Prevalence Of Diabetic Nephropathy Research Articles

Association of different domains of physical activity with diabetic kidney disease: a population-based study

BackgroundThe aim of this cross-sectional study was to elucidate the associations between various domains of physical activity, such as occupation-related (OPA), transportation-related (TPA), leisure-time (LTPA) and overall physical activity (PA), and diabetic kidney disease.MethodsOur study encompassed 2,633 participants, drawn from the cross-sectional surveys of the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, and employed survey-weighted logistic regression, generalized linear regression, and restricted cubic spline (RCS) analyses to ascertain the relationship between different domains of physical activity and diabetic kidney disease.ResultsAfter controlling for all confounders, multivariate logistic regression analyses revealed a lack of correlation between the various domains of physical activity and the prevalence of diabetic kidney disease. Multiple generalized linear regression analyses showed that durations of PA (β = 0.05, 95% CI, 0.01–0.09, P = 0.012) and TPA (β = 0.32, 95% CI, 0.10–0.55, P = 0.006) were positively associated with eGFR levels; and LTPA durations were inversely associated with UACR levels (β = -5.97, 95% CI, -10.50 - -1.44, P = 0.011). The RCS curves demonstrated a nonlinear relationship between PA, OPA, and eGFR, as well as a nonlinear correlation between PA and ACR. Subgroup and sensitivity analyses largely aligned with the outcomes of the multivariate generalized linear regression, underscoring the robustness of our findings.ConclusionOur population-based study explored the association between different domains of physical activity and diabetic kidney disease. Contrary to our expectations, we found no significant association between the duration of physical activity across all domains and the prevalence of diabetic nephropathy. Nonetheless, renal function markers, including eGFR and UACR, exhibited significant correlations with the duration of total physical activity (TPA) and leisure-time physical activity (LTPA), respectively, among diabetic patients. Interestingly, our findings suggest that diabetic patients engage in physical activity to preserve renal function, ensuring moderate exercise durations not exceeding 35 hours per week.

#1227 The role of P-selectin (CD62P) expression in renal tissue in the development of diabetic nephropathy

Abstract Background and Aims The prevalence of diabetic nephropathy (DN) is increasing in line with the increase in the incidence of diabetes mellitus (DM) worldwide. The latest data from the International Diabetes Federation (IDF) predicts that by 2045, more than 10.5% of adults worldwide will have diabetes. This will lead to kidney damage in 100-250 million people. DN is characterized by structural and functional changes. As a result of chronic hyperglycemia, pathogenic changes in the vascular wall develop, and the frequency of micro- and macrovascular complications associated with morbidity and mortality among patients with diabetes increases. However, the exact mechanism of vascular complications is not completely clear. Endothelial dysfunction plays a key role in triggering the development of inflammatory mechanisms that are associated with vascular complications in patients with type 2 diabetes mellitus (T2DM). Activation of the endothelium due to increased release of cytokines and expression of adhesion molecules promotes platelet activation and their adhesion to the activated endothelium. Selectins (E-selectin, L-selectin and P-selectin) play a major role in the development of microvascular complications. The aim of the study was to examine the role of P-selectin (CD62p) expression in the glomerular endothelium and peritubular capillaries in patients with different morphological classes of DN and to evaluate its effect on the development and progression of morphological changes in renal tissue. Method Was examined 49 patients with T2DM complicated by the development of DN. The average age of the patients was 66.58 ± 3.27 years. There were 35 women, 14 men. The duration of the disease was 17.70 ± 0.35 years. The duration of DN from the moment of detection of microalbuminuria to the morphological examination of the renal tissue and diagnosis was 1.65 ± 0.34 years. All patients underwent light and immunofluorescence microscopy of kidney tissue biopsies obtained by intravital puncture biopsy. Morphological changes in tissue were assessed in accordance with the latest international classification of diabetic nephropathy developed by the Scientific Committee of the Pathology Society, USA. According to light microscopy data, class IIa (mild mesangial expansion) was detected in 12 patients, class IIb (severe mesangial expansion) in 14 patients, class III (Kimmelstil–Wilson nodular lesions) in 19 patients, and class IV (advanced diabetic glomerulosclerosis) in 5 patients. In addition to light microscopy, the expression of CD62β (P-selectin) in the glomerular endothelium and in peritubular capillaries was determined in all patients. FITc-labeled monoclonal antibodies (FITC anti-human CD62p Antibody, clone AK4 Cat#304904), were used (Biolegend, USA). Results Analysis of biopsy tissue from DN patients showed that CD62p expression is detected both in the glomerular endothelium (1.6383 ± 0.4789 (95% CI: 0.9574-2.7234)) and in peritubular capillaries (1.1702 ± 0.1308 (95% CI: 0.9149–1.4250)). Using the linear regression method with the calculation of the coefficients of determination R2 (R Square), the values of the F criterion, significant regression models were obtained: Expression of CD62p in the glomerular endothelium promotes the development and progression of arteriolar hyalinosis (R2=0.213, F=12.476 p=0.001); expansion of the mesangial matrix (R2=0.362, F=26.09, p=0.0001); thickening of the basement membrane (R2=0.127, F=6.57, p=0.014); development and progression of nodular Kimmelstiel–Wilson lesions (R2=0.106, F=5.360, p=0.025). Expression of CD62p in peritubular capillaries promotes the development of interstitial sclerosis (R2=0.549, F=54.732, p=0.0001). The severity of CD62p expression in the glomerular endothelium depends on the morphological class of DN in patients (R2=0.216, F=12.684, p=0.001). Conclusion

