Urinary Albumin-creatinine Ratio Research Articles

Effect of spironolactone wash-out on albuminuria after long-term treatment in individuals with type 2 diabetes and high risk of kidney disease-An observational follow-up of the PRIORITY study.

This study aimed to explore the effect of discontinuation of long-term spironolactone treatment on markers of kidney function in individuals with type 2 diabetes (T2D) at high risk of kidney disease enrolled in the Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria (PRIORITY) study. An observational study following the nested randomised part of the PRIORITY study was conducted. A total of 115 individuals with T2D and normoalbuminuria but high risk for progression based on urinary proteomics, randomised to daily spironolactone (n = 50) or placebo (n = 65) for a median of 2.5 years, were re-examined approximately 6 weeks after the final visit in the PRIORITY study. Primary endpoint was relative change in geometric mean of urinary albumin-creatinine ratio (UACR) between the final visit in PRIORITY (baseline) and follow-up. Secondary endpoints were change in estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP) and serum potassium. No change in UACR was observed in neither the spironolactone (geometric mean change: 17%; 95% CI -12, 55; p = 0.28) nor the placebo (5%; 95% CI -13, 26; p = 0.63) group at follow-up. No difference in UACR between the groups was observed at follow-up (relative difference in geometric mean: 11%, 95% CI -26, 67; p = 0.60). For eGFR and SBP, an increase after discontinuation of spironolactone was observed, as well as for SBP after placebo discontinuation. Potassium levels were lower after discontinuation of spironolactone, but higher after placebo discontinuation (all p < 0.05). UACR did not change after discontinuation of long-term treatment with spironolactone. However, an increase in eGFR was observed supporting a haemodynamic effect of spironolactone in the kidneys.

Effects of empagliflozin on cardio-renal interaction in heart failure with reduced ejection fraction: results from in-vivo experiments and the CINNAMON-study

Abstract Background Heart failure is often accompanied by renal dysfunction, which indicates a pathophysiological connection between the heart and kidneys. Empagliflozin, a SGLT2 inhibitor, showed beneficial effects on both cardiovascular and renal endpoints. Mechanistically, however, it is unclear whether the empagliflozin-dependent renal protection is mediated via the inhibition of renal SGLT2 or rather indirectly via improved cardiac function. Interestingly, in the EMPEROR trials, there was a significant interaction of empagliflozin-dependent kidney protection with systolic contractile dysfunction. We hypothesized that Empagliflozin treatment ameliorates heart failure in response to chronic pressure overload in mice leading to improved renal function. We correlated these findings with data from our prospective, single-armed trial. Methods Transverse aortic constriction (TAC) or sham surgery was performed in C57BL/6J (wildtype, WT) and SGLT2 deficient mice (SGLT2-/-). Animals received either Empagliflozin (10 mg/kg bodyweight) or vehicle by daily oral gavage. Cardiac function was evaluated by echocardiography and kidney function by transdermal FITC-Sinistrin measurement (GFR), urinary albumin/creatinine ratio (UACR) and Siriusred fibrosis staining. Results After 10 weeks, echocardiography confirmed TAC induced pressure-overload, leading to reduced left ventricular ejection fraction (LVEF) and diastolic dysfunction. Empagliflozin attenuated changes in LVEF (Fig. A) and improved diastolic dysfunction (data not shown). Interestingly, at 10 weeks, TAC reduced GFR, increased UACR and tended to increase renal fibrosis, which was attenuated by empagliflozin (Fig. B, C and D). To test if direct inhibition of SGLT2 in the heart and kidney is mechanistically involved, TAC surgery was repeated in SGLT2-deficient mice (SGLT2-/-). In fact, exposure to TAC resulted in comparable reduction of LVEF in SGLT2-/- mice and Empagliflozin prevented this deterioration similar to WT mice (Fig. E vs. A). Surprisingly, Empagliflozin also prevented GFR deterioration 10 weeks after TAC in mice lacking SGLT2 (SGLT2-/-) with comparable magnitude as in WT mice (Fig. F), suggesting that the reno-protective effect of Empagliflozin was independent from renal SGLT2 inhibition. The effect of empagliflozin on the heart and kidney was also investigated in patients with HF (prospective, single-arm CINNAMON-study, DRKS00031101). After 180 days of Empagliflozin treatment (10 mg), there was a significant improvement in LVEF, NT-proBNP levels and KCCQ-12 Scores (Fig. G-I) and the effects on UACR and GFR are subject of investigation. Conclusion This is the first study investigating the role of SGLT2 in Empagliflozin-dependent kidney protection of mice that develop heart failure after TAC. Importantly, empagliflozin treatment prevented deterioration of LVEF and GFR independent of the presence of SGLT2 in mice and improved cardiac markers and quality of life in patients.

