Chronic Kidney Disease In Type Research Articles

A digital twin model incorporating generalized metabolic fluxes to identify and predict chronic kidney disease in type 2 diabetes mellitus

We have developed a digital twin-based CKD identification and prediction model that leverages generalized metabolic fluxes (GMF) for patients with Type 2 Diabetes Mellitus (T2DM). GMF digital twins utilized basic clinical and physiological biomarkers as inputs for identification and prediction of CKD. We employed four diverse multi-ethnic cohorts (n = 7072): a Singaporean cohort (EVAS, n = 289) and a North American cohort (NHANES, n = 1044) for baseline CKD identification, and two multi-center Singaporean cohorts (CDMD, n = 2119 and SDR, n = 3627) for 3-year CKD prediction and risk stratification. We subsequently conducted a comprehensive study utilizing a single dataset to evaluate the clinical utility of GMF for CKD prediction. The GMF-based identification model performed strongly, achieving an AUC between 0.80 and 0.82. In prediction, the GMF generated with complete parameters attained high performance with an AUC of 0.86, while with incomplete parameters, it achieved an AUC of 0.75. The GMF-based prediction model utilizing complete inputs is the standard implementation of our algorithm: HealthVector Diabetes®. We have established the GMF digital twin-based model as a robust clinical tool capable of predicting and stratifying the risk of future CKD within a 3-year time horizon. We report the correlation of GMF with basic input parameters, their ability to differentiate between future health states and medication status at baseline, and their capability to quantify CKD progression rates. This holistic methodology provides insights into patients’ health states and CKD progression rates based on GMF metabolic profile differences, enabling personalized care plans.

#2955 Incidental findings in a renal magnetic resonance imaging study for evaluation of chronic kidney disease in type 2 diabetes population

Abstract Background and Aims Novel Magnetic Resonance Imaging (MRI) techniques are potential methods to non-invasively assess and quantify functional, structural and pathophysiological changes in chronic kidney disease (CKD) that may improve diagnosis, prognosis and treatment of these patients. Advances in imaging techniques are also likely to result in the detection of unexpected and asymptomatic incidental findings. We retrospectively analyzed the overall prevalence of incidental findings in the participants of our previously reported study utilizing a non-contrast multiparametric MRI protocol in patients with type 2 DM (T2DM) as compared to healthy controls. Method The subjects of this sub-study were participants of our original prospective, single-center, observational study, in which several MRI biomarkers were evaluated to differentiate diabetic versus healthy kidneys, and various stages of CKD. A complete medical history and physical examination were performed. The inclusion criteria for the T2DM cohort were: Age 18-70 years, type II DM with CKD staged 3-4 (estimated glomerular filtration rate [eGFR] 15-60 ml/min/1.73 m2, body mass index (BMI) 18-35 and provision of written informed consent. The control group comprised of healthy volunteers who were age- and sex-matched and had the following inclusion criteria: Age 18-70 years, eGFR >80 ml/min/1.73 m2, UACR <30 mmol/g, BMI 18-35 and provision of written informed consent. Exclusion criteria for the diabetic group were any apparent cause/s of CKD other than diabetes, previous kidney transplantation, pregnancy, contraindication for MRI examination, heart failure (NYHA class III or IV), allergies to iodine-based contrast agents. Factors that excluded healthy participants were pregnancy, contraindication for MRI examination, allergy to iodine-based contrast agents and any active or chronic disease/diagnosis. Measured GFR (mGFR) was assessed in all participants using iohexol clearance. An MRI scan using a wide range of non-contrast techniques was performed at baseline. Total scan time for patients did not exceed 45 min per session and no gadolinium-based contrast agents were used in any of the MRI examinations. All patients with incidental findings on MRI were further evaluated and referred to appropriate specialists for management. Results A total of 38 T2DM patients with CKD and 20 age- and gender-matched healthy volunteers who completed the study were included in the analysis. Of the T2DM patients, 2 were found to have CKD stage 2 by mGFR and 36 CKD stages 3–4. Clinically significant incidental findings (excluding 4 cases of renal cysts requiring only follow-up without further intervention) were found in 13 of the 38 (34%) T2DM patients. The most frequent findings were intraductal papillary mucinous neoplasm (IPMN) in 7 patients, followed by 3 cancers (1 case of kidney cancer, 1 bladder cancer and 1 lymphoma) and 3 cases of adrenal gland mass later diagnosed to be benign adenoma on further investigation. In contrast, of the 20 healthy volunteers, 2 (10%) were found to have significant incidental findings, which were IPMN in both. The follow-up duration varied between 2-6 years. The patient with bladder cancer had metastatic disease and died shortly after the diagnosis, the one with kidney cancer is under observation and the one with lymphoma underwent adequate treatment and is under remission. The cases of IPMN are being followed up regularly at our surgical department. Conclusion Clinically important incidental findings on renal MRI appear to be more common in T2DM patients than in healthy volunteers, which would have been missed without MRI examination. Mechanisms for reporting and strategies for dealing with incidental findings need to be taken into account in such investigational imaging studies. The detection of incidental findings also poses various practical and ethical issues. Further larger studies with long-term follow-up are needed to delineate the clinical relevance, natural course and management of such incidental findings.

