Factors associated with risk analysis for asymptomatic left ventricular diastolic dysfunction in nondialysis patients with chronic kidney disease.

Heart failure (HF) constitutes a major determinant of outcome in chronic kidney disease (CKD) patients. The main pattern of HF in CKD patients is preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD) is a frequent pathophysiological mechanism and specific preclinical manifestation of HFpEF. Therefore, exploring and intervention of the factors associated with risk for LVDD is of great importance in reducing the morbidity and mortality of cardiovascular disease (CVD) complications in CKD patients. We designed this retrospective cross-sectional study to collect clinical and echocardiographic data from 339 nondialysis CKD patients without obvious symptoms of HF to analyze the proportion of asymptomatic left ventricular diastolic dysfunction (ALVDD) and its related factors associated with risk by multivariate logistic regression analysis. Among the 339 nondialysis CKD patients, 92.04% had ALVDD. With the progression of CKD stage, the proportion of ALVDD gradually increased. The multivariate logistic regression analysis revealed that increased age (OR 1.237; 95% confidence interval (CI) 1.108-1.381, per year), diabetic nephropathy (DN) and hypertensive nephropathy (HTN) (OR 25.000; 95% CI 1.355-48.645, DN and HTN vs chronic interstitial nephritis), progression of CKD stage (OR 2.785; 95% CI 1.228-6.315, per stage), increased mean arterial pressure (OR 1.154; 95% CI 1.051-1.268, per mmHg), increased urinary protein (OR 2.825; 95% CI 1.484-5.405, per g/24 h), and low blood calcium (OR 0.072; 95% CI 0.006-0.859, per mmol/L) were factors associated with risk for ALVDD in nondialysis CKD patients after adjusting for other confounding factors. Therefore, dynamic monitoring of these factors associated with risk, timely diagnosis and treatment of ALVDD can delay the progression to symptomatic HF, which is of great importance for reducing CVD mortality, and improving the prognosis and quality of life in CKD patients.

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

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

A review regarding the article 'Diabetic peripheral neuropathy is associated with diabetic kidney disease and cardiovascular disease: The silesia diabetes-heart project'.

One of the most common micro vascular complications of diabetes is diabetic peripheral neuropathy (DPN). The well-recognized risk factors for DPN are hyperglycemia, dyslipidemia, and hypertension. DPN is associated with a high mortality rate and poor prognosis. Its pathogenesis is not fully understood, and clinical treatment is focused on relieving its clinical symptoms, as well as improving blood sugar control and cardiovascular risk factors. DPN and its clinically effective treatments need to be studied. Microvascular complications of diabetes present a significant challenge due to their diverse presentations, significant morbidity, and as strong predictors of cardiovascular disease. Prevention and management strategies should focus on lifestyle modification, education and awareness, systematic screening for early complications, and intensive management of modifiable risk factors. There was an association between DPN and DKD as well as CVD, BMI and age demonstrated. These may indicate that in case of having one diabetes complication diagnosed, it is important to screen for others, including macrovascular ones, as they may be undiagnosed due to their "silent" nature. Further studies are expected to strengthen basic research on the subject, reveal modern medical mechanisms, and provide fresh ideas and innovative methods for the treatment of DPN.

Association between Albumin Alterations and Renal Function in Patients with Type 2 Diabetes Mellitus.

Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether albumin structural alterations correlate with DKD severity and evaluate whether native and reduced albumin concentrations could complement the diagnosis of DKD. To this end, one hundred and seventeen T2DM patients without (n = 42) and with (n = 75) DKD (DKD I-III upon KDIGO classification) were evaluated; the total albumin concentration (tHA) was quantified by a bromocresol green assay, while structural alterations were profiled via liquid chromatography-high-resolution mass spectrometry (LC-HRMS). The concentrations of native albumin (eHA, effective albumin) and reduced albumin (rHA) were subsequently assessed. The HRMS analyses revealed a reduced relative amount of native albumin in DKD patients along with an increased abundance of altered forms, especially those bearing oxidative modifications. Accordingly, both eHA and rHA values varied during the stages of progressive renal failure, and these alterations were dose-dependently correlated with renal dysfunction. A ROC curve analysis revealed a significantly greater sensitivity and specificity of eHA and rHA than of tHA for diagnosing DKD. Importantly, according to the multivariate logistic regression analysis, the eHA was identified as an independent predictor of DKD.

