Can remote testing for chronic kidney disease improve outcomes without widening existing health inequalities? A collaborative quality improvement project in primary care.

BACKGROUND: In the UK, chronic kidney disease (CKD) is a prevalent, silent and strong predictor of cardiovascular disease. Identification of CKD is poor in primary care, particularly in minority ethnic and socio-economically deprived groups. AIM: To investigate feasibility of remote ACR testing to improve the detection and management of CKD in underserved groups. METHOD: 13 591 tests were sent out across South East London. Individuals with diabetes and no ACR in the past year were offered a remote ACR test to complete at home with a smartphone using a validated app (Healthy.io). We extracted data on demographics, medical comorbidities and medication. Analyses (Stata) describe who completed the test. RESULTS: Twenty-seven practices agreed to participate. Analyses of 6082 tests sent show the test completion rate was 46.8%. Adjusted odds ratios demonstrated that people were less likely to complete testing if over 70 years (OR 0.71, 95% CI 0.57 to 0.89) and over 80 (OR 0.43, CI 95% 0.33 to 0.56) compared to <40 years old; people from CORE20 groups (most deprived quintile) were also less likely to complete testing (OR 0.68, 95% CI 0.61 to 0.76) and those with missing data and those with no recorded healthcare interactions within the last 5 years were also less likely to complete testing. DISCUSSION: Remote ACR testing presents an opportunity to diagnose early CKD but there is still inequity in who completes testing. Engagement with stakeholders is needed to explore innovative ways to implement remote ACR testing to achieve equitable CKD screening.

Causal association between urine albumin-to-creatinine ratio and risk of colorectal cancer: A two-sample Mendelian randomization study.

Previous observational studies have investigated the association between urinary albumin excretion and the risk of colorectal cancer (CRC), but the results have been inconsistent. This study aimed to explore the causal association between urine albumin-to-creatinine ratio (ACR) and CRC risk through a two-sample Mendelian randomization (MR) analysis. The genome-wide association study (GWAS) data of ACR (n = 382,500) and CRC (CRC: 6,509 cases and 287,137 controls) were obtained from the IEU OpenGWAS project website and the FinnGen database, respectively. The TwoSampleMR and MR-PRESSO R packages were used to search for and analyze genetic variations that served as instrumental variables for ACR. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the inverse-variance weighted method, MR-Egger, and weighted median. Genetically predicted ACR was not associated with CRC risk (all P > 0.05). Further analysis based on the site of onset (colon or rectum) also did not show a significant association (all P > 0.05). MR-PRESSO, MR-Egger regression and leave-one-out sensitivity analysis all indicated that the current results were robust and reliable. These findings suggest that ACR does not affect CRC risk and may not be used as a marker of CRC risk in clinical practice. However, relevant studies especially in ethnically diverse populations are still needed to confirm the current findings.

[Evaluation of an algorithm based on quantitative assays of glomerular parameters (albuminuria and urinary IgG) for proteinuria typing]. / Évaluation d'un algorithme basé sur des dosages quantitatifs de paramètres glomérulaires (albuminurie et IgG urinaires) afin de typer une protéinurie.

The first orientation test for proteinuria typing is electrophoresis. However, this technique has several drawbacks, such as delayed turnaround time and subjective readings. Some laboratories therefore use quantitative assays of glomerular markers combined with tubular markers. However, the cost of reagents and the instability of certain markers are significant drawbacks for some peripheral laboratories. The aim of this study is to evaluate the implementation of an algorithm based on parameters that can be used by all laboratories for proteinuria typing within a timeframe compatible with the urgency of the situation. Albuminuria and urinary IgG were determined on 161 urines. ROC curves were produced, using urine electrophoresis read by an expert center as the reference method. The decision thresholds used are: glomerular proteinuria is defined by a Albumin+IgGproteinsratio greater than 75.4% (100% specificity), and tubular or overload proteinuria is defined by by a Albuminproteinsratio less than 37.3% (100% sensitivity). Agreement between the results of the algorithm selected and the reference method used in our study was 88 %, with a kappa value of 0.807 (95% CI [0.729 to 0.885]). The algorithm's performance suggests that it can find its place in the diagnostic strategy for clinically significant proteinuria, despite its limited indications. It is up to each biologist to assess the value of this algorithm in relation to the recruitment, habits and needs of clinicians.

Determinants of early chronic kidney disease in patients with recently diagnosed type 2 diabetes mellitus: a retrospective study from the Taiwan Diabetes Registry.

