Diabetic Kidney Research Articles

The prognostic value of metabolic dysfunction associated steatotic liver disease in acute myocardial infarction

Abstract Background Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. Methods This study compared the characteristics, and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. Results In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 24 years. The MASLD group had higher rates of obesity, diabetes, and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs 3.6%, p<0.001) at 30 days, with unfavorable mortality rates sustained in the long-term (18.3% vs 14.5%, p=0.001) compared to those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (HR 1.338, 95% CI 1.115-1.604). Conclusion MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.Kaplan Meier curve of long-term all-caus

Implications of five different risk models in primary prevention guidelines

Abstract Background A lack of consensus exists across guidelines as to which risk model should be used for the primary prevention of cardiovascular disease (CVD). Purpose The objective of this study was to determine potential improvements in the number needed to treat (NNT) with statins using different risk models in patients eligible for risk stratification. Methods A retrospective observational cohort was assembled from primary care patients in Ontario, Canada between January 1st, 2010, to December 31st, 2014 and followed for up to 5 years. Risk estimation was undertaken in patients 40-75 years of age, without CVD, diabetes, or chronic kidney disease using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs), a recalibrated FRS (R-FRS), Systematic Coronary Risk Evaluation 2 (SCORE2), and the low-risk region recalibrated SCORE2 (LR-SCORE2). Results The cohort consisted of 47,399 patients (59% women, mean age 54). The NNT at 5 years with statins was lowest for SCORE2 at 40, followed by LR-SCORE2 at 41, R-FRS at 43, PCEs at 55, and FRS at 65. Models that selected for individuals with a lower NNT recommended statins to fewer, but higher risk patients. For instance, SCORE2 recommended statins to 7.9% of patients (5-year CVD incidence 5.92%). The FRS, however, recommended statins to 34.6% of patients (5-year CVD incidence 4.01%; Figure). Conclusions Newer models such as SCORE2 may improve statin allocation to higher risk groups with a lower NNT.Figure

Association of third-trimester N-terminal pro-brain natriuretic peptide levels and pre-eclampsia development

Abstract Background Pre-eclampsia shares numerous risk factors with cardiovascular diseases and is associated with postpartum cardiovascular complications. Natriuretic peptides, outside pregnancy valid biomarkers for detecting subclinical cardiac dysfunction, are typically elevated at the time of pre-eclampsia diagnosis. However, their role before disease manifestation is still puzzling. Aims To assess whether third-trimester natriuretic peptide levels are associated with a diagnosis of pre-eclampsia in pregnant individuals. Methods This study measured NT-proBNP levels in third-trimester samples of 1454 pregnant individuals prior to disease manifestation. Pre-eclampsia was diagnosed using the American College of Obstetrics and Gynecology (ACOG) criteria. Linear regression analyses were performed, and multivariable adjustments were done for age, body mass index (BMI), preexisting hypertension, diabetes, and chronic kidney disease. Odds ratios were calculated per doubling of NT-proBNP levels. Results Of the 1454 individuals, 118 (7.6 %) developed pre-eclampsia. The median week of gestation for blood sampling was 29.0 (IQR 28.4 – 29.4) in both groups (p = 0.68). Individuals with pre-eclampsia manifestation had higher BMI, were more often nulliparous, and had lower placental growth factor levels (all p < 0.01). Higher NT-proBNP levels were associated with a lower risk of pre-eclampsia, which persisted after controlling for confounders (adjusted odds ratio (OR), 0.84; 95 % CI, 0.70 - 1.00). This inverse relationship was particularly pronounced in cases of late-onset pre-eclampsia, defined as onset after 34 + 0 weeks of gestation. Specifically, for preterm pre-eclampsia between weeks 34 + 0 and 36 + 9, the adjusted OR was 0.78 (95 % CI, 0.56-1.09), and for term pre-eclampsia at or after week 37 + 0, the adjusted OR was 0.77 (95 % CI, 0.61 - 0.95). Conversely, a positive association was observed between NT-proBNP levels and the occurrence of early-onset pre-eclampsia < 34 + 0 weeks, with an adjusted OR of 1.69 (95 % CI, 1.00 - 2.91). Causal mediation analyses indicated that the association between higher BMI and pre-eclampsia mediated only a minor fraction (11.5 % [95 % CI, 4.3 % - 36.0 %, p < 0.01]) of the observed association. Conclusion These findings reveal the complex interplay between third-trimester NT-proBNP levels and the risk of pre-eclampsia. They unravel an inverse association for late-onset disease but a contrasting positive correlation for early-onset cases in temporal proximity to NT-proBNP assessment. The latter may reflect acute physiological responses to pre-eclampsia nearing diagnosis. However, the inverse relationship observed for later manifestations underscores the importance of further research to dissect the underlying pathophysiological mechanisms, which suggest cardiovascular maladaption to pregnancy prior to pre-eclampsia manifestation.

