Risk Of Proteinuria Research Articles

Association between Frailty and Albuminuria among Older Chinese Inpatients.

Older adults with frailty are vulnerable to cardiovascular event and subsequent mortality. Frailty and albuminuria share atherosclerotic risk factors. The present study investigated the association of frailty and albuminuria among elderly Chinese inpatients. Cross-sectional study. A total of 202 patients aged over 60 years from the Center of Gerontology and Geriatric, West China Hospital. Frailty was defined using the five-item FRAIL scale. This included measurements of fatigue, resistance, ambulation, illness, and loss of weight. We further determined the random urine albumin/creatinine ratio (UACR) of all patients. Random UACR ≥30 mg/g was defined as albuminuria, and < 30mg/g as normoalbuminuria. The relationship between albuminuria and frailty was assessed through multiple regression analysis. The 202 participants (156 men, 77.2%) had an average age of 78.99±7.60 years, which ranged from 60 to 95. Compared to those without albuminuria, elderly patients with albuminuria were of an older age, had a higher prevalence of diabetes and poorer renal function. The prevalence of frailty, pre-frailty and ambulation (one of the FRAIL components) were higher in the albuminuria group than the normoalbuminuria group (23.9% vs. 12.2%, 47.9% vs.37.4%, 33.8% vs. 16.0%, respectively, P<0.05). Following the adjustment for age, eGFR, hypertension, diabetes and using ACEI/ARB, being frail or pre-frail led to an enhanced risk of albuminuria (OR frail 2.60, 95% CI frail 1.01-6.72; OR pre-frail 2.14, 95% CI pre-frail 1.03-4.44). Frailty is independently associated with albuminuria when adjusted for classic cardiovascular risk factors.

Serum levels of mac-2 binding protein are associated with diabetic microangiopathy and macroangiopathy in people with type 2 diabetes

IntroductionNon-alcoholic fatty liver disease is reportedly associated with type 2 diabetes and progressive liver fibrosis, as evaluated by transient elastography, and has been linked with micro- and macroangiopathy in people...

Lifestyle-Related Exposure to Cadmium and Lead is Associated with Diabetic Kidney Disease.

Background: Environmental factors contributing to diabetic kidney disease are incompletely understood. We investigated whether blood cadmium and lead concentrations were associated with the prevalence of diabetic kidney disease, and to what extent lifestyle-related exposures (diet and smoking) contribute to blood cadmium and lead concentrations. Material and methods: In a cross-sectional analysis in 231 patients with type 2 diabetes included in the DIAbetes and LifEstyle Cohort Twente (DIALECT-1), blood cadmium and lead concentrations were determined using inductively coupled plasma mass spectrometry. The associations between diet (derived from food frequency questionnaire), smoking and cadmium and lead were determined using multivariate linear regression. The associations between cadmium and lead and diabetic kidney disease (albumin excretion >30 mg/24 h and/or creatinine clearance <60 mL/min/1.73 m2) were determined using multivariate logistic regression. Results: Median blood concentrations were 2.94 nmol/L (interquartile range (IQR): 1.78–4.98 nmol/L) for cadmium and 0.07 µmol/L (IQR: 0.04–0.09 µmol/L) for lead, i.e., below acute toxicity values. Every doubling of lead concentration was associated with a 1.75 (95% confidence interval (CI): 1.11–2.74) times higher risk for albuminuria. In addition, both cadmium (odds ratio (OR) 1.50 95% CI: 1.02–2.21) and lead (OR 1.83 95% CI: 1.07–3.15) were associated with an increased risk for reduced creatinine clearance. Both passive smoking and active smoking were positively associated with cadmium concentration. Alcohol intake was positively associated with lead concentration. No positive associations were found between dietary intake and cadmium or lead. Conclusions: The association between cadmium and lead and the prevalence of diabetic kidney disease suggests cadmium and lead might contribute to the development of diabetic kidney disease. Exposure to cadmium and lead could be a so far underappreciated nephrotoxic mechanism of smoking and alcohol consumption.

Cross-sectional associations between central and general adiposity with albuminuria: observations from 400,000 people in UK Biobank

