigated these conditions in middle-aged populations. The objective of this study was to investigate whether T2DM, its duration, the presence of albuminuria, and glycemic control are associated with sarcopenia and its components in adults. The cross-sectional analysis was based on data from visit 2 of the Brazilian Longitudinal Study of Adult Health (2012-2014). The 2018 European Working Group on Sarcopenia in Older People criteria were used to define dynapenia, low appendicular muscle mass (LAMM), and sarcopenia (absent/probable/confirmed). The explanatory variables were: T2DM; duration of T2DM; T2DM according to the presence of albuminuria; and glycemic control (HbA1C < 7%) among people with T2DM. A total of 12,132 participants (mean age = 55.5, SD: 8.9 years) were included. The odds ratio for LAMM was greater among those with T2DM, T2DM duration from 5 to 10 years, and T2DM without albuminuria. Chances of dynapenia were higher among those with T2DM, T2DM duration > 10 years, and T2DM with and without albuminuria. The variables T2DM, T2DM ≥ 10 years, and T2DM with albuminuria increased the odds of probable sarcopenia, and T2DM duration from 5 to 10 years increased the odds of confirmed sarcopenia. The results support the importance of frequently monitoring the musculoskeletal mass and strength of individuals with T2DM to prevent sarcopenia and related outcomes.

Increased serum methylmalonic acid levels were associated with the presence of cognitive dysfunction in older chronic kidney disease patients with albuminuria.

BACKGROUND: This study aimed to evaluate the correlation between serum methylmalonic acid (MMA) levels and cognition function in patients with chronic kidney disease (CKD). METHODS: In this cross-sectional study, we included 537 CKD individuals aged ≥ 60-year-old with albuminuria from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Four cognitive tests including the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Delayed Recall and Word Learning tests, and the Animal Fluency test (AF) were performed. Associations between MMA and cognition scores were assessed with linear regression models. RESULTS: MMA level was negatively associated with residual renal function and nutrition status. After multivariate adjustment, elevated serum MMA levels were independently correlated with decline of cognition in CKD patients with albuminuria. CONCLUSION: Our study showed that higher serum MMA levels were independently associated with the presence of cognition dysfunction in CKD patients. The exact pathogenesis of MMA and cognition needs further research.

Prevalence and the factors associated with microalbuminuria among patients with type 2 diabetes mellitus and/or hypertension in the urban areas of Puducherry district: a cross-sectional study.

BACKGROUND: Microalbuminuria is an early indicator for renal and cardiovascular diseases, especially among patients with diabetes mellitus (DM) and hypertension (HTN). We determined the prevalence and the factors associated with microalbuminuria among patients with type 2 DM and/or HTN in the urban areas of the Puducherry district in India. METHODS: We included 225 patients aged 40-69 years with DM and/or HTN from a non-communicable diseases (NCDs) survey conducted during 2019-2020 in the urban areas of Puducherry district. The prevalence of microalbuminuria and various biological risk factors of NCDs were assessed as per the WHO STEPS methodology. The prevalence of microalbuminuria was presented as proportions (95% CI), and the adjusted prevalence ratio (aPR) was estimated using weighted forward stepwise generalized linear modelling. P-value ≤0.05 was considered statistically significant. RESULTS: The mean (SD) age of the patients was 54 (11) years. Over one-third (38.2%) (95% CI: 31.6-44.4) of patients with DM and/or HTN had microalbuminuria. The prevalence was highest among those having both DM and HTN 48% (95% CI: 37-59), followed by those having only DM 40.6% (95% CI: 29-52.2) and only HTN 27.7% (95% CI: 18.1-38.6). The prevalence of microalbuminuria was twice (aPR = 2.1, 95% CI: 1.1-3.9) higher among women and 2.4 times (95% CI: 1.12-5.1) higher among those having both DM and HTN as compared to those with only HTN. CONCLUSION: The prevalence of microalbuminuria among patients with DM and/or HTN is concerningly high. Population-based screening for microalbuminuria, especially among women and those having both DM and HTN, needs to be undertaken in the urban areas of Puducherry district.