Association of Sleep Apnea and cardiovascular mortality in CAD patients

Abstract Background A growing body of epidemiological and clinical research has uncovered a significant relationship between sleep apnea and the exacerbation of cardiovascular outcomes, notably myocardial infarction, stroke, and cardiac death. Individuals diagnosed with coronary artery disease (CAD) alongside sleep apnea are identified to have a heightened likelihood of experiencing recurrent cardiovascular events. Despite these associations, the link between sleep apnea and an elevated risk of mortality among CAD patients remains insufficiently explored. Purpose Our study aims to shed light on the impact of sleep apnea on mortality rates within this patient population, potentially guiding future therapeutic strategies. Methods Our cohort study leveraged data from the TriNetX multinational electronic health record network, focusing on patients aged 18 and above diagnosed with coronary artery disease. Participants were stratified into two groups based on the diagnosis of sleep apnea. To ensure a fair comparison, we adjusted for prevalent risk factors such as hypertension, diabetes, dyslipidemia, obesity, and chronic kidney disease, which are commonly observed in CAD patients. Results The study encompassed 1,799,812 patients, equally divided into two groups of 899,906 individuals each, one with sleep apnea and the other without. Over a 5-year observation period, the primary endpoint, defined as event-free survival, was significantly lower in the sleep apnea group (74.385%) compared to the non-sleep apnea group (76.606%), with a Log Rank confidence interval of 1.128 to 1.148 and a p-value of <0.0001. This outcome highlights a association between sleep apnea and increased mortality rates in CAD patients. Conclusion The findings from our large cohort study underscore the critical impact of sleep apnea on mortality among patients with coronary artery disease. The diagnosis of sleep apnea in CAD patients within the TriNetX cohort was significantly associated with a higher mortality rate over a span of five years. These insights emphasize the need for integrated care strategies that not only address the primary cardiovascular conditions but also prioritize the diagnosis and management of sleep apnea to potentially improve survival outcomes in this vulnerable patient group. Our study calls for heightened clinical awareness and further research to elucidate the mechanisms behind this association and to explore the benefits of targeted sleep apnea interventions in reducing mortality rates among CAD patients.5-year Kaplan-Meier curves for mortality

Unequal effects of adolescent health behaviors on adult cardiometabolic conditions: a cohort study

Abstract Background Health behaviors in adolescence could have a life-long effect on cardiometabolic health and differ by parental socioeconomic conditions. Adopting a life course perspective and a causal inference framework, we aimed to quantify the differential effect of adolescent unhealthy behaviors on adult cardiometabolic conditions by parental financial situation. Methods Using the National Longitudinal Study of Adolescent to Adult Health in the United States (n = 3,772), we estimated conditional causal effect by parental financial situation through inverse probability-weighted marginal structural models. Exposures were adolescent health behaviors (dietary habits, cigarette smoking, alcohol consumption and physical activity) and the effect modifier was parental financial situation (difficulty paying bills vs. no difficulty), both measured at ages 12-19 (1994-1995). Outcomes were cardiometabolic conditions (hypertension, stroke, cardiac failure, diabetes, chronic kidney disease), measured at ages 33 - 43 (2016-2018) using biomarkers and self-reports. Results There were 1,206 participants with cardiometabolic conditions after 20 years of follow-up. Alcohol consumption among adolescents with parental financial difficulty led to 325 more cardiometabolic cases (95% confidence interval: 2 - 647) compared to alcohol consumption by their peers without financial difficulty. This differential effect is driven more by cardiovascular conditions (hypertension, stroke, or cardiac failure) than by metabolic conditions (diabetes or chronic kidney disease). There were no differential effects of dietary habits, cigarette smoking and physical inactivity on the occurrence of adult cardiometabolic conditions. Conclusions Public health initiatives targeting alcohol consumption during adolescence could mitigate socioeconomic inequalities in adult cardiometabolic conditions. Key messages • Socioeconomically disadvantaged adolescents are more susceptible to the long-term detrimental health effects of alcohol consumption. • These susceptible groups may need targeted interventions to mitigate the cardiometabolic effect of alcohol consumption.