[Correlation between weight variability and the risk of diabetic nephropathy in patients with type 2 diabetes mellitus].

Objective: To evaluate the relationship between different indexes of weight variability and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort study. The clinical data of 2 180 T2DM patients without DKD who underwent case management at Lee's United Clinic in Taiwan, China from 2002 to 2018 were retrospectively analyzed, including 1 103 females and 1 077 males, with an average age of (64.8±12.4) years. Regular follow-up was conducted for patients for at least 2 years, and their metabolic indexes were monitored annually. BMI variability independent of the mean (BMI-VIM), average yearly mean square successive difference (BMI-ASV), coefficient of variation (BMI-CV) and standard deviation (BMI-SD) were calculated,based on the body mass index (BMI) recorded annually by the patients. Patients were divided into four groups (Q1-Q4) based on the quartiles of the four weight variability indexes. DKD group and non-DKN group(NDKD group) were defined based on the occurrence of DKD at the end of the follow-up. Cox proportional hazards regression models were used to analyze the relationship between the four weight variability indicators and the incidence of DKD. Subgroup analysis was performed by categorizing patients into non-obesity (BMI<28 kg/m2) and obesity groups (BMI≥28 kg/m2) to investigate the impact of the four weight variability indicators on the risk of DKD. Results: After a follow-up of (4.55±2.13) years, 904 patients developed DKD. Compared with the NDKD group, patients in the DKD group had a higher proportion of females, older age, longer duration of diabetes, more insulin users, higher waist-to-hip ratio, higher levels of BMI-VIM, BMI-ASV, BMI-CV, BMI-SD, systolic blood pressure, diastolic blood pressure, and urine albumin-creatinine ratio, a lower proportion of hypoglycemic drugs, estimated glomerular filtration rate, and high-density lipoprotein cholesterol level, with statistically significant differences between the two groups(all P<0.05). Cox proportional hazards regression analysis results revealed that the risk of DKD in T2DM patients increased with the increase in BMI-SD, BMI-CV, BMI-VIM, and BMI-ASV after correcting a series of influencing factors. In the BMI-VIM subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.4% [HR=1.224 (95%CI:1.008-1.487), P=0.041]. In the BMI-ASV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 51.1% [HR=1.511 (95%CI:1.240-1.841), P<0.01]. In the BMI-CV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.006-1.485), P=0.044]. In the BMI-SD subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.002-1.490), P=0.048]. Sub-group analysis showed that when the non-obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.551 (95%CI:1.228-1.958), P<0.001];when the obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.703 (95%CI:1.168-2.485), P=0.006]. Conclusion: Increases in BMI-VIM, BMI-ASV, BMI-CV, and BMI-SD are associated with an increased risk of DKD in T2DM patients.

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.

The number of nephroprotection targets attained is associated with cardiorenal outcomes and mortality in patients with diabetic kidney disease. The CKD-REIN cohort study.

