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 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.

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.

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.

Association between kidney measurements and cognitive performance in patients with ischemic stroke.

BACKGROUND: Individuals with chronic kidney disease (CKD) are at a substantially higher risk for stroke, which may predispose individuals to cognitive impairment. However, the association of low estimated glomerular filtration rate (eGFR) and albuminuria with poorer cognitive performance in patients with stroke is not fully understood, and the current evidence for this association is contradictory. Our aim was to retrospectively investigate whether low eGFR and albuminuria, as indicated by the urine albumin-creatinine ratio (UACR), are independently or jointly associated with worse cognitive performance in patients with ischemic stroke. METHODS: This retrospective study included 608 patients with acute ischemic stroke. Their UACR and eGFR values were obtained from inpatient medical records. Global cognitive function was assessed with the mini-mental state exam (MMSE) and Montreal Cognitive Assessment (MoCA) one month after hospital discharge. The relationship between renal measures and cognitive performance was assessed using univariate and multiple linear regression analyses. Potential confounders included age, gender, BMI, education, diabetes and hypertension history, NIHSS score, smoking and alcohol consumption status, serum total cholesterol, triglyceride, fasting glucose, uric acid, homocysteine, systolic blood pressure, and either eGFR or UACR. RESULTS: Patients had an average age of 66.6±4.1 years, and 48% were females. Average eGFR and UACR were 88.4±12.9 ml/min/1.73m2 and 83.6±314.2 mg/g, respectively. The number of patients with eGFR ≥90, 60-89, and <60 ml/min/1.73 m2 was 371 (61%), 207 (34%), and 30 (5%), respectively, and the percentage of patients with UACR <30 mg/g, 30-300 mg/g, and >300 mg/g was 56%, 39%, and 5%, respectively. Multivariate adjusted models showed that eGFR was independently associated with MMSE (ß = -0.4; 95% CI = -0.5,-0.4; p <0.001) and MoCA (ß = -0.6; 95% CI = -0.7,-0.5; p <0.001). However, UACR was not significantly correlated with MMSE or MoCA. CONCLUSION: In patients with ischemic stroke, reduced eGFR but not albuminuria was associated with lower cognitive performance. These results show that the eGFR decline could be an effective indicator of cognitive impairment after a stroke. Therefore, regular monitoring and early detection of mild renal dysfunction in patients with acute ischemic stroke might be needed.

Cardiovascular risk and renal injury profile in subjects with type 2 diabetes and non-albuminuric diabetic kidney disease.

BACKGROUND: In the last years, the classical pattern of diabetic kidney disease (DKD) has been partially overcome, because of the uncovering of a new DKD phenotype with significant renal dysfunction without presence of albuminuria: the non-albuminuric DKD (NA-DKD). To date, the cardiovascular risk associated with this phenotype is still debated. We investigated the cardiovascular risk and renal injury profile of NA-DKD subjects in comparison with other DKD phenotypes. METHODS: Pulse wave velocity (PWV), intima-media thickness, presence of carotid atherosclerotic plaque, renal resistive index (RRI), and a panel of urinary biomarkers of kidney injury were evaluated in 160 subjects with type 2 diabetes, stratified according to estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR) into four groups: controls (UACR < 30 mg/g and eGFR ≥ 60 mL/min/1.73 m2), A-DKD (Albuminuric-DKD, UACR ≥ 30 mg/g and eGFR ≥ 60 mL/min/1.73 m2), NA-DKD (UACR < 30 mg/g and eGFR < 60 mL/min/1.73 m2), AL-DKD (Albuminuric and Low eGFR-DKD; UACR ≥ 30 mg/g and eGFR < 60 mL/min/1.73 m2). RESULTS: Subjects with NA-DKD showed a higher PWV (11.83 ± 3.74 m/s vs. 10.24 ± 2.67 m/s, P = 0.045), RRI (0.76 ± 0.11 vs. 0.71 ± 0.09, P = 0.04), and prevalence of carotid atherosclerotic plaque (59% vs. 31%, P = 0.009) compared with controls. These characteristics were similar to those of subjects with AL-DKD, whereas the profile of A-DKD subjects was closer to controls. After multiple regression analyses, we found that RRI, that is in turn influenced by eGFR (ß = - 0.01, P = 0.01), was one of the major determinants of PWV (ß = 9.4, P = 0.02). Urinary TreFoil Factor 3, a marker of tubular damage, was higher in NA-DKD subjects vs. controls (1533.14 ± 878.31 ng/mL vs. 1253.84 ± 682.17 ng/mL, P = 0.047). Furthermore, after multiple regression analyses, we found that urinary osteopontin was independently associated with PWV (ß = 2.6, P = 0.049) and RRI (ß = 0.09, P = 0.006). CONCLUSIONS: Our data showed a worse cardiovascular and renal injury profile in NA-DKD subjects. This finding emphasizes the central role of eGFR in the definition of cardiovascular risk profile of diabetic subjects together with albuminuria.