Microalbuminuria serves as an early indicator for kidney and cardiovascular diseases, especially among patients with diabetes mellitus (DM) and hypertension (HTN). Our study focussed on determining the prevalence of microalbuminuria among individuals with type 2 DM and/or HTN in the urban areas of the Puducherry district in India. We included 225 patients aged 40­69 years with DM and/or HTN who participated in a non-communicable diseases (NCDs) survey conducted during 2019­2020 in urban Puducherry. We found that over one-third (38.2%) of patients with DM and/or HTN had microalbuminuria. The prevalence was highest among those having both DM and HTN (48%), followed by those having only DM (40.6%) and only HTN (27.7%). The prevalence of microalbuminuria was 2.1 times higher among women than men and 2.4 times higher among individuals with both DM and HTN compared to those with only HTN. These findings highlight the concerningly high prevalence of microalbuminuria among patients with DM and/or HTN in the urban areas of Puducherry district. To address this issue, it is crucial that the public health authorities of Puducherry district implement population-based screening initiatives for microalbuminuria, particularly targeting women and individuals with both DM and HTN in the urban areas of the Puducherry district.

Effects of Dipeptidyl Peptidase-4 Inhibitor and Angiotensin-Converting Enzyme Inhibitor on Experimental Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease in the United States and worldwide. Proteinuria is a major marker of the severity of injury. Dipeptidyl peptidase-4 inhibitor (DPP-4I) increases incretin-related insulin production and is, therefore, used to treat diabetes. We investigated whether DPP4I could have direct effect on kidney independent of its hypoglycemic activity. We, therefore, tested the effects of DPP4I with or without angiotensin-converting enzyme inhibitor (ACEI) on the progression of diabetic nephropathy and albuminuria in a murine model of DKD. eNOS-/-db/db mice were randomized to the following groups at age 10 weeks and treated until sacrifice: baseline (sacrificed at week 10), untreated control, ACEI, DPP4I, and combination of DPP4I and ACEI (Combo, sacrificed at week 18). Systemic parameters and urine albumin-creatinine ratio were assessed at baseline, weeks 14, and 18. Kidney morphology, glomerular filtration rate (GFR), WT-1, a marker for differentiated podocytes, podoplanin, a marker of foot process integrity, glomerular collagen IV, and alpha-smooth muscle actin were assessed at the end of the study. All mice had hyperglycemia and proteinuria at study entry at week 10. Untreated control mice had increased albuminuria, progression of glomerular injury, and reduced GFR at week 18 compared with baseline. DPP4I alone reduced blood glucose and kidney DPP-4 activity but failed to protect against kidney injury compared with untreated control. ACEI alone and combination groups showed significantly reduced albuminuria and glomerular injury, and maintained GFR and WT-1+ cells. Only the combination group had significantly less glomerular collagen IV deposition and more podoplanin preservation than the untreated control. DPP-4I alone does not decrease the progression of kidney injury in the eNOS-/-db/db mouse model, suggesting that targeting only hyperglycemia is not an optimal treatment strategy for DKD. Combined DPP-4I with ACEI added more benefit to reducing the glomerular matrix.

Albuminuria-lowering effect of adding semaglutide on top of empagliflozin in individuals with type 2 diabetes: A randomized and placebo-controlled study.

AIM: To investigate whether combined treatment with empagliflozin (a sodium-glucose cotransporter-2 inhibitor) and semaglutide (a glucagon-like peptide-1 receptor agonist) can reduce urinary albumin-creatinine ratio (UACR) compared to treatment with empagliflozin alone in individuals with type 2 diabetes (T2D) and albuminuria. METHODS: We conducted a randomized, placebo-controlled, double-blind, parallel study including 60 individuals with T2D and albuminuria. All participants initiated open-label empagliflozin 25 mg once daily, on top of renin-angiotensin system inhibition, in a run-in period of 26 weeks. Subsequently, participants were randomized to semaglutide or placebo 1 mg once weekly for 26 weeks. The primary endpoint was change in UACR. Secondary endpoints were change in: (i) measured glomerular filtration rate (GFR); (ii) 24-hour systolic blood pressure; (iii) glycated haemoglobin (HbA1c) level; (iv) body weight; and (v) plasma renin and aldosterone levels. RESULTS: Addition of semaglutide to empagliflozin provided no additional change in UACR from randomization to end-of-treatment. The mean (95% confidence interval) difference in UACR was -22 (-44; 10)% (P = 0.15) between treatment groups. Neither GFR, 24-hour blood pressure, body weight, nor plasma renin activity was changed with semaglutide. HbA1c (-8 [-13; -3] mmol/mol; P = 0.003) and plasma aldosterone (-30 [-50; -3] pmol/L; P = 0.035) were reduced with semaglutide compared to placebo. CONCLUSIONS: Semaglutide added to empagliflozin did not change UACR, measured GFR, 24-hour systolic blood pressure, body weight or plasma renin levels in individuals with T2D and albuminuria. Semaglutide improved glycaemic control and plasma aldosterone levels compared to placebo.