Rationale and design of the Innsbruck Diabetic Kidney Disease Cohort (IDKDC)—a prospective study investigating etiology and progression of early-stage chronic kidney disease in type 2 diabetes

ABSTRACT Background The development of chronic kidney disease (CKD) in about 20%–40% of patients with type 2 diabetes (T2D) aggravates cardiovascular morbidity and mortality. Pathophysiology is of increasing relevance for individual management and prognosis, though it is largely unknown among T2D patients with CKD as histologic work-up is not routinely performed upon typical clinical presentation. However, as clinical parameters do not appropriately reflect underlying kidney pathology, reluctance regarding timely histologic assessment in T2D patients with CKD should be critically questioned. As the etiology of CKD in T2D is heterogeneous, we aim to assess the prevalence and clinical disease course of typical diabetic vs atypical/non-specific vs non-diabetic vs coexisting kidney pathologies among T2D patients with mild-to-moderate kidney impairment [KDIGO stage G3a/A1–3 or G2/A2–3; i.e. estimated glomerular filtration rate (eGFR) 59–45 mL/min irrespective of albuminuria or eGFR 89–60 mL/min and albuminuria >30 mg/g creatinine]. Methods The Innsbruck Diabetic Kidney Disease Cohort (IDKDC) study aims to enroll at least 65 T2D patients with mild-to-moderate kidney impairment to undergo a diagnostic kidney biopsy. Six-monthly clinical follow-ups for up to 5 years will provide clinical and laboratory data to assess cardio-renal outcomes. Blood, urine and kidney tissue specimen will be biobanked to identify diagnostic and prognostic biomarkers. Conclusions While current risk assessment is primarily based on clinical parameters, our study will provide the scientific background for a potential change of the diagnostic standard towards routine kidney biopsy and clarify its role for individual risk prediction regarding cardio-renal outcome in T2D patients with mild-to-moderate kidney impairment.

Excess body weight, duration of insulin and antihypertensive therapy slow down the rate of progression of chronic kidney disease in type 2 diabetes

Objective: to study and clinically substantiate the relationship between overweight and the dynamics of CKD progression in patients with type 2 diabetes of different age groups using the diagnostic parameter Index of glomerular filtration rate reduction. Material and methods: a single-stage cross-sectional observational study of clinical indicators in a population sample of patients with type 2 diabetes of different age groups was performed, patterns of relationships, significance of differences in mean values and measures of influence (OR (95%CI)) were studied between the indicators of BMI, the stage of obesity and the presence of a diagnosis of obesity in the anamnesis and the original calculated diagnostic parameter, the Index of glomerular filtration rate reduction (RI_GFR), which allows to give an objective quantitative characteristic of the rate of progression of CKD. Results: significant correlations were established between RI_GFR and indicators of age, BMI, DM experience and duration of insulin therapy, a significant inverse relationship with BMI was noted only in the older group; when analyzing differences in the average values of clinical indicators in the groups of rapid and slow progression of CKD, divided by the threshold value of RI_GFR, significant factors affecting the rate of progression were determined CKD: DM experience, duration of insulin therapy, BMI; the logistic regression analysis determined the measure of the influence of the above factors on the dynamics of GFR reduction, confirmed its significance; when analyzing the factors of drug treatment in the elderly group, it was revealed that an integrated approach to the appointment of antihypertensive therapy (prescribing drugs of three or more groups) significantly reduces the risk of rapid progression of CKD. Conclusions: the most significant risk factors for the high rate of progression of CKD in patients with type 2 diabetes and overweight in the general sample and in patients of the older age group are the length of diabetes and duration of insulin therapy; the dynamics of GFR reduction in patients with type 2 diabetes of different age groups is interrelated with BMI, and in patients with overweight CKD progresses more slowly; an integrated approach to prescribing antihypertensive therapy (prescribing drugs of three or more groups) in elderly patients with type 2 diabetes significantly reduces the risk of rapid progression of CKD.