Obesity and renal impairment in patients with heart failure and reduced ejection fraction: another obesity paradox?

Abstract Background Obesity is associated with poor cardiovascular outcomes in patients with HF and reduced ejection fraction (HFrEF). However, whether obesity is associated with worse kidney outcomes in HFrEF has not been evaluated. Purpose To estimate the association between obesity and change in estimated glomerular filtration rate (eGFR) over time in patients with HFrEF. Methods In this post hoc analysis of the PARADIGM-HF trial, body mass index (BMI) and eGFR was collected in 8,389 patients. Change in eGFR over time was assessed according to baseline BMI (normal weight: BMI &amp;lt;25.0, overweight: BMI 25-29.9, and obesity: BMI ≥30). Results The number of patients in each BMI category was: 2,421 (BMI &amp;lt;25.0), 3,249 (BMI 25-29.9), and 2,719 (BMI ≥30), respectively. Patients with obesity were younger but had worse health status (worse NYHA class and KCCQ scores) and had more comorbidities including diabetes mellitus and hypertension. At baseline, eGFR was lower in patients who were overweight (BMI 25-29.9) and obese (BMI ≥30), compared to those with normal weight. Urine albumin-creatinine ratio (UACR) and kidney injury molecule-1 (KIM-1) were also higher in patients with obesity. However, the rate of change in eGFR per year (eGFR "slope") in the overall cohort did not differ according to BMI: change in eGFR per year was -1.8 [-2.1, -1.6] mL/min/1.73m2 for the normal weight category, -1.6 [-1.8, -1.3] mL/min/1.73m2 for those who were overweight, and -1.5 [-1.8, -1.3] mL/min/1.73m2 for those with obesity; P=0.21) (Figure 1). Among those without diabetes at baseline, those who were obese had a significantly less steep eGFR slope compared to patients in the other BMI categories. In those with diabetes at baseline, the eGFR slope was steeper than in patients without diabetes but was similar across all three BMI categories (Figure 2). Conclusions Although baseline kidney function was more impaired in HFrEF patients with obesity, high BMI was not associated with a more rapid subsequent rate of decline in eGFR. Figure 1. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF Figure 2. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF with and without diabetes at baselineFigure 1Figure 2-A and 2-B

Exploratory mediation analysis of the effect of semaglutide on cardiovascular outcomes in people with overweight or obesity in the SELECT randomised trial

Abstract Background Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to reduce major adverse cardiovascular (CV) events (MACE) in people with diabetes. The SELECT trial investigated weekly subcutaneous semaglutide 2.4 mg versus placebo in people with pre-existing CV disease and body mass index ≥27kg/m², but without diabetes at randomisation. Over a mean duration of follow-up of 39.8 months, risk of MACE was lower in patients treated with semaglutide vs placebo (6.5% vs 8.0%, hazard ratio, 0.80; 95% CI, 0.72, 0.90; P&amp;lt;0.001). There were improvements in several CV risk factors; however, mechanisms underlying the MACE reduction are unclear. Purpose This prespecified analysis explored whether the effects on measured CV risk factors may mediate the 20% reduction in MACE in SELECT. Methods CV risk factors measured during the trial and included as potential mediators in the analysis were: body weight, waist circumference, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA1c), lipids, blood pressure, estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Mediation analyses were performed using the Vansteelandt repeated regression approach. First, the observed difference in MACE-free survival between semaglutide and placebo at 36 months was estimated as the total effect. The direct effect of semaglutide was then estimated as the difference in MACE-free survival, had the semaglutide arm experienced the values of the mediator observed in the placebo arm during follow-up. The % mediation was then calculated as 100 × (1 – [direct effect] / [total effect]). A reversed counterfactual approach estimating the direct effect as the difference between arms in MACE-free survival, had the placebo arm experienced the mediator values observed in the semaglutide arm, was also conducted. A large disparity between the % mediation from the two approaches can indicate potential treatment–mediator interaction or hidden confounding. Results Statistically significant (P&amp;lt;0.05) improvements in all potential mediators were observed with semaglutide. Table 1 shows the estimated mediation of each potential mediator when evaluated separately. Point estimates for the % mediation were largest for waist circumference (64.0%), hsCRP (42.1%), HbA1c (29.0%) and body weight (19.5%), but with wide 95% CIs. For waist circumference, the estimated mediation was markedly lower using the reversed counterfactual approach, suggesting potential hidden confounding or treatment–mediator interaction (Figure 1). In a multivariable analysis, the estimated joint mediation was 31.4% (−30.1%, 143.6%). Conclusions The results suggest that neither change in body weight nor other measured CV risk factors fully explain the effect of semaglutide on MACE in SELECT. Substantial unmeasured pleiotropic effects of semaglutide on MACE not mediated through these risk factors remain possible.