Levosimendan improves the early prognosis of patients with Non ST-segment elevation myocardial infarction and Killip class > II

Abstract Background Levosimendan is an inotropic agent known for its calcium-sensitizing myofilament effect and ATP-dependent potassium channel opening mechanism, which enhances myocardial contractility without increasing oxygen consumption. Despite its potential benefits, the impact of levosimendan on the prognosis of patients with myocardial infarction remains uncertain and requires further investigation through larger-scale studies. Purpose This study aimed to investigate the effect of levosimendan on the short-term prognosis of patients with Non-ST-segment elevation myocardial infarction (NSTEMI) and Killip> II. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals in the City from 2010 to 2023. A total of 12472 patients with NSTEMI and Killip > II were included. Patients were divided into the levosimendan group and the non-leosimendan group based on whether levosimendan was used during hospitalization. Propensity score matching (PSM) was employed to balance covariates between the two groups. Multivariate Cox regression was used to evaluate the relationship between levosimendan and clinical outcomes. Covariates adjusted in PSM included age, sex, Killip class, early PCI, previous PCI, previous medical conditions (diabetes, hypertension, ischemic stroke, and chronic kidney disease), and medications during hospitalization (aspirin, clopidogrel, indobufen, ticagrelor, statins, cedilanid, recombinant human brain natriuretic peptide [rhBNP], milrinone, dopamine, dobutamine, and angiotensin converting enzyme inhibitor/angiotensin receptor blockers [ACEI/ARB]). The primary endpoint was major cardiovascular and cerebrovascular adverse events (MACCE), defined as the composite endpoint of cardiac death, myocardial infarction, and ischemic stroke within 3 months. Results The levosimendan group comprised 782 patients, while the non-leosimendan group included 11690 patients. After PSM, the covariates were balanced, resulting in 756 well-matched pairs. In PSM patients, the levosimendan group exhibited a significantly lower incidence of MACCE (aHR, 0.573; 95%CI, 0.466–0.704; p < 0.001) and cardiac death (aHR, 0.500; 95%CI, 0.399-0.626; p < 0.001). However, there was no significant difference in the incidence of myocardial infarction and ischemic stroke. Conclusions Levosimendan was associated with a lower incidence of MACCE within 3 months in patients with NSTEMI and Killip> II, mainly driven by lower incidence of cardiac death. However, these findings are based on observational data and require confirmation through adequately powered, randomized, controlled trials.

Prognostic values of lipoprotein(a) levels for secondary prevention of acute coronary syndrome among patients who underwent primary percutaneous coronary intervention

Abstract Background Lipoprotein(a) [Lp(a)] is known to be a residual risk factor for acute coronary syndrome(ACS). However, in the current era where primary percutaneous coronary intervention (PCI) and lipid-lowering therapies have advanced, the role of Lp(a) levels in secondary prevention among ACS patients remains unclear. Purpose The purpose of this study is to determine whether Lp(a) levels play a role in secondary prevention by studying patients with ACS who underwent primary PCI and survived discharge. Methods Consecutive ACS patients who were admitted to our institution between December 2016 and March 2021, requiring primary PCI and were discharged alive were enrolled for the current study (n = 471). Of these patients, those with the following circumstances were excluded: (1) multidisciplinary treatment such as mechanical ventilation management and percutaneous cardiopulmonary support (n = 74), (2) incomplete clinical data (n = 34), (3) ACS classified as other than type 1 in the universal definition (n = 6), and (4) unknown prognosis at 6 months after discharge (n = 8). A total of 349 consecutive patients were included in the current study. They were divided into two groups according to Lp(a) levels: Lower Lp(a) group (Lp(a) < 30 mg/dL, n = 277) and Higher Lp(a) group (Lp(a) ≥ 30 mg/dL, n = 72). The primary endpoints were major adverse cardiac events (MACEs), composite of all cause death, nonfatal myocardial infarction, nonfatal stroke and congestive heart failure requiring admission. Event-free survival curves were estimated using Kaplan-Meier method and log-rank test was used to detect statistically significant differences. In addition, influence of Lp(a) levels on MACE was examined using three cox regression analyses. Model 1 was adjusted for age, gender and body mass index, model 2 was adjusted for hypertension, diabetes and chronic kidney disease (CKD), model 3 was adjusted for old myocardial infarction (OMI), smoking and multivessel disease, respectively. Results The mean age was 67.0 ± 12.8 years, and 70.5% were male. The median serum Lp(a) levels of the entire population was 14 mg/dL (interquartile range, 7 to 26). There were no significant differences about baseline patient’s characteristics, laboratory findings, and medications at discharge including statin treatment. The MACE was observed in 15.5% of the Lower Lp(a) group and 20.8% of the Higher Lp(a) group (p=0.29). No difference was observed about MACE between the two groups (log-rank p=0.45). After adjusting for cardiovascular risk factors, Lp(a) levels were not associated with MACEs in all three models. However, in model 2 and model 3, CKD and OMI were associated with MACEs (hazard ratio 4.29, 95% confidence interval 2.17 to 8.46, p < 0.001, hazard ratio 3.02, 95% confidence interval 1.39 to 6.51, p = 0.005, respectively). Conclusions In the current era, Lp(a) levels are not associated with secondary prevention among ACS patients who underwent primary PCI.