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

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

Association of anxiety, depression symptoms and sleep quality with chronic kidney disease among older Chinese.

This study aimed to explore the association of anxiety, depression symptoms and sleep quality with chronic kidney disease (CKD) among older Chinese adults. A total of 1025 participants from the Chinese Longitudinal Healthy Longevity Survey (CLHLS, 2011-2012) were included in our study. The Generalized Anxiety Disorder scale was used to assess anxiety and the Center for Epidemiologic Studies Depression Scale was used to evaluate depressive symptoms. Logistic regression models were conducted to explore the odds ratios (ORs) and 95% confidential intervals (CIs). We found that anxiety, depression symptoms and poor sleep quality were positively associated with albuminuria, impaired estimated glomerular filtration (eGFR) and CKD, after adjusting for other covariates. For anxiety symptom, the ORs and 95% CIs were 1.20 (1.15-1.38) for albuminuria, 1.16 (1.12-1.35) for impaired eGFR and 1.18 (1.12-1.36) for CKD, respectively. For depression symptom, the ORs and 95% CIs were 1.15 (1.05-1.23) for albuminuria, 1.14 (1.05-1.20) for impaired eGFR and 1.14 (1.05-1.22) for CKD, respectively. Compared with good sleep quality, the OR and 95% CI of poor sleep quality were 1.12 (1.04-1.35) for albuminuria, 1.10 (1.02-1.30) for impaired eGFR and 1.11 (1.03-1.32) for CKD, respectively. And the positive association was more evident among females, body mass index ≥ 28, smoking and drinking adults. Anxiety, depression symptoms and poor sleep quality are positively associated with CKD. Future cohort studies are needed to confirm the results.

Prevalence, clinical profile, and risk factors of peripheral artery disease in an Iraqi cohort of chronic kidney disease.

Peripheral artery disease (PAD) is prevalent in patients with chronic kidney disease (CKD) and is associated with substantial morbidity, mortality, and a lower quality of life. This study aimed to determine the prevalence of PAD, clinical profile, and related risk factors among patients with CKD in Iraq (a low-to middle-income country). A cross sectional study comprised 175 CKD patients, of them 60% were male, their mean age was 56 ± 12.5 years, attending Nephrology unit, Hawler Teaching Hospital, Erbil, Iraq between march 2022 and November 2022. Data on demographic and baseline characteristics were collected. Laboratory tests were performed. All participants underwent a detailed history and clinical examination. Vascular lesions in the lower limbs were assessed using the ankle-brachial index. PAD was diagnosed based on an ankle-brachial index value ˂ 0.9, relevant symptoms, and clinical findings. Forty-nine patients (28%) had PAD, and only 17 (34.7%) were symptomatic. PAD was significantly associated with older age (P = .008), male sex (P = .039), diabetes (P = .012), and hypertension (P = .023). In addition, PAD prevalence was significantly higher in patients with prior coronary artery disease (P < .001), advanced CKD stages (P .032), low estimated glomerular filtration rate (P .03), albuminuria (P .002), elevated glycated hemoglobin (P .04), and high sensitive C-reactive protein (P < .001). No significant association was detected between PAD and body mass index, smoking, CKD duration, cerebrovascular disease, dyslipidemia, albumin, creatinine, hemoglobin, total PTH, and phosphate. Peripheral artery disease was prevalent in patients with CKD in Iraq, and the most affected patients were asymptomatic. Older age, male sex, hypertension, diabetes, prior coronary artery disease, advanced CKD stages, albuminuria, higher glycated hemoglobin level, and increased high-sensitivity C-reactive protein level were identified as risk factors. Early detection of occult PAD might enhance efforts toward proper prevention and treatment.