Advancing Community Care and Access to Follow-Up after Acute Kidney Injury Hospitalization: A Randomized Clinical Trial.

Key Points A risk-guided intervention improved adherence to processes of care for AKI survivors.Further supports are necessary to improve uptake of processes of care for AKI survivors in primary care. Background AKI is associated with development and progression of CKD. Gaps in recommended care for CKD are common after AKI. Methods In this randomized controlled trial conducted in Alberta, Canada, we allocated adults hospitalized with Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or greater AKI to a risk-guided, transition of care intervention versus usual practices at the time of hospital discharge. For people in the intervention group, we used a validated risk index to predict risk of severe CKD after AKI. People at low risk (&lt;1%) received patient education alone. People at medium risk received additional clinical guidance, provided to their primary care physician. People at high risk (&gt;10%) were referred to nephrology. The primary outcome was the proportion of patients who received treatment with an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB), statin, and nephrology specialist follow-up within 90 days of discharge. Results One hundred fifty-five patients were recruited; the mean (SD) age was 60 (15) years, 91 (60%) were male, and 96 (62%) had eGFR &lt;60 ml/min per 1.73 m2 or urine albumin-creatinine ratio &gt;30 mg/g at discharge. The proportion of participants who received ACE-I/ARB, statin treatment, and nephrologist follow-up was 28% in the intervention group versus 3% in the usual care group (absolute risk difference [RD], 25%; 95% confidence interval [CI], 15% to 36%). The use of ACE-I or ARB in participants with urine albumin-creatinine ratio &gt;300 mg/g or diabetes was greater in the high-risk group with the intervention versus usual care (RD, 37%; 95% CI, 6% to 67%), as was statin use among those with CKD (RD, 30%; 95% CI, 5% to 56%) and nephrologist follow-up for those with sustained eGFR &lt;30 ml/min per 1.73 m2 at discharge (RD, 78%; 95% CI, 56% to 100%). Hyperkalemia was more frequent in the intervention group (RD, 10%; 95% CI, 9% to 19%). Conclusions A risk-guided intervention for patients hospitalized with AKI increased recommended processes of care for CKD for high-risk patients after hospital discharge. Clinical Trial registry name and registration number: Improving Post Discharge Care after Acute Kidney Injury (AFTER AKI), NCT02915575.

Development and validation of a chronic kidney disease progression model using patient-level simulations

Chronic disease progression models are available for several highly prevalent conditions. For chronic kidney disease (CKD), the scope of existing progression models is limited to the risk of kidney failure and major cardiovascular (CV) events. The aim of this project was to develop a comprehensive CKD progression model (CKD-PM) that simulates the risk of CKD progression and a broad range of complications in patients with CKD. A series of literature reviews informed the selection of risk factors and identified existing risk equations/algorithms for kidney replacement therapy (KRT), CV events, other CKD-related complications, and mortality. Risk equations and transition probabilities were primarily sourced from publications produced by large US and international CKD registries. A patient-level, state-transition model was developed with health states defined by the Kidney Disease Improving Global Outcomes categories. Model validation was performed by comparing predicted outcomes with observed outcomes in the source cohorts used in model development (internal validation) and other cohorts (external validation). The CKD-PM demonstrated satisfactory modeling properties. Accurate prediction of all-cause and CV mortality was achieved without calibration, while prediction of CV events through CKD-specific equations required implementation of a calibration factor to balance time-dependent versus baseline risk. Predicted annual changes in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio were acceptable in comparison to external values. A flexible eGFR threshold for KRT equations enabled accurate prediction of these events. This CKD-PM demonstrated reliable modeling properties. Both internal and external validation revealed robust outcomes.

The Effect of Nerolidol on Renal Dysfunction following Bilateral Ureteral Obstruction.

Background/Objectives: Obstructive uropathy is a common cause of renal impairment. Recently, there has been a burgeoning interest in exploring natural products as potential alternative remedies for many conditions due to their low toxicity, affordability and wide availability. Methods: We investigated the effect of nerolidol in a rat model of bilateral ureteral obstruction (BUO) injury. Nerolidol, dissolved in a vehicle, was administered orally as a single daily dose of 200 mg/kg to Wistar rats. Sham group (n = 12) underwent sham surgery, whereas the BUO (n = 12) and BUO/NR groups (n = 12) underwent reversible 24-h BUO and received the vehicle or nerolidol, respectively. The treatment started 9 days prior to the BUO/sham surgery and continued for 3 days after reversal. Renal functions were assessed before starting the treatment, just prior to the intervention and 3 days after BUO reversal. Results: Neither nerolidol nor the vehicle affected the basal renal functions. Nerolidol resulted in a significant attenuation in the BUO-induced alterations in renal functional parameters such as serum creatinine and urea, creatinine clearance and urinary albumin-creatinine ratio. Nerolidol also attenuated the changes in several markers associated with renal injury, inflammation, apoptosis and oxidative stress and mitigated the histological alterations. Conclusions: The findings of this study demonstrated the potent reno-protective effects of nerolidol in mitigating the adverse renal effects of bilateral ureteral obstruction. This is attributed to its anti-inflammatory, anti-fibrotic, anti-apoptotic and anti-oxidant properties. These effects were reflected in the partial recovery of renal functions and histological features. These findings may have potential therapeutic implications.