Utilization of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for noninvasive assessment of chronic kidney disease in type 2 diabetes

BackgroundsAccumulating data demonstrated that the cortico-medullary difference in apparent diffusion coefficient (ΔADC) of diffusion-weighted magnetic resonance imaging (DWI) was a better correlation with kidney fibrosis, tubular atrophy progression, and a predictor of kidney function evolution in chronic kidney disease (CKD). ObjectivesWe aimed to assess the value of ΔADC in evaluating disease severity, differential diagnosis, and the prognostic risk stratification for patients with type 2 diabetes (T2D) and CKD. MethodsTotal 119 patients with T2D and CKD who underwent renal MRI were prospectively enrolled. Of them, 89 patients had performed kidney biopsy for pathological examination, including 38 patients with biopsy-proven diabetic kidney disease (DKD) and 51 patients with biopsy-proven non-diabetic kidney disease (NDKD) and Mix (DKD + NDKD). Clinicopathological characteristics were compared according to different ΔADC levels. Moreover, univariate and multivariate-linear regression analyses were performed to explore whether ΔADC was independently associated with estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR). The diagnostic performance of ΔADC for discriminating DKD from NDKD + Mix was evaluated by receiver operating characteristic (ROC) analysis. In addition, an individual's 2- or 5-year risk probability of progressing to end-stage kidney disease (ESKD) was calculated by the kidney failure risk equation (KFRE). The effect of ΔADC on prognostic risk stratification was assessed. Additionally, net reclassification improvement (NRI) was used to evaluate the model performance. ResultsAll enrolled patients had a median ΔADC level of 86 (IQR 28, 155) × 10−6 mm2/s. ΔADC significantly decreased across the increasing staging of CKD (P < 0.001). Moreover, those with pathological-confirmed DKD has a significantly lower level of ΔADC than those with NDKD and Mix (P < 0.001). It showed that ΔADC was independently associated with eGFR (β = 1.058, 95% CI = [1.002,1.118], P = 0.042) and UACR (β = −3.862, 95% CI = [-7.360, -0.365], P = 0.031) at multivariate linear regression analyses. Besides, ΔADC achieved an AUC of 0.707 (71% sensitivity and 75% specificity) and AUC of 0.823 (94% sensitivity and 67% specificity) for discriminating DKD from NDKD + Mix and higher ESKD risk categories (≥50% at 5 years; ≥10% at 2 years) from lower risk categories (<50% at 5 years; <10% at 2 years). Accordingly, the optimal cutoff value of ΔADC for higher ESKD risk categories was 66 × 10−6 mm2/s, and the group with the low-cutoff level of ΔADC group was associated with 1.232 -fold (95% CI 1.086, 1.398) likelihood of higher ESKD risk categories as compared to the high-cutoff level of ΔADC group in the fully-adjusted model. Reclassification analyses confirmed that the final adjusted model improved NRI. ConclusionsΔADC was strongly associated with eGFR and UACR in patients with T2D and CKD. More importantly, baseline ΔADC was predictive of higher ESKD risk, independently of significant clinical confounding. Specifically, ΔADC <78 × 10−6 mm2/s and <66 × 10−6 mm2/s would help to identify T2D patients with the diagnosis of DKD and higher ESKD risk categories, respectively.