BackgroundWhether measures of central adiposity are more or less strongly associated with risk of albuminuria than body mass index (BMI), and by how much diabetes/levels of glycosylated haemoglobin (HbA1c) explain or modify these associations, is uncertain.MethodsOrdinal logistic regression was used to estimate associations between values of central adiposity (waist-to-hip ratio) and, separately, general adiposity (BMI) with categories of urinary albumin-to-creatinine ratio (uACR) in 408,527 UK Biobank participants. Separate central and general adiposity-based models were initially adjusted for potential confounders and measurement error, then sequentially, models were mutually adjusted (e.g. waist-to-hip ratio adjusted for BMI, and vice versa), and finally they were adjusted for potential mediators.ResultsLevels of albuminuria were generally low: 20,425 (5%) had a uACR ≥3 mg/mmol. After adjustment for confounders and measurement error, each 0.06 higher waist-to-hip ratio was associated with a 55% (95%CI 53–57%) increase in the odds of being in a higher uACR category. After adjustment for baseline BMI, this association was reduced to 32% (30–34%). Each 5 kg/m2 higher BMI was associated with a 47% (46–49%) increase in the odds of being in a higher uACR category. Adjustment for baseline waist-to-hip ratio reduced this association to 35% (33–37%). Those with higher HbA1c were at progressively higher odds of albuminuria, but positive associations between both waist-to-hip ratio and BMI were apparent irrespective of HbA1c. Altogether, about 40% of central adiposity associations appeared to be mediated by diabetes, vascular disease and blood pressure.ConclusionsConventional epidemiological approaches suggest that higher waist-to-hip ratio and BMI are independently positively associated with albuminuria. Adiposity–albuminuria associations appear strong among people with normal HbA1c, as well as people with pre-diabetes or diabetes.

MicroRNAs and Risk Factors for Diabetic Nephropathy in Egyptian Children and Adolescents with Type 1 Diabetes.

PurposeCurrently available markers for early detection of diabetic nephropathy (DN), the leading cause of end stage renal disease, have some limitations. There is insufficient evidence from previous studies about the role of several circulating microRNAs (miRNAs) in the early development of DN. This study aimed to describe the expression of miRNA-377, miRNA-93, miRNA-25, miRNA-216a, and miRNA-21 in a sample of type 1 diabetic children and adolescents to explore their association with DN and some indices of kidney injury.Patients and MethodsSeventy type 1 diabetic patients, with 5 years’ duration of diabetes or more, were recruited from Children’s Hospital, Faculty of Medicine, Cairo University. Quantitative real-time reverse-transcription PCR (qRT-PCR) was used to measure the expression of the above mentioned miRNAs in serum and to assess its association with DN, and the studied risk factors.ResultsThere was a significantly higher percentage of up-regulation of miRNA-377 and miRNA-93 (P=0.03, 0.02, respectively) in addition to significant down-regulation of miRNA-25 (P=0.01) in patients with DN than in patients without DN. In patients with DN, expression of miR-216a was significantly negatively correlated with creatinine (r=−0.4, P=0.04) and positively correlated with eGFR using creatinine (r=0.5, P=0.03). In the same group, expression of miR-21 was positively correlated with urinary cystatin C (r=0.6, P=0.01) and was negatively correlated with e-GFR using cystatin c (r=−0.6, P=0.01). miRNA-93 was associated with increased risk (odds ratio=15, 95% CI=12.03–24.63, P=0.01), while miRNA-25 was associated with decreased risk for albuminuria (odds ratio=0.15, 95% CI=0.08–0.55, P=0.03).ConclusionmiRNA-377, miRNA-93, miRNA-216a, and miRNA-21 may be implicated in the pathogenesis of DN, while miRNA-25 may have a reno-protective role. More studies are needed to document the value of these miRNAs as diagnostic biomarkers as well as therapeutic targets in DN.

P0803SYNERGISTIC INTERACTION OF ACUTE HYPERGLYCEMIC STRESS AND NON-ALCOHOLIC FATTY LIVER DISEASE ON THE DEVELOPMENT OF ALBUMINURIA IN GENERAL POPULATION

Abstract Background and Aims Both increased glycemic exposure and non-alcoholic fatty liver disease (NFALD) are independent risks of vascular endothelial dysfunction. To find interactive effects of acute hyperglycemia and hepatic necro-inflammation on initiation of albuminuria, we conducted this nation-wide, population-based interaction analysis using acute-to-chronic glycemic ratio (ACGR) as a candidate indicator of acute increased glycemic exposure and ZJU index as an indicator of NFALD. Method Eligible as cases were all native Koreans aged 20 years or older without significant medical illness. A total of 9494 participants were divided into quintiles according to their ACGR results and stratified by sex. Results: Participants in the highest ACGR quintile were more obese and they were more likely to have elevated BP and increased glycemic exposure as compared with other quintiles. Restricted cubic regression analyses revealed that there was non-linear relationship of ACGR and ZJU index with albuminuria. Multiple logistic regression, adjusted for various conventional risk factor of kidney disease, demonstrated that both ACGR (adjusted OR = 5.388, 95% CI = 1.119-25.95) and ZJU index (adjusted OR = 1.057, 95% CI = 1.002-1.114) were independent predictor of albuminuria. Interestingly, our interaction analysis revealed that ACGR had bigger effect on the risk of albuminuria in participant with elevated ZJU index than those without (adjusted RERI = 2.296, 95% CI = 2.277-2.313; adjusted AP = 0.643, 95% CI = 0.472-0.814; adjusted SI = 8.135, 95% CI = 7.267-9.003). Conclusion Our findings suggest that the interaction of acute hyperglycemia and abnormal hepatic fat metabolism may exert synergistic biologic effect on the development of albuminuria.