Clinical value of lymphocyte count in autoimmune diabetic nephropathy.

In recent years, the prevalence of diabetic nephropathy (DN) has increased significantly. An increasing number of studies have shown that lymphocyte-associated inflammatory responses play a role in DN. This study aims to investigate the relationship between lymphocytes and DN in patients with autoimmune diabetes. The clinical data of 226 patients with Type 1 diabetes (T1D) and 79 patients with latent autoimmune diabetes in adults (LADA) were retrospectively studied and stratified according to the urinary albumin to creatinine ratio (ACR). Risk factors associated with DN were analyzed using correlation analysis and logistic regression. In T1D and LADA patients, systolic blood pressure (SBP), uric acid duration, and diabetes duration in patients with normoalbuminuria were lower or shorter than those in patients with macroalbuminuria (P<0.05). The lymphocyte count of T1D patients was significantly higher than that in LADA patients (P<0.05), while the neutrophil to lymphocyte ratio (NLR) of T1D patients was significantly lower than that in LADA patients (P<0.05). The lymphocyte count in the T1D patients with normoalbuminuria was lower than that those with macroalbuminuria (P<0.05). The NLR was lower in the T1D patients with macroalbuminuria than those with microalbuminuria and normoproteinuria (all P<0.01). Based on logistic regression analysis, lymphocytes were independently associated with DN in T1D after adjusting for various known risk factors such as course of disease, age, gender, dyslipidemia, hypertension, and smoking status. Analysis of the receiver operating characteristic curve of subjects predicting lymphocytes in normoalbuminuria showed that the area under the curve was 0.601 (95% CI 0.510 to 0.693, P=0.039), and when the cutoff value of lymphocytes was 2.332, the sensitivity was 37.0%, and the specificity was 82.5%. Lymphocyte counts in autoimmune diabetic patients are closely associated with DN, suggesting that lymphocyte-mediated inflammation may be involved in the pathogenesis of DN in autoimmune diabetic patients. This study provides a possible perspective for using lymphocytes as a potential biomarker for the early identification of individuals at risk for DN and potential therapeutic targets for DN.

MicroRNA-21 Silencing in Diabetic Nephropathy: Insights on Therapeutic Strategies.

In diabetes, possibly the most significant site of microvascular damage is the kidney. Due to diabetes and/or other co-morbidities, such as hypertension and age-related nephron loss, a significant number of people with diabetes suffer from kidney diseases. Improved diabetic care can reduce the prevalence of diabetic nephropathy (DN); however, innovative treatment approaches are still required. MicroRNA-21 (miR-21) is one of the most studied multipotent microRNAs (miRNAs), and it has been linked to renal fibrosis and exhibits significantly altered expression in DN. Targeting miR-21 offers an advantage in DN. Currently, miR-21 is being pharmacologically silenced through various methods, all of which are in early development. In this review, we summarize the role of miR-21 in the molecular pathogenesis of DN and several therapeutic strategies to use miR-21 as a therapeutic target in DN. The existing experimental interventions offer a way to rectify the lower miRNA levels as well as to reduce the higher levels. Synthetic miRNAs also referred to as miR-mimics, can compensate for abnormally low miRNA levels. Furthermore, strategies like oligonucleotides can be used to alter the miRNA levels. It is reasonable to target miR-21 for improved results because it directly contributes to the pathological processes of kidney diseases, including DN.

Roflumilast ameliorates diabetic nephropathy in rats through down-regulation of JAK/STAT signaling pathway.

