Microalbuminuria is defined as increased urinary albumin excretion (30-300 mg/day) or microalbumin/creatinine ratio (30-300 mg/g) in a spot urine sample. Although microalbuminuria is a predictor of clinical nephropathy and cardiomyopathy, few studies have investigated microalbuminuria in children with urinary tract infection (UTI).
Therefore, we compared the spot urine microalbumin/creatinine ratio in pediatric UTI patients with that of control subjects. We investigated the correlation between the ratio in children with UTI and age, height, weight, blood pressure, glomerular filtration rate (GFR), hematuria, vesicoureteral reflux, renal parenchymal defect, and renal scar, and its predictability for UTI complications.
We studied 66 patients (42 boys, 24 girls) and 52 healthy children (24 boys, 28 girls). The mean microalbumin/creatinine ratio in UTI patients was statistically significantly increased compared to the control group (340.04±321.36 mg/g (38.47±36.35 mg/mmol) in patient group vs. 225.68±154.61 mg/g (25.53±17.49 mg/mmol) in control group, P=0.0141). The mean value of spot urine microalbumin/creatinine ratio (384.70±342.22 mg/g (43.47±37.67 mg/mmol) in patient group vs. 264.92±158.13 mg/g (29.94±17.86 mg/mmol) in control group, P=0.0341) in 1-23 months age patient group showed statistically significant increase compared to control group. Microalbumin/creatinine ratio showed negative correlation to age (r=-0.29, P=0.0167), body surface area (BSA) (r=-0.29, P=0.0173) and GFR (r=-0.26, P=0.0343). The presence of hematuria (P=0.0169) was found to be correlated.
The spot urine microalbumin/creatinine ratio in children with UTI was significantly greater than that in normal children, and it was positively correlated with GFR. This ratio is a potential prescreening and prognostic marker in UTI patients. Further studies are required to validate the predictability of microalbuminuria in pediatric UTI patients.
Microalbuminuria; Child; Urinary tract infection
Twenty-four hour urinary albumin excretion (UAE) is considered as gold standard method for albuminuria measurement, but collection of 24-h urine is inconvenient. The aim of present study was to evaluate whether albumin: creatinine ratio (ACR) and urinary albumin concentration (UAC) in different spot urine samples correlate or not with 24-h UAE for screening of microalbuminuria in type 2 diabetic patients. We collected first morning void (FMV), random urine sample (RUS) and 24-h urine, separately on consecutive days from 104 type 2 diabetic patients. ACR and UAC in each spot urine sample compared with 24-h UAE with regard to Pearson correlation coefficient. Pearson’s correlation of albumin: creatinine ratio (ACR) with 24-h UAE was (r = 0.802 and 0.623) in first morning void (FMV) and random urine sample (RUS), respectively. Pearson’s correlation coefficient of urinary albumin concentration (UAC) compared with 24-h UAE was (r = 0.943 and 0.920), in FMV and RUS, respectively, P < 0.01. Results revealed that values in first morning void (FMV) were better correlated with 24-h urinary albumin excretion (UAE), than the values in random urine sample (RUS). We conclude that the first morning void (FMV) may be able to replace 24-h urine collection, preferably urinary albumin concentration (UAC) in the initial screening of microalbuminuria in diabetic patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s12291-011-0136-0) contains supplementary material, which is available to authorized users.
Diabetes mellitus; Microalbuminuria; Screening; Spot urine sample; Urinary albumin concentration
Although microalbuminuria is known as a predictor of clinical nephropathy and cardiomyopathy, few studies have investigated the incidence and reference range of microalbuminuria in healthy children. This study aimed to establish a reference range and to study the age-related trend for spot urine microalbumin/creatinine ratio in a Korean pediatric population.
Materials and Methods
352 healthy children were studied from July 2007 through March 2010. Height, weight, serum creatinine, spot urine microalbumin/creatinine ratio, and glomerular filtration rate (GFR) were obtained for each subject. We divided the study population into 5 groups according to age, and compared the spot urine microalbumin/creatinine ratio with other variables using one-way analysis of variance (ANOVA), regression analysis and Pearson's correlation analysis.