12380 Point Of Care Microscale Magnetic Resonance (µNMR) Effectively Monitors Mitigation Of Oxidative Stress By GLP-1 Treatment In A Preclinical Model Of Diabetic Nephropathy

Abstract Disclosure: A.T. Alves: ; co-founder. ; LarmorBio. S.S. Thamarath: ; co-founder. ; LarmorBio. S. Fjordside: Employee; Self; Novo Nordisk. S. Sassower, MS.EE: ; Co-founder. ; LarmorBio. R. Rohr: ; co-founder,CEO. ; LarmorBio. A.P. Chambers: Employee; Self; Novo Nordisk. Oxidative stress is a major driver in the pathogenesis of diabetes, obesity, and related (cardio-renal) disorders. Early detection and prevention of an oxidative stress overload can improve and potentially modify the long-term harmful outcomes associated with chronic hyperglycaemia. A novel assay was developed, that uses µNMR technology to directly monitor oxidative stress from 5 µL of plasma at the point of collection in less than 10 minutes. This assay is highly sensitive to redox changes in the blood microenvironment, including increased ferric iron (Fe3+), protein oxidation and lipid peroxidation. Here, we show the oxidative stress profiling of three groups of ZSF1 rats in a twelve week (11th -23rd week of age) observational study. Vehicle lean, vehicle obese, and glucagon-like-peptide-1 (GLP-1) treated obese ZSF1 rats (n = 8/group) were studied with the assay along with conventional diabetic/metabolic markers, blood glucose (BG), HbA1c, Albumin Creatinine Ratio (ACR). The kidney (immuno)histology studies, alpha-smooth muscle actin (aSMA) and leucocyte common antigen (CD45) were performed at the termination phase of the ZSF1 rats (23rd week of age). The results demonstrated that the assay distinguished obese rats from lean rats with statistical significance (P ≤ 0.01) independent of other in-life diabetic/metabolic markers. Significant correlations with urinary Albumin Creatinine Ratio (ACR, ρ = 0.64, P ≤ 0.0001) were established throughout the study. A positive quantitative association is highlighted with classic histological end points of organ damage, kidney fibrogenesis (aSMA, ρ = 0.23), and inflammation (CD45, ρ = 0.45). Moreover, the assay detected significantly reduced oxidative stress levels (e.g., P ≤ 0.01) in the GLP-1 drug treatment group at five weeks of follow-up. In summary, the µNMR assay effectively monitored oxidative stress and captured disease-modifying therapeutics. Presentation: 6/1/2024

Early Identification and Management of Chronic Kidney Disease: A Narrative Review of the Crucial Role of Primary Care Practitioners.

Early-stage (stage1-3) chronic kidney disease (CKD) has an asymptomatic presentation such that most people with CKD are unaware of their disease status and remain undiagnosed. CKD is associated with multiple long-term conditions (MLTC), or multimorbidity, the most common of these being cardiovascular disease, hypertension, and type2 diabetes. Primary care practitioners (PCPs) are crucial in the early identification and management of patients with CKD. For individuals at high risk of CKD, measurements of estimated glomerular filtration rate, urine albumin-creatinine ratio, and blood pressure should be obtained regularly and recorded in a timely manner. The importance of lifestyle changes in the prevention and management of CKD should also be highlighted. A recent addition to the treatment of CKD in people with and without type2 diabetes has been the recommendation by clinical practice guidelines of a sodium-glucose co-transporter2 (SGLT2) inhibitor alongside a renin-angiotensin-aldosterone system inhibitor as foundational therapy. SGLT2 inhibitors prevent CKD progression and reduce fatal and non-fatal kidney and cardiovascular events, hospitalization for heart failure, and all-cause mortality, and they have a favorable safety and tolerability profile. However, uptake has been slow, particularly in people with CKD without type2 diabetes. A multifaceted approach is required to ensure that people with CKD receive optimal kidney protection. Measures to raise awareness of the importance of early identification and intervention include local/national campaigns via social media and practice-based education; clinical education programs; integration of clinical decision support tools into electronic health records; detection programs built around electronic health records; and good interdisciplinary communication. PCPs at the forefront of multidisciplinary care are best placed to implement the evidence-based clinical practice CKD guidelines for lifestyle modification and guideline-directed medical therapy.

