Microalbuminuria Research Articles

Relationships of Office, Ambulatory, and Self-measured Blood Pressure With Cardiac, Renal, and Atherosclerotic Biomarkers.

Previous studies with several limitations have comparatively analyzed the relationship between ambulatory blood pressure (BP) and self-measured BP and biomarkers of organ damage. This study extends this line of research by examining the relationship between ambulatory and self-measured BP and cardiac, renal, and atherosclerotic biomarkers in outpatients at cardiovascular risk. In 1,440 practice outpatients who underwent office, ambulatory, and self-measured BP monitoring, we assessed the relationships of each BP with organ damage biomarkers including b-type natriuretic peptide (BNP), echocardiographic left ventricular mass index (LVMI), urine albumin-creatinine ratio (UACR), and brachial-ankle pulse wave velocity (baPWV). In the comparison of correlation, self-measured systolic BP (SBP) was more strongly correlated to log-transformed (Ln) BNP (n = 1,435; r = 0.123 vs. r = -0.093, P < 0.001), LVMI (n = 1,278; r = 0.223 vs. r = 0.094, P < 0.001), Ln-UACR (n = 1,435; r = 0.244 vs. r = 0.154, P = 0.010), and baPWV (n = 1,360; r = 0.327 vs. r = 0.115, P < 0.001) than daytime ambulatory SBP. In the linear regression models including office, ambulatory, and self-measured SBP, only self-measured SBP was significantly related to Ln-BNP (P = 0.016) and LVMI (P < 0.001). In the logistic regression models for the top quartile of LVMI, adding self-measured SBP improved the model predictability (P = 0.027), but adding daytime ambulatory SBP did not. However, adding daytime ambulatory SBP improved the model predictability in the logistic model for the top quartile of baPWV including office and self-measured SBP (P = 0.030). Our study findings suggested that self-measured BP was associated with cardiac biomarkers independent of ambulatory BP.

Machine learning progressive CKD risk prediction model is associated with CKD-mineral bone disorder

BackgroundRecently, we developed the machine learning (ML)-based Progressive CKD Risk Classifier (PCRC), which accurately predicts CKD progression within 5 years. While its performance is robust, it is unknown whether PCRC categorization is associated with CKD-mineral bone disorder (CKD-MBD), a critical, yet under-recognized, downstream consequence. Therefore, we aimed to 1) survey real-world testing utilization data for CKD-MBD and 2) evaluate ML-based PCRC categorization with CKD-MBD. MethodsThe cohort study utilized deidentified data from a US laboratory outpatient network, composed of 330,238 outpatients, over 5 years. The main outcomes were: 1) Laboratory testing utilization of eGFR, urine albumin creatinine ratio (UACR), parathyroid hormone (PTH), calcium, phosphate; and 2) PCRC categorization and biochemical abnormalities associated with CKD-MBD over 5 years. ResultsWe identified significant under-utilization of laboratory testing for UACR, phosphate and PTH, which ranged from −40 % to −100 % against the minimum standard-of-care. At five years, the CKD progression group, as predicted by the PCRC, was associated with 15.5 % increase in phosphate (P value <<0.01) and 94.9 % increase in PTH (P value <<0.01), consistent with CKD-MBD. ConclusionsWe identified significant under-utilization of laboratory testing for CKD-MBD. Moreover, we demonstrated that CKD progression, as predicted by the PCRC, is associated with CKD-MBD, several years in advance of disease. To our knowledge, this investigation is the first to examine the role of predictive analytics for CKD progression on mineral bone disorder. While further studies are required, these findings have the potential to advance AI/ML-based risk stratification and treatment of CKD and CKD-MBD.

Agrochemical use in Farming Practices and Risk Factors for Kidney Disease among Dwellers of Rural Farming Communities in South-West Nigeria.