AIM: The risk of cardiorenal events remains high among patients with diabetes and chronic kidney disease (CKD), despite the prescription of recommended treatments. We aimed to determine whether the attainment of a combination of nephroprotection targets at baseline (glycated haemoglobin <7.0%, urinary albumin-creatinine ratio <300 mg/g, blood pressure <130/80 mmHg, renin-angiotensin system inhibition) was associated with better cardiorenal outcomes and lower mortality. MATERIALS AND METHODS: From the prospective French CKD-REIN cohort, we studied 1260 patients with diabetes and CKD stages 3-4 (estimated glomerular filtration rate: 15-60 ml/min/1.73 m2); 69% were men, and at inclusion, mean ± SD age: 70 ± 10 years; estimated glomerular filtration rate: 33 ± 11 ml/min/1.73 m2. The median follow-up was 4.9 years. RESULTS: In adjusted Cox regression models, the attainment of two nephroprotection targets was consistently associated with a lower risk of cardiorenal events [hazard ratio 0.70 (95% confidence interval 0.57-0.85)], incident kidney failure with replacement therapy [0.58 (0.43-0.77)], four major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure) [0.75 (0.57-0.99)] and all-cause mortality [0.59 (0.42-0.82)] when compared with the attainment of zero or one target. For patients with a urinary albumin-creatinine ratio ≥300 mg/g, those who attained at least two targets had lower hazard ratios for cardiorenal events [0.61 (0.39-0.96)], four major adverse cardiovascular events [0.53 (0.28-0.98)] and all-cause mortality [0.35 (0.17-0.70)] compared with those who failed to attain any targets. CONCLUSIONS: These findings suggest that the attainment of a combination of nephroprotection targets is associated with better cardiorenal outcomes and a lower mortality rate in people with diabetic kidney disease.

Clinicopathologic Characteristics, Etiologies, and Outcome of Secondary Oxalate Nephropathy.

OBJECTIVE: To report the clinicopathologic characteristics, prognostic indicators, prognosis, and transplant outcome of secondary oxalate nephropathy (ON). PATIENTS AND METHODS: We performed a retrospective analysis of 113 consecutive patients with secondary ON diagnosed at Mayo Clinic in Rochester, Minnesota, between January 1, 2001, and March 1, 2023. RESULTS: The incidence of secondary ON among all native biopsies from Mayo Clinic patients over the study period (n=11,617) was 0.97%. ON was attributed to enteric hyperoxaluria in 60% of the 113 patients (68; most commonly Roux-en-Y gastric bypass), excessive ingestion of foods high in oxalate or oxalate precursors in 23% (26) (most commonly vitamin C), and idiopathic in 17% (19). Most patients presented with acute kidney injury (AKI) (particularly in the ingestion group) or AKI on chronic kidney disease, and 53% (60 of 113) were diabetic. Calcium oxalate crystals were accompanied by acute tubular injury, inflammation, and interstitial fibrosis and tubular atrophy. Concurrent pathologic conditions were present in 53% of the patients (60 of 113), most commonly diabetic nephropathy. After a median follow-up of 36 months, 27% of the patients (30 of 112) had kidney recovery, 19% (21 of 112) had persistent kidney dysfunction, 54% (61 of 112) had development of kidney failure, and 29% (32 of 112) died. The mean kidney survival was worse for patients with a concurrent pathologic lesion (30 months vs 96 months for those without a concurrent pathologic lesion; P<.001). Independent predictors of kidney failure were the degree of interstitial fibrosis and tubular atrophy and nadir estimated glomerular filtration rate but not the degree of crystal deposition. After a median follow-up of 58 months in 23 patients who received kidney transplant, 4 had graft loss (due to ON in 3). The 2-, 5-, and 10-year graft survivals were 90% (18 of 20), 79% (11 of 14), and 50% (6 of 12). CONCLUSION: ON is a rare cause of AKI or AKI on chronic kidney disease. Most patients have comorbid pathologic conditions, particularly diabetic nephropathy, which worsen the prognosis. Recurrence in the renal allograft and graft loss may occur if hyperoxaluria is not controlled.

Disrupting circadian control of autophagy induces podocyte injury and proteinuria.