Roflumilast is a potent selective inhibitor of the phosphodiesterase-4 enzyme which greatly manifest an anti-inflammatory activity in chronic obstructive pulmonary patients. Inflammation is a prominent factor in the prevalence of diabetic nephropathy, one of the most prevalent microvascular complications of Diabetes Mellitus. The present study was undertaken to assess the potential role of roflumilast in diabetic nephropathy. The model was developed by feeding a high-fat diet for four weeks and following streptozotocin (30mg/kg) injection intraperitoneally. The rats with > 13.8mmol/L blood glucose were treated with roflumilast (0.25, 0.5, 1mg/kg) and standard metformin (100mg/kg) orally once a day for eight weeks. Roflumilast (1mg/kg) remarkably improved renal damage, indicated by an increase in 16% albumin, a decrease in 5% serum creatinine, 12% BUN, 19% HbA1c, and 34% blood glucose. It also significantly improves the oxidative stress levels, which was indicated by a decrease in 18% MDA level and an increase in GSH, SOD, and catalase by 6%, 4%, and 5%, respectively. In addition, Roflumilast (1mg/kg) decreased the HOMA-IR index by 28% and increased the pancreatic β-cells functioning by 30%. Moreover, significant improvement in histopathological abnormalities were observed in roflumilast treatment groups. Roflumilast treatment was shown to down-regulate the gene expressions of TNF-α (2.1-fold), NF-kB (2.3-fold), MCP-1 (2.5-fold), fibronectin (2.7-fold), collagen IV (2.7-fold), STAT 1(1.06-fold), and STAT 3 (1.20-fold) and upregulated the expression of the Nrf2 (1.43-fold) gene. Roflumilast manifested a potential role in diabetic nephropathy as a renoprotective agent. Roflumilast effectively down-regulates the JAK/STAT pathway and restores renal functions.

Rationale and design of a prospective, clinical study of kidney biopsies in people with type 2 diabetes and severely increased albuminuria (the PRIMETIME 2 study)

IntroductionDiabetic kidney disease is a severe complication of diabetes. The diagnosis is based on clinical characteristics such as persistently elevated albuminuria, hypertension and decline in kidney function, although this definition...

The Association of Diabetic Cheiroarthropathy With Microvascular Complications of Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Introduction Diabetic cheiroarthropathy (DCA), also known as the syndrome of limited joint mobility (LJM), is among the most underdiagnosed complications of diabetes mellitus (DM). Although not severe, it can hamper the day-to-day activities of the patient and significantly reduce the quality of life. It is hypothesized to be due to increased glycation of collagen around joints. The objective of our study was to examine the association of diabetic cheiroarthropathy with microvascular complications of type 2 diabetes mellitus. Methods The study was conducted on 251 previously diagnosed cases of type 2 DM. Patients with previous contractures due to any other cause, who are diagnosed cases of rheumatoid arthritis and scleroderma, and other risk factors such as cardiac or renal disease were excluded from the study. All subjects were subjected to a detailed clinical history including a past history, thorough physical examination, prayer test, tabletop sign, and passive extension of fingers. Patients who are diagnosed with diabetic cheiroarthropathy were then screened for microalbuminuria, fundus examination, and monofilament testandclinical examination to look for the presence of microvascular complications. Results Out of the 251 patients, 46 (18.3%) were found to have diabetic cheiroarthropathy. Fifteen (34.9%) cheiroarthropathy patients had neuropathy compared to 14.9% without diabetic cheiroarthropathy, which was statistically significant. We found that there was an increased incidence of diabetic neuropathy in subjects with cheiroarthropathy. Thirty (35.7%) patients with diabetic cheiroarthropathy had diabetic retinopathy compared to 9.6% without diabetic cheiroarthropathy. Twenty-six (26.8%) patients with diabetic cheiroarthropathy had diabetic nephropathy compared to 13% without diabetic cheiroarthropathy. We identified from our study that patients with diabetic cheiroarthropathy had an increased risk of developing microvascular complications. Conclusion There is an increased prevalence of diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy in patients with diabetic cheiroarthropathy. The presence of diabetic cheiroarthropathy hence warrants better control of the patient's glycemic status to preventfurther deterioration of diabetes-related complications.

Prevalence and association of diabetic nephropathy in newly diagnosed Chinese patients with diabetes in the Hebei province: A single-center case-control study.