FIDELIO study: significance and place of finerenone as nonsteroidal mineralocorticoid receptor antagonist in therapy of patients with chronic kidney disease in type 2 diabetes

Patients with diabetes mellitus and renal pathology are at high risk of developing end-stage kidney disease (ESKD) and cardiovascular disease (CVD), including atrial fibrillation as an life-threatening condition. The intense annual increase in patients with diabetes mellitus, mainly due to the patients with type 2 diabetes mellitus (T2D), and diabetic nephropathy sets a new goal for researchers to expand the range of drugs with cardio- and nephroprotective effects to offset the residual risks of development and progression of chronic kidney disease (CKD) and CVD in this cohort of patients. One of such drugs is finerenone — a novel selective non-steroidal mineralocorticoid receptor (MR) antagonist (MRA), hyperactivation of which mediates renal inflammation and fibrosis, cardiac remodeling and changes in its structural and electrical characteristics. This review presents the results of the sub-analysis of FIDELIO devoted to the mechanism of drug action, the finerenone efficacy evaluation, its comparison with the efficacy of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists with already proven organoprotective properties with respect to reducing the risk of renal and cardiovascular endpoints.

Perturbational phenotyping of human blood cells reveals genetically determined latent traits associated with subsets of common diseases

Although genome-wide association studies (GWAS) have successfully linked genetic risk loci to various disorders, identifying underlying cellular biological mechanisms remains challenging due to the complex nature of common diseases. We established a framework using human peripheral blood cells, physical, chemical and pharmacological perturbations, and flow cytometry-based functional readouts to reveal latent cellular processes and performed GWAS based on these evoked traits in up to 2,600 individuals. We identified 119 genomic loci implicating 96 genes associated with these cellular responses and discovered associations between evoked blood phenotypes and subsets of common diseases. We found a population of pro-inflammatory anti-apoptotic neutrophils prevalent in individuals with specific subsets of cardiometabolic disease. Multigenic models based on this trait predicted the risk of developing chronic kidney disease in type 2 diabetes patients. By expanding the phenotypic space for human genetic studies, we could identify variants associated with large effect response differences, stratify patients and efficiently characterize the underlying biology.

New possibilities of nephroprotection in type 2 diabetes using finerenone Consensus of the board of experts

Patients with chronic kidney disease (CKD) belong to the category of patients with diabetes mellitus (DM), which are the most difficult to treat. They require a multidisciplinary, multifactorial approach to slow disease progression, reduce glomerular filtration rate (GFR), and prevent cardiovascular morbidity and mortality. Modern treatment of CKD in patients with type 2 diabetes involves influencing various links of its pathogenesis. The use of finerenone is a fundamentally new approach in treatment of CKD. Inflammation and fibrosis, which develop as a result of excessive activation of mineralocorticoid receptors, are key pathophysiological mechanisms of the development and progression of CKD in patients with type 2 DM. Therefore, the blocking of mineralocorticoid receptors (MCR) with the innovative nonsteroidal selective MCR antagonist finerenone is a promising way to improve the clinical course of CKD, and has a favorable prognostic effect on the rate of progression of CKD and on the risk of cardiovascular events. The feasibility of adding finerenone to the treatment regimens of patients with CKD and type 2 diabetes in order to reduce the rate of progression of CKD and reduce the frequency of cardiovascular events is substantiated by convincing data from clinical studies and reflected in the recommendations of the American Diabetes Association, 2023. The innovative drug finerenone has a direct nephroprotective effect, which reliably slows down the progression of CKD in patients with type 2 diabetes. Therefore, finerenone should be considered for prescribing from the initial stage of kidney damage. When using finerenone, the risk of developing hyperkalemia is low, which minimizes the risk of withdrawal of the drug during treatment. Despite the available modern methods of treatment, which are primarily aimed at the hemodynamic and metabolic factors of the development of CKD in type 2 diabetes mellitus, the introduction of the specified new pathogenetic approach using finerenone, as a means whose mechanism of action is due to a direct effect on inflammation and fibrosis, is considered necessary from the point of view of improving the clinical course of CKD and the prognosis.

Chronic kidney disease in type 1 diabetes: translation of novel type 2 diabetes therapeutics to individuals with type 1 diabetes.