527-P: Risk Factors for Nephropathy among Children and Young Adults with Type 1 Diabetes: A Swedish Cohort

Background: Persons with diabetic nephropathy have an increased risk to progress to severe renal failure and have a high cardiovascular risk. To better understand the impact of risk factors on diabetes complications information from diagnosis and onward is needed. Less focus has been on evaluating other risk factors than HbA1c following large populations from diagnosis with repeated measurements. Therefore, we aimed to evaluate risk factors for albuminuria in children and young adults. Methods: In a population-based cohort study persons with type 1 diabetes (T1D), both children (data from SWEDIABKIDS) and adults (data from Swedish National Diabetes Registry) were included, and followed from January 1, 2001 to December 31, 2017. The association between risk factors and albuminuria was evaluated. The gradient of risk per 1 SD (standard deviation) was estimated to compare the impact of each risk factor. Results: A total of 10398 individuals with T1D were followed, 43.4% female, mean age 14.7 years and mean HbA1c 8.0% (63.4 mmol/mol). HbA1c was the strongest risk factor with an odds ratio (OR) of 1.51 (95% 1.39-1.64, p&amp;lt;0.0001). After adjustment for age, sex and mean HbA1c the OR per 1 SD increase were for mean diastolic blood pressure (DBP) 1.27 (95% 1.16-1.39, p&amp;lt;0.0001), mean triglycerides 1.21 (95% 1.14-1.28, p&amp;lt;0.0001), mean systolic blood pressure (SBP) 1.21 (95% 1.10-1.33, p&amp;lt;0.0001), mean cholesterol 1.16 (95% 1.07-1.25, p=0.0002) and mean LDL 1.12 (95% 1.03-1.21, p=0.0051). Risk for albuminuria increased at the following levels: SBP 140 mmHg, DBP 80 mmHg, triglycerides &amp;gt;89 mg/dL (&amp;gt;1.0 mmol/L), total cholesterol &amp;gt;193 mg/dL (&amp;gt;5.0 mmol/L), LDL &amp;gt;135 mg/dL (&amp;gt;3.5 mmol/L) and BMI &amp;gt;30 kg/m2. Smoking showed no association. Conclusion: For individuals with type 1 diabetes, higher HbA1c, blood pressure, triglycerides, LDL and cholesterol were the most prominent risk factors for albuminuria. Blood pressure levels 140/80 mmHg were associated with increased risk of albuminuria. Disclosure S.S. Ahmadi: None. A. Pivodic: None. A. Svensson: None. H. Wedel: None. J. Ludvigsson: None. M. Lind: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc. Consultant; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. Research Support; Self; Dexcom, Inc., Novo Nordisk Inc. Funding Swedish Child Diabetes Foundation

Environment-Wide Association Study of CKD.

Exposure to environmental chemicals has been recognized as one of the possible contributors to CKD. We aimed to identify environmental chemicals that are associated with CKD. We analyzed the data obtained from a total of 46,748 adults who participated in the National Health and Nutrition Examination Survey (1999-2016). Associations of chemicals measured in urine or blood (n=262) with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), reduced eGFR (<60 ml/min per 1.73 m2), and a composite of albuminuria or reduced eGFR were tested and validated using the environment-wide association study approach. Among 262 environmental chemicals, seven (3%) chemicals showed significant associations with increased risk of albuminuria, reduced eGFR, or the composite outcome. These chemicals included metals and other chemicals that have not previously been associated with CKD. Serum and urine cotinines, blood 2,5-dimethylfuran (a volatile organic compound), and blood cadmium were associated with albuminuria. Blood lead and cadmium were associated with reduced eGFR. Blood cadmium and lead and three volatile compounds (blood 2,5-dimethylfuran, blood furan, and urinary phenylglyoxylic acid) were associated with the composite outcome. A total of 23 chemicals, including serum perfluorooctanoic acid, seven urinary metals, three urinary arsenics, urinary nitrate and thiocyanate, three urinary polycyclic aromatic hydrocarbons, and seven volatile organic compounds, were associated with lower risks of one or more manifestations of CKD. A number of chemicals were identified as potential risk factors for CKD among the general population.

Prevalence of Albuminuria in Cardiology and Endocrinology Departments and Its Influencing Factors: A Multicenter, Real-World Evidence Study in China.