Clinical profile and outcomes of patients with chronic kidney disease on chronic hemodialysis hospitalized for acute coronary syndrome in a tertiary public hospital in the Philippines

Abstract Introduction Acute coronary syndrome (ACS) and end-stage renal disease (ESRD) are both prevalent globally. Of the many risk factors for ACS, chronic kidney disease (CKD) remains to be of great concern because the interplay of cardiac and renal disease is inherently complicated. Cardiovascular mortality rates are 10-30 times higher in the ESRD population. The risk for cardiovascular disease in CKD extends beyond the traditional risk factors. Purpose The guidelines for ACS may not be applicable to the ESRD population because the landmark ACS trials mostly excluded ESRD patients. Due to the gaps in knowledge regarding ACS in ESRD, our study sought to explore the clinical profile and outcomes of these patients in the our institution. Methods We did a retrospective cohort study among ESRD patients presenting with ACS in our institution from May 2021 to November 2023. The data was analyzed using univariate and bivariate statistics using PRISM software. Results A total of 48 patients with ESRD were admitted for ACS in this study - 8 with STEMI and 40 with NSTEMI. The mean age was 61 years old and 33 (68.8%) were male. The average length of hospital stay was 12 days. The most common comorbidities were hypertension (91.7%), heart failure (83.3%), and diabetes mellitus (60.4%). The most common cause of ESRD in our cohort is concomitant hypertensive and diabetic kidney disease (45.8%) with an average length of hemodialysis at 31 months. The most common chief complaints were chest pain (39.6%), dyspnea (29.2%), and decreased sensorium (10.4%). On admission, 18 (37.5%) presented with systolic BP >160mmHg, 7 (14.6%) presented with shock, and 4 (8.3%) presented with cardiac arrest. On electrocardiogram, 21 (43.8%) had left ventricular hypertrophy while 34 (70.8%) had cardiomegaly on chest radiography. On two-dimensional echocardiogram, the average left ventricular ejection fraction was 46% and 27 (90%) had segmental wall motion abnormalities. The most common angiographic finding was 3-vessel coronary artery disease (50%). Only 5 patients (10.4%) had an LDL-C greater than 55mg/dL. Among those with STEMI, 6 (75%) presented with Kilip II or more. While among those with NSTEMI, 27 (67.5%) had a TIMI risk score >2. Almost all patients received dual-antiplatelet therapy, high dose statin, and beta-blocker. The mortality rate was 43.8% with acute coronary syndrome being the most common cause of death. Conclusion Our study did not show significant associated predictors of mortality possibly due to the low sample size. Despite this, our study portrays that patients admitted for ACS with ESRD present with higher risk features reflected by derangement in vital signs, abnormal laboratories, significant imaging abnormalities, high prognostication scores, and high in-hospital morbidity.Predictors of Mortality

Preclinical Evidence of Mulberry Leaf Polysaccharides on Diabetic Kidney Disease: a Systematic Review and Meta-Analysis.

Mulberry leaf polysaccharides (MLPs) have a variety of biological activities. Preliminary scattered evidence of preclinical studies have reported their potenzial effects on diabetic kidney disease (DKD). Here, we intended to assess the preclinical evidence of MLPs and explore their potenzial mechanisms on DKD, offering a scientific reference for the therapeutic use of MLPs. The study has been registered under the CRD42022309117 registration number at PROSPERO. Comprehensive search was conducted across eight databases from their establishment till January 2024, and eight studies with 270 animals were included in the meta-analysis. The primary outcome measurements in the MLP group, including serum creatinine (Scr) (P = 0.0005), blood urea nitrogen (BUN) (P = 0.02), 24-hour urinary protein (UP) (P = 0.001), and urinary microalbumin (UAlb) (P < 0.0001), were significantly reduced compared to the control group. Additionally, MLP treatment was significantly correlated with fasting blood glucose (FBG), total cholesterol (TC), protein expression of TGF-β1, CTGF mRNA, and the kidney index (all P values < 0.05) and delayed the progression of local pathological changes in the kidney. Subgroup analysis revealed significant species differences in the efficacy of MLPs. Also, it showed that the dosage of streptozotocin potenzially affected the Scr and UAlb results, while the duration of MLP treatment influenced UAlb results. MLPs may exert potenzial renal protection by delaying renal fibrosis, inhibiting inflammatory reactions, suppressing the growth hormone-insulin-like growth factor-insulin-like growth factor binding protein axis, and regulating the insulin receptor pathway. In summary, MLPs have multifaceted renal protective effects, suggesting their potenzial for treating DKD.