Prevalence of chronic kidney disease and metabolic related indicators in Mianzhu, Sichuan, China.

Background: Chronic kidney disease (CKD) is a major public health problem worldwide. Periodic surveys are essential for monitoring the prevalence of CKD and its risk factors. We assessed the prevalence of CKD and its risk factors in Mianzhu City in 2020. Method: The Natural Population Cohort Study surveyed 7,770 individuals aged>20 years in Mianzhu City of Sichuan province in 2020. Our investigation encompassed the measurement of CKD prevalence, the evaluation of various renal function indicators, and comparisons based on age, gender, and hukou status. Additionally, some metabolic indices were also measured to identify the underlying causes of CKD. Results: (1) Overall, the prevalence of reduced renal function (eGFR<60 mL/min/1.73m2), albuminuria, and CKD were 1.3, 10.0, and 10.4%, respectively, (2) the overall prevalence of CKD was higher among men than among women (14.5% vs. 8.6%). Similarly, the prevalence of CKD was higher among men than women in most age groups, (3) among urban residents, the prevalence of CKD was higher among middle-aged individuals and lower among young individuals and older adults, and (4) considering eGFR, the albuminuria and CKD for group definition, Blood pressure, triglyceride, high-density lipoprotein, blood sugar, and BMI were all statistically different among between normal groups and abnormal groups s in the albuminuria and CKD. Conclusion: The incidence of CKD greatly varied between Mianzhu City and other regions in China and other countries. The differences in risk factors of CKD should be explored in the future. The gender difference in the prevalence of CKD in this study was markedly different from that in previous studies. More high-quality studies are needed to further explore this controversy. Based on the different prevalence of CKD and metabolism-related indices in rural and urban areas in this study, we speculated that the high incidence of CKD in Mianzhu City might be related to diet, lifestyle, and availability of healthcare services.

Effects of the ABCC8 R1420H loss-of-function variant on beta-cell function, diabetes incidence, and retinopathy.

INTRODUCTION: The ABCC8 gene regulates insulin secretion and plays a critical role in glucose homeostasis. The effects of an ABCC8 R1420H loss-of-function variant on beta-cell function, incidence of type 2 diabetes, and age-at-onset, prevalence, and progression of diabetes complications were assessed in a longitudinal study in American Indians. RESEARCH DESIGN AND METHODS: We analyzed beta-cell function through the relationship between insulin secretion and insulin sensitivity in members of this population without diabetes aged ≥5 years using standard major axis regression. We used hierarchical logistic regression models to study cross-sectional associations with diabetes complications including increased albuminuria (albumin-to-creatinine ratio (ACR) ≥30 mg/g), severe albuminuria (ACR ≥300 mg/g), reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m2), and retinopathy. This study included 7675 individuals (254 variant carriers) previously genotyped for the R1420H with available phenotypic data and with a median follow-up time of 13.5 years (IQR 4.5-26.8). RESULTS: Variant carriers had worse beta-cell function than non-carriers (p=0.0004; on average estimated secretion was 22% lower, in carriers), in children and adults, with no difference in insulin sensitivity (p=0.50). At any body mass index and age before 35 years, carriers had higher type 2 diabetes incidence. This variant did not associate with prevalence of increased albuminuria (OR 0.87, 95% CI 0.66 to 1.16), severe albuminuria (OR 0.96, 95% CI 0.55 to 1.68), or reduced eGFR (OR 0.44, 95% CI 0.18 to 1.06). By contrast, the variant significantly associated with higher retinopathy prevalence (OR 1.74, 95% CI 1.19 to 2.53) and this association was only partially mediated (<11%) by glycemia, duration of diabetes, risk factors of retinopathy, or insulin use. Retinopathy prevalence in carriers was higher regardless of diabetes presence. CONCLUSIONS: The ABCC8 R1420H variant is associated with increased risks of diabetes and of retinopathy, which may be partially explained by higher glycemia levels and worse beta-cell function.