Trajectories of eGFR and risk of albuminuria in youth with type 2 diabetes: results from the TODAY cohort study.

BACKGROUND: We conducted exploratory analyses to identify distinct trajectories of estimated glomerular filtration rate (eGFR) and their relationship with hyperfiltration, subsequent rapid eGFR decline, and albuminuria in participants with youth-onset type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. METHODS: Annual serum creatinine, cystatin C, urine albumin, and creatinine measurements were obtained from 377 participants followed for ≥ 10 years. Albuminuria and eGFR were calculated. Hyperfiltration peak is the greatest eGFR inflection point during follow-up. Latent class modeling was applied to identify distinct eGFR trajectories. RESULTS: At baseline, participants' mean age was 14 years, type 2 diabetes duration was 6 months, mean HbA1c was 6%, and mean eGFR was 120 ml/min/1.73 m2. Five eGFR trajectories associated with different rates of albuminuria were identified, including a "progressive increasing eGFR" group (10%), three "stable eGFR" groups with varying starting mean eGFR, and an "eGFR steady decline" group (1%). Participants who exhibited the greatest peak eGFR also had the highest levels of elevated albuminuria at year 10. This group membership was characterized by a greater proportion of female and Hispanic participants. CONCLUSIONS: Distinct eGFR trajectories that associate with albuminuria risk were identified, with the eGFR trajectory characterized by increasing eGFR over time associating with the highest level of albuminuria. These descriptive data support the current recommendations to estimate GFR annually in young persons with type 2 diabetes and provide insight into eGFR-related factors which may contribute to predictive risk strategies for kidney disease therapies in youth with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00081328, date registered 2002. A higher resolution version of the Graphical abstract is available as Supplementary information.

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

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

Characteristics of patients with chronic kidney disease and Type 2 diabetes initiating finerenone in the USA: a multi-database, cross-sectional study.

Aim: Finerenone is safe and efficacious for treating patients with chronic kidney disease (CKD) and Type 2 diabetes (T2D). Evidence on the use of finerenone in clinical practice is lacking. Objective: To describe demographic and clinical characteristics of early adopters of finerenone in the United States, according to sodium-glucose cotransporter 2 inhibitor (SGLT2i) use and urine albumin-creatinine ratio (UACR) levels. Methods: Multi-database, observational, cross-sectional study, using data from two US databases (Optum Claims and Optum EHR). Three cohorts were included: finerenone initiators with prior CKD-T2D, finerenone initiators with prior CKD-T2D and concomitant SGLT2i use, finerenone initiators with prior CKD-T2D stratified according to UACR. Results: In total, 1015 patients were included, 353 from Optum Claims and 662 from Optum EHR. Mean age was 72.0 and 68.4 years in Optum claims and EHR, respectively. Median eGFR was 44 and 44 ml/min/1.73 m2; and median UACR was 132 (28-698)/365 (74-1185.4) mg/g, in Optum Claims and EHR, respectively. 70.5/70.4% were taking renin-angiotensin system inhibitors, 42.5/53.3% SGLT2i. Overall, 9.0/6.3% of patients had baseline UACR <30 mg/g, 15.0/20.2% had UACR 30-300 mg/g, and 14.4/27.6% had UACR >300 mg/g. Conclusion: Current management of patients with CKD-T2D reflects use of finerenone independently from background therapies and clinical characteristics, suggesting implementation of therapeutic strategies based on different modes of action.

Interaction effect of psoriasis and chronic kidney disease on the risk of all-cause mortality: a prospective cohort study of NHANES data.