To analyse the correlation between UAER and eGFR and the risk factors for reducing eGFR in patients with type 2 diabetes

ObjectiveTo analyse the correlation between urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (eGFR) and the risk factors for reducing eGFR in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 431 T2DM patients admitted between January 2019 and March 2020 were selected and divided into two groups according to eGFR level. Comparing the differences between baseline data and clinical indicators, multivariate logistic regression was used to analyse the risk factors of eGFR reduction and to analyse the association between UAER and eGFR.ResultsIn total, 167 patients were included in the study group and 264 patients were included in the conventional group. The study group participants were older, had longer diabetes duration, and had higher fatty liver, peripheral vascular disease (PVD), hypertension prevalence, and mean body mass index (P < 0.05). The levels of various indicators were lower than those of the conventional group (P < 0. 05). Additionally, PVD, nocturnal systolic blood pressure, fatty liver, and beta-2-microglobulin (β 2-MG) were independent risk factors for eGFR decline, with high density lipoprotein (HDL) and fasting C-peptide (CP) as protective factors. There was no obvious correlation between UAER and eGFR.ConclusionPeripheral vascular disease, systolic blood pressure, fatty liver, and beta-2-microglobulin are risk factors for decreased eGFR levels in patients with T2DM, which should be applied for control DKD. HDL and fasting CP have important effects on maintaining eGFR, and blood pressure and fasting CP can be used as new targets for subsequent diabetic kidney disease treatment.

Kidney lesions and risk of cardiovascular events in biopsy-proven diabetic kidney disease with type 2 diabetes

Kidney lesions and risk of cardiovascular events in biopsy-proven diabetic kidney disease with type 2 diabetes

Independent and joint effects of self-reported physical activity and sedentary behaviors on mortality in community-dwelling older persons: a prospective cohort study

BackgroundThis study aims to assess the joint and independent effects of self-reported physical activity and sedentary behavior on mortality in older persons.MethodsA prospective community-based cohort study was conducted to examine physical activity (PA) level and sitting time (ST) in relation to mortality among 1,786 older persons aged 65 years and above. PA was assessed by a checklist of 26 self-reported items about PA and hours per week, and the metabolic equivalent hours/week was derived, and ST was measured by a self-reported item asking the average number of hours spent sitting per day. The participants were divided into four combination groups of PA and ST based on WHO guideline and values found in literature: high PA/short ST group, high PA/long ST group, low PA/long ST group, and low PA/short ST group. Data on death ascertainment were obtained through linkage with the national death datasets and expanded cardiovascular disease (CVD) included cardiovascular disease, diabetes, and chronic kidney disease.ResultsAfter follow-up for a median 11.1 years, 599 mortality cases were recorded, giving a crude all-cause mortality of 32.5/1,000 person-years, CVD mortality of 8.6/1,000 person-years, expanded CVD mortality of 11.9/1,000 person-years, and nonexpanded CVD mortality of 20.8/1,000 person-years. For all-cause, and expanded CVD, the hazards ratios (HRs) for the low PA/long ST group remained significant compared with that for the high PA/short ST group after all covariates were considered [HRs for all-cause mortality: 1.4 [95% confidence interval (CI) 1.1, 1.8]; and expanded CVD mortality: 1.7 (95% CI 1.1, 2.4).ConclusionsThe independent effect of PA and the joint effects of PA and ST are associated with all-cause and expanded CVD death risks. Expanded CVD mortality may be minimized by engaging in PA and reducing sedentary behaviors.