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Diabetic kidney disease (DKD) is a common complication of diabetes mellitus and approximately 1/3 of diabetic patients may progress to DKD. A typical early clinical manifestation of DKD is microalbuminuria and patients may present with macroproteinuria accompanied by a decrease in renal function condition as the disease progresses. It is generally believed that the likelihood of a reversal of the disease is reduced after the development of macroproteinuria in patients with DKD, and that eventually some patients' condition may develop into end-stage renal disease (ESRD). Moreover, the thickening of the glomerular basement membrane, mesangial matrix expansion, Kimmelstiel-Wilson (K-W) nodules, and glomerulosclerosis in end-stage diabetes mellitus are typical pathologic changes of DKD. However, some DKD patients, especially those with type 2 diabetes mellitus (T2DM) combined with DKD, may have diverse clinical manifestations, showing variations in disease progression and regression, and manifesting as non-classical types of DKD, such as normoalbuminuric DKD, proteinuria-reduced DKD, and DKD with rapid decline in renal function. In addition, the formation of crescents, a special pathological change, is observed in renal biopsy. However, this issue is currently under-recognized by clinicians and therefore deserves more attention. In order to improve clinicians' understanding of the presentations and pathological changes of non-classical DKD and the level of DKD prevention and treatment in China, we present a preliminary introduction to the clinical phenotypes and pathological changes of non-classical types of DKD in this paper by summarizing the findings of our prior studies as well as domestic and international literature.

Microalbuminuria como marcador de daño renal en pacientes con hipertensión arterial / Microalbuminuria as a marker of kidney damage in patients with arterial hypertension

Introducción: La hipertensión arterial es un poderoso factor de riesgo de daño renal. La prevalencia es muy alta entre los pacientes con Enfermedad Renal Crónica. Objetivo: Determinar la presencia de Microalbuminuria y su valor como marcador de daño renal en pacientes con diagnóstico de Hipertensión arterial. Material y Métodos: Se realizó un estudio descriptivo, longitudinal y prospectivo de 123 pacientes. Se determinó edad, sexo, cifras de colesterol, triglicéridos, creatinina y microalbuminuria y factores de riesgo vascular. Se utilizó la estadística descriptiva e inferencial. Resultados: El 40,7 Microalbuminuria as a marker of kidney damage in patients with arterial hypertension de los pacientes pertenecen al grupo de más de 70 años con predominio del sexo masculino (65 por ciento), 62,6 Microalbuminuria as a marker of kidney damage in patients with arterial hypertension presentaron microalbuminuria, 97,3 Microalbuminuria as a marker of kidney damage in patients with arterial hypertension tenían factores de riesgo asociados con prevalencia aumentada del tabaquismo, dislipidemia, obesidad y enfermedades vasculares asociadas con RP>1. Predominó el grupo mayor de 70 años, del sexo masculino, con presencia de microalbuminuria. La presencia de más de tres factores de riesgo se asoció a la microalbuminuria. La presencia de microalbuminuria aumentó con los años de evolución de la enfermedad. Predominó el estadio 3 de la Enfermedad Renal Crónica en los pacientes con hipertensión arterial y microalbuminuria y se relacionó directamente con los años de evolución de la hipertensión arterial. Conclusiones: La determinación de la microalbuminuria en los pacientes con hipertensión arterial es un marcador de riesgo importante y sencillo para determinar el daño renal subclínico y está muy relacionado con el incremento de la edad del paciente, años de hipertensión y asociación con otros factores de riesgo vasculares(AU)