BACKGROUND: We tried to identify the risk factor associate with early chronic kidney disease (CKD) in recently diagnosed type 2 diabetes mellitus patients by utilizing real-world data from Taiwan Diabetes Registry. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus recently diagnosed within 1 year. We divided the study participants into control group and early CKD group. Early CKD was defined as either CKD stage G1 with albuminuria, CKD stage G2 with albuminuria, or CKD stage G3a regardless of albuminuria (Urine-albumin to creatinine ratio (UACR) ≥ 3 mg/mmol). Control group was defined as CKD G1 or CKD G2 without albuminuria. Logistic regression analyses were used to compare differences in clinical characteristics between the subgroups. Linear regression models were employed to examine the factors predicting estimated glomerular filtration rate (eGFR) and UACR. RESULTS: Total 2217 patients with recently diagnosed type 2 diabetes mellitus were included. 1545 patients were assigned to control group and 618 patients were assigned to the early CKD group. Age (odds ratio (OR) 1.215, 95% confidence interval [CI] 1.122-1.316), systolic blood pressure (OR 1.203, 95% CI 1.117-1.296), glycated hemoglobin (OR 1.074, 95% CI 1.023-1.129) and triglyceride (OR 2.18, 95% CI 1.485-3.199) were found to be significant risk factors. Further, presence of bidirectional association between UACR and eGFR was found. CONCLUSIONS: We reported factors associated with early CKD in recently diagnosed type 2 diabetes mellitus patients. Variables that associated with eGFR and UACR were identified respectively, included a mutual influence between UACR and eGFR.

Using nephropathy as an outcome to determine the HbA1c diagnostic threshold for type 2 diabetes.

OBJECTIVE: The hemoglobin A1c (HbA1c) diagnostic threshold for type 2 diabetes (T2D) of 6.5 % (48 mmol/mol) was based on the prevalence of retinopathy found in populations not known to have T2D. It is unclear if nephropathy has a similar HbA1c threshold, partly because it is a rarer complication of early diabetes. This cohort study investigated a very high diabetes prevalence population to determine if a better diagnostic HbA1c value can be established for predicting nephropathy rather than retinopathy in subjects without T2D. METHODS: The urine albumin:creatinine ratios (UACRs) of 2920 healthy individuals from the Qatar Biobank who had an HbA1c ≥ 5.6 %. were studied. Nephropathy was defined as a UACR≥30 mg/g and its prediction by HbA1c was assessed using cut-points ranging from 5.7 to 7.0 % to dichotomize high from low HbA1c. RESULTS: Although there was a significant trend for an increased prevalence of abnormal UACR as the HbA1c threshold increased (p < 0.01), significance was due mostly to subjects with HbA1c ≥ 7.0 % (53 mmol/mol). The odds ratios for abnormal UACR were similar over the 5.7-6.9 % HbA1c threshold range, with a narrow odds ratio range of 1.2-1.6. Utilizing area-under-receiver-operating characteristic curves, no HbA1c threshold <7.0 % was identified as the best predictor of nephropathy. CONCLUSION: Even in a population with a high prevalence of known and unknown diabetes, no HbA1c threshold <7.0 % could be found predicting an increased prevalence of nephropathy. This means there is not a requirement to change the existing retinopathy-based HbA1c threshold of 6.5 % to also accommodate diabetes nephropathy risk.

Frail hypertensive older adults with prediabetes and chronic kidney disease: insights on organ damage and cognitive performance - preliminary results from the CARYATID study.

BACKGROUND: Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR). METHODS: We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min. RESULTS: 237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable. CONCLUSIONS: Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD.

A candidate panel of eight urinary proteins shows potential of early diagnosis and risk assessment for diabetic kidney disease in type 1 diabetes.