Diabetes is a chronic disease and has huge pressure on patients and the medical system, especially for patients with diabetic complications, for example, diabetic nephropathy. Diabetic nephropathy is a diabetic complication associated with damage to the kidney. To improve the quality of life of patients with diabetes, it is necessary to understand the factors that are associated with diabetic nephropathy. The objective of the study was to find the prevalence of diabetic nephropathy in newly diagnosed patients with diabetes and to develop the association between clinicopathological parameters and diabetic nephropathy. In a case-control study, demographics, anthropometric, and clinicopathological parameters of a total of 305 newly diagnosed patients with diabetes (the fasting blood glucose ≥ 7.0 mM/L and/or glycosylated hemoglobin ≥ 6.5 mM/L) in Hebei province were included in the analysis. If the urine albumin to creatinine ratio was ≥ 30 (microalbuminuria) then patients were considered diabetic nephropathy. Among enrolled patients, 206 (68%) were males and 99 (32%) were females and they were 46 to 71 years old. Demographic variables and health-related behaviors were the same among patients with diabetes either with nephropathy (case group, n = 135) or patients without nephropathy (control group, n = 170, P > .05 for all). The prevalence of diabetic nephropathy was 44%. Female to male ratio was 1:1.7 in the case group. Patients with diabetic nephropathy had higher body weight (P < .0001), waist circumference (P = .0006), and body mass index (P = .0002) than those of patients without nephropathy. Abnormal urinary globulin (P = .041, odd ratio (OR): 1.1231) was associated with diabetic nephropathy. Aspartate transaminase (P = .0651, OR: 0.8541), alkaline phosphatase (P = .0661, OR: 0.8122), hypertension (P = .0821, OR: 0.8214), and blood urea nitrogen (P = .0842, OR: 0.9411) were not significantly associated with diabetic neuropathy. However, they are near the statistical cutoff value. The prevalence of diabetic nephropathy in newly diagnosed diabetic patients of Hebei province is higher than those of the other provinces. Urinary globulin excretion had a weak association with the presence of nephropathy defined by urinary albumin excretion in patients with diabetes. The presence of other diabetic complications is also an essential parameter for diabetic nephropathy. Males are more susceptible to diabetic nephropathy than females if diabetic (Evidence Level: V; Technical Efficacy: Stage 3).

Prevalence of Diabetic Retinopathy and Use of Common Oral Hypoglycemic Agents Increase the Risk of Diabetic Nephropathy-A Cross-Sectional Study in Patients with Type 2 Diabetes.

This study investigated the effect of amino acid metabolism on the risk of diabetic nephropathy under different conditions of the diabetic retinopathy, and the use of different oral hypoglycemic agents. This study retrieved 1031 patients with type 2 diabetes from the First Affiliated Hospital of Liaoning Medical University in Jinzhou, which is located in Liaoning Province, China. We conducted a spearman correlation study between diabetic retinopathy and amino acids that have an impact on the prevalence of diabetic nephropathy. Logistic regression was used to analyze the changes of amino acid metabolism in different diabetic retinopathy conditions. Finally, the additive interaction between different drugs and diabetic retinopathy was explored. It is showed that the protective effect of some amino acids on the risk of developing diabetic nephropathy is masked in diabetic retinopathy. Additionally, the additive effect of the combination of different drugs on the risk of diabetic nephropathy was greater than that of any one drug alone. We found that diabetic retinopathy patients have a higher risk of developing diabetic nephropathy than the general type 2 diabetes population. Additionally, the use of oral hypoglycemic agents can also increase the risk of diabetic nephropathy.

Diabetic Neuropathy Assessed with Multifrequency Vibrometry Develops Earlier than Nephropathy but Later than Retinopathy.

Diabetes is associated with systemic complications. Prevalence of diabetic nephropathy, and retinopathy, in type 1 diabetes mellitus (T1DM) is declining, but it is not known if this is true also for diabetic neuropathy. To investigate the relationship between large fibre diabetic neuropathy and other diabetic complications. Neuropathy, defined here as large fibre neuropathy, was assessed by measuring vibration perception thresholds at four different frequencies on the sole of the foot, using a standard VibroSense Meter and/or neuropathic symptoms, in 599 individuals with T1DM. Retinopathy status was graded using the International Clinical Disease Severity Scale. Grade of albuminuria and previous history of any macrovascular complications were registered. Diabetic individuals without retinopathy had similar vibration thresholds as age- and gender-matched control participants without diabetes, whereas those without microalbuminuria had higher thresholds than controls. Two individuals out of 599 (0.3%) had microalbuminuria, but not retinopathy or neuropathy, and 12/134 (9%) without retinopathy had signs of neuropathy. Totally 119/536 (22%) of the patients without microalbuminuria had neuropathy. Vibration thresholds increased with the rising severity of retinopathy and grade of albuminuria. In a multinomial logistic regression analysis, neuropathy was associated with retinopathy (OR 2.96 [1.35-6.49], p=0.007), nephropathy (OR 6.25 [3.21-12.15]; p=6.7×10-8) and macrovascular disease (OR 2.72 [1.50-4.93], p=0.001). Despite recent changes in the incidence of diabetic complications, the onset of large fibre neuropathy follows that of retinopathy but precedes the onset of nephropathy in T1DM.