Concentration of kidney markers and detection of exosomes in urine samples collected in cotton wool balls in preterm and term neonates

Collecting urine samples in neonates by catheterisation or suprapubic puncture causes trauma, whereas self-adhesive collection bags can damage fragile skin. An alternative method is the collection of samples from urine-soaked cotton wool balls placed in diapers. The aim of this study was to compare the concentration of albumin, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and uromodulin between clean-catch urine and samples collected in cotton balls in neonates and assess the efficiency of exosome extraction. Standard clean-catch urine samples (SSs) were assayed for albumin, creatinine, NGAL, and uromodulin using commercial ELISA kits. Concentrations were compared to the same urine samples extracted immediately from soaked cotton wool balls (sample 2, S2) or the urine extracted from cotton wool balls placed in diaper in a warm incubator for 2 h before extraction (sample 3, S3). Exosomes were extracted from all three samples of one patient for visualisation by electron microscopy. Twenty-six infants (17 males) of median gestational age at birth of 32+1 weeks had urine collected at a median age of 29 days at 37+6 weeks corrected age. Concentrations in S2 and S3 were within 10% of the concentration of SS in 46% and 35% of specimens for albumin, 69% and 58% for creatinine, 12% and 12% for NGAL, and 27% and 15% for uromodulin, respectively, without consistent positive or negative bias. Urine albumin/creatinine ratios (UACRs) were 4.3% less in S2 and 4.5% less in S3 than in SS. Exosomes were extracted and visualised from all three sample types. Neonatal urine samples extracted from cotton wool balls can be used to screen for relevant albuminuria ​but provide imprecise estimates of NGAL and uromodulin. The proof of exosome extraction from urine collection in cotton wool balls opens the potential to examine exosomal cargo.

Knowledge and competence of primary healthcare physicians in the management of diabetes-related chronic kidney disease

BACKGROUND: Diabetes mellitus (DM) is a primary cause of chronic kidney disease (CKD), a significant and growing global health issue. Primary healthcare physicians (PHPs) are crucial in detecting, managing, and preventing CKD, but many lack the necessary knowledge and skills to effectively diagnose and manage the disease. This study assessed the knowledge and competence of PHPs in managing diabetes-related CKD. MATERIALS AND METHODS: This cross-sectional study was conducted among all Primary Healthcare Physicians (PHPs) working at Primary Healthcare Center (PHC) in King Abdulaziz Medical City of the National Guard, Jeddah, Saudi Arabia. An online questionnaire was sent to all PHPs and data were collected from January 2024 to February 2024. Data analysis performed utilizing RStudio (version 4.3.1). Categorical variables were expressed as frequencies and percentages, whereas mean and standard deviations were computed for continuous variables. Kruskal–Wallis rank sum test was used to determine differences in confidence scores across various demographic and occupational characteristics. A multivariable linear regression analysis was performed to identify factors related to confidence. RESULTS: Of 141 PHPs, 122 filled online questionnaire yielding a response rate of 86.5%. responded. The majority (90.2%) were 18–45 years of age, 68.0% were qualified as family physicians, 38.0% belonged to the specialized poly clinic, and 54.9% had less than 5 years of experience. PHPs showed a varied levels of confidence and knowledge. While 76.2% were confident about the stages of kidney disease and 65.6% acknowledged the importance of the urine albumin-creatinine ratio (uACR) test, 58.1% were uncertain of interpreting uACR results and CKD diagnostic criteria. More than 60.0% were uncertain of the treatment steps postdiagnosis and prediction of CKD prognosis. Age, qualification, specialization in family medicine, and clinic affiliation were significantly related to confidence levels. CONCLUSION: The study underscores notable gaps in PHPs' knowledge and confidence concerning CKD screening, diagnosis, and management. Continuous education and targeted interventions are essential for the improvement of PHPs' competence and patient outcomes in the management of CKD.

Polycystic Ovary Syndrome Accompanied by Hyperandrogenemia or Metabolic Syndrome Triggers Glomerular Podocyte Injury.