Diabetic kidney disease (DKD) poses a significant health challenge for individuals with diabetes. At its initial stages, DKD often presents asymptomatically, and the standard for non-invasive diagnosis, the albumin-creatinine ratio (ACR), employs discrete categorizations (normal, microalbuminuria, macroalbuminuria) with limitations in sensitivity and specificity across diverse population cohorts. Single biomarker reliance further restricts the predictive value in clinical settings. Given the escalating prevalence of diabetes, our study uses proteomic technologies to identify novel urinary proteins as supplementary DKD biomarkers. A total of 158 T1D subjects provided urine samples, with 28 (15 DKD; 13 non-DKD) used in the discovery stage and 131 (45 DKD; 40 pDKD; 46 non-DKD) used in the confirmation. We identified eight proteins (A1BG, AMBP, AZGP1, BTD, RBP4, ORM2, GM2A, and PGCP), all of which demonstrated excellent area-under-the-curve (AUC) values (0.959 to 0.995) in distinguishing DKD from non-DKD. Furthermore, this multi-marker panel successfully segregated the most ambiguous group (microalbuminuria) into three distinct clusters, with 80% of subjects aligning either as DKD or non-DKD. The remaining 20% exhibited continued uncertainty. Overall, the use of these candidate urinary proteins allowed for the better classification of DKD and offered potential for significant improvements in the early identification of DKD in T1D populations.

[InspeCKD - Analysis of the use of diagnostics in patients at high risk for chronic kidney disease in German general practitioner (GP) practices]. / InspeCKD - Analyse zur Nutzung von Labordiagnostik im Kontext der chronischen Nierenerkrankung : Daten von Risikopatientinnen und -patienten in deutschen Hausarztpraxen.

BACKGROUND: Despite the high prevalence of chronic kidney disease (CKD) in Germany, only a small proportion of patients are currently diagnosed with CKD. Patients with hypertension, diabetes mellitus, and/or cardiovascular disease have a significantly increased risk of developing CKD and rapid disease progression and should therefore be screened and monitored in accordance with the guidelines. OBJECTIVES: The aim of this retrospective, cross-sectional study was to gain insights into appropriate diagnosis of patients at risk for CKD in German general practitioner practices. METHOD: For the analysis of the use of CKD-relevant diagnostics, electronic patient records from German general practitioner practices were analyzed. Adults with hypertension and/or diabetes mellitus and/or cardiovascular disease with a documented observation period of at least one year were included in the study. RESULTS: Data from a total of 448,837 patients from 1244 general practitioner practices were analyzed. 75.8% of patients had hypertension, 35.1% had cardiovascular disease, and 32.4% had diabetes mellitus. During a mean observation period of 1.7 years, serum creatinine was assessed at least once in 45.5% of patients. A urine dipstick test for albuminuria was performed in 7.9% of patients and in 0.4% of patients, urine albumin-to-creatine ratio (UACR) was measured. Laboratory diagnostics were initiated a little more frequently in high-risk patients compared to the overall cohort. CONCLUSIONS: The study highlights that despite known risk factors, guideline compliant CKD screening is rarely performed in German general practitioner practices, which implicates the need to increase the awareness of early diagnosis of CKD in patients at risk.

Study of Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 in Patients with Type 2 Diabetes Mellitus Nephropathy.

BACKGROUND: There is a need for accurate and rapid biomarkers for the early diagnosis of diabetic nephropathy (DN). We aimed to study the accuracy of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1), and blood NGAL (bNGAL) in type 2 diabetics as biomarkers for diagnosis of DN. METHODS: The study was a retrospective case-control study that included 30 control subjects, 40 diabetics with normo-albuminuria < 30 mg/g and eGFR > 60 mL/minute/1.73 m2, and 30 diabetics with albuminuria > 30mg/g and eGFR < 60mL/minute/1.73 m2. Blood and urine samples were obtained to determine levels of bNGAL, uNAGAL, and uKIM1. RESULTS: There was a significant increase in bNGAL, uNGAL, uKIM 1, uNGAL/creatinine and uKIM 1/creatinine among diabetics with albuminuria compared to diabetics with normoalbuminuria and normal control (p < 0.001 for all markers). For diagnosis of early DN, both bNGAL and uKIM 1 had sensitivity and specificity of 100% for each at cutoff values of 322.5 pg/mL and 74.25 ng/mL, respectively. uNGAL had a sensitivity of 97.5% and a spec-ificity of 100% at a cutoff point of 565 ng/mL. uKIM1/creatinine at a cutoff of 51.2 had a sensitivity of 100% and specificity of 100%. CONCLUSIONS: The present study highlights the accuracy of urinary KIM1 and NGAL and blood NGAL as biomarkers for the diagnosis of nephropathy in the early stage of diabetic nephropathy. There were positive correlations with kidney function tests creatinine, blood urea nitrogen, and the presence of albuminuria.

Urine Albumin-Creatinine Ratio Variability in People With Type 2 Diabetes: Clinical and Research Implications.