Aims To evaluate the prevalence of albuminuria and compare its risk factors in diabetic and hypertensive patients. Methods This was an observational, cross-sectional, multicenter registry across China. Consecutive patients were registered with the Cardiology and Endocrine departments in 40 centers. Clinical characteristics were collected, and urinary albumin-to-creatinine ratio (UACR) was measured using the immunochemical method. Results Of the 2510 patients enrolled in the study, 1515 underwent UACR testing and were included in the present analysis. The prevalence of microalbuminuria was 13.0% and 16.1% while that of macroalbuminuria was 2.5% and 5.0%, in the Cardiology and Endocrinology departments, respectively. HbA1c and systolic blood pressure (SBP) were independent risk factors for albuminuria. The relationship of blood pressure (BP) and HbA1c with albuminuria was continuous and graded. Compared with the reference level of SBP 130–139 mm Hg, an SBP level of <130 mmHg was significantly associated with a lower risk of albuminuria in all subjects (OR = 0.60; 95% CI: 0.40–0.89; P < 0.001) and in subjects with concomitant hypertension and diabetes (OR = 0.48; 95% CI: 0.25–0.92; P < 0.001). Conclusions In China, nearly one-fifth of patients in the Cardiology and Endocrinology departments have albuminuria although ACEI/ARB were widely used. More effective therapy is needed in this population.

Correlation between sarcopenia and albuminuria in patients with type 2 diabetes

To investigate the correlation between sarcopenia and albuminuria in patients with type 2 diabetes mellitus (T2DM). A total of 360 T2DM patients (including 206 male and 154 female patients) hospitalized in our hospital between January, 2015 and December, 2018 were enrolled. According to their medical history and laboratory test results, the patients were divided into albuminuria group (n=122) and non-albuminuria group (n=238). The clinical and anthropological data were collected and skeletal muscle index (SMI), appendage lean mass, muscle index, total body fat, bone mineral capacity and bone mineral density were measured using dual-energy X-ray absorptiometry. Logistic regression was used to analyze the correlation of these body composition parameters with albuminuria or chronic kidney disease (CKD) in the diabetic patients. The disease course of T2DM, history of hypertension, age, systolic blood pressure, low density lipoprotein cholesterol, triglyceride, uric acid, waistline, Urinary albumin creatinine ratio, serum creatinine, and glomerular filtration rate differed significantly between the diabetic patients with albuminuria and those without albuminuria (P < 0.05). The prevalence rate of sarcopenia was significantly higher in patients with albuminuria (31.4% vs 13.1%, P < 0.01). Compared with those without albuminuria, the patients with albuminuria had significantly decreased SMI (t=-2.304, P=0.021) and body mass index (Z=- 5.534, P < 0.01) and significantly increased total body fat (Z=- 2.838, P=0.005). Multivariate logistic regression analysis showed that after adjustment for age, gender, total body fat, smoking history, drinking history, duration of diabetes, HbA1c, history of hypertension, systolic blood pressure, low density lipoprotein cholesterol, body mass index, and triglyceride, the patients with a decreased SMI had a significantly increased risk of albuminuria (P=0.011 and 0.010), but SMI was not correlated with the risk of CKD in patients with T2DM (P > 0.05). Sarcopenia is probably an independent risk factor for albuminuria in patients with T2DM.