The circadian clock influences a wide range of biological process and controls numerous aspects of physiology to adapt to the daily environmental changes caused by Earth's rotation. The kidney clock plays an important role in maintaining tubular function, but its effect on podocytes remains unclear. Here, we found that podocytes expressed CLOCK proteins, and that 2666 glomerular gene transcripts (13.4%), including autophagy related genes, had 24-hour circadian rhythms. Deletion of Clock in podocytes resulted in 1666 gene transcripts with the loss of circadian rhythm including autophagy genes. Podocyte-specific Clock knockout mice at age three and eight months showed deficient autophagy, loss of podocytes and increased albuminuria. Chromatin immunoprecipitation (ChIP) sequence analysis indicated autophagy related genes were targets of CLOCK in podocytes. ChIP-PCR further confirmed Clock binding to the promoter regions of Becn1 and Atg12, two autophagy related genes. Furthermore, the association of CLOCK regulated autophagy with chronic sleep fragmentation and diabetic kidney disease was analyzed. Chronic sleep fragmentation resulted in the loss of glomerular Clock rhythm, inhibition of podocyte autophagy, and proteinuria. Rhythmic oscillations of Clock also disappeared in high glucose treated podocytes and in glomeruli from diabetic mice. Finally, circadian differences in podocyte autophagy were also abolished in diabetic mice. Deletion Clock in podocytes aggravated podocyte injury and proteinuria in diabetic mice. Thus, our findings demonstrate that clock-dependent regulation of autophagy may be essential for podocyte survival. Hence. loss of circadian controlled autophagy may play an important role in podocyte injury and proteinuria.

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

Detoxification of Hyperglycemia-induced Glucose Toxicity by the Hexosamine Biosynthetic Pathway.

The abnormal intermediate glucose metabolic pathways induced by elevated intracellular glucose levels during hyperglycemia often establish the metabolic abnormality that leads to cellular and structural changes in development and to progression of diabetic pathologies. Glucose toxicity generally refers to the hyperglycemia-induced irreversible cellular dysfunctions over time. These irreversible cellular dysfunctions in diabetic nephropathy include: (1) inflammatory responses, (2) mesangial expansion, and (3) podocyte dysfunction. Using these three cellular events in diabetic nephropathy as examples of glucose toxicity in the diabetic complications, this review focuses on: (1) the molecular and cellular mechanisms associated with the hexosamine biosynthetic pathway that underly glucose toxicity; and (2) the potential therapeutic tools to inhibit hyperglycemia induced pathologies. We propose novel therapeutic strategies that directly shunts intracellular glucose buildup under hyperglycemia by taking advantage of intracellular glucose metabolic pathways to dampen it by normal synthesis and secretion of hyaluronan, and/or by intracellular chondroitin sulfate synthesis and secretion. This could be a useful way to detoxify the glucose toxicity in hyperglycemic dividing cells, which could mitigate the hyperglycemia induced pathologies in diabetes.

Determinants of diabetic nephropathy among diabetic patients in Ethiopia: Systematic review and meta-analysis.

INTRODUCTION: Diabetic nephropathy (DN) is a long-term kidney disease among diabetic patients. It is the leading cause of end-stage renal failure. In Ethiopia, DN affects the majority of diabetic populations, but there were inconsistent findings about the determinant factors across the studies. METHODS: We have accessed studies using PubMed, Embase, EBSCO, Web of Science, OVID, and search engines including Google and Google Scholar published up to June 2023. The study populations were diabetic patients with nephropathy. The quality of each included article was assessed using the Newcastle-Ottawa quality assessment scale. The odds ratios of risk factors were pooled using a random-effect meta-analysis model. Heterogeneity was assessed using the Cochrane Q statistics and I-Square (I2). The publication bias was detected using the funnel plot and/or Egger's test (p< 0.05). Trim and fill analysis was carried out to treat the publication bias. The protocol has been registered with the reference number CRD42023434547. RESULTS: A total of sixteen articles were used for this reviewed study. Of which, eleven articles were used for advanced age, ten articles for duration of diabetic illness, ten articles for poor glycemic control, and eleven articles for having co-morbid hypertension. Diabetic patients with advanced age (AOR = 1.11, 95% CI: 1.03-120, I2 = 0.0%, p = 0.488), longer duration of diabetic illness (AOR = 1.23, 95% CI = 1.05-1.45, I2 = 0.0%, p = 0.567), poor glycemic control (AOR = 2.57, 95% CI: 1.07-6.14; I2 = 0.0%, p = 0.996), and having co-morbid hypertension (AOR = 4.03, 95% CI: 2.00-8.12, I2 = 0.0%, p = 0.964) were found to be factors associated with DN. CONCLUSIONS: The findings of the study revealed that diabetic patients with advanced age, longer duration of diabetic illness, poor glycemic control status, and co-morbid hypertension were the determinant factors of DN. Therefore, treatment of co-morbid hypertension and high blood glucose and regular screening of renal function should be implemented to detect, treat, and reduce the progression of DN. Furthermore, healthcare workers should give due attention to diabetes with advanced age and a longer duration of diabetes illness to prevent the occurrence of DN.

