Risk Of Proteinuria Research Articles

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.

PAIT-survey—Prevalence of albuminuria in patients with diabetes and hypertension in Turkey

BackgroundAlbuminuria is an early marker of kidney disease in patients with diabetes and/or hypertension undetected or untreated albuminuria is a leading cause of chronic kidney disease and cardiovascular events, The purpose of the present survey was to assess the prevalence of albuminuria in patients with diabetes and hypertension, treated with a combinations of renin angiotensin aldosterone system inhibitors and dihydropyridine calcium channel blockers. MethodsThe survey was performed in 105 Primary Care Units in Turkey and involved outpatients, routinely visited by either a specialist or a non-specialist physician.Albuminuria was evaluated in a spot morning urine sample, as albumin–creatinine ratio, using the Multistic-Clinitek-device analyzer (Siemens), that has a strong correlation with 24-h urinary albumin excretion. Microalbuminuria was defined as a loss of 3.4–33.9mg albumin/mmol creatinine and macroalbuminuria as a loss of >33.9mg albumin/mmol creatinine. Diabetes was assessed through documented blood glucose concentration or use antidiabetic drugs, whereas hypertension through blood pressure measurement and current antihypertensive treatment. ResultsThe survey enrolled 1708 subjects with a prevalence of type 2 diabetes (87.6%). Albuminuria was detected in 52.0% of patients. Blood pressure was controlled in 37.0% and diabetes in 56.7%. The risk of albuminuria was significantly high in patients with uncontrolled diabetes (p<0.001) and blood pressure (p=0.009). ConclusionsIn a large cohort of treated hypertensive patients with diabetes, albuminuria was present in about 50% and was correlated with poor diabetes and blood pressure control. Systematic screening of albuminuria, particularly in Primary Care, is an important tool for the early diagnosis of nephropathy.

Towards adulthood with a solitary kidney.

Around 1/1000 people have a solitary kidney. Congenital conditions mainly include multicystic dysplastic kidney and unilateral renal aplasia/agenesis; acquired conditions are secondary to nephrectomy performed because of urologic structural abnormalities, severe parenchymal infection, renal trauma, and renal or pararenal tumors. Children born with congenital solitary kidney have a better long-term glomerular filtration rate than those with solitary kidney secondary to nephrectomy later in life. Acute and chronic adaptation processes lead to hyperfiltration followed by fibrosis in the remnant kidney, with further risk of albuminuria, arterial hypertension, and impaired renal function. Protective measures rely on non-pharmacological renoprotection (controlled protein and sodium intake, avoidance/limitation of nephrotoxic agents, keeping normal body mass index, and limitation of tobacco exposure). Lifelong monitoring should include blood pressure and albuminuria assessment, completed by glomerular filtration rate (GFR) estimation in case of abnormal values. In the absence of additional risk factors to solitary kidney, such assessment can be proposed every 5years. There is no current consensus for indication and timing of pharmacological intervention.

Nonalcoholic fatty liver disease and albuminuria: a systematic review and meta-analysis.

The relationship between nonalcoholic fatty liver disease (NAFLD) and albuminuria has been shown in many epidemiologic studies, although the results were inconsistent. This meta-analysis was conducted to summarize all available data and to estimate the risk of albuminuria among patients with NAFLD. Comprehensive literature review was conducted utilizing Medline and Embase database through January 2018 to identify studies that compared the risk of albuminuria among patients with NAFLD versus those without NAFLD. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Nineteen studies (17 cross-sectional studies and two cohort studies) with 24 804 participants fulfilled the eligibility criteria and were included in this meta-analysis. The risk of albuminuria among patients with NAFLD was significantly higher than those without NAFLD with the pooled odds ratio (OR) of 1.67 [95% confidence interval (CI): 1.32-2.11]. Subgroup analysis demonstrated the significantly increased risk of albuminuria among patients with NAFLD without diabetes with pooled OR of 2.25 (95% CI: 1.65-3.06). However, we found no significant association between albuminuria and NAFLD among diabetic patients [pooled OR 1.28 (95% CI: 0.94-1.75)]. A significantly increased risk of albuminuria among patients with NAFLD was observed in this meta-analysis. Physicians should pay more attention to the early detection and subsequent treatment of individuals with microalbuminuria especially in patients with NAFLD.