SUN-110 THE EFFECT OF PRETERM BIRTH ON BLOOD PRESSURE AND RENAL FUNCTION IN ADOLESCENTS AND YOUNG ADULTS IN YAOUNDE

Both prematurity and low birth weight are associated with a higher risk of hypertension and chronic kidney disease in later life. However, most of the evidence stems from high income countries where better perinatal organisation and policies have greatly improved the survival of this population. In sub-Saharan Africa where the burden of prematurity is highest, data on the effect of preterm births on blood pressure and renal function in later life is lacking. Our aim was thus to investigate the effect of preterm birth on renal function and blood pressure in adolescents and young adults. We conducted a retrospective cohort study in selected secondary schools in Yaounde from January 2019 to April 2019. We included consenting/assenting adolescents and young adults born between January 1, 1994 and December 31, 2009. We excluded participants with no birth records, and those with known risk factors for kidney disease. Relevant perinatal data was obtained from interview of mothers and perinatal records. Participants were programmed for physical examination and handed sterile containers for first morning urine on the day of the physical examination. The infirmary of the schools served as the examination room. Three blood pressure measurements were taken 10 minutes apart and the mean value recorded. A venous blood sample was collected for serum creatinine assay while the urine sample was used to measure the urine albumin/ creatinine ratio (UACR). The glomerular filtration rate (GFR) was estimated by the modified Schwartz formula or the 4-variable MDRD equation when appropriate. Albuminuria was defined as a UACR >30mg/g. Preterm birth was defined as birth before 37 completed weeks of gestation and was classified as very preterm: < 32 weeks 6 days and near term: 33 weeks to 36 weeks 6 days of gestation. The study was approved by the regional ethics committee in Yaounde. A total of 153 participants (100 preterm births, 53 term births) were enrolled in the study. Their mean age was 15.33 (3.67) years with no difference between preterm and term birth groups. As expected, there was a significant decrease in birth weight with increasing severity of prematurity (p=0.001) Prematurity increased the risk of albuminuria by 80% (HR:1.8, 95%CI: 1.1-3.4, p=0.03). We found no significant effect of preterm birth on blood pressure (HR:1.2, 95%CI: 0.3-4.1, p=0.77), however, preterm births had a non-significantly higher blood pressure values compared to their term peers (115.3 vs 110.4 p=0.267). There was no effect of prematurity on eGFR (HR:2.1, 95%CI: 0.2-32.9, p=0.6); however, all 11(7.2%) participants with eGFR <60ml/min/1.73m2 were preterm births. No risk factors of renal function abnormalities were identified in pre-terms. Pre-term birth adversely affects renal function in Cameroonian adolescents and young adults. The effect of prematurity on blood pressure needs further studies.

Blood pressure and glucose control and the prevalence of albuminuria and left ventricular hypertrophy in patients with hypertension and diabetes.

We investigated association between blood pressure and glucose control and the prevalence of albuminuria and left ventricular hypertrophy (LVH) in patients with hypertension and diabetes. Our study participants were treated patients with both diseases, enrolled in a China nationwide registry. The 773 patients were classified into four groups according to the control status of hypertension (systolic/diastolic blood pressure [BP] ≤140/90mmHg) and diabetes (HbA1c <7.0%): both uncontrolled (n=208), only diabetes (n=175) or hypertension controlled (n=172), and both controlled (n=218). Albuminuria was defined as a urinary albumin-to-creatinine ratio of ≥30mg/g. LVH was assessed by the electrocardiogram Cornell product method. Antihypertensive therapy was not different between the four groups (P≥.48). The use of insulin alone or insulin plus oral antidiabetic agents was significantly higher than those with both diseases controlled (P≤.02). Patients with controlled hypertension and diabetes had a significantly (P<.0001) lower prevalence of albuminuria (odds ratio 0.22, 95% confidence interval 0.11-0.43) than those with both diseases uncontrolled. Intensive BP control to <130/80mmHg was associated with lower risks of albuminuria in all patients (P=.001) and patients with HbA1c <7.0% (P=.048). Intensive glycemic control to HbA1c <6.5% was also associated with a significantly lower risk of albuminuria in all patients (P=.01), but not those with controlled BP (P=.43). Similar trends were observed for LVH, but statistical significance was not achieved on either intensive control condition (P≥.07). In patients with hypertension and diabetes, blood pressure and glucose control were associated with a lower prevalence of albuminuria and LVH, especially when achieving a more stringent target.

The Risk of Albuminuria to The Ischemic Acute Patient With or Without Metabolic Syndrome

Stroke is not only a major cause of death, but also a leading cause of disability worldwide. Metabolic syndrome is one of the predictor of stroke since it has been linked to the development of atherosclerosis that will lead to cerebrovascular event. Albuminuria is known to be an indicator of endothelial dysfunction that is a major cause of cerebrovascular disease. In this study, 50 subjects of acute ischemic stroke consist of 25 subjects of acute ischemic stroke with metabolic syndrome and 25 subjects of acute ischemic stroke without metabolic syndrome. The ischemic stroke with metabolic syndrome population is significantly associated with increased risk of albuminuria 16 times higher than the ischemic stroke without metabolic syndrome (OR = 16, IK95% 1.855 – 137.97, p=0.002).Subjects of ischemic stroke with metabolic syndrome is significantly associated with increased risk of albuminuria.

Independent association between the visceral adiposity index and microalbuminuria in patients with newly diagnosed type 2 diabetes.