The outlook of chronic kidney disease (CKD) in low-and-medium-income-countries is poor. Modern farming practices in Nigeria are becoming increasingly associated with the use of herbicides and pesticides. The study aimed to evaluate agrochemical use in farming practices and risk factors for kidney disease among dwellers of rural farming communities in South-West Nigeria. This was a cross-sectional survey of adult dwellers of an agrarian rural farming community in South-West Nigeria. Participants provided information on demographics, lifestyles, knowledge, and awareness of risk factors for kidney disease, and the use of agrochemicals in farming practice. Anthropometric measurements and blood pressure values were obtained while blood and spot urine were collected for random blood glucose, serum creatinine, urinalysis, and albumin-creatinine ratio. A total of 572 rural dwellers were enrolled in the study, with a mean age of 49.9 ± 17.5 years while 39.3% were male and 88.9% engaged in active farming. The prevalence of traditional risk factors for kidney disease was hypertension (24.3%), Diabetes mellitus (2.8%), cigarette smoking (7.5%), alcohol intake (20.8%) and herbal consumption (57.1%). The use of pesticides/herbicides was reported in 69.9%, while 25.3% did not use protective gear during its use. Proteinuria, hematuria, and reduced eGFR were observed in 29.8%, 6.1%, and 33.9% of participants, respectively. This study showed a high prevalence of herbicides and pesticide use and traditional risk factors for kidney disease, in addition to the high prevalence of markers of kidney damage among the dwellers of rural farming settlements in South-West Nigeria.

Higher Dietary Inflammatory Index and Systemic Immune-Inflammation Index Score are Associated With Higher Risk of Chronic Kidney Disease: Analysis of the National Health and Nutrition Examination Survey From 1999 to 2018

ObjectiveChronic kidney disease (CKD) is characterized by a gradual decline in kidney function over time. The influence of dietary inflammatory potential on systemic inflammation has been acknowledged, albeit limited research exists on the association between dietary inflammatory index (DII) and CKD. Although inflammation has been implicated in kidney damage, the role of systemic immune-inflammation index (SII) in individuals with CKD remains uncertain. Therefore, the objective of this study was to explore the potential correlation between DII and SII with the prevalence of CKD in adult Americans. MethodsThis cross-sectional study used data from the National Health and Nutrition Examination Study (NHANES) between 1999 and 2018. The DII was calculated based on the 24 h dietary history interview, while the SII was calculated as the product of platelet count multiplied by neutrophil count and divided by lymphocyte count. CKD was diagnosed based on impaired glomerular filtration rate (< 60 ml/min per 1.73 m2) or urinary albumin-creatinine ratio (UACR) ≥30 mg/g. Multivariable logistic regression analyses and subgroup analyses were performed to examine the association between DII/SII and CKD. ResultsIn total, this study included 40,388 participants, of whom 7443 (18.4%) had CKD for the diagnosis. The prevalence of CKD changed from 14.84 % (95% CI: 13.20 to 16.48%) in 1999-2000 to 12.76% (95% CI: 11.10 to 14.43%) in 2017-2018. According to adjusted multivariate logistic regression models, individuals with higher DII scores had a higher likelihood of having CKD (OR = 1.24; 95% CI: 1.12-1.37). Similarly, Logistic regression analysis confirmed that higher SII scores were associated with a higher risk of CKD (OR = 1.37; 95% CI: 1.25-1.50). Subgroup analyses further demonstrated relatively stronger associations between DII/SII and CKD among individuals with other factors such as sex, age, BMI, smoking status, drinking status, hypertension, and diabetes. ConclusionsThe DII and SII scores were significantly positively associated with higher risks of CKD. Anti-inflammatory diet might have the potential to prevent CKD. The SII may serve as a cost-effective and straightforward approach for detecting CKD. Further prospective longitudinal studies are needed to verify the causality.

Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease : A Systematic Review and Retrospective Individual Participant-Level Meta-analysis of Clinical Trials.

In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear. To examine the association of ACEi or ARB treatment initiation, relative to a non-ACEi or ARB comparator, with rates of KFRT and death. Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023. Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2. The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m2), albuminuria (urine albumin-creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes. A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m2, of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all). Individual participant-level data for hyperkalemia or acute kidney injury were not available. Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD. National Institutes of Health. (PROSPERO: CRD42022307589).