RATIONALE & OBJECTIVE: Evidence has demonstrated that albuminuria is a key diagnostic and prognostic marker of diabetic chronic kidney disease, but the impact of its day-to-day variability has not been adequately considered. This study quantified within-individual variability of albuminuria in people with type 2 diabetes to inform clinical albuminuria monitoring. STUDY DESIGN: Descriptive cross-sectional analysis. SETTING & PARTICIPANTS: People with type 2 diabetes (n=826, 67.1 [IQR, 60.3-72.4] years, 64.9% male) participating in the Progression of Diabetic Complications (PREDICT) cohort study. EXPOSURE: Four spot urine collections for measurement of urinary albumin-creatinine ratio (UACR) within 4 weeks. OUTCOME: Variability of UACR. ANALYTICAL APPROACH: We characterized within-individual variability (coefficient of variation [CV], 95% limits of random variation, intraclass correlation coefficient), developed a calculator displaying probabilities that any observed difference between a pair of UACR values truly exceeded a 30% difference, and estimated the ranges of diagnostic uncertainty to inform a need for additional UACR collections to exclude or confirm albuminuria. Multiple linear regression examined factors influencing UACR variability. RESULTS: We observed high within-individual variability (CV 48.8%; 95% limits of random variation showed a repeated UACR to be as high/low as 3.78/0.26 times the first). If a single-collection UACR increased from 2 to 5mg/mmol, the probability that UACR actually increased by at least 30% was only 50%, rising to 97% when 2 collections were obtained at each time point. The ranges of diagnostic uncertainty were 2.0-4.0mg/mmol after an initial UACR test, narrowing to 2.4-3.2 and 2.7-2.9mg/mmol for the mean of 2 and 3 collections, respectively. Some factors correlated with higher (female sex; moderately increased albuminuria) or lower (reduced estimated glomerular filtration rate and sodium-glucose cotransporter 2 inhibitor/angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment) within-individual UACR variability. LIMITATIONS: Reliance on the mean of 4 UACR collections as the reference standard for albuminuria. CONCLUSIONS: UACR demonstrates a high degree of within-individual variability among individuals with type 2 diabetes. Multiple urine collections for UACR may improve capacity to monitor changes over time in clinical and research settings but may not be necessary for the diagnosis of albuminuria. PLAIN-LANGUAGE SUMMARY: Albuminuria (albumin in urine) is a diagnostic and prognostic marker of diabetic chronic kidney disease. However, albuminuria can vary within an individual from day to day. We compared 4 random spot urinary albumin-creatinine ratio (UACR) samples from 826 participants. We found that a second UACR collection may be as small as a fourth or as large as almost 4 times the first sample's UACR level. This high degree of variability presents a challenge to our ability to interpret changes in albuminuria. Multiple collections have been suggested as a solution. We have constructed tools that may aid clinicians in deciding how many urine collections are required to monitor and diagnose albuminuria. Multiple urine collections may be required for individual monitoring but not necessarily for diagnosis.

Paper spray mass spectrometry combined with machine learning as a rapid diagnostic for chronic kidney disease.

A new analytical method for chronic kidney disease (CKD) detection utilizing paper spray mass spectrometry (PS-MS) combined with machine learning is presented. The analytical protocol is rapid and simple, based on metabolic profile alterations in urine. Anonymized raw urine samples were deposited (10 µL each) onto pointed PS-MS sample strips. Without waiting for the sample to dry, 75 µL of acetonitrile and high voltage were applied to the strips, using high resolution mass spectrometry measurement (15 s per sample) with polarity switching to detect a wide range of metabolites. Random forest machine learning was used to classify the resulting data. The diagnostic performance for the potential diagnosis of CKD was evaluated for accuracy, sensitivity, and specificity, achieving results >96% for the training data and >91% for validation and test data sets. Metabolites selected by the classification model as up- or down-regulated in healthy or CKD samples were tentatively identified and in agreement with previously reported literature. The potential utilization of this approach to discriminate albuminuria categories (normo, micro, and macroalbuminuria) was also demonstrated. This study indicates that PS-MS combined with machine learning has the potential to be used as a rapid and simple diagnostic tool for CKD.

Soluble tumor necrosis factor receptor type 1 is an alternative marker of urinary albumin-creatinine ratio and estimated glomerular filtration rate for predicting the decline of renal function in subjects with type 2 diabetes mellitus.