Current management of chronic kidney disease (CKD) in type 1 diabetes centres on glycaemic control, renin-angiotensin system inhibition and optimisation of risk factors including blood pressure, lipids and body weight. While these therapeutic approaches have significantly improved outcomes among people with type 1 diabetes and CKD, this population remains at substantial elevated risk for adverse kidney and cardiovascular events, with limited improvements over the last few decades. The significant burden of CKD and CVD in type 1 diabetes populations highlights the need to identify novel therapies with the potential for heart and kidney protection. Over the last decade, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide 1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists have emerged as potent kidney-protective and/or cardioprotective agents in type 2 diabetes. The consistent, substantial kidney and cardiovascular benefits of these agents has led to their incorporation into professional guidelines as foundational care for type 2 diabetes. Furthermore, introduction of these agents into clinical practice has been accompanied by a shift in the focus of diabetes care from a 'glucose-centric' to a 'cardiorenal risk-centric' approach. In this review, we evaluate the potential translation of novel type 2 diabetes therapeutics to individuals with type 1 diabetes with the lens of preventing the development and progression of CKD.

Management Strategies for the Prevention and Treatment of Chronic Kidney Disease in Patients with Type 2 Diabetes

Type 2 diabetes mellitus (DM2) is one of the leading causes of chronic kidney disease (CKD) worldwide. This represents a growing public health problem. It is well known the relationship between chronic kidney disease and type 2 diabetes, and one of the main objectives of the treatment is based on the prevention and education of patients and optimal pharmacological management. The prevention of CKD demands a multifaceted approach that addresses glycemic control, blood pressure management, and lipid control. These preventive measures, combined with dietary modifications, exercise, and patient education, can significantly reduce the risk of CKD development and progression. Accordingly, managing CKD in type 2 diabetes patients demands a comprehensive and individualized approach, considering these conditions’ multifaceted nature. With the right strategies and a patient-centered approach, it is possible to mitigate the impact of CKD, improve patient outcomes, and empower individuals to take control of their health in the face of these complex health challenges. This review article aims to provide a comprehensive overview of pharmacological and non-pharmacological strategies for preventing and treating chronic kidney disease in patients with type 2 diabetes and delay progression to end-stage renal disease (ESRD)

Screening for Chronic Kidney Disease in Type 2 Diabetic Patients: Single Centre Study

Abstract Background Diabetes mellitus is the most common cause of chronic kidney disease in the world, leading to multiple complications including end-stage renal disease, cardiovascular disease and even death so, Screening is an important strategy to address the burden of CKD in diabetic population. International clinical guidelines recommend CKD screening for individuals with risk factors such as diabetes, using laboratory assessments of glomerular filtration rate (GFR) and urine albumin excretion. Objective This study describes the implementation and outcomes of screening programme for chronic kidney disease in type 2 diabetic patients to assess the burden of renal disease in diabetic population. Patients and Methods The present study included two hundred type 2 diabetic patients complicated with diabetic nephropathy. Fifty five percent of the studied patients were males. Age ranged from 42 to 82 years with mean ± SD of 60.09 ± 8.55 years. They were screened in Alagouza Hospital for CKD by using urinary ACR and average eGFR. Patients with CKD were further investigated for extrarenal diabetic complications as PVD, amputation and cardiovascular complications by using LL arterial duplex and echocardiography. Results As regard diabetic complications, nephropathy came in the 1st rank with 106 patients (53%) presented with either average eGFR&amp;lt;60 ml/min/1.73 m2(10.5%), ACR &amp;gt;30 mg albumin/gm creatinine (30%) or both(12.5%). That was followed by history of neuropathy which represented 44.5% of the studied patients. Retinopathy evidenced in fundus examination compromised about 34.516% out of our studied population. Patients with past history of stroke represented 17.5% of the studied population Peripheral neuropathy was more common in patients with nephropathy 69.7 % (n = 62) (4 patients with decline eGFR, 36 patients with albuminuria and 22 patients with both), compared to only 30.3 % (n = 27) non- nephropathic diabetic patients gave positive history of neuropathy. retinopathy was more common in patients with nephropathy (11 patients with declined GFR, 25 patients with albuminuria and 25 patients with albuminuria and declined GFR), versus only 8 patients in among the non-nephropathic diabetic patients had retinopathy evidenced in fundus examination. Stroke was more common among patients with nephropathy (4 patients with decline eGFR, 6 patients with albuminuria and 12 patients with albuminuria and declined eGFR), versus 13 patients with positive stroke history in non- nephropathic diabetic patients. Patients with nephropathy were further investigated for the presence of extra renal diabetic complications as PVD and cardiovascular complications. Arterial LL duplex revealed PVD in 32.1% (34 patients) with 3 patients underwent amputation. As regard cardiovascular complications, 17.9 % (19 patients) were found to have abnormal findings in echocardiography examination including heart failure and ischemic changes. Conclusion From our study, we showed the high burden of diabetic complications among the patients with type 2 diabetes especially renal diabetic complications. Therefore, screening of diabetic nephropathy in patients with type 2 diabetes mellitus can help in early treatment and avoid its more serious complications not only the progression to ESRD but also development of other extra-renal diabetic complications.