Investigating the Effect of Thyroid Hormones on Diabetic Nephropathy in Type 2 Diabetic Patients Referred to Ahvaz Hospitals in 2017

Background: Nephropathy is one of the most common microvascular complications of diabetes. Type 2 diabetic patients with subclinical hypothyroidism are associated with a high prevalence of diabetic nephropathy. Objectives: This study aims to investigate the effect of thyroid hormones on diabetic nephropathy in type 2 diabetic patients referred to Ahvaz hospitals in 2017. Methods: In this case-control study, 200 diabetic patients (100 with nephropathy and 100 without nephropathy) referred to Ahvaz hospitals were randomly selected. After sampling, biochemical parameters such as fasting blood sugar, BUN, creatinine, uric acid, calcium, and phosphorus were measured. Then, thyroid hormones and thyroid-stimulating hormone (TSH) hormones were measured by the quantitative luminescence method. Results: Thyroid hormones in the patient group were lower than in the control group (P &lt; 0.001). The concentration of TSH in the patient group was higher than in the control group (P &lt; 0.001). Thyroid hormones were negatively and significantly related, and TSH hormone was positively and significantly related to kidney assessment markers. Other results showed that increased TSH and decreased thyroid hormones could increase the risk of developing diabetic nephropathy. So that the T3 hormone was associated with diabetic nephropathy with a greater effect (0.000002 - 0.001057) (CI) = 0.000048 = Odds ratio T3 hormone at 0.73 ng/mL levels has a diagnostic value with a sensitivity of 83% and the specificity was 84% for the differentiation of nephropathy in diabetic patients. Conclusions: The results of this study showed that an increase in TSH hormone and a decrease in thyroid hormones could increase the chance of developing diabetic nephropathy. The T3 hormone is more effective with diabetic nephropathy, and with high diagnostic value, it can be suggested as a biomarker for predicting nephropathy in diabetic patients.

Prevalence of diabetic nephropathy in the diabetes mellitus population: A protocol for systematic review and meta-analysis.

Background:Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide, placing enormous pressure on healthcare systems and creating a heavy socioeconomic burden. It is urgent to comprehensively study the epidemiological characteristics of DN in diabetic patients and to analyze the related factors to its incidence in order to implement effective prevention and control measures.Methods and analysis:Computer-aided searches of the MEDLINE, EMBASE, Web of Science, PsycINFO, and CINAHL databases will be performed for prospective cohort studies reporting the prevalence of DN in diabetic populations. Studies will be pooled using a generalized linear mixed model, and a single proportion of included studies will be calculated to derive the overall incidence of DN in the diabetic population, and to analyze the effect of different factors on the incidence of DN. Publication bias will be assessed using a funnel plot combined with Begg test. Sensitivity analyses will be performed using the separation method, the exclusion of low-quality studies, and the trim and fill method.Results:The primary outcome will be the prevalence of DN in the diabetic population; secondary outcomes will be the influence of factors such as age, gender, region, ethnicity, duration of diabetes, type of diabetes, baseline body mass index, baseline glycated hemoglobin level, baseline blood pressure, quality of included studies, and follow-up time on the prevalence of DN in diabetic patients.Conclusion:Through this systematic review and meta-analysis, the study will more comprehensively obtain the prevalence of DN in diabetic populations worldwide, and gain a deeper understanding of the differences in the prevalence of DN in diabetic populations with different characteristics, so as to provide evidence for the management of diabetes and the prevention of DN.

Long-term analysis of сanagliflozin budget impact in adult patients with type 2 diabetes mellitus and diabetic nephropathy in the Russian Federation

Background. Diabetic nephropathy (DN) is a specific kidney lesion in patients with diabetes mellitus, which leads to the development of endstage kidney disease and requires substitutive renal therapy (dialysis or transplantation). Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor, which exerts a renoprotective effect. According to the published data, the application of canagliflozin in patients with type 2 diabetes mellitus (DM2) and DN could postpone dialysis therapy for almost 13 years.Objective: to perform a long-term analysis of canagliflozin budget impact in adult patients with DM2 and DN from the point of view of the constituent entities of the Russian Federation.Material and methods. A group of comparison for canagliflozin was placebo (no renoprotective pharmacotherapy). The authors proposed a mathematical model for DN progression in groups of patients who received canagliflozin (100 mg orally, daily, long-term) or placebo. The model was based on the extrapolation of the CREDENCE study data. The model was used for the analysis of the direct costs on the lifetime pharmacotherapy and dialysis per one patient. Epidemiologic data from the federal register on the number of adult patients with DM and DN prevalence among these patients were used to evaluate the size of the target population. Based on the clinical recommendations and the medical care standards for patients with DM and the data on the actual state procurement of SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists in 2021, we evaluated the share of patients with DM2+DN who currently do not receive renoprotective therapy but who must be supplied with canagliflozin according to the standards. Among this population, we determined the patients with the glomerular filtration rate within 30–90 ml/min/1.73 m2, which provides the comparability of the target population with patients included in CREDENCE clinical study.Results. Direct medical costs per one patient receiving canagliflozin therapy were 678 108 rubles, which was 52.8% (759,239 rubles) lower than without renoprotective pharmacotherapy (1,437,347 rubles). As a result, considering the modeling period and current practice, the budget costs for pharmacotherapy of patients with DM2+DN were 99.82 billion rubles, in comparison with the proposed practice, which was 47.09 billion rubles (difference in budget costs is 52.73 billion rubles, or 52.8%). The accumulated costs of the regional health care system were lower in patients receiving canagliflozin in comparison with patients without renoprotective pharmacotherapy 11 years after the beginning of treatment.Conclusion. The expansion of canagliflozin application in the therapy for patients with DM2+DN leads to the budget cost cuts in the long run due to the extension of the dialysis-free period.