Visceral adiposity and albuminuria are commonly observed in patients with type 2 diabetes mellitus (T2DM). Recently, the visceral adipose index (VAI) was found to be an indicator of visceral fat accumulation. However, the relationship between the VAI and urinary albumin has not been investigated in T2DM patients, and whether the predictive value of the VAI is superior to that of the triglyceride/high-density lipoprotein cholesterol (TG/HDL-c) ratio remains unknown. Three hundred and forty one newly diagnosed T2DM patients were enrolled. The anthropometric parameters, blood pressure, glucose, lipid profiles, urinary albumin, and other biochemical indices were examined. Linear and logistic regression models were developed to assess the association between the VAI and urinary albumin. The prevalence of microalbuminuria was 41.3% (n=141) and increased with increasing levels of VAI. An age-adjusted partial correlation analysis showed that the VAI and TG/HDL-c ratio were significantly associated with the waist-to-hip ratio, heart rate, total cholesterol, low-density lipoprotein cholesterol, and uric acid. In the stepwise linear regression analysis, the VAI (β=.21, .009) and TG/HDL-c (β=.25, .002) were significant determinants of urinary albumin. Moreover, in the multiple logistic regression model, the odds ratio (OR) of microalbuminuria per one SD increase in the VAI was 1.94 (95% CI, 1.11-3.38), and a similar result was observed with a higher TG/HDL-c ratio (OR=2.03, 95% CI, 1.13-3.65). We are the first to show a clear association between the VAI and urinary albumin in Chinese type 2 diabetic patients. Additionally, the VAI and TG/HDL-c ratio had similar predictive power regarding albuminuria risk. The VAI could be a rapid and reliable tool for assessing early-stage renal damage in newly diagnosed T2DM patients.

Association of estimated dietary acid load with albuminuria in Japanese adults: a cross-sectional study

BackgroundAcid-base imbalance might promote the progression of chronic kidney disease (CKD), but whether nutrient-derived dietary acid load increases the risk of albuminuria or even high normoalbuminuria is unclear.MethodsA Japanese cohort comprising 3250 men and 3434 women aged 40–97 years with urine albumin-to-creatinine ratio (ACR) < 33.9 mg/mmol or estimated glomerular filtration rate ≥ 15 ml/min/1.73 m2 were assessed. We performed a cross-sectional evaluation of the association between net endogenous acid production (NEAP), estimated as dietary protein to potassium content ratio, and the presence of high normoalbuminuria (ACR: 1.13–3.38 mg/mmol) or microalbuminuria.ResultsMedian NEAP was 43.4 (interquartile range (IQR): 34.2–53.4) mEq/day in men and 35.0 (IQR: 27.7–43.6) mEq/day in women. Median ACR was 1.11 (IQR: 0.57–2.49) mg/mmol in men and 1.47 (IQR: 0.82–2.83) mg/mmol in women. In multivariate analysis, the adjusted odds ratio of the highest versus lowest NEAP quartile for microalbuminuria was 1.47 (95% confidence interval (CI): 1.08–1.99) in men and 1.54 (95% CI: 1.11–2.14) in women. For high normoalbuminuria or microalbuminuria, the adjusted odds ratio was 1.28 (95% CI: 1.02–1.59) in men and 1.39 (95% CI: 1.11–1.74) in women. From nutrient composition analysis, subjects with the highest potassium intake, but not protein intake, had lower adjusted odds ratios for the presence of microalbuminuria than those in the lowest quartile for potassium intake.ConclusionsHigher NEAP was associated with albuminuria and its association might negatively relate to potassium intake in an adult Japanese population.

A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia

Preeclampsia is a pregnancy-related syndrome of variable severity, classically characterized by acute kidney involvement, with hypertension and/or proteinuria and reduced kidney function. Once considered a self-limited disease healed by delivery, it is now acknowledged that preeclampsia can affect cardiovascular and kidney health in the long term. The entity of risk has not been established and consequently follow-up policies have not been defined. Here we undertook a systematic review to gain better insights into the need for post-preeclampsia follow-up. Articles published between January 2000 and March 2018 were selected, dealing with at least 20 preeclampsia patients, with follow-up of 4 years or more (MEDLINE, Embase, and Cochrane Library). No quality selection or language restriction was performed. Of the 10,510 titles and abstracts originally considered, 21 papers were selected, providing information on 110,803 cases with and 2,680,929 controls without preeclampsia, with partial overlap between studies on the same databases. Heterogeneity was high, and a random meta-analytic model selected. The increase in risk of end stage renal disease after preeclampsia was significant (meta-analytic risk ratios (95% confidence interval) 6.35 (2.73-14.79)); the risk of albuminuria and chronic kidney disease increased but statistical significance was not reached (4.31 (0.95-19.58) and 2.03 (0.58-7.32), respectively). Translating meta-analytic risk into the number of patients who need follow-up to detect one adverse event, 310 patients with preeclampsia are needed to identify one woman with end stage renal disease or four to identify one woman with albuminuria. Heterogeneity in definitions, insufficient follow-up and incomplete recruitment may account for discrepancies. Thus, preeclampsia significantly increases the risk of end stage renal disease. However, there is lack of sufficient data to show a relationship between preeclampsia, albuminuria and chronic kidney disease, underlining the need for further prospective studies.