Objective: To determine whether the urinary excretion of podocyte degradation products varies according to PCOS phenotype and metabolic syndrome (MetS). Methods: The concentrations of podocalyxin (PDX) and nephrin, chronic markers of podocyte damage, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute glomerular damage, were analyzed in the morning urine samples of 50 PCOS patients and 50 healthy controls matched by age and BMI. Albuminuria was assessed by calculating the urine albumin-creatinine ratio (uACR). Results: The PDX, nephrin and NGAL concentrations of PCOS participants were significantly higher than those of the control group. While PDX, nephrin and NGAL levels of classic phenotypes were similar, they were higher than ovulatory and non-hyperandrogenic phenotypes. Significant increases in urinary levels of each podocyte protein were detected in PCOS patients with MetS compared to patients without MetS. A positive significant correlation between podocyte proteins and BMI, systolic blood pressure, testosterone, glucose, HOMA-IR and uACR. After adjusting for age and BMI, podocyte proteins were an independent risk factor for microalbuminuria. The incidence of microalbuminuria in PCOS increased 6-fold compared to controls. The frequency of microalbuminuria was higher in classical phenotypes than in ovulatory phenotype. The frequency of microalbuminuria in PCOS patients with MetS was 6.5 times higher than in PCOS patients without MetS. Conclusions: In PCOS accompanied by hyperandrogenemia or metabolic syndrome, leakage of acute and chronic podocyte breakdown products into the urine becomes more pronounced.

Low estimated glomerular filtration rate and proteinuria among adult diabetic patients in a tertiary hospital in Eastern Uganda - a cross-sectional study

BackgroundChronic kidney disease (CKD) is one of the most common complications of diabetes mellitus (DM). Diabetes mellitus contributes to about 66% of CKD cases globally. CKD results in increased morbidity and mortality and advanced stages often require kidney replacement therapy that is unaffordable for the majority of the patients. Developing countries have scanty data regarding CKD burden in diabetic patients.ObjectivesThis study aimed at determining the prevalence of low estimated glomerular filtration rate (eGFR) and proteinuria and associated clinical and socio-demographic factors among adult diabetic patients attending the diabetic clinic of Mbale Regional Referral Hospital (MRRH).MethodsA cross-sectional study was conducted at the adult diabetic clinic of MRRH in Eastern Uganda. A total of 374 adult diabetic patients were enrolled. A urine sample for urine albumin creatinine ratio (UACR) determination and a venous blood sample for measurement of serum creatinine were obtained from each participant. The eGFR was determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and CKD was staged according to the Kidney Disease Improving Global Outcomes (KDIGO) classification.ResultsA total of 318 (85%) participants had an eGFR of ≤ 60 mL/min/1.73m2, UACR of ≥ 30g/g, or both. Only 6.1% were aware. Age, duration of DM, hypertension, and dyslipidemia were associated with low eGFR and proteinuria.ConclusionThere is a high prevalence of low eGFR and proteinuria among DM patients, 85% of the participants had these markers of CKD and the majority of them were undiagnosed. Over half of the DM patients had an eGFR consistent with advanced CKD. Strengthening routine screening for CKD biomarkers and equipping DM clinics with more diagnostic resources is recommended.

Patients with STEMI after Revascularization: Is There a Relationship Between Coronary Artery Lesion and Renal Function?

The aim. To establish the relationship between coronary bed lesions and glomerular filtration rate (GFR) calculated on the basis of creatinine, cystatin C and urine albumin-creatinine ratio in patients with ST-elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention. Materials and methods. We examined 286 patients with STEMI, aged 39 to 87 years (mean age 62.8 ± 9.8, median age 64, interquartile range 56 to 71 years), 202 (70.6%) were men and 84 (29.4%) were women. All the patients underwent general clinical tests, coronary angiography with subsequent percutaneous coronary intervention, and echocardiography. Results. The most frequent infarct-related coronary artery (CA) was the anterior interventricular branch of the left coronary artery in the proximal and middle segments, and the right coronary artery in the proximal segment. In general, there was no significant difference in the number of affected CAs among the examined patients. The division of patients into groups according to the level of GFR, determined both on the basis of creatinine and cystatin C, did not reveal significant differences in the distribution of infarct-related CAs. At the same time, the number of patients with multivessel lesions significantly increases with decreased GFR. Depending on the level of the urinary albumin-to-creatinine ratio, a significant increase in the number of patients with two- and multivessel lesions of the CAs was noted. Conclusions. Close correlations between multivessel lesions of CAs and gender, age, urinary albumin-to-creatinine ratio, GFR, left and right atrial size, duration of history of hypertension and diabetes mellitus, presence of II-III degree atrioventricular block and mortality were established.

The hidden impact: the rate of nicotine metabolism and kidney health.