Dietary Potential Renal Acid Load and Risk of Albuminuria and Reduced Kidney Function in the Jackson Heart Study

Diets high in sulfur-rich protein and low in fruit and vegetables affect human acid-base balance adversely and may have a harmful effect on progression of chronic kidney disease (CKD). Little is known about the relationship of participant characteristics, dietary acid load (DAL), and kidney injury in African-Americans with high risk of CKD progression. We examined the association of DAL with CKD in 3,257 African-Americans aged >20years in Jackson Heart Study. DAL was measured with nutrient intakes assessed with a food frequency questionnaire, using a model described by Remer and Manz. We tested associations of participant characteristics with DAL using median regression, and associations of DAL with albuminuria (>17mg/g for men, >25mg/g for women), reduced kidney function (eGFR <60mL/minute/1.73m2), or CKD defined as albuminuria or reduced kidney function using logistic regression. We further explored whether endothelin and aldosterone production in participants with hypertension mediated risk of albuminuria or reduced kidney function due to the intake of an acid-inducing diet. Younger adults, men, and those with higher body mass index had higher DAL. Higher DAL, compared with lower, was associated with greater odds of reduced kidney function (OR [95% CI]: 2.82 [1.40-4.75]). Higher DAL was also associated with greater risk of CKD, and this persisted after adjustment for confounders. Results were similar in adults with hypertension; the OR [95% CI] for highest, versus lowest, tertile of DAL with albuminuria was 1.66 [1.01-2.59]. Aldosterone and endothelin mediated the association between DAL and albuminuria; the OR [95% CI] in the highest tertile was no longer significant 1.53 [0.97-2.40] after their inclusion. Higher DAL was associated with higher prevalence of CKD and with reduced kidney function. DAL may be an important target for future interventions in African-Americans at high risk of CKD.

Non-alcoholic fatty liver disease and risk of developing chronic kidney disease: a new piece of a recent puzzle from a large Asian study

In a recent cross-sectional study published on J Hepatol, Yeung et al. have showed that advanced liver fibrosis (detected by transient elastography), which is a severe form of non-alcoholic fatty liver disease (NAFLD), was associated with an increased risk of albuminuria in a cohort of approximately 1,800 Chinese patients with type 2 diabetes mellitus, independent of several cardio-metabolic risk factors (1).

Cigarette smoking and risk of albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis ofobservational studies.

The aim of this study was to assess the effects of smoking on albuminuria risk in adults with type 2 diabetes mellitus (T2DM). A literature search was conducted using MEDLINE, EMBASE, and China National Knowledge Infrastructure from the established date to October 2017. Summary relative risks (SRR) and 95% confidence intervals (CI) were computed utilizing a random effect inverse variance method. This meta-analysis included a total of 19 relevant observational studies (four prospective cohort, seven case-control, and eight cross-sectional studies), reporting 105,031 participants and 23,366 albuminuria events. Compared with never-smokers with T2DM, the SRRs of albuminuria were 1.43 (95% CIs 1.27-1.61) for ever-smokers, 2.61 (95% CIs 1.86-3.64) for current smokers, and 1.86 (95% CIs 1.37-2.52) for former smokers. Considerable heterogeneity was observed among these studies, and study design was a significant modifier for this association. There were significantly elevated risk associations for microalbuminuria (SRRs=1.24, 95% CIs 1.05-1.46) and for macroalbuminuria (SRRs=1.65, 95% CIs 1.03-2.66), respectively. Our systematic review and meta-analysis indicates that cigarette smoking might be a potential factor for the development of albuminuria in adults with T2DM. Future studies are required to investigate the association between smoking cessation and intensity and incident albuminuria in adults with T2DM.

Differential Association of Vitamin D Deficiency With Albuminuria by Sex in the Korean General Population: A Cross-sectional Study of the Korea National Health and Nutrition Examination Survey 2011-2012.

ObjectivesAlbuminuria has emerged as a biomarker for several medical conditions, and vitamin D has received attention due to its associations with various disorders. We evaluated the association between low serum vitamin D levels and prevalent albuminuria by sex in the Korean general population. MethodsWe analyzed 9823 participants (4401 males, 5422 females) from the Korea National Health and Nutrition Examination Survey 2011-2012 (KNHANES V-2), and categorized them as having a normal range of vitamin D levels, vitamin D insufficiency, or vitamin D deficiency. A multivariable logistic regression model was used to compare the risk of albuminuria across these groups. Stratified analyses were conducted by smoking status, obesity, and renal function. ResultsAlbuminuria was found in 325 of the 4401 male participants (7.4%) and in 455 of the 5422 female participants (8.4%). Among the males, vitamin D deficiency was associated with an odds ratio (OR) for albuminuria of 1.78 (95% confidence interval [CI], 1.07 to 2.97, p<0.05). However, such an association was not found in females. The association was stronger in male current smokers (OR, 3.54; 95% CI, 1.47 to 8.50; p=0.005). ConclusionsThe findings of this study suggest that sex differences exist in the association between serum vitamin D deficiency and albuminuria. Additionally, we observed that the association was stronger in current smokers than in the overall male population, but was not seen in non-smokers. Therefore, different approaches by sex and smoking status might be needed when considering using vitamin D as a biomarker for renal function.