Body-mass index and the risk of albuminuria in hypertensive patients with a poor estimated glomerular filtration rate and the potential role of diabetes mellitus

BackgroundObesity-related to metabolic syndrome was associated with a greater risk for development of chronic kidney disease (CKD). We aimed to assess the association between obesity and micro/macroalbuminuria in hypertensive patients with a poor estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. MethodsOne hundred old patients (median age 79 years ± inter-quartile range 68–84.7) with manifested hypertension (systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 85 mmHg) and a permanently poor eGFR for a duration time more than 3 months were enclosed. Albuminuria was defined as urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/gr and it was classified according to KDIGO 2012. The obesity was defined by a high body mass index (BMI>30 kg/m2). The waist circumference, HDL-C, triglycerides and serum glucose were measured. Chi-square tests and an adjusted model were performed. ResultsChi-square tests showed significant association between classified albuminuria and both obesity and high serum triglycerides (x2 = 7.2, p = 0.02 and x2 = 8.3, p = 0.01 respectively). However, the adjusted model for the prediction of albuminuria showed that the presence of a high BMI was a non-significant risk factor, although diabetes mellitus and eGFR value were found to be significant risk factors (p = 0.03, OR = 4.3, 1.2–22.07 and p = 0.04, OR = 0.9, 0.9–1.007 respectively) adjusting to covariates including the high waist circumference. ConclusionObesity defined by a high BMI was not found to be a significant risk factor for micro/macroalbuminuria in hypertensive patients with a poor estimated glomerular filtration rate, when diabetes mellitus and the low eGFR value act as confounders.

Lower Leg Fat Depots Are Associated with Albuminuria Independently of Obesity, Insulin Resistance, and Metabolic Syndrome (Korea National Health and Nutrition Examination Surveys 2008 to 2011).

BackgroundAlthough the involvement of obesity in metabolic disorders is well known, leg fat depot influences on albuminuria have not been determined.MethodsThis population-based, cross-sectional study used a nationally representative sample of 2,076 subjects aged ≥20 years from the Korea National Health and Nutrition Examination Surveys of 2008 to 2011. The ratio of leg fat to total fat (LF/TF ratio) was assessed by dual X-ray absorptiometry, and albuminuria was defined as more than one positive dipstick test or an albumin-to-creatinine ratio of ≥30 mg/g.ResultsIndividuals whose LF/TF ratio was in the lowest tertile showed a higher proportion of albuminuria than those in the highest tertile (odds ratio [OR], 2.82; 95% confidence interval [CI], 2.01 to 3.96; P<0.001). This association was observed in both sexes, all age groups, and all subgroups stratified by body mass index, waist circumference, homeostasis model assessments of insulin resistance, and the presence of metabolic syndrome (all, P<0.05). Multiple logistic regression analyses also demonstrated that the lowest LF/TF ratio was independently associated with albuminuria risk (OR, 1.55 to 2.16; all, P<0.05). In addition, the risk of albuminuria was higher in sarcopenic individuals with lower LF/TF ratios than in the highest LF/TF ratio subjects without sarcopenia (OR, 3.73; 95% CI, 2.26 to 6.13).ConclusionA lower LF/TF ratio was associated with an increased risk of albuminuria independent of obesity, insulin resistance, and metabolic syndrome, and when combined with sarcopenia, the albuminuria risk synergistically increased. Hence, our findings may have implications to improve risk stratification and recommendations on body fat distribution in the general population.

Children with Sickle Cell Anemia and APOL1 Gene Variants Develop Albuminuria Early in Life