Early choroidal and retinal changes detected by swept-source oct in type 2 diabetes and their association with diabetic kidney disease: a longitudinal prospective study.

BACKGROUND: To evaluate structural changes in retina and choroid in patients with type 2 diabetes (T2D) and their association with diabetic kidney disease (DKD). METHODS: T2D patients with mild or no diabetic retinopathy (DR) were followed for 3 years using structural SS-OCT and OCT angiography (OCT-A) taken every 6 months. Parameters were compared longitudinally and according to the DKD status on baseline. RESULTS: One hundred and sixty eyes from 80 patients were followed for 3 years, 72 with no DKD (nDKD) at baseline and 88 with DKD. Trend analysis of T2D showed significant thinning in GCL + and circumpapillary retinal fiber neural layer (cRFNL), choroid, and decreased vascular density (VD) in superficial plexus and central choriocapillaris with foveal avascular zone (FAZ) enlargement. Patients with no DKD on baseline presented more significant declines in retinal center and choroidal thickness, increased FAZ and loss of nasal and temporal choriocapillaris volume. In addition, the nDKD group had worse glycemic control and renal parameters at the end of the study. CONCLUSION: Our data suggests the potential existence of early and progressive neurovascular damage in the retina and choroid of patients with Type 2 Diabetes (T2D) who have either no or mild Diabetic Retinopathy (DR). The progression of neurovascular damage appears to be correlated with parameters related to glycemic control and renal damage.

Presentation of glomerulocystic disease in a young onset diabetes: A case report.

RATIONALE: This case report presents a challenging medical scenario involving a young adult male who exhibited an unusual combination of symptoms, including abrupt weight loss, declining renal function, proteinuria, and concurrent onset of diabetes mellitus. Remarkably, the patient had no previous medical history or family history of similar conditions, necessitating a comprehensive investigation. PATIENT CONCERNS: On March 10, 2021, a 25-year-old male sought medical attention due to the aforementioned symptoms. Initial assessments revealed stage 5 chronic kidney disease, with elevated blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as significant proteinuria. The only notable physical finding was obesity, and renal ultrasound showed normal-sized kidneys without cysts. DIAGNOSIS: A treatment plan was initiated to stabilize creatinine levels, including medications such as Glimepiride, Glyxambi, Bisoprolol, Amlodipine, and Valsartan. However, despite diligent medication management, proteinuria persisted, prompting further evaluation. A renal biopsy was performed on April 12th, 2023, leading to the diagnosis of glomerulocystic kidney disease with early-stage changes indicative of diabetic nephropathy. INTERVENTIONS: The patient continues to receive ongoing care and follow-up at our outpatient clinic to optimize therapeutic interventions and elucidate the underlying etiology of this complex clinical scenario. OUTCOMES: Ongoing investigations and therapeutic interventions are crucial to understand the underlying cause and optimize patient care in this intricate clinical scenario. LESSONS: This case underscores the complexity of diagnosing and managing a young adult presenting with concurrent renal dysfunction, proteinuria, and diabetes mellitus in the absence of prior underlying conditions. It highlights the importance of comprehensive evaluation and ongoing care in such challenging cases.

The effects of Tripterygium wilfordii Hook F on renal outcomes in type 2 diabetic kidney disease patients with severe proteinuria: a single-center cohort study.