BACKGROUND: Urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rates (eGFR) help predict worsening diabetic kidney disease (DKD) but have their limitations. Soluble tumor necrosis factor receptor type 1 (sTNFR1) is a biomarker of DKD. The predictive abilities of sTNFR1 and UACR plus eGFR have not been compared. METHODS: This prospective cohort study included patients with type 2 diabetes (T2D) to identify the risk factors of worsening DKD. Renal events were defined as > 30 % loss in eGFR based on consecutive tests after 6 months. The associations of sTNFR1, UACR, and eGFR levels and the risks of renal events were tested using a Cox regression model and the area under the curve (AUC) was compared between sTNFR1 levels and UACR plus eGFR using receiver-operating characteristic (ROC) analysis. The accuracy of stratification was evaluated using Kaplan-Meier analysis. RESULTS: Levels of sTNFR1 and UACR were associated with risks of > 30 % decline in eGFR after adjusting for relevant factors. The association between sTNFR1 levels and renal outcomes was independent of UACR and eGFR at baseline. The AUC of sTNFR1 level was comparable with that of combined UACR and eGFR (0.73 vs. 0.71, respectively, p = 0.72) and the results persisted for quartile groups of sTNFR1 and risk categories of Kidney Disease: Improving Global Outcomes (KDIGO) (0.70 vs. 0.71, respectively, p = 0.84). Both stratifications by sTNFR1 levels and KDIGO were accurate. CONCLUSION: sTNFR1 could be an alternative marker for identifying patients with diabetes at risk of declining renal function.

A quantitative assessment of renal function utilizing albuminuria in pediatric heart transplant recipients.

INTRODUCTION: Kidney disease is common after pediatric heart transplantation. Serum creatinine-based glomerular filtration rate is the most frequently reported measure of kidney function. Albuminuria is an additional marker of kidney dysfunction and is not well described in this population. In this study, we evaluate the prevalence and degree of albuminuria and describe clinical factors associated with albuminuria in a cohort of pediatric heart transplant recipients. METHODS: This was a cross-sectional study of pediatric heart transplant recipients. Albuminuria was assessed using spot urine albumin-to-creatinine ratio collected at the most recent annual screening cardiac catheterization through August 2019. RESULTS: In 115 patients at a median duration of 10.2 years post-transplant, 39% had albuminuria. Stage 3 or greater chronic kidney disease was present in 6%. The immunosuppressive regimen at the time of measurement contained a calcineurin inhibitor (CNI) in 88% and a proliferation signal inhibitor (PSI) in 62%. In multivariable modeling, lower eGFR, PSI use, and younger age at transplant were associated with higher levels of albuminuria, whereas CNI use was associated with lower levels of albuminuria. CONCLUSION: Albuminuria is a prevalent finding in medium-term follow up of pediatric heart transplant recipients, reflecting kidney injury, and is associated with other markers of kidney dysfunction, such as low eGFR. Younger age at transplant, lower eGFR, and PSI use were among the associations with albuminuria.

Increased serum methylmalonic acid levels were associated with the presence of cognitive dysfunction in older chronic kidney disease patients with albuminuria.

BACKGROUND: This study aimed to evaluate the correlation between serum methylmalonic acid (MMA) levels and cognition function in patients with chronic kidney disease (CKD). METHODS: In this cross-sectional study, we included 537 CKD individuals aged ≥ 60-year-old with albuminuria from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Four cognitive tests including the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Delayed Recall and Word Learning tests, and the Animal Fluency test (AF) were performed. Associations between MMA and cognition scores were assessed with linear regression models. RESULTS: MMA level was negatively associated with residual renal function and nutrition status. After multivariate adjustment, elevated serum MMA levels were independently correlated with decline of cognition in CKD patients with albuminuria. CONCLUSION: Our study showed that higher serum MMA levels were independently associated with the presence of cognition dysfunction in CKD patients. The exact pathogenesis of MMA and cognition needs further research.