Introduction: Gene variants in the apolipoprotein L-1 (APOL1) gene are strong modifiers for the development of chronic kidney disease in individuals of African descent and are associated with progression of renal disease and albuminuria in cross-sectional studies of individuals with sickle cell anemia (SCA). While the association of APOL1 with albuminuria in older SCA patients is established, it is unclear whether participants with APOL1 G1 (rs73885319/ rs6090145) and G2 (rs71785313) variants (Ashley-Koch Br J Hematol 2011; Kormann Br J Haematol 2017) are more likely to develop albuminuria early in life. We hypothesized that individuals with SCA with the APOL1 G1 and G2 variants experience albuminuria at a higher rate and at a younger age than individuals without these APOL1 mutations.Methods: APOL1 G1 (rs73885319/ rs6090145) and G2 (rs71785313) variants were identified from whole genome sequence (WGS) data for individuals with SCA (HbSS or HbSβ0 thalassemia) enrolled in the longitudinal Sickle Cell Clinical Research and Intervention Program (SCCRIP; NCT02098863) (Hankins et al, Pediatr Blood Cancer 2018). WGS data were generated by aligning paired-end 150 bp reads to the GRCh38 human reference using the Burrows-Wheeler Aligner (BWA-ALN v0.7.12) and the GATK best-practices workflow implemented in GATK v3.4.0. We modeled the time to first albuminuria diagnosis defined by abnormal urine albumin:creatinine ratio (>30mg/g). Covariates included age, sex, and hydroxyurea therapy. We considered two risk models. Model 1 defined high risk APOL1 mutation as either APOL1 G1 homozygotes or G2 homozygotes or G1/G2 double heterozygotes. Model 2 was defined additively wherein G1 or G2 homozygotes were assumed to confer more risk compared to G1/G2 double heterozygotes.Results: In 285 individuals with SCA, 93% (n=266) with HbSS and 7% (n=19) with HbSβ0 thalassemia, 14% (n=41) experienced albuminuria at a mean age of 11.4 (±3.3) years. In total, 11% (n=32) of this SCA cohort had an APOL1 mutation; 6% (n=17) were G1/G2 double heterozygote, 4% (n=11) were G1 homozygotes, and 1% (n=4) were G2 homozygotes. Among the 32 participants with an APOL1 mutation, 40% (n=13) had albuminuria as compared to 11% (n=28) of the 253 participants without an APOL1 mutation (OR: 9.85, 95% CI 3.84-25.25). There was also a significant association with albuminuria based on the additive genetic model (OR: 4.38, 95% CI 2.39 -8.02) (Table). In a survival analysis, participants with an APOL1 mutation had a hazard ratio (HR) of 3.75 (95% CI: 1.93-7.29, p<0.0001) associated with time to diagnosis of albuminuria compared with individuals with other non-risk APOL1 genotypes. The mean age for individuals having albuminuria with APOL1 G1/G2 risk alleles was 9.8 (±3.2) years, roughly 2 years younger than those without the risk alleles (11.8 ±4.7 years) (Satterthwaite t value=3.10, p=0.003). APOL1 G1 alleles also contributed individual risk of albuminuria (HR=1.66, p=0.0374).Summary: Our analyses found that pediatric individuals with SCA who have APOL1 two risk alleles are at high risk of developing albuminuria which many will experience early in childhood. This important finding has significant implications for clinical care. First, using a genetic screening program for all patients with SCAC can identify individuals with APOL1 mutations. Second, individuals with SCA and an APOL1 mutation should be screened for albuminuria during childhood. Finally, early initiation of therapeutic strategies to ameliorate renal dysfunction needs to be evaluated in the presence of APOL1 mutations. [Display omitted] DisclosuresHankins:Global Blood Therapeutics: Research Funding; Novartis: Research Funding; NCQA: Consultancy; bluebird bio: Consultancy. Estepp:ASH Scholar: Research Funding; Daiichi Sankyo: Consultancy; NHLBI: Research Funding; Global Blood Therapeutics: Consultancy, Research Funding.

Phthalates Exposure as Determinant of Albuminuria in Subjects With Type 2 Diabetes: A Cross-Sectional Study.

Recent epidemiological observations have reported an association among phthalates exposure and insulin resistance, obesity, and diabetes but have not related exposure to these environmental pollutants with microvascular complications of diabetes. To explore the relationship between phthalates and renal function in subjects with diabetes. Cross-sectional, case-only study. Concentrations of three urinary metabolites of di-2-ethylhexylphthalate were quantified in a spot morning urine sample, normalized for creatinine urinary excretion, and related to clinical parameters and phenotype, adjusting for confounders. Two hundred and nine patients with diabetes consecutively referred to our clinic. Relationship between phthalates and renal function [evaluated with estimated glomerular filtration rate (eGFR) and albuminuria]. Creatinine-adjusted urinary concentrations of mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-2-ethyl-5-hydroxyhexyl phthalate were 7.53 µg/g (range, 4.84 to 12.60), 3.04 µg/g (range, 1.03 to 5.14), and 10.70 µg/g (7.02 to 17.40), respectively. Age, sex, body mass index, diabetes duration, smoking, blood pressure, glycated Hb, and eGFR did not influence their levels. Exposure to MEHP and MEOHP was greater in individuals with microalbuminuria/macroalbuminuria (MEHP, P = 0.0173; MEOHP, P = 0.0306). The fourth vs first quartile showed a greater risk of albuminuria (MEHP: OR, 4.83; 95% CI, 1.45 to 16.06; P = 0.0297; MEOHP: OR, 3.29; 95% CI, 1.08 to 10.04); P = 0.0352). MEOHP was greater (P = 0.034) in subjects with cardiovascular events; MEHP showed a positive trend (P = 0.061). Our findings have revealed an association between exposure to di-2-ethylhexylphthalate metabolites and the degree of albuminuria in subjects with diabetes; the lack of a relationship with eGFR suggests their urinary levels are independent of renal function.