In this study, the data showed that the spot urine microalbumin/creatinine ratio decreased with age: 1-12 months, 22.72±13.80 mg/mmol (2SD: 3.33-54.40 mg/mmol); 13-28 months, 16.34±9.58 mg/mmol (2SD: 3.16-35.19 mg/mmol); 29-48 months, 13.12±9.74 mg/mmol (2SD: 3.01-41.57 mg/mmol); 4-6 years, 10.58±8.13 mg/mmol (2SD: 0.00-30.19 mg/mmol); and 7-19 years, 5.13±5.44 mg/mmol (2SD: 0.45-14.45 mg/mmol). The spot urine microalbumin/creatinine ratio showed correlation with age, height, height z-score, weight, weight z-score, GFR, body mass index (BMI) and body surface area (BSA).
The spot urine microalbumin/creatinine ratio in normal Korean children decreased with age. This ratio could potentially be used to establish reference ranges and cutoff values for Korean children and to predict nephropathy and cardiomyopathy.
Foamy urine is widely regarded as a sign of proteinuria. However, there is no objective definition of foamy urine and there are no reports on the proportion of involved patients who have overt proteinuria or microalbuminuria. We performed this study to investigate this proportion and to identify possible risk factors for these two conditions. We reviewed all new outpatients from 1 November 2011 to 30 April 2012 and identified patients complaining of foamy urine. Their demographic data and medical records were examined. In particular, we tabulated the patients' spot urinary protein to creatinine ratio, spot urinary microalbumin to creatinine ratio (ACR), blood urea nitrogen (BUN), and serum levels of creatinine (Cr), uric acid, calcium, phosphate, and glucose. In addition, we calculated estimated glomerular filtration rates (eGFRs) by using the CKD-EPI equation. We also performed risk factor analysis with the Chi-squared test and by logistic regression. Seventy-two patients (6.3% of total new outpatients) complained of foamy urine; of these, there were 59 males with a median age of 65.5 years (range, 36-87 years). Of the 72 patients, 16 (22.2%) had overt proteinuria. We found that diabetes, poor renal function (high Cr, BUN, low eGFR), increased serum phosphate, and increased serum glucose were associated with overt proteinuria. Multiple logistic regression analysis showed that serum Cr and serum phosphate were associated with overt proteinuria. The ACR was available for 38 patients, and in this subgroup, 12 (31.6%) showed microalbuminuria or overt proteinuria. In this subgroup, a high serum Cr was the only statistically significant risk factor. Among patients who complained of foamy urine, approximately 20% had overt proteinuria, and increased serum Cr and phosphate were statistically significant risk factors.
Proteinuria; Creatinine; Phosphates
Glomerular filtration rate (GFR) and urinary albumin excretion (UAE) are markers of kidney function that are known to be heritable. Many endocrine conditions have strong familial components. We tested for association between the Affymetrix GeneChip Human Mapping 100K single nucleotide polymorphism (SNP) set and measures of kidney function and endocrine traits.
Genotype information on the Affymetrix GeneChip Human Mapping 100K SNP set was available on 1345 participants. Serum creatinine and cystatin-C (cysC; n = 981) were measured at the seventh examination cycle (1998–2001); GFR (n = 1010) was estimated via the Modification of Diet in Renal Disease (MDRD) equation; UAE was measured on spot urine samples during the sixth examination cycle (1995–1998) and was indexed to urinary creatinine (n = 822). Thyroid stimulating hormone (TSH) was measured at the third and fourth examination cycles (1981–1984; 1984–1987) and mean value of the measurements were used (n = 810). Age-sex-adjusted and multivariable-adjusted residuals for these measurements were used in association with genotype data using generalized estimating equations (GEE) and family-based association tests (FBAT) models. We presented the results for association tests using additive allele model. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg Equilibrium p-value ≥ 0.001, and call rates of at least 80%.