Fatty liver index is an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes: an 11-year observational study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), identified by the Fatty Liver Index (FLI), is associated with increased mortality and cardiovascular (CV) outcomes. Whether this also applies to type 1 diabetes (T1D) has not been yet reported. METHODS: We prospectively observed 774 subjects with type 1 diabetes (males 52%, 30.3 ± 11.1 years old, diabetes duration (DD) 18.5 ± 11.6 years, HbA1c 7.8 ± 1.2%) to assess the associations between FLI (based on BMI, waist circumference, gamma-glutamyl transferase and triglycerides) and all-cause death and first CV events. RESULTS: Over a median 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 individuals with retrievable incidence data. At baseline, FLI was < 30 in 515 subjects (66.5%), 30-59 in 169 (21.8%), and ≥ 60 in 90 (11.6%). Mortality increased steeply with FLI: 3.9, 10.1, 22.2% (p < 0.0001). In unadjusted Cox analysis, compared to FLI < 30, risk of death increased in FLI 30-59 (HR 2.85, 95% CI 1.49-5.45, p = 0.002) and FLI ≥ 60 (6.07, 3.27-11.29, p < 0.0001). Adjusting for Steno Type 1 Risk Engine (ST1-RE; based on age, sex, DD, systolic BP, LDL cholesterol, HbA1c, albuminuria, eGFR, smoking and exercise), HR was 1.52 (0.78-2.97) for FLI 30-59 and 3.04 (1.59-5.82, p = 0.001) for FLI ≥ 60. Inclusion of prior CV events slightly modified HRs. FLI impact was confirmed upon adjustment for EURODIAB Risk Engine (EURO-RE; based on age, HbA1c, waist-to-hip ratio, albuminuria and HDL cholesterol): FLI 30-59: HR 1.24, 0.62-2.48; FLI ≥ 60: 2.54, 1.30-4.95, p = 0.007), even after inclusion of prior CVD. CV events incidence increased with FLI: 3.5, 10.5, 17.2% (p < 0.0001). In unadjusted Cox, HR was 3.24 (1.65-6.34, p = 0.001) for FLI 30-59 and 5.41 (2.70-10.83, p < 0.0001) for FLI ≥ 60. After adjustment for ST1-RE or EURO-RE, FLI ≥ 60 remained statistically associated with risk of incident CV events, with trivial modification with prior CVD inclusion. CONCLUSIONS: This observational prospective study shows that FLI is associated with higher all-cause mortality and increased risk of incident CV events in type 1 diabetes.

Prevalence of chronic kidney disease in Tunisian diabetics: the TUN-CKDD survey.

BACKGROUND: In Tunisia, the prevalence of diabetes mellitus increased from 15.5% on 2016 to 23% by 2023. While Chronic Kidney Disease (CKD) stills the most dreaded complications of diabetes, studies on the prevalence of chronic kidney disease non-dialysis diet are scarce. The aim of this study was to assess the prevalence of chronic kidney disease among the Tunisian diabetic population based on investigators' specialty, demographic criteria (gender, age, duration of diabetes and geographic distribution) and diagnosis criteria (albuminuria and/or eGFR). METHODS: This observational, multicentric, and cross-sectional study enrolled all diabetic subjects from all regions of Tunisia with at least 3 months of follow-up before the inclusion date, from 09 January to 08 February 2023. CKD diagnosis was established based on the KDIGO guidelines. The study was carried out at medical departments and ambulatory clinics of different healthcare providers. Baseline data were collected by investigators using an electronic case report form (eCRF). Continuous variables were described by means, median, standard deviation, and quartiles. Categorical data were tabulated in frequencies and percentages. RESULTS: The overall prevalence of CKD among the 10,145 enrolled patients with diabetes mellitus was 38.7% with a 95%CI [37.8-39.6%]. 50.9% were male, with a mean age of 67.5 (± 11.3) years. The mean diabetes duration was 16.1 years (± 8.9). The highest CKD prevalence was noted among nephrologists (82.2%), while it was similar between the cardiologists and the primary care physicians (30.0%). CKD prevalence was highest among males (43.0% versus 35.1%) and increased proportionally with patients' age and diabetes duration. CKD was more frequent in the Mid-East Area when compared to other regions (49.9% versus 25.3 to 40.1% in other regions). Albuminuria was present within 6.6% of subjects with CKD, and it was found an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² within 13.3% of subjects wit h CKD. 18.9% had both criteria. CONCLUSIONS: In Tunisia, CKD among diabetics had a prevalence of 38.7%, approaching European prevalence. The prevalence discrepancy worldwide of CKD can be improved with a larger population size and by implementing standardized practices.

A comprehensive analysis of albuminuria in canine chronic kidney disease.