BACKGROUND: The association between psoriasis, chronic kidney disease (CKD) and mortality remains unclear. This study aimed to examine the combined impact of psoriasis and CKD on mortality in a representative sample of US adults. METHODS: The data for this analysis came from 13 208 participants of the National Health and Nutrition Examination Survey conducted between 2003-06 and 2009-14. Psoriasis was determined through self-reported questionnaire data, while CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or urinary albumin to creatinine ratio (UACR) ≥30 mg/g. A four-level variable was created using the information on psoriasis and CKD, and survival probability was estimated using the Kaplan-Meier method. The survival analysis was conducted using weighted Cox proportional hazards regression models. RESULTS: In a 9.83-year average follow-up period, 539 deaths occurred, with a prevalence of psoriasis in CKD at 2.94% and an all-cause mortality rate of 33.30%. In the multivariable analyses, individuals with both psoriasis and CKD had hazard ratios (HRs) of 5.38 (95% CI 2.43-11.91) for all-cause mortality compared with those with neither psoriasis nor CKD. Participants with both psoriasis and low eGFR had an HR of 6.40 (95% CI 2.01-20.42), while those with both psoriasis and albuminuria had an HR of 5.30 (95% CI 2.24-12.52). A significant interaction between psoriasis, CKD and all-cause mortality was found in the fully adjusted model (P = .026), and a significant synergistic effect between psoriasis and albuminuria was discovered (P = .002). However, the interaction effects between psoriasis, low eGFR and all-cause mortality were only observed in the unadjusted model (P = .036). CONCLUSIONS: Screening for psoriasis in individuals at risk for developing CKD may help in risk stratification for all-cause mortality related to psoriasis. The assessment of UACR may be useful in identifying psoriasis at increased risk for all-cause mortality.

Association of kidney function and albuminuria with frailty worsening and death in very old adults.

BACKGROUND AND OBJECTIVES: Studies analysing the association of albuminuria and prevalent frailty in community-dwelling very old adults are scarce and lack information on incident frailty. We investigated the association of kidney function decline and increase of albuminuria with frailty worsening or death in very old adults. DESIGN: Longitudinal analyses with biennial visits of the Berlin Initiative (cohort) Study and a frailty follow-up of 2.1 years. SETTING/SUBJECTS: 1,076 participants with a mean age of 84.3 (5.6) years of whom 54% were female. METHODS: Partial proportional odds models were used to assess the association of estimated glomerular filtration rate (eGFR) decline and/or albuminuria (albumin creatinine ratio, ACR) with frailty worsening or death. RESULTS: At frailty baseline, 1,076 participants with an eGFR of 50 (13) ml/min/1.73 m2, 48% being prefrail and 31% frail were included. After median 2.1 years, 960 (90%) participants had valid information on frailty transition: 187 (17.5%) worsened and 111 (10.3%) died. In the multivariable model, the odds of frailty worsening for participants with albuminuria in combination with eGFR <60 ml/min/1.73 m2 were elevated [OR (95% CI): 2.47 (1.41-4.31)] compared to participants without albuminuria and eGFR ≥60 ml/min/1.73 m2 as there was a rapid eGFR decline of ≥3 ml/min/1.73 m2 per year [1.55 (1.04-2.33)] and albuminuria trajectories six years prior [1.53 (1.11-2.10)] to frailty baseline. The odds of death for each exposure were even higher. CONCLUSIONS: In older adults, advanced stages of CKD and albuminuria alone were associated with 2-fold odds of frailty worsening independent of death.

Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence.

BACKGROUND: In clinical trials enrolling patients with type 2 diabetes (T2D) at high cardiovascular risk, many glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved albuminuria status and possibly mitigated kidney function loss. However, limited data are available regarding the effects of GLP-1 RAs on albuminuria status and kidney function in real-world settings, including populations with a lower baseline cardiovascular and kidney risk. We assessed the association of GLP-1 RAs initiation with long-term kidney outcomes in the Maccabi Healthcare Services database, Israel. METHODS: Adults with T2D treated with ≥ 2 glucose-lowering agents who initiated GLP-1 RAs or basal insulin from 2010 to 2019 were propensity-score matched (1:1) and followed until October 2021 (intention-to-treat [ITT]). In an as-treated (AT) analysis, follow-up was also censored at study-drug discontinuation or comparator-initiation. We assessed the risk of a composite kidney outcome, including confirmed ≥ 40% eGFR loss or end-stage kidney disease, and the risk of new macroalbuminuria. Treatment-effect on eGFR slopes was assessed by fitting a linear regression model per patient, followed by a t-test to compare the slopes between the groups. RESULTS: Each propensity-score matched group constituted 3424 patients, 45% women, 21% had a history of cardiovascular disease, and 13.9% were treated with sodium-glucose cotransporter-2 inhibitors at baseline. Mean eGFR was 90.6 mL/min/1.73 m2 (SD 19.3) and median UACR was 14.6 mg/g [IQR 0.0-54.7]. Medians follow-up were 81.1 months (ITT) and 22.3 months (AT). The hazard-ratios [95% CI] of the composite kidney outcome with GLP-1 RAs versus basal insulin were 0.96 [0.82-1.11] (p = 0.566) and 0.71 [0.54-0.95] (p = 0.020) in the ITT and AT analyses, respectively. The respective HRs for first new macroalbuminuria were 0.87 [0.75-0.997] and 0.80 [0.64-0.995]. The use of GLP-1 RA was associated with a less steep eGFR slope compared with basal insulin in the AT analysis (mean annual between-group difference of 0.42 mL/min/1.73 m2/year [95%CI 0.11-0.73]; p = 0.008). CONCLUSION: Initiation of GLP-1 RAs in a real-world setting is associated with a reduced risk of albuminuria progression and possible mitigation of kidney function loss in patients with T2D and mostly preserved kidney function.