ASSOCIATION OF SERUM ADENOSINE DEAMINASE LEVELS WITH ACUTE KIDNEY INJURY IN DIABETIC PATIENTS

Diabetes mellitus is a significant global health issue, and complications such as acute kidney injury (AKI) are prevalent in patients with type 2 diabetes. Serum adenosine deaminase (ADA) has been suggested as a potential biomarker for various metabolic conditions, including inflammation and kidney injury, but its association with diabetic kidney health remains understudied. Objective: To assess the association of serum adenosine deaminase (ADA) levels with acute kidney injury (AKI) in patients with type 2 diabetes. Methods: This observational comparative study was conducted at DHQ Teaching Hospital KDA, Kohat, from February 7, 2023, to August 7, 2023, following ethical approval. A total of 120 participants were enrolled, including 60 patients with type 2 diabetes and 60 non-diabetic controls. Laboratory investigations for both groups included serum ADA (U/L), HbA1c (%), and estimated glomerular filtration rate (eGFR) (mL/min/1.73 m²). Statistical comparisons between groups were made using appropriate tests, and correlations between serum ADA and other parameters were assessed. Results: The mean age of diabetic patients was 55.40 ± 8.29 years, and that of controls was 54.58 ± 21.64 years. The mean serum ADA level in diabetic patients was significantly higher at 43 ± 4.29 U/L compared to 16.32 ± 1.20 U/L in controls (p = 0.0001). Diabetic patients had a mean HbA1c of 8.30 ± 0.59%, significantly higher than that of controls (5.28 ± 0.59%) (p = 0.0001). The mean eGFR in diabetic patients was 82.61 ± 17.22 mL/min/1.73 m², lower than in controls (105.97 ± 12.07 mL/min/1.73 m²) (p = 0.0001). In diabetic patients, serum ADA levels were positively correlated with HbA1c (indicating poorer glycemic control) and negatively correlated with eGFR (suggesting declining kidney function). Conclusion: Elevated serum adenosine deaminase levels in type 2 diabetic patients are significantly associated with poor glycemic control and decreased kidney function. These findings indicate that serum ADA could serve as a potential biomarker for monitoring glycemic status and kidney health in diabetic patients at risk for acute kidney injury.

Integrated multiomic analyses: An approach to improve understanding of diabetic kidney disease.

Diabetes is increasing in prevalence worldwide, with a 20% rise in prevalence predicted between 2021 and 2030, bringing an increased burden of complications, such as diabetic kidney disease (DKD). DKD is a leading cause of end-stage kidney disease, with significant impacts on patients, families and healthcare providers. DKD often goes undetected until later stages, due to asymptomatic disease, non-standard presentation or progression, and sub-optimal screening tools and/or provision. Deeper insights are needed to improve DKD diagnosis, facilitating the identification of higher-risk patients. Improved tools to stratify patients based on disease prognosis would facilitate the optimisation of resources and the individualisation of care. This review aimed to identify how multiomic approaches provide an opportunity to understand the complex underlying biology of DKD. This review explores how multiomic analyses of DKD are improving our understanding of DKD pathology, and aiding in the identification of novel biomarkers to detect disease earlier or predict trajectories. Effective multiomic data integration allows novel interactions to be uncovered and empathises the need for harmonised studies and the incorporation of additional data types, such as co-morbidity, environmental and demographic data to understand DKD complexity. This will facilitate a better understanding of kidney health inequalities, such as social-, ethnicity- and sex-related differences in DKD risk, onset and progression. Multiomics provides opportunities to uncover how lifetime exposures become molecularly embodied to impact kidney health. Such insights would advance DKD diagnosis and treatment, inform preventative strategies and reduce the global impact of this disease.

Efficacy of continuous glucose monitoring in people living with diabetes and end stage kidney disease on dialysis: a systematic review

BackgroundPatients with diabetes on dialysis experience wide variations in glucose levels and an increased risk of hypoglycaemia. Due to the inaccuracies of HbA1c in dialysis patients, JBDS-IP and KDIGO recommend the use of continuous glucose monitoring (CGM). We conducted a systematic review to examine the current evidence for CGM use and its impact on clinical outcomes in patients with diabetes on dialysis.MethodsA search of MEDLINE(R) ALL, Ovid Emcare, Journals@Ovid Full Text and Embase databases were conducted. Clinical or observational trials in adults with Type 1(T1D) or Type 2 (T2D) diabetes on dialysis and CGM intervention reporting on glycaemic outcomes were included.ResultsOf the 936 citations identified, 49 duplicates were removed. 887 citations were screened by title and abstract. 9 full texts were reviewed and a further 7 excluded due to duplications or failure to meet to selection criteria. Data was extracted for 2 studies, both prospective before-and-after interventional studies with no control group. Joubert et al. (2015) showed results for 15 participants with T1D. Mean CGM glucose level decreased from 8.37mmol/L at baseline to 7.7mmol/L at the end of the CGM period (p < 0.05) while HbA1c decreased from 6.9 to 6.5% (p < 0.05) during the same period. Mean CGM was lower on dialysis days (7.68mmol/L vs. 7.8mmol/L, p < 0.05). Képénékian et al. (2014) reported on data from 29 T2D patients. Following a 3 month CGM-adapted insulin regimen, HbA1c decreased from 8.4% at baseline to 7.6% (p < 0.01) by the end of study. Mean CGM values decreased from 9.9mmol/L to 8.9mmol/L (p = 0.05) and the frequency of glucose values > 10mmol/L decreased from 41 to 30% (p < 0.05), without a significant increase in hypoglycaemia frequency. Both studies were deemed to be of ‘good’ quality.ConclusionEvidence demonstrating the benefits of CGM in patients with diabetes receiving dialysis is lacking. There is a need for well-designed randomised controlled trials to ascertain the benefits of this technology in this patient group.Trail registrationPROSPERO registration number: CRD42023371635, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=371635.

Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial.

Semaglutide reduces albuminuria and the risk of kidney disease progression in patients with type 2 diabetes and chronic kidney disease (CKD). We conducted a randomized placebo-controlled double-blind clinical trial in adults with CKD (estimated glomerular filtration rate (eGFR) ≥25 ml min-1 1.73 m-2 and urine albumin-to-creatinine ratio (UACR) ≥30 and <3,500 mg g-1) and body mass index ≥27 kg m-2. Participants were randomized to semaglutide 2.4 mg per week or placebo. The primary endpoint was percentage change from baseline in UACR at week 24. Safety was monitored throughout. Overall, 125 participants were screened, of whom 101 were randomized to semaglutide (n = 51) or placebo (n = 50). Mean age was 55.8 (s.d. 12) years; 40 participants (39.6%) were female; median UACR was 251 mg g-1 (interquartile range 100, 584); mean eGFR was 65.0 (s.d. 25) ml min-1 1.73 m-2; and mean body mass index was 36.2 (s.d. 5.6) kg m-2. Chronic glomerulonephritis (n = 25) and hypertensive CKD (n = 27) were the most common CKD etiologies. Treatment for 24 weeks with semaglutide compared to placebo reduced UACR by -52.1% (95% confidence interval -65.5, -33.4; P < 0.0001). Gastrointestinal adverse events were more often reported with semaglutide (n = 30) than with placebo (n = 15). Semaglutide treatment for 24 weeks resulted in a clinically meaningful reduction in albuminuria in patients with overweight/obesity and non-diabetic CKD. ClinicalTrials.gov registration: NCT04889183 .

ACE Inhibitors and Angiotensin Receptor Blockers for the Primary and Secondary Prevention of Cardiovascular Outcomes: Recommendations from the 2024 Egyptian Cardiology Expert Consensus in Collaboration with the CVREP Foundation.

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in regulating blood pressure (BP), with dysregulation of RAAS resulting in hypertension and potentially heart failure (HF), myocardial infarction (MI), cardio-renal syndrome, and stroke. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), have advantages beyond BP control. However, differences between these two drug classes need to be considered when choosing a therapy for preventing cardiovascular events. A panel of 36 Egyptian cardiologists developed consensus statements on RAAS inhibitors for primary and secondary prevention of cardiovascular outcomes and stroke, using a modified three-step Delphi process. The consensus statements highlight the importance of effective BP control and the role of RAAS blockade for prevention and management of various cardiovascular diseases. ACEis and ARBs differ in their mode of action and, thus, clinical effects. On the basis of available evidence, the consensus group recommended the following: ACEis should be considered as first choice (in preference to ARBs) to reduce the risk of MI, for primary prevention of HF, and for secondary prevention of stroke. ACEis and ARBs show equivalent efficacy for the primary prevention of stroke. Evidence also favors the preferential use of ACEis in patients with type 2 diabetes, for BP control, for the primary prevention of diabetic kidney disease, and to reduce the risk of major cardiovascular and renal outcomes. Treatment with an ACEi should be started within 24 h of ST segment elevation MI (and continued long term) in patients with HF, left ventricular systolic dysfunction, and/or diabetes. Angiotensin receptor/neprilysin inhibitors (ARNIs) are the first choice for patients with HF and reduced ejection fraction, with ACEis being the second choice in this group. ARBs are indicated as alternatives in patients who cannot tolerate ACEis. ACEis may be associated with cough development, but the incidence tends to be overestimated, and the risk can be reduced by use of a lipophilic ACEi or combining the ACEi with a calcium channel blocker. RAAS blockade is an essential component of hypertension therapy; however, the protective effects provided by ACEis are superior to those of ARBs. Therefore, an ACEi is indicated in almost all cases, unless not tolerated.