Modifiability of Composite Cardiovascular Risk Associated With Chronic Kidney Disease in Type 2 Diabetes With Finerenone

It is currently unclear whether chronic kidney disease (CKD)-associated cardiovascular risk in type 2 diabetes (T2D) is modifiable. To examine whether cardiovascular risk can be modified with finerenone in patients with T2D and CKD. Incidence rates from Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis (FIDELITY), a pooled analysis of 2 phase 3 trials (including patients with CKD and T2D randomly assigned to receive finerenone or placebo) were combined with National Health and Nutrition Examination Survey data to simulate the number of composite cardiovascular events that may be prevented per year with finerenone at a population level. Data were analyzed over 4 years of consecutive National Health and Nutrition Examination Survey data cycles (2015-2016 and 2017-2018). Incidence rates of cardiovascular events (composite of cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, or hospitalization for heart failure) were estimated over a median of 3.0 years by estimated glomerular filtration rate (eGFR) and albuminuria categories. The outcome was analyzed using Cox proportional hazards models stratified by study, region, eGFR and albuminuria categories at screening, and cardiovascular disease history. This subanalysis included a total of 13 026 participants (mean [SD] age, 64.8 [9.5] years; 9088 male [69.8%]). Lower eGFR and higher albuminuria were associated with higher incidences of cardiovascular events. For recipients in the placebo group with an eGFR of 90 or greater, incidence rates per 100 patient-years were 2.38 (95% CI, 1.03-4.29) in those with a urine albumin to creatinine ratio (UACR) less than 300 mg/g and 3.78 (95% CI, 2.91-4.75) in those with UACR of 300 mg/g or greater. In those with eGFR less than 30, incidence rates increased to 6.54 (95% CI, 4.19-9.40) vs 8.74 (95% CI, 6.78-10.93), respectively. In both continuous and categorical models, finerenone was associated with a reduction in composite cardiovascular risk (hazard ratio, 0.86; 95% CI, 0.78-0.95; P = .002) irrespective of eGFR and UACR (P value for interaction = .66). In 6.4 million treatment-eligible individuals (95% CI, 5.4-7.4 million), 1 year of finerenone treatment was simulated to prevent 38 359 cardiovascular events (95% CI, 31 741-44 852), including approximately 14 000 hospitalizations for heart failure, with 66% (25 357 of 38 360) prevented in patients with eGFR of 60 or greater. Results of this subanalysis of the FIDELITY analysis suggest that CKD-associated composite cardiovascular risk may be modifiable with finerenone treatment in patients with T2D, those with eGFR of 25 or higher, and those with UACR of 30 mg/g or greater. UACR screening to identify patients with T2D and albuminuria with eGFR of 60 or greater may provide significant opportunities for population benefits.

High-normal unconjugated bilirubin is associated with decreased risk of chronic kidney disease in type 2 diabetes: Areal-world study.

To investigate the association between serum unconjugated bilirubin (UCB) within normal limits and chronic kidney disease (CKD) in T2DM patients. This cross-sectional, real-world study was performed in 8661 hospitalised T2DM patients. The subjects were stratified into quintiles based on serum UCB levels. The clinical characteristics and CKD prevalence were compared among the UCB quantile groups. The associations of serum UCB levels and quintiles with CKD were also analysed by binary logistic regression. After controlling for age, sex, and diabetes duration (DD), the CKD prevalence (20.4%, 12.2%, 10.6%, 8.3%, and 6.4% for the first, second, third, fourth, and fifth quintiles, respectively, p<0.001 for trend) was significantly decreased across the serum UCB quintiles. The fully adjusted regression model showed negative associations of serum UCB levels (OR: 0.660, 95% CI: 0.585-0.744; p<0.001 for trend) and quintiles (p<0.001) with the presence of CKD. Compared with the subjects in the lowest UCB quintile, the risk of CKD decreased by 36.2%, 54.3%, 53.8%, and 62.1%, respectively, in those from the second to the highest UCB quintile. Additionally, C-reactive protein (CRP) levels were significantly higher in the subjects with CKD than in those without CKD (p<0.001), and significantly decreased across the UCB quintiles (p<0.001 for trend). Serum UCB levels within the normal range were significantly and negatively linked to CKD in T2DM patients. High-normal UCB may be an independent protective factor for CKD by its antioxidant and the following anti-inflammatory activities through its signalling activity, which was indicated by clearly decreased CRP levels across the UCB quintiles.