Urinary albumin excretion and cancer risk: the PREVEND cohort study.

BACKGROUND: Chronic kidney disease (CKD) is believed to be associated with an increased risk for cancer, especially urinary tract cancer. However, previous studies predominantly focused on the association of decreased estimated glomerular filtration rate (eGFR) with cancer. In this study, we investigated the association of albuminuria with cancer incidence, adjusted for eGFR. METHODS: We included 8490 subjects in the Prevention of Renal and Vascular End-stage Disease (PREVEND) observational study. Urinary albumin excretion (UAE) was measured in two 24-hour urine specimens at baseline. Primary outcomes were the incidence of overall and urinary tract cancer. Secondary outcomes were the incidence of other site-specific cancers, and mortality due to overall, urinary tract, and other site-specific cancers. RESULTS: Median baseline UAE was 9.4 (IQR, 6.3-17.8) mg/24 h. During a median follow-up of 17.7 years, 1341 subjects developed cancer (of which 177 were urinary tract cancers). After multivariable adjustment including eGFR, every doubling of UAE was associated with a 6% (hazard ratios (HR), 1.06, 95% confidence intervals (CI), 1.02-1.10), and 14% (HR, 1.14, 95% CI, 1.04-1.24) higher risk of overall and urinary tract cancer incidence, respectively. Except for lung and hematological cancer, no associations were found between UAE and the incidence of other site-specific cancer. Doubling of UAE was also associated with a higher risk of mortality due to overall and lung cancer. CONCLUSIONS: Higher albuminuria is associated with a higher incidence of overall, urinary tract, lung, and hematological cancer, and with a higher risk of mortality due to overall and lung cancers, independent of baseline eGFR.

Clinical outcomes in patients with type 2 diabetes mellitus-related kidney disease: A Jordanian population cohort study.

BACKGROUND: Diabetic kidney disease (DKD) increases the risk of cardiovascular (CV) complications, kidney disease progression, and mortality. We aimed to determine the incidence and risk of these outcomes according to DKD phenotype among the Jordanian population. METHODS: A total of 1172 type 2 diabetes mellitus patients with estimated glomerular filtration rates (eGFRs) of >30 ml/min/1.73 m2 were followed-up from 2019 to 2022. At baseline, patients were classified according to the presence of albuminuria (>30 mg/g creatinine) and reduced eGFR (<60 ml/min/1.73 m2) into four phenotypes: non-DKD (reference category), albuminuric DKD without decreased eGFR, non-albuminuric DKD with decreased eGFR, and albuminuric DKD with decreased eGFR. RESULTS: Mean follow-up was 2.9 ± 0.4 years. Overall, 147 patients (12.5 %) experienced CV events, while 61 (5.2 %) demonstrated kidney disease progression (eGFR: <30 ml/min/1.73 m2). The mortality rate was 4.0 %. Multivariable-adjusted risk for CV events and mortality was greatest for the albuminuric DKD with decreased eGFR group (hazard ratio [HR]: 1.45, 95 % confidence interval [CI]: 1.02-2.33 and HR: 6.36, 95 % CI: 2.98-13.59, respectively), with the risk increasing when adjusted for prior CV history (HR: 1.47, 95 % CI: 1.06-3.42 and HR: 6.70, 95 % CI: 2.70-16.60, respectively). Risk of a ≥40 % decline in eGFR was greatest for the albuminuric DKD with decreased eGFR group (HR: 3.45, 95 % CI: 1.74-6.85), followed by the albuminuric DKD without decreased eGFR group (HR: 1.6, 95 % CI: 1.06-2.75). CONCLUSION: Thus, patients with albuminuric DKD and decreased eGFR were at greater risk for poor CV, renal, and mortality outcomes compared to other phenotypes.