The top SNPs associated with these traits using the GEE method were rs2839235 with GFR (p-value 1.6*10-05), rs1158167 with cysC (p-value 8.5*10-09), rs1712790 with UAE (p-value 1.9*10-06), and rs6977660 with TSH (p-value 3.7*10-06), respectively. The top SNPs associated with these traits using the FBAT method were rs6434804 with GFR(p-value 2.4*10-5), rs563754 with cysC (p-value 4.7*10-5), rs1243400 with UAE (p-value 4.8*10-6), and rs4128956 with TSH (p-value 3.6*10-5), respectively. Detailed association test results can be found at . Four SNPs in or near the CST3 gene were highly associated with cysC levels (p-value 8.5*10-09 to 0.007).
Kidney function traits and TSH are associated with SNPs on the Affymetrix GeneChip Human Mapping 100K SNP set. These data will serve as a valuable resource for replication as more SNPs associated with kidney function and endocrine traits are identified.
The balance between the intake of animal and the intake of plant foods may influence renal vascular integrity as reflected by urinary albumin excretion.
We assessed cross-sectional associations between urinary albumin excretion and dietary patterns and intake of plant and animal foods.
At baseline, diet (food-frequency questionnaire) and the urinary albumin-to-creatinine ratio (ACR; spot urine collection) were measured in 5042 participants in the Multi-Ethnic Study of Atherosclerosis who were aged 45−84 y and were without clinical cardiovascular disease, diabetes, or macroalbuminuria (sex-adjusted ACR ≥ 250). We derived dietary patterns by principal components analysis. We also summed food groups to characterize plant food intake (fruit, fruit juice, vegetables, nuts, legumes, whole grains, and refined grains), animal food intake (red meat, processed meat, poultry, fish, high-fat dairy, and low-fat dairy), and nondairy animal food intake.
After adjustment for multiple demographic and lifestyle confounders, a dietary pattern characterized by high consumption of whole grains, fruit, vegetables, and low-fat dairy foods was associated with 20% lower ACR across quintiles (P for trend = 0.004). Neither total animal nor total plant food intake was associated with ACR. However, greater low-fat dairy consumption was associated with 13% lower ACR across quartiles (P for trend = 0.03). Total nondairy animal food consumption was associated with 11% higher ACR across quintiles (P for trend = 0.03).
A high intake of low-fat dairy foods and a dietary pattern rich in whole grains, fruit, and low-fat dairy foods were both associated with lower ACR. In contrast, collectively, nondairy animal food intake was positively associated with ACR.
Objective: To investigate prevalence, persistence and clinical correlates of increased microalbumin excretion in random urine samples collected in a paediatric diabetes clinic.
Method: Random urine samples were collected annually in patients >10 years attending the diabetes clinic in the Royal Hospital for Sick Children, Edinburgh. Albumin excretion is expressed as albumin:creatinine ratio (ACR) and classified as normal (10mg/mmol), or macroalbuminuria (>47 mg/mmol in females, >35 mg/mmol in males). We analyzed retrospectively results on 421 urine samples collected from 217 patients (109 males), of a median age of 12.3 years (94% 10−16 years) over 3 years. For each sample, the corresponding mean HbA1c over the previous year was calculated.
Results: Prevalence of micro− and macro−albuminuria in individual samples was 1% and 0.5% respectively. ACR was equivocal in 10.1% and 4.7% in samples from females and males respectively (p=0.03). HbA1c showed borderline significant differences across ACR groups (p=0.06). Equivocal ACR excretion was associated with slightly higher mean HbA1c (9.5±1.3%) compared to normal albuminuria (9.0±1.1%, p3.5 mg/mmol. The 14−16 years age group patients were most likely to have ACR >3.5 mg/mmol (p=0.05).
Conclusions: Female sex and increasing age, but not HbA1c, were independently associated with increased ACR. A robust mechanism for collection of repeat early morning urine samples from patients with increased ACR in random urine samples, and follow−up of those patients who have persistently high microalbumin excretion are important. It is also important to confirm the usefulness of ACR measurements in random urine samples as a marker of incipent nephropathy.