Metabolic Syndrome and Chronic Renal Disease.

Background: The influence of metabolic syndrome (MetS) on kidneys is related to many complications. We aimed to assess the association between MetS and chronic renal disease defined by a poor estimated glomerular filtration rate (eGFR) and/or the presence of microalbuminuria/macroalbuminuria. Methods: 149 patients (77 males/72 females) were enrolled in the study. Chronic renal disease was defined according to KDIGO 2012 criteria based on eGFR category and classified albuminuria. MetS was studied as a dichotomous variable (0 to 5 components) including hypertension, waist circumference, low HDL-cholesterol, high triglycerides, and high glucose. Results: The association between clustering MetS and both classified eGFR and classified albuminuria (x2 = 50.3, p = 0.001 and x2 = 26.9, p = 0.003 respectively) was found to be significant. The MetS presence showed an odds 5.3-fold (1.6–17.8) higher for low eGFR and 3.2-fold (1.2–8.8) higher for albuminuria in combination with the presence of diabetes mellitus, which also increased the risk for albuminuria by 3.5-fold (1.1–11.3). Albuminuria was significantly associated with high triglycerides, hypertension, high glucose (x2 = 11.8, p = 0.003, x2 = 11.4, p = 0.003 and x2 = 9.1, p = 0.01 respectively), and it was mildly associated with a low HDL-C (x2 = 5.7, p = 0.06). A significant association between classified eGFR and both high triglycerides and hypertension (x2 = 9.7, p = 0.04 and x2 = 16.1, p = 0.003 respectively) was found. Conclusion: The clustering of MetS was significantly associated with chronic renal disease defined by both classified eGFR and albuminuria. The definition of impaired renal function by classified albuminuria was associated with more MetS components rather than the evaluation of eGFR category. MetS may contribute to the manifestation of albuminuria in patients with diabetes mellitus.

Associations of sodium intake with obesity, metabolic disorder, and albuminuria according to age.

Sodium intake is associated with obesity and metabolic disorder in the general population. However, sodium intake is significantly reduced according to the decrease of energy intake in older adults although the prevalence of obesity is higher than younger adults. We evaluate the association of sodium excretion (UNa) with blood pressure, obesity, metabolic disorders, and albuminuria according to age. An observational study using data from the Korean National Health and Nutrition Examination Survey IV-V (2008–2011) was performed (N = 18,146). The 24 hour UNa was estimated from a single fasting urine sample.Participants aged≥75 years showed the highest risk for hypertension (HTN) in the highest quartile of UNa (1.769, 95% CI, 1.174–2.665), and the risks for HTN increased with advancing age. Obesity was not associated with UNa in participants aged≥75 years, and hypertriglyceridemia and body fat were not related to UNa in participants aged≥65 years, although these values were significantly associated with UNa in participants aged<65 years. Impaired fasting glucose (IFG) and insulin resistance (IR) were associated with UNa only in participants aged 20–39 years. The highest quartile of UNa showed a 3.777 fold increased risk for albuminuria in those aged 20–39 years (95% CI, 1.130–12.630), and a 1.885 fold increased risk (95% CI, 1.156–3.075) among participants aged 40–64 years. In participants aged≥65 years, albuminuria was not associated with UNa. In contrast with HTN, UNa was not associated with albuminuria, obesity, hypertriglyceridemia, IFG, and IR in older adults despite a strong association in younger adults.