Association of Kidney Tubule Biomarkers With Cardiac Structure and Function in the Multiethnic Study of Atherosclerosis.

Markers of glomerular disease, estimated glomerular filtration rate (eGFR) and albuminuria, are associated with cardiac structural abnormalities and incident cardiovascular disease (CVD). We aimed to determine whether biomarkers of kidney tubule injury, function, and systemic inflammation are associated with cardiac structural abnormalities. Among 393 Multi-Ethnic Study of Atherosclerosis participants without diabetes, CVD, or chronic kidney disease, we assessed the association of 12 biomarkers of kidney tubule injury, function, and systemic inflammation with the left ventricular mass/volume ratio (LVmvr) and left ventricular ejection fraction (LVEF) on cardiac magnetic resonance imaging using linear regression. The average age was 60 ± 10 years; 48% were men; mean eGFR was 96±16 ml/min/1.73 m2; mean LVmvr was 0.93±0.18 g/ml, and mean LVEF was 62±6%. Each twofold greater concentration of plasma soluble urokinase plasminogen activator receptor was associated with a 0.04 g/ml (95% confidence interval [CI] 0.01 to 0.08 g/ml) higher LVmvr and 2.1% (95% CI 0.6 to 3.5%) lower LVEF, independent of risk factors for CVD, eGFR, and albuminuria. Each twofold greater plasma monocyte chemoattractant protein 1 was associated with higher LVmvr with a similar coefficient to that of plasma soluble urokinase plasminogen activator receptor. Each twofold greater concentration of plasma chitinase-3-like protein 1 and urine alpha-1-microglobulin was associated with a 1.1% (95% CI 0.4 to 1.7%) and 1.2% (95% CI 0.2 to 2.2%) lower LVEF, respectively. In conclusion, abnormal kidney tubule health may lead to cardiac dysfunction above and beyond eGFR and albuminuria.

Associations of non-invasive indices of liver steatosis and fibrosis with progressive kidney impairment in adults with type 2 diabetes.

AIMS: Longitudinal data linking non-alcoholic fatty liver disease to kidney dysfunction in type 2 diabetes (T2D) are limited. This study evaluated the associations of non-invasive indices of liver steatosis and liver fibrosis with kidney impairment, and the mediatory role of the pro-angiogenic factor leucine-rich α-2 glycoprotein 1 (LRG1). METHODS: T2D adults (n = 2057) were followed for a mean period of 6.1 ± 1.6 years. Baseline liver steatosis [(hepatic steatosis index (HSI) and Zhejiang University index (ZJU)] and liver fibrosis [aspartate transaminase/alanine transaminase ratio (AAR) and BARD] indices derived from composite scoring systems were calculated. Plasma LRG1 levels were quantified using immunoassay. The study outcomes were progressive kidney function decline defined as estimated glomerular filtration rate (eGFR) decline of ≥ 40% and albuminuria progression defined as an increase in albuminuria category. RESULTS: Cross-sectionally, liver steatosis and liver fibrosis indices were associated with increased albuminuria (urinary albumin/creatinine ratio ≥ 30 µg/mg) and reduced renal function (eGFR < 60 mL/min/1.73 m2) after covariate adjustment, respectively. Approximately 32% of the participants experienced progressive kidney function decline, while 38% had albuminuria worsening over time. Longitudinal analysis revealed that baseline AAR (hazard ratio: 1.56; 95% CI 1.15-2.11) and BARD (hazard ratio: 1.16, 95% CI 1.04-1.28) predicted progressive kidney function decline, partly mediated by LRG1. In contrast, liver steatosis (HSI and ZJU) but not liver fibrosis (AAR and BARD) indices were independently associated with albuminuria progression. CONCLUSIONS: Increased liver steatosis scores were associated with albuminuria deterioration. Conversely, liver fibrosis indices may be associated with progressive kidney function decline, potentially driven by increased inflammation and angiogenesis.