AIM: Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD. METHODS: Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m2 were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes. RESULTS: By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111-0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081-0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018). CONCLUSION: In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD.

Association between ELMO1 gene polymorphisms and diabetic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Previous research has suggested that the ELMO1 gene may play a role in the development of diabetic kidney disease. Diabetic kidney disease (DKD) is a serious complication of diabetes and the leading cause of chronic kidney disease and end-stage renal disease (ESRD). OBJECTIVE AND RATIONALE: This study aim was to systematically review and explore the association between ELMO1 gene polymorphisms and diabetic kidney disease. A comprehensive systematic review provides a clear conclusion and high-level evidence for the association between ELMO1 gene and DKD for future application in personalized medicine. METHODS: A comprehensive search of electronic databases, per PRISMA instructions, was conducted in Scopus, EMBASE, Web of Science, and PubMed databases from 1980 to January 2023. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using appropriate models. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity and assess the robustness of the findings. RESULTS: A total of 5794 diabetes patients with DKD, 4886 diabetes patients without DKD, and 2023 healthy controls were included in the 17 studies that made up this systematic review. In the investigation of DM (Diabetes Mellitus) with DKD vs. DM without DKD, the susceptibility for DKD for the EMLO1 rs741301 polymorphism indicated a significant difference under the dominant, homozygote, and recessive genetic models. The susceptibility for DKD for the EMLO1 rs1345365, rs10255208, and rs7782979 polymorphisms demonstrated a significant difference under the allele genetic models in the analysis of DM with DKD vs. DM without DKD groups. There was a considerable increase in DKD risk in the Middle East when the population was stratified by the region. CONCLUSION: The findings of the meta-analysis show that there are a significant connection between the EMLO1 rs741301 polymorphism and DKD susceptibility in overall analyses; as well as rs1345365, rs10255208, and rs7782979 polymorphisms; especially in the Middle East region.

Association of remnant cholesterol with glycemic control and presence of microvascular complications in individuals with type 1 diabetes mellitus.

INTRODUCTION: This study examines the relationship between remnant cholesterol, glucose metrics, and chronic complications of type 1 diabetes in users of glucose monitoring systems. MATERIAL AND METHODS: Clinical variables and glucose metrics were collected from individuals using glucose sensors. Statistical models were employed to investigate the association of remnant cholesterol with glucose metrics, diabetic retinopathy, and diabetic nephropathy. RESULTS: A total of 383 individuals, aged 48.3 ±â€¯16.2 years, with 54.1% women, and a remnant cholesterol level of 16 ±â€¯10 mg/dL, were included. The results demonstrated that remnant cholesterol was associated with less time within the target range (p = 0.015) and more time above the target range (p = 0.003). Diabetic nephropathy was the only complication associated with remnant cholesterol levels exceeding 30 mg/dL, OR 8.93, 95% CI (2.99-26.62), p < 0.001. CONCLUSION: Remnant cholesterol is independently associated with hyperglycemia and diabetic nephropathy in individuals with type 1 diabetes.

Efficacy and Safety of Dapagliflozin in Patients With Chronic Kidney Disease Across the Spectrum of Frailty.

BACKGROUND: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety and efficacy of dapagliflozin in patients with CKD by frailty level. METHODS: Adults with CKD, with/without type 2 diabetes, with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200-5 000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), or death from kidney or cardiovascular (CV) causes. RESULTS: Frailty index (FI), assessed by Rockwood cumulative deficit approach, was calculable in 4 303/4 304 (99.9%) patients: 1 162 (27.0%) in not-to-mildly frail (FI ≤0.210), 1 642 (38.2%) in moderately frail (FI 0.211-0.310), and 1 499 (34.8%) in severely frail categories (FI >0.311). Dapagliflozin reduced the risk of the primary composite endpoint across all FI categories (hazard ratios [95% confidence interval {CI}]: 0.50 [0.33-0.76], 0.62 [0.45-0.85], and 0.64 [0.49--0.83], respectively; p-interaction = 0.67). Results were similar for secondary outcomes including kidney composite outcome (sustained ≥50% eGFR decline, ESKD or death from kidney cause; p-interaction = 0.44), CV endpoint (heart failure hospitalization or CV death; p-interaction = 0.63), and all-cause mortality (p-interaction p = .42). Results were consistent when using FI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin versus placebo in all FI categories (16.9% vs 20.1%, 26.3% vs 30.7%, and 42.9% vs 47.8%, in not-to-mildly, moderately, and severely frail categories, respectively). CONCLUSIONS: The relative benefit of dapagliflozin for all outcomes was consistent across all frailty categories, with no difference in associated safety.