Conflict of interest:None declared.
type 1 diabetes; Microalbuminuria; children and adolescents
Increased urinary albumin excretion rates have been linked to nephropathy and macrovascular disease. We here describe the baseline prevalence and effect of Diabetes Prevention Program (DPP) interventions on the development and reversal of elevated albumin excretion.
RESEARCH DESIGN AND METHODS
Urine albumin-to-creatinine ratios (ACRs) were calculated from untimed urine collections. Analyses compared participants by treatment group, diabetes and hypertension status, and use of ACE inhibitors or angiotensin II receptor blockers (ARBs).
Elevated ACR levels (≥30 mg/g creatinine) were present at baseline in 198 (6.2%) of 3,188 participants: placebo 5.3%, metformin 6.5%, and intensive lifestyle (ILS) 6.8%. Of the 2,802 with ACR measurements at baseline and at the end of the study, the percentage with elevated levels declined (incident and regression) from 6.2 to 6.1%, with no significant differences between the groups even with adjustment for ACE inhibitor and ARB use. The odds of developing an elevated ACR were 59% higher for a participant who developed diabetes compared with one who did not.
At entry into the DPP, an elevated ACR was present in 6.2%. Despite the marked decrease in progression to diabetes and the improvement in insulin resistance and other cardiovascular risk markers in the ILS and metformin groups, there was no improvement in ACR, on average, in those two groups. However, the frequency of an elevated ACR was higher in participants who developed diabetes. An increased ACR may have multiple causes, thus obscuring the improvements that might have been expected with the reduction in insulin resistance seen in the DPP.
Albuminuria and impaired glomerular filtration rate (GFR) are each associated with poor health outcomes among individuals with diabetes. Joint associations of albuminuria and impaired GFR with mortality have not been comprehensively evaluated in this population.
RESEARCH DESIGN AND METHODS
This is a cohort study among Cardiovascular Health Study participants with diabetes, mean age 78 years. GFR was estimated using serum cystatin C and serum creatinine. Albumin-to-creatinine ratio (ACR) was measured in single-voided urine samples.
Of 691 participants, 378 died over 10 years of follow-up. Cystatin C–estimated GFR <60 ml/min per 1.73 m2, creatinine-based estimated GFR <60 ml/min per 1.73 m2, and urine ACR ≥30 mg/g were each associated with increased mortality risk with hazard ratios of 1.73 (95% CI 1.37–2.18), 1.54 (1.21–1.97), and 1.73 (1.39–2.17), respectively, adjusting for age, sex, race, diabetes duration, hypoglycemic medications, hypertension, BMI, smoking, cholesterol, lipid-lowering medications, prevalent cardiovascular disease (CVD), and prevalent heart failure. Cystatin C–estimated GFR and urine ACR were additive in terms of mortality risk. Cystatin C–estimated GFR predicted mortality more strongly than creatinine-based estimated GFR.
Albuminuria and impaired GFR were independent, additive risk factors for mortality among older adults with diabetes. These findings support current recommendations to regularly assess both albuminuria and GFR in the clinical care of patients with diabetes; a focus on interventions to prevent or treat CVD in the presence of albuminuria, impaired GFR, or both; and further consideration of cystatin C use in clinical care.
The association of albuminuria with cardiovascular disease (CVD) is increasingly recognized, but its association with peripheral arterial disease (PAD) is not well characterized in subjects with or without diabetes.
Using data from the Multi-Ethnic Study of Atherosclerosis, a cohort free of clinical vascular disease, we analyzed the cross-sectional association between albuminuria and PAD in diabetic and nondiabetic subjects. A spot urine albumin-creatinine ratio (ACR) was used to define albuminuria in two ways: presence or absence of albuminuria and the degree of albuminuria (no albuminuria defined as urine ACR < 17 mg/g for men and < 25 mg/g for women, microalbuminuria as urine ACR 17 to 249 mg/g for men and 25 to 334 mg/g for women, and macroalbuminuria as urine ACR ≥ 250 mg/g for men and ≥ 355 mg/g for women). PAD was defined by ankle-brachial index (ABI) < 0.9.