Prevalence of diabetic nephropathy and subsequent cardiovascular outcomes: a nationwide study of 74,014 patients with type 2 diabetes

Abstract Background Nonsteroidal, selective mineralocorticoid receptor antagonists (MRAs) have been shown to reduce cardiovascular events among patients with diabetic nephropathy, a clinical syndrome characterized by persistent albuminuria. However, prior reports have suggested a substantial underuse of MRAs among eligible patients. In real-life, it is unknown how many have urinary excretion of albumin measured, and the cardiovascular outcomes among type 2 diabetes (T2D) patients with versus without albuminuria is relatively unknown. Purpose To identify candidates eligible for treatment with MRAs and compare the risk of cardiovascular events in real-life T2D patients with albuminuria versus without albuminuria. Methods Using the Danish nationwide registers, we identified all patients ≥18 years old with prevalent T2D at index date 1st January 2015 with an albumin-creatinine ratio (ACR) and a creatinine level measured within 365 days prior to the index date. For each patient, the last ACR and estimated glomerular filtration rate (eGFR) registered prior to the index date were used. eGFR was calculated using the CKD-EPI formula. The patients were separated into two groups consisting of patients with T2D with ACR ≥30 mg/g (albuminuria) or ACR&amp;lt;30 mg/g (no albuminuria), respectively. Outcomes for both groups were analyzed as time-to-event as a composite cardiovascular outcome of heart failure (HF), myocardial infarction (MI), stroke, and all-cause death and each component of the composite endpoint was analyzed individually. In both groups, we estimated the 4-year absolute risk of the cardiovascular outcome and the risk of experiencing HF, MI, and stroke. Results A total of 158,904 patients with T2D were identified and of those 74,014 patients (47%) had urinary ACR analyzed within the last year. Of those who had ACR analyzed 29,581 (40%) patients had albuminuria. The absolute 4-year risk of the composite cardiovascular outcome in patients with albuminuria and no albuminuria was 28.6% (95% confidence interval (CI): 28.1–29.1) versus 18.7% (95% CI: 18.4–19.1), respectively. The absolute 4-year risk for the individual components were HF 7.0% (95% CI: 6.7–7.3), MI 4.4% (95% CI: 4.2–4.6), and stroke 7.6% (95% CI: 7.3–7.9) for patients with albuminuria, versus HF 4.0% (95% CI: 3.8–4.2), MI 3.2% (95% CI: 3.1–3.4), and stroke 5.5% (95% CI: 5.3–5.7) for patients with no albuminuria. Conclusion In Denmark, only 47% of patients with T2D had ACR analyzed within a year indicating lack of adherence to the national T2D guidelines. A total of 40% of those who had albuminuria analyzed were eligible for treatment with MRAs based on trial inclusion criteria, and the absolute 4-year risk of experiencing a cardiovascular event was significant. However, patients with no albuminuria still displayed a substantial risk of experiencing a composite event of HF, MI, stroke, and all-cause death. Our analyses may have implications for implementation of new MRAs in patients with T2D. Funding Acknowledgement Type of funding sources: None.

Solasonine alleviates high glucose-induced podocyte injury through increasing Nrf2-medicated inhibition of NLRP3 activation.

The worldwide high prevalence of diabetic nephropathy is one of the common causes of renal failure in diabetic patients. Hyperglycemia-caused podocyte injury is considered as a major contributor to diabetic kidney disease, accompanied by a chronic inflammatory condition. Pyroptosis, a characterized inflammatory form of programmed cell death, is believed to be involved in the pathogenesis of diabetic nephropathy. Solasonine (SS) is a natural alkaloid and received attention as a potential anticancer agent. However, its protective effect against hyperglycemia-caused podocyte injury remains to be determined. Our study found that SS alleviates cell apoptosis, and reduces pyroptosis and oxidative damage in high glucose (HG)-treated MPC5 podocytes. Pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18, and caspase-1 activity were markedly suppressed by SS in HG-treated MPC5 podocytes. SS also reduced HG-induced oxidative damage in MPC5 podocytes. Nrf2 expression was activated by SS in vitro under a HG condition. In addition, Nrf2 silencing attenuated the protective effect of SS against apoptosis, pro-inflammatory cytokines release, caspase-1 activity, and oxidative damage in MPC5 podocytes under a HG condition. Taken together, our findings revealed for the first time that SS alleviated high glucose-induced podocyte apoptosis, pyroptosis, and oxidative damage via regulating the Nrf2/NLRP3 signaling pathway. Our results indicate that SS has the potential as a therapeutic agent for podocyte injury in diabetic nephropathy.