Finerenone for chronic kidney disease in type 2 diabetes

Finerenone (Kerendia) is a mineralocorticoid‐receptor antagonist for the treatment of chronic kidney disease in patients with type 2 diabetes. This article discusses its indications, efficacy and adverse effects.

Effects of Finerenone on Cardiovascular and Chronic Kidney Diseases: A New Weapon against Cardiorenal Morbidity and Mortality-A Comprehensive Review.

Patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) show high rates of cardiorenal outcomes. In addition, the progression towards renal failure and cardiovascular events rises as CKD worsens. Several studies suggest that the activation of the mineralocorticoid receptor (MR) induces cardiac and renal injury, including inflammation and fibrosis. Finerenone is a novel, nonsteroidal, selective MR antagonist (MRA) which has demonstrated anti-inflammatory and anti-fibrotic effects in pre-clinical studies. Moreover, two large trials (FIDELIO-DKD and FIGARO-DKD) investigated the renal and cardiovascular outcomes in patients with mild to severe CKD in type 2 diabetes which received finerenone. On these bases, this comprehensive review aims to summarize the current knowledge regarding finerenone and its effects on CKD and the cardiovascular system, emphasizing its role in modifying cardiorenal outcomes.

Drugs that slow the progression of diabetic kidney disease: are renoprotective effects attenuated in heart failure?

Top panel: meta-analysis (random effects model) for occurrence of end-stage kidney disease in four major outcomes trials of SGLT2 inhibitors in heart failure. Bottom panel: depiction of different mechanisms driving the progression of chronic kidney disease in type 2 diabetes, as compared with chronic heart failure. Drugs that lower intraglomerular pressures may be beneficial in type 2 diabetes (characterized by glomerular hyperfiltration), but detrimental in chronic heart failure (characterized by glomerular hypofiltration).

Adropin Predicts Chronic Kidney Disease in Type 2 Diabetes Mellitus Patients with Chronic Heart Failure.

Adropin is a multifunctional secreted protein, which is involved in the metabolic modulation of the heart-brain-kidney axis in heart failure (HF). The aim of the study was to detect the plausible predictive value of serum levels of adropin for chronic kidney disease (CKD) grades 1-3 in type 2 diabetes mellitus (T2DM) patients with chronic HF. We enrolled 417 T2DM individuals with chronic HF and subdivided them into two groups depending on the presence of CKD. The control group was composed of 25 healthy individuals and 30 T2DM patients without HF and CKD. All eligible patients underwent an ultrasound examination. Adropin was detected by ELISA in blood samples at the study baseline. We found that adropin levels in T2DM patients without HF and CKD were significantly lower than in healthy volunteers, but they were higher than in T2DM patients with known HF. The optimal cut-off point for adropin levels was 2.3 ng/mL (area under the curve [AUC] = 0.86; 95% CI = 0.78-0.95; sensitivity = 81.3%, specificity = 77.4%). The multivariate logistic regression adjusted for albuminuria/proteinuria showed that serum levels of adropin <2.30 ng/mL (OR = 1.55; p = 0.001) independently predicted CKD. Conclusions: Low levels of adropin in T2DM patients with chronic CH seem to be an independent predictor of CKD at stages 1-3.