Among the 6,760 subjects, aged 45-84 years, 326 (4.8%) had prevalent PAD. 813 (12.0%) subjects had microalbuminuria and 100 (1.5%) had macroalbuminuria. Among diabetic subjects, those with albuminuria (micro and macroalbuminuria combined) were 1.90 times more likely to have PAD (95% CI: 1.19-3.04) than those with no albuminuria. After adjusting for CVD risk factors, the odds ratio modestly attenuated to 1.65 (95% CI: 1.00-2.74). For nondiabetic subjects, there were no statistically significant associations observed in the univariable and multivariable analyses. The degree of albuminuria was not associated with PAD in either diabetic or nondiabetic subjects.
The presence, but not magnitude of albuminuria, is an important risk factor for PAD in diabetic but not in nondiabetic subjects.
Albuminuria; Peripheral arterial disease; Epidemiology; Risk factors
This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m2 estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m2 estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.
Cystatin C; Diabetic Nephropathies; Albuminuria
This study was aimed to evaluate renal dysfunction during three weeks after the burn injuries in 12 patients admitted to the Hallym University Hankang Medical Center with flame burn injuries (total body surface area, 20-40%). Parameters assessed included 24-hr urine volume, blood urea nitrogen, serum creatinine, creatinine clearance, total urinary protein, urinary microalbumin, 24-hr urinary N-acetyl-beta-D-glucosaminidase (NAG) activity, and urinary malondialdehyde (MDA). Statistical analysis was performed using repeated measures ANOVA test. The 24-hr urine volume, creatinine clearance, and urinary protein significantly increased on day 3 post-burn and fell thereafter. The urine microalbumin excretion showed two peak levels on day 0 post-burn and day 3. The 24-hr urinary NAG activity significantly increased to its maximal level on day 7 post-burn and gradually fell thereafter. The urinary MDA progressively increased during 3 weeks after the burn injury. Despite recovery of general renal function through an intensive care of burn injury, renal tubular damage and lipid peroxidation of the renal tissue suggested to persist during three weeks after the burn. Therefore, a close monitoring and intensive management of renal dysfunction is necessary to prevent burn-induced acute renal failure as well as to lower mortality in patients with major burns.
Research on the relationship between urinary albumin excretion and serum cystatin C in diabetes is restricted to cross-sectional studies. In this study, we investigated how well serial measurements of serum cystatin C level reflect changes in the urinary albumin excretion rate.
We enrolled and retrospectively collected data on 1,058 participants with type 2 diabetes who were older than 18 years and who had more than 3 years of follow-up with serial measurements of albuminuria and serum cystatin C at an outpatient clinic.
With the use of a linear mixed model, we found that the albuminuria level for each patient over time corresponded with the annual change in serum cystatin C-based estimated glomerular filtration rate (cysC-eGFR) but did not correspond with the creatinine-based eGFR calculated by the modification of diet in renal disease formula (MDRD-eGFR). The discrepancy in the direction of the trend was smaller with cysC-eGFR than with MDRD-eGFR.
Serum cystatin C level reflects the trend in albuminuria level more accurately than serum creatinine level in Korean type 2 diabetes mellitus patients.
Albuminuria; Cystatin C; Creatinine; Diabetes mellitus, type 2; Diabetic nephropathies
The evolution of abnormal albumin excretion and its association
with suggested risk factors were studied in 233 children with insulin
dependent diabetes mellitus (IDDM) attending a single paediatric
diabetic clinic over an eight year period. Yearly albumin:creatinine ratios (ACR; measured in mg/mmol) in early morning urine samples, glycated haemoglobin (HbA1c), and blood pressure were recorded. Thirty
four (14.5%) children had a persistently raised ACR (ACR ⩾ 2.5 mg/mmol on at least three consecutive occasions) and 21(9%) had
an intermittently raised ACR (ACR ⩾ 2.5 mg/mmol on at least two
occasions). Factors associated with a persistently raised ACR compared
with normal albuminuria in IDDM included longer duration of diabetes,
raised median HbA1c during the first five years after diagnosis, and
final age adjusted systolic and diastolic blood pressure represented as
standard deviation scores. The onset of persistently raised ACR in 13 of 34 children was before puberty and in 23 of 34 children it was
within the first four years of diagnosis. The cross sectional
prevalence of raised ACR was 12.9% at one year, 18.3% at five years,
and 33% at 10 years after diagnosis. Raised ACR occurs frequently
before puberty and in the early stages of childhood diabetes.