Self-care or assisted PD: development of a new approach to evaluate manual peritoneal dialysis practice ability

Background Peritoneal dialysis (PD) is a home-based therapy which requires the patients or their caregivers to perform the practice. We aimed to develop a practical approach to evaluate PD practice ability of the patients and to identify berries to self-care PD. Methods A structural form was designed comprising measures of physical, cognitive, and operational abilities which were required to perform manual PD independently. The evaluation was jointly conducted by a PD nurse, a nephrologist and a close family member of the patient. Patients who met all the requirements were deemed as capable of performing PD independently (self-care PD) and others were deemed as needing an assistant (assisted PD). Results The evaluation form was applied in 280 prevalent PD patients and 33.9% of them were assessed as needing assisted PD, mainly due to physical (62.1%) or operational (66.3%) disabilities. The evaluation result was consistent with current dialysis status in 79.3% patients and it matched better in patients who performed PD with the help of an assistant (93.0 vs. 76.8%, p = 0.014). Patients who were evaluated as having barriers to self-care PD but still performed PD without an assistant were older and demonstrated higher prevalence of diabetic nephropathy and PD-related infection, lower education level, and lower serum albumin (p < 0.05). Conclusions The PD practice ability assessment form is useful to identify patients with barriers to self-care PD. It provides objective information to the patients and their family to choose feasible PD practice modality, self-care, or assisted PD.

Peritoneal dialysis in the era of COVID-19: experience of a Tunisian center.

The COVID-19 pandemic has transformed the health landscape by hampering the management of patients with chronic diseases. Providing optimal healthcare has become a critical issue, especially for patients with end-stage renal disease (ESRD) receiving in-center dialysis. Peritoneal Dialysis (PD) has the advantage of being a home-based therapy. Several papers about COVID-19 in the chronic kidney disease (CKD) population have been published, but few studies focused on the PD population, with limited case series. In this paper, we share our strategy for managing PD patients during the pandemic and describe the characteristics of 24 episodes of COVID-19 that occurred in our PD patients. Also, we report the impact of the pandemic on different outcomes and discuss the challenges of renal replacement therapy (RRT) in the time of COVID-19 and the advantages of PD. During the period from December 2019 to September 2021, 127 patients received PD in our center. Among them, we recorded 24 episodes of COVID-19 that occurred in 20 patients, corresponding to an incidence of 8.4 per 1000 patient-months. None of the 20 patients with COVID-19 were vaccinated and there was a significant male gender predominance in the COVID-19 group compared to the non-COVID-19 group. The prevalence of diabetic nephropathy and primary glomerulonephritis were also significantly higher in the COVID-19 group. The revealing symptoms were asthenia, dry cough, and the deterioration of general conditions in 100%, 75%, and 63% of the patients, respectively. A biological inflammatory syndrome was found in 30% of the patients. Chest computed tomography (CT) scan, performed in 5 patients, showed features of COVID pneumonia with an average extent of damage of 55%. The rate of patients starting PD during the study period was comparable to that before the pandemic. Furthermore, we did not find a significant difference between the infected and the non-infected groups regarding the incidence of peritonitis, PD technique failure, and mortality (6.1 [0–1.46] vs 3.9 [0.15–0.64] deaths per 1000 patient-months. COVID-19 does not seem to have influenced the outcomes of our patients treated with PD even before the launch of mass immunization in our country. Thus, PD can be a great option for RRT in the era of the COVID-19 pandemic since many issues could be managed remotely to avoid regular hospital visits and contribute to maintaining social distancing, which is the cornerstone of breaking the chain of transmission of the novel virus.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40620-022-01396-9.

Clinical Characteristics, Glycemic Control, and Microvascular Complications Compared Between Young-Onset Type 1 and Type 2 Diabetes Patients at Siriraj Hospital - A Tertiary Referral Center.