Advanced liver fibrosis but not steatosis is independently associated with albuminuria in Chinese patients with type 2 diabetes

Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for chronic kidney disease (CKD). Given the high prevalence of NAFLD among patients with diabetes who are also at risk of CKD, we aimed to investigate the association between NAFLD and albuminuria, a marker commonly found in diabetic nephropathy. This study included a cohort of Chinese patients with type 2 diabetes from the Hong Kong Diabetes Registry recruited between March 2013 and May 2014. Liver stiffness measurement (LSM), with probe-specific cut-offs, was used to detect advanced liver fibrosis. While controlled attenuation parameter (CAP) was used to assess liver steatosis using transient elastography. A total of 1,763 Chinese patients with type 2 diabetes were recruited in this analysis. The mean (standard deviation) age and duration of diabetes were 60.7 (11.5) years and 10.8 (8.5) years, respectively. The prevalence of albuminuria was higher in diabetic patients with liver steatosis and those with advanced fibrosis (no NAFLD vs. liver steatosis vs. advanced fibrosis: 41.4% vs. 46.2% vs. 64.2%, p <0.001). After adjustment for potential confounders including glycated hemoglobin, hypertension and body mass index, advanced fibrosis, but not liver steatosis, was associated with increased risk of albuminuria (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.02-2.28; p = 0.039) in patients with eGFR ≥60 ml/min/1.73 m2. The odds of albuminuria increased with greater severity of liver fibrosis in a dose dependent manner, with the highest odds observed in patients with LSM scores ≥11.5 kPa assessed by M probe or ≥11.0 kPa assessed by XL probe (adjusted OR 1.53; 95% CI 1.07-2.20; p = 0.021). Advanced liver fibrosis, but not steatosis, is independently associated with albuminuria in Chinese patients with type 2 diabetes. Attention should be paid to liver fibrosis in patients with obesity and type 2 diabetes complicated with albuminuria. In this study, we assessed the link between non-alcoholic fatty liver disease (NAFLD) and albuminuria in a cohort of 1,763 Chinese patients with type 2 diabetes. This study shows that advanced liver fibrosis, a severe form of NAFLD, was independently associated with increased risk of albuminuria. The risk of albuminuria increased with greater severity of liver fibrosis.

The incidences of and risk factors for severe retinopathy requiring photocoagulation and albuminuria in Japanese patients with childhood-onset type 1 diabetes.

The aim of this study was to clarify the incidences of and the risk factors for severe retinopathy requiring photocoagulation therapy and albuminuria in Japanese patients with childhood-onset type 1 diabetes mellitus. A total of 756 patients from a cohort study by the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes were included in the study. Patients were registered in 1995 or 2000, and HbA1cwas measured every 4months and analyzed in central hospital for an average of 6years. The presence of severe retinopathy requiring laser photocoagulation and the presence of albuminuria was checked for during the period 2010-2011. During a median of 18 (range: 15-21) years, 34 out of 756 patients underwent laser photocoagulation and 57 out of 605 patients developed albuminuria. A Cox proportional hazards model showed that the risk of severe retinopathy requiring laser photocoagulation increased by 1.15 (95% confidence interval [CI] 1.03-1.29, p=0.012) with each increase of a year in the age at onset, by 4.03 (95% CI 1.20-13.5, p=0.024) in females, and by 2.05 (95% CI 1.69-2.49, p<0.0001) with each increase of 1% in HbA1c. The risk of albuminuria increased significantly, by 1.09 (95% CI 1.01-1.18 p=0.037), with each increase of a year in the age at onset and by 2.38 (95% CI 1.93-2.97 p<0.0001) with each increase of 1% in HbA1c. In Japanese patients with childhood-onset type 1 diabetes, older age at the onset of diabetes, female rather than male gender, and higher HbA1c were found to increase the risk of requiring photocoagulation. No patients with HbA1c < 7.5% developed severe retinopathy requiring photocoagulation therapy. The risk of developing albuminuria increased with age at onset of diabetes and HbA1c. Female gender was a strong risk factor for severe retinopathy requiring photocoagulation, but not for albuminuria.

Genome-wide association studies of albuminuria: towards genetic stratification in diabetes?

Genome-wide association studies (GWAS) have been very successful in unraveling the polygenic structure of several complex diseases and traits. In the case of albuminuria, despite the large sample size achieved by some studies, results look sparse with a limited number of loci reported so far. This review searched for GWAS studies of albumin excretion, albuminuria, and proteinuria. The resulting picture sets elements of uniqueness for albuminuria GWAS with respect to other complex traits. So far, very few loci associated with albuminuria have been validated by means of genome-wide significant evidence or formal replication. With rare exceptions, the validated loci are ethnicity specific. Within a given ethnicity, variants are common and have relatively large effects, especially in the presence of diabetes. In most cases, the identified variants were functional and a biological involvement of the target genes in renal damage was established. Recently reported variants associated with albuminuria in diabetes may be potentially combined into a genetic risk score, making it possible to rank diabetic patients by increasing risk of albuminuria. Validation of this model is required. To expand the understanding of the biological basis of albumin excretion regulation, future initiatives should achieve larger sample sizes and favor a transethnic study design.