Correlation of Urinary Gamma Glutamyl Transferase to Creatinine Ratio with Albumin Creatinine Ratio in Patients with Type 2 Diabetes Mellitus

Correlation of Urinary Gamma Glutamyl Transferase to Creatinine Ratio with Albumin Creatinine Ratio in Patients with Type 2 Diabetes Mellitus

Urinary albumin creatinine ratio is associated with lipid profile

Moderately elevated albuminuria (30–300 mg/g) is a marker of renal dysfunction and a risk factor of cardiovascular disease. Additionally, several recent studies have reported a relationship between moderately elevated albuminuria and triglyceride (TG) levels. Therefore, we aimed to evaluate the relationship between the urine albumin-to-creatinine ratio (UACR) and total cholesterol (TC), TG, and high-density lipoprotein C (HDL-C) levels. We analyzed data from 19,340 patients from the 2011–2014 and 2019–2020 from the Korea National Health and Nutrition Examination Surveys. Multivariate linear regression analysis showed that the UACR was positively associated with TC and TG levels and negatively associated with HDL-C levels in both Korean women and men. These results were reanalyzed according to the degree of proteinuria (normal, moderately elevated albuminuria, and severely elevated albuminuria (≥ 300 mg/g)). We found a positive relationship between UACR and TC and TG levels, but a negative association with HDL-C levels, except for TC (moderately elevated albuminuria) and HDL-C (moderately elevated albuminuria) in Korean men and TC (severely elevated albuminuria), TG (severely elevated albuminuria), and HDL-C (normal range albuminuria) in Korean women. The correlation between albuminuria and lipid profiles became more evident as albuminuria shift from normal to the severely elevated albuminuria. Thus our multivariate linear regression analysis showed that lipid profiles (TG, TC, and HDL-C levels) were associated with the UACR.

High prevalence of albuminuria among adult males living with HIV in Botswana

Chronic HIV disease is associated with a fivefold increase in albuminuria outside of sub-Saharan Africa. However, very little is known about albuminuria risk among people living with HIV (PLWH) in sub-Saharan Africa. Therefore, we conducted a cross-sectional observational HIV clinic-based study of albuminuria among 1533 adults aged 21 years or older between January 2020 and January 2021 in Gaborone, Botswana. Clinical albuminuria was defined using a sex-based albumin‒creatinine ratio (ACR) of 25–355 mg/g for females and 17–250 mg/g for males. The study population mean age was 48.5 (SD 10.3) years, and 764/1533 (49.7%) were female. The overall prevalence of albuminuria was 20.7% (95% CI 18.7%, 22.8%). A higher proportion of males were more likely to be categorized as having albuminuria than females, 25% (95% CI 22.0, 28.2) versus 16.4% (95% CI 13.8,19.2), P value < 0.001. In the final multivariate models, predictors of albuminuria differed by sex group. Larger longitudinal studies are required to evaluate the impact of albuminuria among PLWH with particular emphasis on the effect of sex on the risk of albuminuria.

APOL1 High-Risk Genotype is Not Associated With New or Worsening of Proteinuria or Kidney Function Decline Following COVID-19 Vaccination

SARS-CoV-2 infection increases systemic inflammatory cytokines which act as a second-hit driver of Apolipoprotein L1 (APOL1)-mediated collapsing glomerulopathy. SARS-CoV-2 vaccination also increases cytokines. Recent reports of new glomerular disease in individuals with APOL1 high-risk genotype (HRG) following SARS-CoV-2 vaccination raised the concern SARS-CoV-2 vaccination may also act as a second-hit driver of APOL1-mediated glomerulopathy. We screened 1507 adults in the Duke's Measurement to Understand Reclassification of Disease of Cabarrus and Kannapolis (MURDOCK) registry and enrolled 105 eligible participants with available SARS-CoV-2 vaccination data, prevaccination and postvaccination serum creatinine, and urine protein measurements. Paired data were stratified by number of APOL1 risk alleles (RAs) and compared within groups using Wilcoxon signed rank test and across groups by analysis of variance. Among 105 participants, 30 (28.6%) had 2, 39 (37.1%) had 1, and 36 (34.3%) had 0 APOL1 RA. Most of the participants (94%) received at least 2 doses of vaccine. Most (98%) received the BNT162B2 (Pfizer) or mRNA-1273 (Moderna) vaccine. On average, the prevaccine and postvaccine laboratory samples were drawn 648 days apart. There were no detectable differences between pre- and post-serum creatinine or pre- and post-urine albumin creatinine ratio irrespective of the participants' APOL1 genotype. Finally, most participants with APOL1 RA had the most common haplotype (E150, I228, and K255) and lacked the recently described protective N264K haplotype. In this observational study, APOL1 HRG is not associated with new or worsening of proteinuria or decline in kidney function following SARS-CoV-2 vaccination. Validation of this result in larger cohorts would further support the renal safety of SARS-CoV-2 vaccine in individuals with APOL1 HRG.