Introduction: Arterial hypertension is a powerful risk factor for kidney damage. The prevalence is very high among patients with chronic kidney disease. Objective: To determine the presence of microalbuminuria as a marker of kidney damage in patients with arterial hypertension admitted between September 2016 and September 2017. Material and Methods: A descriptive, longitudinal, prospective study was conducted in 123 patients. Age; sex; cholesterol, triglycerides, creatinine and microalbuminuria levels and vascular risk factors were determined. Descriptive and inferential statistics were used. Results: The 40.7 percent of patients belong to the group of patients of age more than 70 years, predominating the male sex (65 percent); 62.6 percent of them presented microalbuminuria and 97.3 percent had risk factors associated with an increased prevalence of smoking, dyslipidemia, obesity, and vascular diseases associated with RP> 1. The group of patients older than 70 years, male, and with presence of microalbuminuria predominated in the study. The presence of more than three risk factors was associated with microalbuminuria. The presence of microalbuminuria increased with the years of evolution of the disease. Stage 3 of chronic kidney disease predominated in patients with arterial hypertension and microalbuminuria and it was directly related to the years of evolution of arterial hypertension. Conclusions: The determination of microalbuminuria in patients with arterial hypertension is a simple and important risk marker to determine subclinical kidney damage and it is closely related to the increase in the age of the patient, the years of hypertension, and the association with other risk factors for vascular disease(AU)

Prevalence of chronic kidney disease in a population in southern Brazil (Pro-Renal Study) / Prevalência da doença renal crônica em uma população do Sul do Brasil (estudo Pro-Renal)

Abstract Introduction: Chronic kidney disease (CKD) affects 10-12% of the adult population in many countries. In Brazil, there is no reliable information about the actual prevalence of CKD. Objective: To determine the prevalence of CKD by estimated glomerular filtration rate (eGFR) and proteinuria/albuminuria in an urban population randomly selected in Southern Brazil. Patients and Methods: 5,216 individuals were randomly selected out of a pool of 10,000 individuals identified from the database of a local energy company. The screening consisted of collection of demographic data, history of diabetes mellitus, hypertension, kidney/cardiovascular disease in the family and obesity through the body mass index - BMI (CKD risk factors). Blood samples were collected for determination of serum creatinine and subsequent eGFR estimation by the MDRD formula and urine samples for determination of albuminuria by dipstick. Albuminuria was further evaluated by HemoCue© in a selected CKD risk group. Results: The population was predominantly Caucasians (93%), 64% were females and the mean age of participants was 45 years old (18-87). BMI (kg/m2) was 27±5. Albuminuria was found in 5.25% of individuals. 88.6% of this population had no CKD (eGFR > 60 ml/min/1.73m2 & normoalbuminuria) and 11.4% were identified as having CKD, with majority on stages 3A (7.2%) and 3B (1.1%). Hypertension, diabetes, older age and obesity was associated with a higher prevalence of CKD (p < 0.001). Conclusions: The prevalence of CKD in an urban population in southern Brazil mirrors other developed countries and indicates that kidney disease is an important public health problem in Brazil.

Resumo Introdução: A doença renal crônica (DRC) afeta 10-12% da população adulta em muitos países. No Brasil, não há informações confiáveis sobre a prevalência real de DRC. Objetivo: Determinar a prevalência de DRC pela taxa de filtração glomerular estimada (eGFR) e albuminúria em uma população urbana selecionada aleatoriamente no sul do Brasil. Pacientes e Métodos: 5216 indivíduos foram selecionados aleatoriamente de um grupo de 10 mil indivíduos identificados a partir do banco de dados de uma empresa de energia local. O rastreio consistiu na coleta de dados demográficos, história de diabetes mellitus, hipertensão, doença renal/cardiovascular na família e obesidade pelo índice de massa corporal -IMC (fatores de risco da DRC). Foram coletadas amostras de sangue para determinação da creatinina sérica e subsequente estimativa de eGFR pela fórmula MDRD e amostras de urina para determinação da albuminúria por fita. Albuminúria foi confirmada por HemoCue© em um grupo de risco de CKD selecionado. Resultados: A população era predominantemente de caucasianos (93%), 64% eram do sexo feminino e a idade média dos participantes de 45 anos (18-87). O IMC (kg/m2) foi de 27 ± 5. Albuminúria foi encontrada em 5,25 % dos indivíduos. 88,6% dessa população não apresentou CKD (eGFR > 60 ml/min/1,73 m2 e normoalbuminúria) e 11,4% foram identificados como portadores de DRC, com maioria nos estádios 3A (7,2%) e 3B (1,1%). Hipertensão arterial, diabetes, idade avançada e obesidade foram associados a maior prevalência de DRC (p < 0,001). Conclusões: A prevalência de DRC em uma população urbana no sul do Brasil reflete outros países desenvolvidos e indica que a doença renal é um importante problema de saúde pública no Brasil.