Gestational Diabetes and Subsequent Risk of Albuminuria in Later Life Among US Women

Local dispersion relations for resistive drift mode in a nonuniform magnetize plasma are derived for thermal and non-thermal distribution of electrons. The coupled mode equations are obtained by using Braginskii's transport equations for ions and electrons with thermal as well as non-thermal (Cairns and kappa) distribution for electrons. The dispersion relations are then analyzed both analytically as well as numerically for all distributions. It is found that growth rate is highest for Maxwellian, Intermediate for kappa and lowest for Cairns distribution. It has been found that increasing values of Γ (which estimate population of non-thermal electrons) for Cairn distributed electrons are able to stabilize the mode. Furthermore, increasing the values of κ (which is spectral index) for the kappa distributed electrons have destabilizing effects on the mode. The result might be useful in the interpretation of electromagnetic fluctuations in nonuniform magneto-plasma in which resistivity is a key element in calculation of drift instabilities in the presence of thermal or nonthermal electron distributions, such systems are extensively observed in laboratory as well as space plasma.

Glycated Hemoglobin is Independently Associated with Albuminuria in Young Nondiabetic People with Obesity: A Cross-Sectional Study.

BackgroundThe aim of this study was to explore the association between glycated hemoglobin (HbA1c) level and albuminuria in young nondiabetic people with obesity.Material/MethodsA total of 537 young nondiabetic people with obesity were enrolled in this cross-sectional study, which was approved by the Rui-jin Hospital Ethics Committee. Albuminuria was defined as a urinary albumin-to-creatinine ratio (ACR) ≥30 mg/g. Multivariate logistic regression was used to analyze the association between HbA1c level and albuminuria.ResultsUrinary ACR progressively increased across the tertiles of HbA1c level (P for trend <0.05). HbA1c levels were positively associated with the risk of albuminuria in the logistic regression analysis after adjustment for confounding factors. The adjusted odds ratio (OR) for albuminuria was 3.72 (95% confidence interval [CI], 1.25–11.00; P=0.017) when comparing between the highest (≥5.7%) and lowest tertiles of HbA1c level (≤5.3%). Moreover, an increment of 1 SD in HbA1c level increased the risk of albuminuria in a fully adjusted model (OR, 1.73; 95% CI, 1.25–2.46).ConclusionsThese data suggest that HbA1c level was independently associated with albuminuria in young nondiabetic people with obesity.

Sarcopenia is associated with incident albuminuria in patients with type 2 diabetes: A retrospective observational study.

Sarcopenia, defined as age‐related loss of skeletal muscle mass and function, increases the risk of albuminuria. However, it has still unknown whether sarcopenia could increase the risk for the progression of albuminuria. A total 238 patients with type 2 diabetes (mean age 64 ± 12 years; 39.2% women) were studied in the present retrospective observational study. The prevalence of sarcopenia was 17.6%. During the median follow‐up period of 2.6 years, albuminuria was measured 5.8 ± 1.8 times, and progression of albuminuria was observed in 14.9% of patients with normoalbuminuria, as was 11.5% in those with microalbuminuria. Sarcopenia was significantly associated with both progression (hazard ratio 2.61, 95% confidence interval 1.08–6.31, P = 0.034) and regression (hazard ratio 0.23, 95% confidence interval 0.05–0.98, P = 0.048) of albuminuria by multivariate Cox regression analysis. The present data suggest that sarcopenia is an important determinant of both progression and regression of albuminuria in patients with type 2 diabetes.

Cardiovascular risk factors and incident albuminuria in screen-detected type 2 diabetes.