Relation between interleukin-13 and annexin-V levels and carotid intima-media thickness in nephrotic syndrome.

The aim of the current study is to assess the relation between carotid intima-media thickness (CIMT) measurements, renal Doppler resistive index (RI) and serum levels of interleukin-13 (IL-13) and annexin-V (An-V) in children with idiopathic nephrotic syndrome (INS). The present case-control study was conducted on 60 children with INS and 60 age- and sex-matched healthy children. All participants were subjected to evaluation of serum levels of IL-13 and An-V and ultrasound Doppler measurement of CIMT and renal RI. Patients expressed significantly higher An-V (5.9 ± 2.6 vs. 2.1 ± 0.8 ng/mL, p<0.001) and IL-13 (19.2 ± 7.6 vs. 3.4 ± 1.4 ng/L) levels when compared with healthy counterparts. Moreover, it was shown that patients had significantly higher CIMT (0.49 ± 0.06 vs. 0.35 ± 0.03, p<0.001) as compared to controls. No significant differences were noted between the studied groups regarding right or left RIs. Correlation analysis identified significant direct correlation between serum An-V levels and albumin/creatinine ratio (ACR) (r = 0.55), cholesterol (r = 0.48), triglycerides (r = 0.36), IL-13 (r = 0.92) and CIMT (r = 0.53). Similar correlations could be found between serum IL-13 levels and CIMT measurements and the corresponding parameters. The present study suggests an association between higher early atherosclerosis expressed as elevated CIMT measurements in children with INS and elevated serum levels of An-V and IL-13.

Is the urinary neutrophil gelatinase-associated lipocalin concentration in children and adolescents with type 1 diabetes mellitus different from that in healthy children?

Diabetic kidney disease (DKD) is one of the major microvascular complications of type 1 diabetes mellitus (T1DM). Some studies suggest that changes of renal tubular components emerge before the glomerular lesions thus introducing the concept of diabetic tubulopathy with urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a potential marker of DKD. This concept was not confirmed in all studies. In 198 T1DM patients with median age 15 years and diabetes duration over one year, an albumin/creatinine ratio (ACR) was determined and uNGAL measured in spot urine sample. Urine samples for ACR and uNGAL were also collected in the control group of 100 healthy children of similar age. There was no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects (6.9 (2.8-20.1) ng/mL vs 7.9 (2.9-21.0) ng/mL, P = 0.969 and 6.8 (2.2-18.4) ng/mg vs 6.5 (1.9-13.4) ng/mg, P = 0.448, respectively) or between T1DM subjects with albuminuria A2 and albuminuria A1 (P = 0.573 and 0.595, respectively). Among T1DM patients 168 (85%) had normal uNGAL concentrations, while in 30 (15%) patients uNGAL was above the defined cut-off value of 30.9 ng/mL. There was no difference in BMI, HbA1c and diabetes duration between patients with elevated uNGAL compared to those with normal uNGAL. We found no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects or between albuminuria A2 and albuminuria A1 T1DM subjects. Therefore, uNGAL should not be recommended as a single marker for detecting diabetic kidney disease in children and adolescents.