DOT1L protects against podocyte injury in diabetic kidney disease through phospholipase C-like 1

BackgroundPodocyte injury causes proteinuria and accelerates glomerular sclerosis during diabetic kidney disease (DKD). Disruptor of telomeric silencing 1-like (DOT1L), an evolutionarily conserved histone methyltransferase, has been reported in preventing kidney fibrosis in chronic kidney disease models. However, whether DOT1L exerts beneficial effects in diabetes induced podocyte injury and the underlying molecular mechanisms need further exploration.MethodsThe expression of DOT1L was confirmed by Western blotting in MPC-5 cells and cortex of kidney from db/db mice, as well as immunofluorescence staining in human renal biopsy samples. The effect of DOT1L on podocyte injury was obtained using MPC-5 cells and db/db mice. The potential target genes regulated by DOT1L was measured by RNA-sequencing. Then, a series of molecular biological experiments was performed to investigate the regulation of PLCL1 by DOT1L in MCP-5 cells and db/db mice. Lipid accumulation was assessed by UPLC-MS/MS analysis and Oil Red O staining.ResultsDOT1L expression was significantly declined in high glucose (HG)-treated MPC-5 cells, podocyte regions of kidney tissues from db/db mice and human renal biopsy samples. Subsequent investigations revealed that upregulation of DOT1L ameliorated HG-induced cell apoptosis in MPC-5 cells as well as primary podocytes. Furthermore, podocyte-specific DOT1L overexpression inhibited diabetic podocyte injury in db/db mice. Mechanistically, we revealed that DOT1L upregulated phospholipase C-like 1 (PLCL1) expression by mediating H3K79me2 at its promoter and PLCL1 silencing suppressed the protective role of DOT1L on podocyte injury. Moreover, DOT1L improved diabetes induced abnormal fatty acid metabolism in podocytes and PLCL1 knockdown reversed its protective effects.ConclusionsTaken together, our results indicate that DOT1L protects podocyte injury via PLCL1-mediated fatty acid metabolism and provides new insights into the therapeutic target of DKD.

A mathematical model of glomerular fibrosis in diabetic kidney disease to predict therapeutic efficacy

BackgroundGlomerular fibrosis is a tissue damage that occurs within the kidneys of chronic and diabetic kidney disease patients. Effective treatments are lacking, and the mechanism of glomerular damage reversal is poorly understood.MethodsA mathematical model suitable for hypothesis-driven systems pharmacology of glomerular fibrosis in diabetes was developed from a previous model of interstitial fibrosis. The adapted model consists of a system of ordinary differential equations that models the complex disease etiology and progression of glomerular fibrosis in diabetes.ResultsWithin the scope of the mechanism incorporated, advanced glycation end products (AGE)—matrix proteins that are modified due to high blood glucose—were identified as major contributors to the delay in the recovery from glomerular fibrosis after glucose control. The model predicted that inhibition of AGE production is not an effective approach for accelerating the recovery from glomerular fibrosis. Further, the model predicted that treatment breaking down accumulated AGE is the most productive at reversing glomerular fibrosis. The use of the model led to the identification that glucose control and aminoguanidine are ineffective treatments for reversing advanced glomerular fibrosis because they do not remove accumulated AGE. Additionally, using the model, a potential explanation was generated for the lack of efficacy of alagebrium in treating advanced glomerular fibrosis, which is due to the inability of alagebrium to reduce TGF-β.ImpactUsing the mathematical model, a mechanistic understanding of disease etiology and complexity of glomerular fibrosis in diabetes was illuminated, and then hypothesis-driven explanations for the lack of efficacy of different pharmacological agents for treating glomerular fibrosis were provided. This understanding can enable the development of more efficacious therapeutics for treating kidney damage in diabetes.

Exercise as a therapeutic approach to alleviate diabetic kidney disease: mechanisms, clinical evidence and potential exercise prescriptions

Diabetic kidney disease (DKD) is a global and severe complication that imposes a significant burden on individual health, families, and society. Currently, the main treatment approaches for DKD include medication, blood glucose control, protein-restricted diet, and blood pressure management, all of which have certain limitations. Exercise, as a non-pharmacological intervention, has attracted increasing attention. This review introduces the mechanisms and clinical evidence of exercise on DKD, and proposes potential exercise prescriptions. Exercise can improve blood glucose stability related to DKD and the renin-angiotensin-aldosterone system (RAAS), reduce renal oxidative stress and inflammation, enhance the crosstalk between muscle and kidneys, and improve endothelial cell function. These mechanisms contribute to the comprehensive improvement of DKD. Compared to traditional treatment methods, exercise has several advantages, including safety, effectiveness, and no significant side effects. It can be used as an adjunct therapy to medication, blood glucose control, protein-restricted diet, and blood pressure management. Despite the evident benefits of exercise in DKD management, there is still a lack of large-scale, long-term randomized controlled trials to provide more evidence and develop exercise guidelines for DKD. Healthcare professionals should actively encourage exercise in DKD patients and develop personalized exercise plans based on individual circumstances.