A clinical study on roxadustat for anemia in diabetic nephropathy: a 8-week study.

PURPOSE: The development of roxadustat is a standard treatment for renal anemia, and multiple clinical trials have proved its safety and efficacy. However, less information is available from trials of the population with diabetic nephropathy (DN). This study aimed to determine whether roxadustat is effective for treating DN. METHODS: This was a single-center, retrospective, institutional review board-approved cohort study. The patients with DN were chosen and given roxadustat or erythropoietin (EPO) for 8 weeks. The mean hemoglobin (Hb) level after 8 weeks of treatment served as the primary outcome. Alterations in the iron index and lipid levels were considered secondary objectives. Sub-group analysis was performed to observe the impact of inflammation and glycemic status on Hb. RESULTS: A total of 80 patients were enrolled, 40 in each group. After 8 weeks of treatment, the Hb levels in the roxadustat group were higher than those in the control group. The number of patients who achieved Hb response was higher in the roxadustat group than in the control group (77.5% versus 27.5%; P < 0.001). In addition to lowering total cholesterol and low-density lipoprotein cholesterol, roxadustat decreased ferritin and elevated total iron-binding capacity. Compared to the control group, roxadustat was more beneficial for patients with an inflammatory condition and poor glycemic control. CONCLUSIONS: Roxadustat treatment remarkably corrected anemia in patients with DN, and its effectiveness was unaffected by inflammation or glycemic control levels. In addition, roxadustat can also reduce a patient's blood lipid level and enhance the body's use of iron. CLINICAL TRIAL REGISTRATION: ChiCTR2200057232.

Repurposing fexofenadine as a promising candidate for diabetic kidney disease: randomized clinical trial.

PURPOSE: Diabetic kidney disease (DKD) is a devastating complication of diabetes mellitus. Inflammation and histamine are potentially involved in the disease progression. This study aimed to evaluate the role of fexofenadine in patients with DKD. METHODS: From January 2020 to February 2022, out of 123 patients screened for eligibility, 61 patients completed the study. Patients were randomized into two groups, the fexofenadine group (n = 30): received ramipril plus fexofenadine, and the control group (n = 31): received ramipril only for six months. Changes in urinary albumin to creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were considered primary outcomes. Measurements of urinary cyclophilin A, monocyte chemoattractant protein-1 (MCP-1), 8-hydroxy-2' deoxyguanosine (8-OHdG), and podocalyxin (PCX) were considered secondary outcomes. The study was prospectively registered on clinicaltrial.gov on January 13, 2020, with identification code NCT04224428. RESULTS: At the end of the study, fexofenadine reduced UACR by 16% (95% CI, - 23.4% to - 9.3%) versus a noticeable rise of 11% (95% CI, 4.1% to 17.8%) in UACR in the control group, (p < 0.001). No significant difference in eGFR was revealed between the two groups. However, the control group showed a significant decrease of - 3.5% (95% CI, - 6.6% to - 0.3%) in eGFR, compared to its baseline value. This reduction was not reported in the fexofenadine group. Fexofenadine use was associated with a significant decline in MCP-1, 8-OHdG, and PCX compared to baseline values. CONCLUSION: Fexofenadine is a possible promising adjuvant therapy in patients with DKD. Further large-scale trials are needed to confirm our preliminary results.