Design and baseline characteristics of the Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) randomized trial

ABSTRACT Background Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improved kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes in two phase 3 outcome trials. The Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) study investigates the effect of finerenone in adults with CKD without diabetes. Methods FIND-CKD (NCT05047263 and EU CT 2023-506897-11-00) is a randomized, double-blind, placebo-controlled phase 3 trial in patients with CKD of non-diabetic aetiology. Adults with a urinary albumin:creatinine ratio (UACR) ≥200–≤3500 mg/g and an estimated glomerular filtration rate (eGFR) ≥25–&amp;lt;90 ml/min/1.73 m2 receiving a maximum tolerated dose of a renin–angiotensin system inhibitor were randomized 1:1 to once-daily placebo or finerenone 10 or 20 mg depending on eGFR &amp;gt;60 or &amp;lt;60 ml/min/1.73 m2. The primary efficacy outcome is total eGFR slope, defined as the mean annual rate of change in eGFR from baseline to month 32. Secondary efficacy outcomes include a combined cardiorenal composite outcome comprising time to kidney failure, sustained ≥57% decrease in eGFR, hospitalization for heart failure or cardiovascular death, as well as separate kidney and cardiovascular composite outcomes. Adverse events are recorded to assess tolerability and safety. Results Across 24 countries, 3231 patients were screened and 1584 were randomized to study treatment. The most common causes of CKD were chronic glomerulonephritis (57.0%) and hypertensive/ischaemic nephropathy (29.0%). Immunoglobulin A nephropathy was the most common glomerulonephritis (26.3% of the total population). At baseline, mean eGFR and median UACR were 46.7 ml/min/1.73 m2 and 818.9 mg/g, respectively. Diuretics were used by 282 participants (17.8%), statins by 851 (53.7%) and calcium channel blockers by 794 (50.1%). Sodium–glucose co-transporter 2 (SGLT2) inhibitors were used in 16.9% of patients; these individuals had a similar mean eGFR (45.6 versus 46.8 ml/min/1.73 m2) and a slightly higher median UACR (871.9 versus 808.3 mg/g) compared with those not using SGLT2 inhibitors at baseline. Conclusions FIND-CKD is the first phase 3 trial of finerenone in patients with CKD of non-diabetic aetiology.

Serum and Urine Metabolites and Kidney Function.

Key Points We provide an atlas of cross-sectional and longitudinal serum and urine metabolite associations with eGFR and urine albumin-creatinine ratio in an older community-based cohort.Metabolic profiling in serum and urine provides distinct and complementary insights into disease. Background Metabolites represent a read-out of cellular processes underlying states of health and disease. Methods We evaluated cross-sectional and longitudinal associations between 1255 serum and 1398 urine known and unknown (denoted with “X” in name) metabolites (Metabolon HD4, 721 detected in both biofluids) and kidney function in 1612 participants of the Atherosclerosis Risk in Communities study. All analyses were adjusted for clinical and demographic covariates, including for baseline eGFR and urine albumin-creatinine ratio (UACR) in longitudinal analyses. Results At visit 5 of the Atherosclerosis Risk in Communities study, the mean age of participants was 76 years (SD 6); 56% were women, mean eGFR was 62 ml/min per 1.73 m2 (SD 20), and median UACR level was 13 mg/g (interquartile range, 25). In cross-sectional analysis, 675 serum and 542 urine metabolites were associated with eGFR (Bonferroni-corrected P &lt; 4.0E-5 for serum analyses and P &lt; 3.6E-5 for urine analyses), including 248 metabolites shared across biofluids. Fewer metabolites (75 serum and 91 urine metabolites, including seven metabolites shared across biofluids) were cross-sectionally associated with albuminuria. Guanidinosuccinate; N2,N2-dimethylguanosine; hydroxy-N6,N6,N6-trimethyllysine; X-13844; and X-25422 were significantly associated with both eGFR and albuminuria. Over a mean follow-up of 6.6 years, serum mannose (hazard ratio [HR], 2.3 [1.6–3.2], P = 2.7E-5) and urine X-12117 (HR, 1.7 [1.3–2.2], P = 1.9E-5) were risk factors of UACR doubling, whereas urine sebacate (HR, 0.86 [0.80–0.92], P = 1.9E-5) was inversely associated. Compared with clinical characteristics alone, including the top five endogenous metabolites in serum and urine associated with longitudinal outcomes improved the outcome prediction (area under the receiver operating characteristic curves for eGFR decline: clinical model=0.79, clinical+metabolites model=0.87, P = 8.1E-6; for UACR doubling: clinical model=0.66, clinical+metabolites model=0.73, P = 2.9E-5). Conclusions Metabolomic profiling in different biofluids provided distinct and potentially complementary insights into the biology and prognosis of kidney diseases.