To assess the prevalence and risk factors of microalbuminuria in nondiabetic
hypertensive patients in Thailand.
Patients and methods:
A cross-sectional study was performed during January to December 2007 at
outpatients departments of Bhumibol Adulyadej hospital. Nondiabetic
hypertensive patients without a history of pre-existing kidney diseases
participated in this study. A questionnaire was used for collecting
information on demographics, lifestyle, and family history of cardiovascular
and kidney disease. Spot morning urine samples were collected for
albuminuria estimation. Albuminuria thresholds were evaluated and defined
using albumin-creatinine ratio (ACR).
A total of 559 hypertensive patients (283 males, 276 females), aged 58.0
± 11.6 years were enrolled in this study. Microalbuminuria (ACR
17 to 299 mg/g in males and 25 to 299 mg/g in females) was found in 93 cases
The independent determinants of elevated urinary albumin excretion in a
multiple logistic regression model were; body mass index ≥30
(odds ratio (OR) = 2.24, 95% confidence intervals
(CI): 1.33–3.76) and dihydropyridine calcium channel blockers
(DCCB) use (OR = 1.92, 95% CI:
In Thai nondiabetic hypertensive patients, microalbuminuria was not uncommon.
Obesity and use of dihydropyridine calcium channel blocker were found to be
the important predictors. Prognostic value of the occurrence of
microalbuminuria in this population remains to be determined in prospective
microalbuminuria; hypertension; obesity; calcium channel blocker; metabolic syndrome
Monocyte chemoattractant protein-1 (MCP-1) plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD) were assessed in African Americans (AAs) with type 2 diabetes (T2D).
Serum MCP-1 concentration, urine albumin:creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and atherosclerotic calcified plaque (CP) in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP.
Participants were 57% female, with mean ± SD (median) age 55.6±9.5 (55.0) years, diabetes duration 10.3±8.2 (8.0) years, urine ACR 149.7±566.7 (14.0) mg/g, CKD-EPI eGFR 92.4±23.3 (92.0) ml/min/1.73m2, MCP-1 262.9±239.1 (224.4) pg/ml, coronary artery CP 280.1±633.8 (13.5), carotid artery CP 47.1±132.9 (0), and aorta CP 1616.0±2864.0 (319.0). Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04) and negatively associated with eGFR (parameter estimate −0.0003, P=0.001). MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes.
Serum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.
African Americans; Albuminuria; Atherosclerotic calcified plaque; Diabetes; GFR; MCP-1
We previously described a cross-sectional association between serum uric acid and reduced glomerular filtration rate (GFR) in nonproteinuric patients with type 1 diabetes. Here, we prospectively investigated whether baseline uric acid impacts the risk of early progressive renal function loss (early GFR loss) in these patients.
RESEARCH DESIGN AND METHODS
Patients with elevated urinary albumin excretion (n = 355) were followed for 4–6 years for changes in urinary albumin excretion and GFR. The changes were estimated by multiple determinations of albumin-to-creatinine ratios (ACRs) and serum cystatin C (GFRcystatin).