BACKGROUND: Albuminuria, an important marker of decreased kidney function in chronic kidney disease (CKD), is not routinely used for CKD detection or proteinuria appearance. Its relationships with biochemical parameters and blood pressure in dogs are poorly understood. OBJECTIVES: This study aimed to evaluate the relationship of albuminuria with various CKD markers, its correlation with the urinary protein to creatinine ratio (UPC), and hypertension in dogs with early stages of CKD. It also sought to determine the usability of the urinary albumin to creatinine ratio (UAC) for CKD screening. METHODS: The study reviewed records of 102 dogs, categorising them into four groups based on disease status. UAC and UPC ratio, biochemistry and haematology variables, age, and systolic blood pressure were determined. RESULTS: The Pearson's correlation coefficient between log-transformed values of UPC and UAC was r = 0.902 (95% CI: 0.87 to 0.93). Median UAC ratio values were 2.1 mg/g for the Healthy control group (n = 17), 54.2 mg/g for early stages CKD (n = 42), 5.8 mg/g for Acute sick control (n = 30), and 104 mg/g for Chronic sick control (n = 13). Thresholding UAC ratio as an indicator for impaired kidney function with the threshold of 10 mg/g (established based on the receiver operating characteristic curve) had a sensitivity 81.8%, specificity of 89.4%, positive predictive value (PPV) 90%, and negative predictive value (NPV) 80.1%. The correlation of UAC with biochemistry and haematology variables was statistically significant; for SDMA (µg/L), it was r = 0.566 and for other variables, it was weak to moderate. UAC was markedly elevated in cases of severe hypertension. CONCLUSIONS: UAC ratio was significantly different among dogs with impaired and not impaired kidney function. The correlation strength for the UAC and UPC ratios was high. UAC ratio may be a promising marker for proteinuria analysis in dogs with CKD or other kidney function alterations.

The impact of urinary albumin-creatinine ratio and glomerular filtration rate on long-term mortality in patients with heart failure: The National Health and Nutrition Examination Survey 1999-2018.

BACKGROUND AND AIMS: The urinary albumin‒creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are important markers of renal dysfunction, but few studies have simultaneously examined their impact on long-term mortality in patients with heart failure (HF). METHODS AND RESULTS: This study included patients with HF from the National Health and Nutrition Survey from 1999 to 2018. The fully adjusted Cox proportional risk model was adopted, and propensity score matching (PSM) was also used for risk adjustment. Among 988 patients, a median follow-up of 7.75 years was recorded. A higher UACR corresponded to a higher risk of cardiovascular death (P < 0.001 for trend). No statistically significant difference was found in the trend of eGFR risk stratification on the risk of cardiovascular death (P = 0.09 for trend). After PSM, the results showed that when grouped by UACR, the high-risk group had a higher risk of cardiovascular death regardless of a cutoff value of 30 or 300 mg/g (all P < 0.05). When grouped by eGFR, regardless of a cutoff value of 45 or 30 mL/min/1.73 m2, compared to the low-risk group, the high-risk group did not have a statistically significant increase in cardiovascular death (P = 0.086 and P = 0.093, respectively). The subgroup analysis of the main outcome showed an interaction between the UACR and eGFR (P = 0.044). CONCLUSIONS: Both the UACR and eGFR are markers for predicting the progression of HF, but the UACR may be a more important indicator than the eGFR, and they synergistically and complementarily reflect the long-term cardiovascular risk of HF patients.

Has the time come for age-adapted glomerular filtration rate criteria to define chronic kidney disease: how soon is now?

PURPOSE OF REVIEW: The conventional definition of chronic kidney disease (CKD) primarily relies on the identification of albuminuria or a decline in estimated glomerular filtration rate (eGFR). For many years, a straightforward eGFR threshold of <60 ml/min/1.73 m 2 has been widely adopted as the standard for defining CKD. Nonetheless, this criterion fails to consider the natural aging process of the kidney, and this oversight may affect the accurate diagnosis of kidney disease particularly at the extremes of age. RECENT FINDINGS: The fixed eGFR threshold of <60 ml/min/1.73 m 2 for defining CKD misses crucial opportunities for risk prevention. Studies have revealed that the eGFR threshold at which the risks for adverse long-term health outcomes such as mortality, cardiovascular events, and kidney failure begin to rise varies substantially by age. Specifically, this threshold is lower for the elderly and higher for young adults. Consequently, this results in the over-diagnosis of kidney disease in the elderly and the under-diagnosis of kidney disease in young adults. SUMMARY: To address these limitations of the current CKD definition, we discuss a number of proposed age-adapted eGFR criteria and weigh their pros and cons against the current, simple, and universally accepted approach.