A Random Forest Algorithm for Assessing Risk Factors Associated With Chronic Kidney Disease: Observational Study.

The prevalence and mortality rate of chronic kidney disease (CKD) are increasing year by year, and it has become a global public health issue. The economic burden caused by CKD is increasing at a rate of 1% per year. CKD is highly prevalent and its treatment cost is high but unfortunately remains unknown. Therefore, early detection and intervention are vital means to mitigate the treatment burden on patients and decrease disease progression. In this study, we investigated the advantages of using the random forest (RF) algorithm for assessing risk factors associated with CKD. We included 40,686 people with complete screening records who underwent screening between January 1, 2015, and December 22, 2020, in Jing'an District, Shanghai, China. We grouped the participants into those with and those without CKD by staging based on the glomerular filtration rate staging and grouping based on albuminuria. Using a logistic regression model, we determined the relationship between CKD and risk factors. The RF machine learning algorithm was used to score the predictive variables and rank them based on their importance to construct a prediction model. The logistic regression model revealed that gender, older age, obesity, abnormal index estimated glomerular filtration rate, retirement status, and participation in urban employee medical insurance were significantly associated with the risk of CKD. On RF algorithm-based screening, the top 4 factors influencing CKD were age, albuminuria, working status, and urinary albumin-creatinine ratio. The RF model predicted an area under the receiver operating characteristic curve of 93.15%. Our findings reveal that the RF algorithm has significant predictive value for assessing risk factors associated with CKD and allows the screening of individuals with risk factors. This has crucial implications for early intervention and prevention of CKD.

Machine learning for prediction of chronic kidney disease progression: Validation of the Klinrisk model in the CANVAS Program and CREDENCE trial.

To validate the Klinrisk machine learning model for prediction of chronic kidney disease (CKD) progression in patients with type 2 diabetes in the pooled CANVAS/CREDENCE trials. We externally validated the Klinrisk model for prediction of CKD progression, defined as 40% or higher decline in estimated glomerular filtration rate (eGFR) or kidney failure. Model performance was assessed for prediction up to 3 years with the area under the receiver operating characteristic curve (AUC), Brier scores and calibration plots of observed and predicted risks. We compared performance of the model with standard of care using eGFR (G1-G4) and urine albumin-creatinine ratio (A1-A3) Kidney Disease Improving Global Outcomes (KDIGO) heatmap categories. The Klinrisk model achieved an AUC of 0.81 (95% confidence interval [CI] 0.78-0.83) at 1 year, and 0.88 (95% CI 0.86-0.89) at 3 years. The Brier scores were 0.020 (0.018-0.022) and 0.056 (0.052-0.059) at 1 and 3 years, respectively. Compared with the KDIGO heatmap, the Klinrisk model had improved performance at every interval (P < .01). The Klinrisk machine learning model, using routinely collected laboratory data, was highly accurate in its prediction of CKD progression in the CANVAS/CREDENCE trials. Integration of the model in electronic medical records or laboratory information systems can facilitate risk-based care.

The Protective Role of KANK1 in Podocyte Injury.

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1-deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.

Assessment and comparison of microalbuminuria in obese and nonobese children

Background Fatty liver, metabolic syndrome, and cardiovascular disease are just a few of the well-known cardiometabolic complications associated with childhood obesity. Microalbuminuria (MA) is a sign of early kidney impairment, as seen in adults, and recent research supports its presence in children with obesity as well as its potential relationship with cardiometabolic variables. Both adults and children share this well-established pathophysiological theory. Indicated a close connection with the main aspect of fatness, such as IR, through the renal hemodynamic effects of insulin. More scientific consideration must be given to the assessment of primary kidney injury in obese children, given the pathological and prognostic implications of this association in everyday practise (counting an elevated danger of developing long term renal disorder over time). Method case-control study is going to be conducted among the patients of AVBRH hospital. A total of thirty participants with fifteen obese and fifteen non obeses controls were included in this study. Result The expected result of the study can determine the correlation between obesity and microalbuminuria, The value of microalbuminuria is high in obese patients as compared to nonobese patients. Conclusion The risk of problems in obese patients can be predicted using microalbuminuria, which can help lower the overall morbidity and mortality associated with renal function. Complications