The effects of nicotine metabolism on the kidneys of healthy individuals have not been determined. The nicotine metabolite ratio (NMR) indicates the rate of nicotine metabolism and is linked to smoking behaviors and responses to tobacco treatments. We conducted this study in order to investigated the relationship between nicotine metabolite ratio (NMR) and kidney function. An analysis of cross-sectional data of adults was conducted using a population survey dataset (National Health and Nutrition Examination Survey Data 2013/2018 of the United States). A weighted multivariate regression analysis was conducted to estimate the correlation between NMR and kidney function. Furthermore, we apply fitting smooth curves to make the relationship between NMR and estimated glomerular filtration rate (eGFR) more visualized. The research included a total of 16153 participants. Weighted multivariate regression analyses adjusted for possible variables showed a negative relationship between NMR and estimated glomerular filtration rate (eGFR).The β (95%CI) of the regression equation between NMR and eGFR was -2.24 (-2.92, -1.55), the trend testing showed consistent results. NMR is positively correlated with urinary albumin creatinine ratio (uACR), but it is not statistically significant. A stratified analysis found a negative correlation between NMR and eGFR in all age, gender and diabetes subgroups, the results were not statistically significant among Mexican Americans and other races. Notably, each unit rise in NMR corresponded to a 4.54 ml/min·1.73m² lower eGFR in diabetic participants and a 6.04 ml/min·1.73m² lower eGFR in those aged 60 and above. Our study shows that nicotine metabolite ratio is negatively associated with kidney function among most adults. It will be necessary to conduct more well-designed prospective clinical trials in order to determine the exact causal interactions between NMR and kidney function. Specific mechanisms also need to be further explored in basic experiments.

The correlation between patients with type 2 diabetes mellitus and chronic microvascular complications during the glucose peak time

IntroductionTo assess the Type 2 Diabetes Mellitus (T2DM) patients in association with Chronic Microvascular Complications at Glucose Peak Time and the association among chronic microvascular complications in T2DM patients and the glucose peak period in the typical steamed bread meal test. MethodsOverall 1095 T2DM patients were classified as three groups: (1) Group G1: glucose peak time ≤ 1 h (n = 84), Group G2: 1 h < glucose peak time ≤ 2 h (n = 648) and Group G3: glucose peak time > 2 h (n = 363). The clinical characteristics, insulin characteristics and glucose peak time and chronic microvascular complications markers of patients in each group was analyzed and compared. Statistical analyses were performed using SPSS 23.0, employing chi-square tests, Kruskal-Wallis tests, one-way ANOVA, and binary logistic regression analysis, with significance set at P < 0.05. ResultsAge, length of disease, glycated hemoglobin (HbA1c), urine albumin-creatinine ratio (UACR), and the number of patients with diabetic retinopathy (DR) increased (all P < 0.05) in those with postponed glucose peak time, while insulinogenic indexes, the AUC for C-p (AUCC-p), fasting, and 120-min C-peptide (C-p) decreased (all P < 0.05). Only age was connected to patients with diabetic kidney disease (DKD) independently in binary logistic regression analysis, although delayed glucose peak time was related to the presence of patients with DR. (all P < 0.05). ConclusionDelayed glucose peak time contributed to DR. Attention should be paid to condition of chronic microvascular complications in T2DM patients with a postponed peak glucose timing.

Association of different obesity indexes with diabetic kidney disease in patients with type 2 diabetes mellitus: a cross-sectional study

The objective of this study is to investigate the association between diabetic kidney disease (DKD) and various adiposity indexes, including the visceral adiposity index (VAI), lipid accumulation product index (LAPI), visceral fat area (VFA), and subcutaneous fat area (SFA) in type 2 diabetes mellitus (T2DM) patients. 1176 T2DM patients was stratified into normoalbuminuria (NO), microalbuminuria (MI), and macroalbuminuria (MA) groups based on their urinary albumin-creatinine ratio (UACR) levels. To analyse the correlation between DKD and VAI, LAPI, VFA, and SFA. Multiple linear, restricted cubic spline (RCS), subgroup analyses, and multinomial logistic regression were employed. After adjusting for confounding variables, UACR levels were positively associated with VAI, LAPI, and VFA. RCS curves demonstrated a J-shaped dose-response relationship between VAI and LAPI levels with UACR levels, while a linear correlation was observed between UACR levels and VFA. Using the NO and MI as reference groups, the MA group was analysed as the observational group. DKD severity was positively associated with VAI, LAPI and VFA. When evaluating DKD prognostic risk, with the low-risk and medium-risk groups serving as reference categories, a significant positive correlation was identified with prognostic risk and VAI, LAPI, and VFA in the high-risk or very high-risk groups. In patients with T2DM, DKD severity and prognostic risk were positively correlated with VAI, LAPI, and VFA levels.

The DPP-4 inhibitor sitagliptin improves glycaemic control and early-stage diabetic nephropathy in adolescents with type 1 diabetes using the MiniMed 780G advanced hybrid closed-loop system: a randomised controlled trial.