Metabolic dysfunction-associated fatty liver disease can significantly increase the risk of chronic kidney disease in adults with type 2 diabetes

AimsThis study is to explore the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and chronic kidney disease (CKD) among populations with type 2 diabetes through longitudinal cohort study. Methods3,627 subjects who had received at least three health examinations between 2008 and 2015 were included. CKD was stated as subjects with an eGFR < 60 mL/min per 1·73 m2 or the occurrence of 2 or more proteinuria during their follow-up. ResultsAfter median of 10·0 years follow up, 837 (23·1%) developed CKD (244·7 per 10,000 person-years; 95 % CI, 228.4 − 261·8). MAFLD ([HR] 1·46; 95 % CI 1·26-1·70, P < 0.001) acts as an important risk factor of developing CKD. After adjusting for confounding factors, this association was consistent (HR 1·30; 95 % CI 1·11-1·53, P < 0.001). In stratified analysis, subjects aged < 60 years were likely to have greater risk of MAFLD-related CKD (HR 1·58 and 1·03; 95 % CI 1·28-1·95 and 0·79-1·33, P < 0.001 in both cases, respectively). ConclusionsThe risk of developing CKD in type 2 diabetes adults with MAFLD was higher, especially if they are below 60 years old. This study underscores the importance of early prevention strategies for MAFLD to reduce the occurrence of CKD in type 2 diabetes adults.

Chronic kidney disease begets heart failure and vice versa: temporal associations between heart failure events in relation to incident chronic kidney disease in type 2 diabetes.

To investigate the interplay of incident chronic kidney disease (CKD) and/or heart failure (HF) and their associations with prognosis in a large, population-based cohort with type 2 diabetes (T2DM). Patients aged ≥18 years with new-onset T2DM, without renal disease or HF at baseline, were identified from the territory-wide Clinical Data Analysis Reporting System between 2000 and 2015. Patients were followed up until December 31, 2020 for incident CKD and/or HF and all-cause mortality. Among 102 488 patients (median age 66 years, 45.7% women, median follow-up 7.5 years), new-onset CKD occurred in 14 798 patients (14.4%), in whom 21.7% had HF. In contrast, among 9258 patients (9.0%) with new-onset HF, 34.6% had CKD. The median time from baseline to incident CKD or HF (4.4 vs. 4.1 years) did not differ. However, the median (interquartile range) time until incident HF after CKD diagnosis was 1.7 (0.5-3.6) years and was 1.2 (0.2-3.4) years for incident CKD after HF diagnosis (P < 0.001). The crude incidence of CKD was higher than that of HF: 17.6 (95% confidence interval [CI] 17.3-17.9) vs. 10.6 (95% CI 10.4-10.9)/1000 person-years, respectively, but incident HF was associated with a higher adjusted-mortality than incident CKD. The presence of either condition (vs. CKD/HF-free status) was associated with a three-fold hazard of death, whereas concomitant HF and CKD conferred a six to seven-fold adjusted hazard of mortality. Cardiorenal complications are common and are associated with high mortality risk among patients with new-onset T2DM. Close surveillance of these dual complications is crucial to reduce the burden of disease.

Clinical implications and guidelines for CKD in type 2 diabetes.

Chronic kidney disease (CKD) is a complication of type 2 diabetes (T2D) with high morbidity and mortality. The prevalence of CKD in T2D is increasing due to rising numbers of persons with T2D. Multiple clinical trials have been conducted testing novel therapies to reduce the progression of CKD, cardiovascular morbidity, in particular hospitalization for heart failure, and mortality. Results of these clinical trials have informed guidelines for the management of CKD in T2D. The epidemiology of CKD in T2D and the process of guideline writing, including data gathering, grading and consensus development, were reviewed. Recent guidelines for the management of CKD in T2D that include recent renal outcome clinical trials are reported, along with supporting evidence. All current guidelines recommend annual screening for CKD, control of blood pressure and glucose, although the target levels and background therapy recommendations vary. Renin-angiotensin system (RAS) inhibition is uniformly recommended. Sodium-glucose cotransporter-2 (SGLT2) inhibition with proven agents is recommended by all guidelines, with minor variations in suggested estimated glomerular filtration rate and albuminuria levels. Finerenone, the first nonsteroidal mineralocorticoid receptor antagonist with renal outcome data, is recommended by the most recent guideline available. Current guidelines continue to recommend screening for CKD, blood pressure control using RAS inhibition as first-line therapy, and glucose control. SGLT2 inhibition and finerenone are recent additions to current guidelines to improve CKD outcomes in T2D, based on robust clinical trial data.