#1642 Influence of potassium intake on the renoprotective response to sodium restriction and hydrochlorothiazide in patients with diabetic nephropathy

Abstract Background and Aims Both salt restriction and hydrochlorothiazide (HCT) potentiate the antihypertensive and antiproteinuric effects of renin-angiotensin-aldosterone-system inhibitors (RAASi) in chronic kidney disease (CKD). Potassium intake is another dietary component that influences blood pressure (BP) and albuminuria. The influence of potassium intake on the response to sodium restriction during RAASi treatment in diabetic nephropathy is unknown. Method We performed a post-hoc analysis of a randomised, double blind, placebo-controlled cross-over trial (n = 43) investigating the combined and separate effects of low sodium (LS; aim 50 mmol Na+/d) and HCT (50 mg/d) on BP and albuminuria during background ACE inhibition (ACEi; lisinopril 40 mg/d) in patients with diabetic nephropathy. Each treatment (normal sodium (NS), LS, NS+HCT, LS+HCT) period consisted of six weeks. Participants were categorised as above or below median 24-hour urinary potassium excretion (UKV) at baseline, stratified by sex. Effects on BP and albuminuria were defined as % reduction from baseline systolic BP (SBP) and urinary albumin-creatinine ratio (ACR). Changes over time within both UKV subgroups were compared to baseline using repeated measures ANOVA (SBP) or paired Wilcoxon rank sum analysis (log-transformed ACR). Post-hoc between-group comparison was performed using Bonferroni testing. Results 43 patients (6 female; mean age 64.9±1.4 yrs) had UKV data available and were included in analysis. 33 patients had complete ACR data. Mean estimated glomerular filtration rate (eGFR) was 65.2 (±3.9), mean SBP was 146.6±2.4 mmHg and median albuminuria 648.6 [251.2 - 1883.0] mg/24 h. Median UKV in the high and low potassium groups was 64 [IQR 49-71] and 94 [90 – 111] mmol/24 u, respectively (p&amp;lt;0.0001). Mean baseline sodium excretion was higher in the high potassium group (191 vs. 260 mmol/d; P = .002), but percentual reduction in sodium excretion at SR was comparable between the two groups. There were no significant differences in baseline SBP, ACR, age and estimated glomerular filtration rate between the groups. LS led to a significant reduction of ACR in the high potassium group (P = .011), whereas in the low potassium group the ACR reduction was not significant (P = .058; Fig. 1). Similarly, addition of HCT to background ACEi therapy without salt restriction reduced ACR compared to ACEi monotherapy in the high potassium group (P &amp;lt; .0001), not the low potassium group (P = .211). LS+HCT combined led to a reduction in ACR in both high (P &amp;lt; .0001) and low potassium (P = .034) groups. A post-hoc between-group analysis showed a significantly larger ACR reduction for the high potassium group (P = .01) upon HCT therapy, and a trend towards larger reduction for HCT+LS (P = .05). The effect of LS alone was similar between high and low potassium groups (P = .485). During LS, within-group analysis showed a significant reduction in SBP compared to baseline for the low potassium group (P = .003), but not for the high potassium group (P = .208). In all further conditions, SBP was significantly reduced from baseline in both groups. Post-hoc analysis showed no significant differences in SBP reduction between high and low potassium groups, although there was a trend towards larger SBP reduction in the low potassium group during LS (P = .07). Conclusion Higher baseline potassium excretion is associated with stronger albuminuria lowering effects of salt restriction and HCT in patients with diabetic nephropathy on background ACEi therapy. These effects were not driven by similar effects on BP.