Dipeptidyl peptidase-4 (DPP-4) inhibition has beneficial effects on various metabolic indicators in diabetes. Stromal cell-derived factor-1 (SDF-1) is expressed in diverse organs including the kidneys and is cleaved and inactivated by DPP-4 enzyme. The aim of this study was to conduct a randomised controlled trial to assess the effect of sitagliptin on diabetic nephropathy when used as an add-on therapy to the advanced hybrid closed-loop (AHCL) system in adolescents with type 1 diabetes and nephropathy. This open-label, parallel-group, randomised controlled trial took place at the Pediatric Diabetes Clinic, Ain Shams University, Egypt. Forty-six adolescents aged 14.13 ± 2.43 years on the MiniMed 780G system for at least 6 months before study, with HbA1c ≤69 mmol/mol (8.5%) and diabetic nephropathy in the form of microalbuminuria, were randomly assigned to two groups (n=23 for each) based on a computer-generated randomisation sequence. The intervention group received oral sitagliptin 50 mg for 3 months. The other group used AHCL only and served as a control group. The primary outcome measure was the change in urinary albumin/creatinine ratio (UACR) after 3 months of administration of sitagliptin. The key secondary outcome measure was the change from baseline in SDF-1 levels after treatment. Data for all participants were analysed. No significant difference was found between the groups as regards baseline clinical and laboratory characteristics as well as AHCL system settings (p>0.05). Serum SDF-1 levels were higher in all individuals with type 1 diabetes vs healthy control individuals (p<0.001). After 3 months, sitagliptin resulted in a significant decrease of SDF-1 levels from 3.58 ± 0.73 to 1.99 ± 0.76 ng/ml (p<0.001), together with improvement of UACR from 7.27 ± 2.41 to 1.32 ± 0.31 mg/mmol (p<0.001). In addition, sitagliptin reduced postprandial glucose, sensor glucose, coefficient of variation and total daily dose of insulin, while time in range 3.9-10.0 mmol/l (70-180 mg/dl) and insulin-to-carbohydrate ratio were significantly increased. Sitagliptin was safe and well-tolerated without severe hypoglycaemia or diabetic ketoacidosis. Sitagliptin as an add-on therapy to AHCL had a reno-protective effect for individuals with type 1 diabetes and diabetic nephropathy, in addition to the improvement of time in range while reducing glycaemic variability and without compromising safety. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. ClinicalTrials.gov NCT06115460.

Coronary Artery Disease among Type-II Diabetic Patient in Bangladesh

This study aimed to evaluate the relationship between microalbuminuria and the angiographic severity of CAD patients with type 2 diabetes by SYNTAX I, SYNTAX II, and Gensini scores. Diabetes mellitus is one of the strongest risk factors for coronary artery disease, so it is imperative to identify CAD in diabetic patients as soon as feasible. In this study, 82 patients with type II diabetes who had a suspected case of coronary artery disease (CAD) had elective coronary angiography. The urine albumin-creatinine ratio (UACR) was measured for each patient, and the severity of each patient's CAD was assessed using the Gensini, SYNTAX, and SYNTAX II scores. In the studied population, there were 26 (31.7%) females and 56 (68.3%) males. On average, they were 56.29 + 9.18 years old. Patients were categorized into two groups based on their UACR level: group 1 consisted of 41 patients whose UACR was less than 30 mg/g, and group 2 consisted of 41 patients whose UACR was greater than or equal to 30 mg/g. The study found that patients in group 2 had significantly higher SYNTAX scores (P=0.001) and significantly higher Gensini scores (P=0.001) than patients in group 1. Age and the length of UACR and DM showed a positive correlation (p=0.003), as did hypertension (HTN) and the length of UACR and DM (p=0.049). Microalbuminuria can be used to predict the severity and presence of CAD in type II diabetes. Keywords: Gensini score, SYNTAX score, microalbuminuria, diabetes, and coronary artery disease.

Association between the lipid accumulation product and chronic kidney disease among adults in the United States

The objective of this research was to explore the potential association between lipid accumulation product (LAP) and chronic kidney disease (CKD) among adult population of United States (US). Using cross-sectional data from the 2013 to 2018 National Health and Nutrition Examination Survey (NHANES), we explored the association of LAP with CKD, low estimated glomerular filtration rate (eGFR), and albuminuria. This analysis encompassed multivariate logistic regression analyses, smoothed curve fitting, subgroup analyses, and interaction tests. We found a significant positive association between higher ln-transformed LAP (LAP was transformed using a natural logarithm) and the prevalence of CKD, low-eGFR and albuminuria. Notably, this association of ln-transformed LAP with CKD and albuminuria was significantly influenced by diabetes status and sex (P for interaction < 0.05), while no significant interaction was observed regarding the association with low-eGFR (P for interaction > 0.05). Additionally, in model 3 (adjusted for all included covariates except eGFR and urinary albumin-creatinine ratio (UACR)), a nonlinear relationship was identified between ln-transformed LAP and the presence of both CKD and albuminuria, with inflection points of 4.57 and 4.49, respectively. This indicates that this correlation is more pronounced on the right of the inflection point. In conclusion, the findings indicate a significant association between LAP and the prevalence of CKD in US adults.