At baseline, the medians (25th–75th percentiles) for uric acid, ACR, and GFRcystatin values were 4.6 mg/dl (3.8–5.4), 26.2 mg/g (15.1–56.0), and 129 ml/min per 1.73 m2 (111–145), respectively. During the 6-year follow-up, significant association (P < 0.0002) was observed between serum uric acid and development of early GFR loss, defined as GFRcystatin decline exceeding 3.3% per year. In baseline uric acid concentration categories (in mg/dl: <3.0, 3.0–3.9, 4.0–4.9, 5.0–5.9, and ≥6), the risk of early GFR loss increased linearly (9, 13, 20, 29, and 36%, respectively). This linear increase corresponds to odds ratio 1.4 (95% CI 1.1–1.8) per 1 mg/dl increase of uric acid. The progression and regression of urinary albumin excretion were not associated with uric acid.
We found a clear dose-response relation between serum uric acid and risk of early GFR loss in patients with type 1 diabetes. Clinical trials are warranted to determine whether uric acid–lowering drugs can halt renal function decline before it becomes clinically significant.
It is unknown whether systemic endothelial dysfunction underlies the association between nephropathy and cardiovascular disease (CVD) in persons infected with human immunodeficiency virus (HIV). Spot urine protein to creatinine ratio, spot urine albumin to creatinine ratio, creatinine clearance, estimated glomerular filtration rate, and flow-mediated dilation (FMD) of the brachial artery were evaluated in 123 study participants infected with HIV (58 receiving antiretroviral therapy [ART] and 65 not receiving ART) with no history of diabetes or hypertension. None of the renal markers, modeled as either continuous or categorical variables, correlated with FMD. Contrary to expectations, endothelial dysfunction may not be the link between nephropathy and CVD in HIV.
In this multicenter, prospective study of 288 children (half under 2 years of age) undergoing cardiac surgery, we evaluated whether the measurement of pre- and postoperative serum cystatin C (CysC) improves the prediction of acute kidney injury (AKI) over that obtained by serum creatinine (SCr). Higher preoperative SCr-based estimated glomerular filtration rates predicted higher risk of the postoperative primary outcomes of stage 1 and 2 AKI (adjusted odds ratios (ORs) 1.5 and 1.9, respectively). Preoperative CysC was not associated with AKI. The highest quintile of postoperative (within 6 h) CysC predicted stage 1 and 2 AKI (adjusted ORs of 6 and 17.2, respectively). The highest tertile of percent change in CysC independently predicted AKI, whereas the highest tertile of SCr predicted stage 1 but not stage 2 AKI. Postoperative CysC levels independently predicted longer duration of ventilation and intensive care unit length of stay, whereas the postoperative SCr change only predicted longer intensive care unit stay. Thus, postoperative serum CysC is useful to risk-stratify patients for AKI treatment trials. More research, however, is needed to understand the relation between preoperative renal function and the risk of AKI.
acute renal failure; cardiovascular; creatinine; epidemiology and outcomes; renal function
We investigated the prevalence of microalbuminuria and its association with the metabolic syndrome and its components in a Chinese population.
The study subjects were recruited from a newly established residential area in the suburb of Shanghai. We measured anthropometry, blood pressure (BP), fasting plasma glucose, and serum lipids, and collected spot urine samples for the determination of albumin-creatinine ratio. We defined microalbuminuria as a urinary albumin-to-creatinine ratio of 30 to 299 mg/g. The metabolic syndrome was defined according to the International Diabetes Federation criteria.
The 1079 participants included 410 (38.0%) hypertensive patients, and 66 (6.1%) diabetic patients. The prevalence of microalbuminuria (4.3%) was 3.2 times higher in 167 patients with the metabolic syndrome than 912 subjects without the metabolic syndrome (12.0% vs. 2.9%, P < 0.0001). In multiple regression adjusted for sex, age, body mass index, current smoking, alcohol intake and the use of antihypertensive drugs, and mutually adjusted for the components, microalbuminuria was significantly associated with diastolic BP (odds ratio 1.74 for +10 mmHg; 95% confidence interval [CI] 1.10-2.76; P = 0.02) and fasting plasma glucose (1.18; 95% CI 1.01-1.41; P = 0.04), but not with waist circumference, systolic BP, or serum HDL cholesterol and triglycerides (P > 0.10).
Microalbuminuria is common in the Chinese population, and much more prevalent in the presence of the metabolic syndrome, mainly attributable to elevated diastolic BP and plasma glucose.