#876 Albuminuria and the risk of dementia and different dementia subtypes: the Stockholm Creatinine Measurements (SCREAM) project

Abstract Background and Aims Studies investigating the association of chronic kidney disease and dementia predominantly focused on estimated glomerular filtration rate (eGFR) rather than albuminuria. The few studies focusing on albuminuria reported conflicting results, probably due to a lack of power, not taking into account the different dementia subtypes, not adjusting for eGFR, and the use of different albuminuria measurement techniques. This study therefore investigated the eGFR-independent risk of all-cause and type-specific dementia associated with albuminuria, quantified as urine albumin-creatinine ratio (ACR) and by dipstick, in a large population. Method We included subjects from the Stockholm Creatinine Measurements (SCREAM) project without a history of dementia and with age ≥65 years. The main analyses involved 138 688 subjects with at least one ACR test, and for sensitivity analyses, we involved 170 572 subjects with at least one dipstick proteinuria test. Albuminuria was quantified as KDIGO albuminuria A1-A3 stages. The primary outcome was incidence of all-cause dementia, and the key secondary outcomes were incidence of type-specific dementia. Dementia incidence was ascertained by record linkage with the national dementia registry (SveDem). ICD-10 coding was also used to classify subtypes only when there were no available dementia records in SveDem. Multivariable Cox regression models were used to calculate hazard ratios (HRs, 95% CIs) crude, and adjusted for confounders including baseline eGFR. Results During a median follow-up of 3.9 (IQR, 1.8-7.2) years, 9 970 subjects developed de novo dementia. After multivariable adjustment including baseline eGFR, subjects with an ACR of 30-299 mg/g or ≥300 mg/g had a 26% (HR, 1.26; 95% CI, 1.20-1.32) and 36% (HR, 1.36; 95% CI, 1.24-1.50) higher risk of developing all-cause dementia, respectively, when compared to subjects with an ACR &amp;lt;30 mg/g. Subjects with an ACR of 30-299 mg/g also presented a higher risk of developing several type-specific dementia, including Alzheimer's dementia (HR, 1.09, 95% CI, 1.01-1.17), vascular dementia (HR, 1.35, 95% CI, 1.22-1.48), and unspecified dementia (HR, 1.54, 95% CI, 1.41-1.69). No significant associations between albuminuria and the incidence of Lewy body dementia and Parkinson's Disease with dementia, frontotemporal dementia, as well as other types of dementia were observed. These results were generally robust in several sensitivity analyses, including replicating our main analyses in subjects with a dipstick proteinuria test instead of an ACR. Conclusion Increased albuminuria is associated with a higher risk of all-cause, Alzheimer's, and vascular dementia, independent of baseline eGFR and different albuminuria measurement techniques.

#604 Oral administration of UNI-494 ameliorates acute kidney injury in a rat model of delayed graft function

Abstract Background and Aims There are no FDA approved drugs for the treatment of acute kidney injury (AKI), which affects 10-15% of hospitalized patients and often results in renal transplantation or lifelong dialysis. UNI-494 is a novel nicotinamide ester derivative and selective mitochondrial ATP-sensitive potassium channel activator that may be beneficial for several disease states, including AKI. We present results from a study evaluating the in vivo efficacy of oral (PO) UNI-494 in the unilateral renal ischemia-reperfusion (I/R) rat model of AKI, which is a well-established model of delayed graft function (DGF) (Cavaille-Coll, 2013). Method Rats were anesthetized, the right kidney was removed, and I/R was induced in three groups of rats by clamping the renal vessels in the left kidney for 30 minutes; a fourth group had no surgery (sham group) without clamping the renal vessels. 50 mg/kg or 100 mg/kg UNI-494 were administered PO 30 minutes prior to I/R. One I/R group and the sham group were not treated. After 24 hours of reperfusion in metabolic cages, blood samples were collected for serum creatinine (sCr), and urinary samples were collected for albumin-creatinine ratio (ACR) and the tubular injury marker neutrophil gelatinase-associated lipocalin (NGAL). The clamped left kidney was collected and processed for histology for tubular injury scores. Results In this study, I/R induced significant increases of sCr, ACR, NGAL, and proximal convoluted tubular injury scores in the vehicle treated I/R group vs No I/R sham group. A single PO dose of UNI-494 at 50 mg/kg/PO or 100 mg/kg/PO reduced the kidney functional markers sCr and ACR, the tubular injury marker (NGAL), and proximal tubular injury scores (all p &amp;lt; 0.001, Fig. 1). Conclusion The results indicate that UNI-494 dose dependently prevented AKI markers and proximal tubular injury in a rat model of AKI and therefore is a potential candidate for the prevention of DGF and other AKI clinical conditions.