It is unclear whether cardiovascular risk factor modification influences the development of renal disease in people with type 2 diabetes identified through screening. We determined predictors of albuminuria 5years after a diagnosis of screen-detected diabetes within the ADDITION-Europe study, a pragmatic cardiovascular outcome trial of multifactorial cardiovascular risk management. In 1826 participants with newly diagnosed, screen-detected diabetes without albuminuria, we explored associations between risk of new albuminuria (≥2.5mgmmol-1 for males and ≥3.5mgmmol-1 for females) and (1) baseline cardio-metabolic risk factors and (2) changes from baseline to 1year in systolic blood pressure (ΔSBP) and glycated haemoglobin (ΔHbA1c ) using logistic regression. Albuminuria developed in 268 (15%) participants; baseline body mass index and active smoking were independently associated with new onset albuminuria in 5years after detection of diabetes. In a model adjusted for age, gender, baseline HbA1c and blood pressure, a 1% decrease in HbA1c and 5-mmHg decrease in SBP during the first year were independently associated with lower risks of albuminuria (odds ratio), 95% confidence interval: 0.76, 0.62 to 0.91 and 0.94, 0.88 to 1.01, respectively. Further adjustment did not materially change these estimates. There was no interaction between ΔSBP and ΔHbA1c in relation to albuminuria risk, suggesting likely additive effects on renal microvascular disease. Baseline measurements and changes in HbA1c and SBP a year after diagnosis of diabetes through screening independently associate with new onset albuminuria 4years later. Established multifactorial treatment for diabetes applies to cases identified through screening.

Albuminuria, renal function and blood pressure in undernourished children and recovered from undernutrition.

The objective of this study was to investigate some biomarkers of renal function and blood pressure in children who had recovered from undernutrition. This was cross-sectional, comparative study in which a convenience sample of children of both genders (n = 126; age range 6-16 years) treated at the Centre for Nutritional Recovery and Education (São Paulo, Brazil) was used. These children were classified into four groups for analysis: (1) children who were well nourished (control group; n = 50), (2) those showing stunted growth (stunted group; n = 22), (3) those who were underweight (underweight group; n = 23) and (4) those who had recovered from undernutrition (recovered group; n = 31). No between-group differences were found for mean levels of albuminuria, serum creatinine and cystatin C, and similar mean estimates of glomerular filtration rate (eGFR; using either creatinine, cystatin C or both). Almost 14% of the stunted group, 4% of the underweight group and 3% of the recovered group had albuminuria of >30mg/g creatinine (chi-square p = 0.034); none of the control children showed albuminuria of >30mg/g creatinine. Mean systolic (SBP) and diastolic blood pressure (DBP) adjusted for age and gender of the children in the stunted [SBP (95% confidence interval): 92 (88-96)mmHg; DBP: 47 (44-49)mmHg] and recovered [SBP: 93 (90-96)mmHg; DBP: 49 (47-51)mmHg] groups were significantly lower than those of the controls [SBP: 98 (95-100)mmHg, P = 0.027; DBP: 53 (52-55)mmHg, P = 0.001]. After additional adjustment for height, mean DBP remained significantly lower in the recovered group compared with the control group [49 (46-51) vs. 53 (51-55)mmHg, respectively; P = 0.018). Logistic regression analysis showed that the stunted group had a 8.4-fold higher chance of developing albuminuria (>10mg/g creatinine) than the control children (P = 0.006). No alterations in renal function were found in underweight children and those who had recovered from undernutrition, whereas children with stunted growth presented with a greater risk for albuminuria. A lower DBP was found in children with stunted growth and those who had recovered from undernutrition.

HbA1c variability in type 2 diabetes is associated with the occurrence of new-onset albuminuria within three years.

To evaluate the association between HbA1c coefficient of variation (HbA1c-CV) and 3-year new-onset albuminuria risk. A retrospective cohort study involving 716 normoalbuminuric type 2 diabetes patients was conducted between 2010 and 2014. HbA1c-CV was used to categorize patients into low, moderate or high variability groups. Multivariate logistic models were constructed and validated. Integrated discrimination (IDI) and net reclassification (NRI) improvement indices were used to quantify the added predictive value of HbA1c-CV. The mean age of our cohort was 56.1±12.9years with a baseline HbA1c of 8.3±1.3%. Over 3-years of follow-up, 35.2% (n=252) developed albuminuria. An incremental risk of albuminuria was observed with moderate (6.68-13.43%) and high (above 13.44%) HbA1c-CV categories demonstrating adjusted odds ratios of 1.63 (1.12-2.38) and 3.80 (2.10-6.97) for 3-year new-onset albuminuria, respectively. Including HbA1c-CV for 3-year new-onset albuminuria prediction improved model discrimination (IDI: 0.023, NRI: 0.293, p<0.05). The final model had a C-statistic of 0.760±0.018 on validation. HbA1c-CV improves 3-year prediction of new-onset albuminuria. Together with mean HbA1c, baseline urine albumin-to-creatinine ratio and presence of hypertension, accurate 3-year new-onset albuminuria prediction may be possible.