PurposeThis study aimed to investigate the clinical characteristics, glycemic control, and microvascular complications compared between young-onset type 1 (T1DM) and type 2 diabetes (T2DM) patients at Siriraj Hospital.Patients and MethodsWe collected demographic, clinical, glycemic control, and microvascular complication data of young-onset (onset <30 years of age) T1DM and T2DM patients at our center using February 2019-December 2020 data from the Thai Type 1 Diabetes and Diabetes diagnosed Age before 30 years Registry, Care and Network (T1DDAR CN).ResultsOf 396 patients, 76% had T1DM and 24% had T2DM. At diagnosis, T1DM were significantly younger (9.7±5.4 vs 16.9±6.4 years, p<0.001), had a lower body mass index (17.2±4.1 vs 30.8±7.9 kg/m2, p<0.001), higher prevalence of diabetic ketoacidosis (DKA) (66.1% vs 13.7%, p<0.001), and higher HbA1c level (12.8±2.6% vs 10.9±3.1%, p=0.002) compared to T2DM. Regarding glycemic control, the mean HbA1c at registry enrollment did not differ between groups (T1DM 8.3±1.8% vs T2DM 8.1±2.2%, p=0.303), but T1DM achieved HbA1c <7% significantly less than T2DM (19.3% vs 47.8%, p<0.001). T1DM showed deterioration of glycemic control during 10–20 years of age, and gradually improved during 20–30 years of age, whereas patients with T2DM showed progressive worsening of glycemic control over time. Concerning microvascular complications, the prevalence of diabetic retinopathy (10.6% vs 9%, p=0.92) and diabetic neuropathy (3.4% vs 5.5%, p=0.514) between T1DM and T2DM was not significantly different. However, T2DM had a significantly higher prevalence of diabetic nephropathy (T1DM 10.1% vs T2DM 40.2%, p<0.001) that developed within a significantly shorter duration of diabetes (T1DM 11.0±6.8 vs T2DM 4.3±5.1 years, p<0.001) compared to T1DM.ConclusionT1DM had a significantly high prevalence of DKA at presentation, and most T1DM did not achieve the glycemic target, especially during adolescence. T2DM had a significantly higher prevalence of diabetic nephropathy that developed within a shorter duration of diabetes compared to T1DM.

IDF21-0688 Correlation between metabolic syndrome and diabetic nephropathy in patients with type 1 diabetes

Background: Metabolic syndrome is responsible of an increased cardiovascular risk and is involved in the pathogenesis of the degenerative complications of diabetes, including diabetic nephropathy. Indeed, the association of metabolic syndrome and diabetic nephropathy may rise morbidity and mortality. Aim: The purpose of our work is to evaluate the prevalence of diabetic nephropathy in type 1 diabetic patients with and without metabolic syndrome. Method: Our study is retrospective, descriptive and analytical, involving 381 type 1 diabetic patients during 7 years. Our patients were divided into 2 groups: type 1 diabetic patients with metabolic syndrome (Group 1), and type 1 diabetic patients without metabolic syndrome (Group 2). The metabolic syndrome was defined according to the IDF criteria. Results: Metabolic syndrome was reported in 20 patients (Group1) (5.3%). The average age in this group was 39±16 years. Female predominance was noticed in 75% of patients. Diabetes exceeded 5 years in 80% of cases in the first group. Patients with metabolic syndrome were overweight/obese in 45% of cases, with an average body mass index of 26.15±4.6kg/m2. The mean HbA1c was 10.1±3.4%. Diabetic nephropathy was identified in 35% of patients, and renal failure in 15% (p<0.04). In the second group, the mean age was 20.5±9.8 years, with a sex ratio F/H of 0.9. The duration of diabetes exceeded 5 years in 41.5% of cases. The mean body mass index was 20.08±4.1kg/m2, and only 8.6% of patients were obese/overweight. The mean HbA1c was 8.09±1.2%. The rate of diabetic nephropathy in this group didn’t exceed 24% and the rate of renal failure was 4.7%. Discussion: The prevalence of metabolic syndrome in type 1 diabetes is still increasing, which rises the risk of degenerative complications, particularly diabetic nephropathy. Hence the importance of optimal glycemic control, strict management of cardiovascular risk factors, and close monitoring of microalbuminuria and renal function with early initiation of nephroprotective therapy.

Role of Polyphenol in Regulating Oxidative Stress, Inflammation, Fibrosis, and Apoptosis in Diabetic Nephropathy.

Diabetic Nephropathy (DN) is known as one of the driving sources of End-Stage Renal Disease (ESRD). DN prevalence continues to increase in every corner of the world andthat has been a major concern to healthcare professionals as DN is the key driver of Diabetes Mellitus (DM) morbidity and mortality. Hyperglycaemia is closely connected with the production of Reactive Oxygen Species (ROS) that cause oxidative stress response as well as numerous cellular and molecular modifications. Oxidative stress is a significant causative factor to renal damage, as it can activate other immunological pathways, such as inflammatory, fibrosis, and apoptosis pathways. These pathways can lead to cellular impairment and death as well as cellular senescence. Natural substances containing bioactive compounds, such as polyphenols, have been reported to exert valuable effects on various pathological conditions, including DM. The role of polyphenols in alleviating DN conditions has been documented in many studies. In this review, the potential of polyphenols in ameliorating the progression of DN via modulation of oxidative stress, inflammation, fibrosis, and apoptosis, as well as cellular senescence, has been addressed. This information may be used as the strategies for the management of DN and development as nutraceutical products to overcome DN development.