Sleep-disordered breathing(SDB) may be deleterious to the cardiovascular system and other organs, including the kidney. Although older men are at increased risk for both kidney disease and SDB, it is unknown whether SDB is associated with higher urinary albumin excretion in this population.
We examined 507 community-dwelling men age ≥67 years(mean 76.0±5.3) enrolled in the MrOS Sleep study who underwent overnight polysomnography and gave a spot urine sample. SDB severity was categorized using the respiratory disturbance index and percent total sleep time <90% oxygen saturation(%time O2<90). Urinary albumin excretion was expressed using the albumin-to-creatinine ratio(ACR).
There was a graded association between respiratory disturbance index and ACR (age and race-adjusted mean ACR=9.35 mg/gCr for respiratory disturbance index≥30 versus 6.72 mg/gCr for respiratory disturbance index<5, p=0.007). This association was attenuated after further adjustment for body mass index(BMI), hypertension and diabetes and no longer reached significance(p=0.129). However, even after adjustment for age, race, BMI, hypertension and diabetes, greater %time O2<90 was associated with higher ACR(10.35 mg/gCr for ≥10%time O2<90 versus 7.45 mg/gCr for <1%time O2<90, p=0.046).
SDB, measured by elevated respiratory disturbance index or nocturnal hypoxemia, was associated with higher ACR. The relationship between respiratory disturbance index and ACR was partially explained by higher BMI and greater prevalence of hypertension and diabetes among men with SDB. However, greater nocturnal hypoxemia was independently associated with higher ACR, suggesting that the hypoxia component of SDB may mediate any detrimental effect of SDB on the kidney.
Albuminuria; sleep-disordered breathing; chronic kidney disease; nocturnal hypoxemia
OBJECTIVE: To evaluate whether the protein:creatinine ratio in spot morning urine samples is a reliable indicator of 24 hour urinary protein excretion and predicts the rate of decline of glomerular filtration rate and progression to end stage renal failure in non-diabetic patients with chronic nephropathy. DESIGN: Cross sectional correlation between the ratio and urinary protein excretion rate. Univariate and multivariate analysis of baseline predictors, including the ratio and 24 hour urinary protein, of decline in glomerular filtration rate and end stage renal failure in the long term. SETTING: Research centre in Italy. SUBJECTS: 177 non-diabetic outpatients with chronic renal disease screened for participation in the ramipril efficacy in nephropathy study. MAIN OUTCOME MEASURES: Rate of decline in filtration rate evaluated by repeated measurements of unlabelled iohexol plasma clearance and rate of progression to renal failure. RESULTS: Protein:creatinine ratio was significantly correlated with absolute and log transformed 24 hour urinary protein values (P = 0.0001 and P < 0.0001, respectively.) Ratios also had high predictive value for rate of decline of the glomerular filtration rate (univariate P = 0.0003, multivariate P = 0.004) and end stage renal failure (P = 0.002 and P = 0.04). Baseline protein:creatinine ratios and rate of decline of the glomerular filtration rate were also significantly correlated (P < 0.0005). In the lowest third of the protein:creatinine ratio (< 1.7) there was 3% renal failure compared with 21.2% in the highest third (> 2.7) (P < 0.05). CONCLUSIONS: Protein:creatinine ratio in spot morning urine samples is a precise indicator of proteinuria and a reliable predictor of progression of disease in non-diabetic patients with chronic nephropathies and represents a simple and inexpensive procedure in establishing severity of renal disease and prognosis.
Familial predisposition to hypertension has been associated with the development of diabetic nephropathy in adults, but there are limited data in adolescents. Our aim was to assess whether parental ambulatory blood pressure (ABP) was associated with ABP and albumin excretion in young offspring with type 1 diabetes.
RESEARCH DESIGN AND METHODS
Twenty-four-hour ABP monitoring was performed in 509 young offspring (mean ± SD age 15.8 ± 2.3 years) with type 1 diabetes, 311 fathers, and 444 mothers. Systolic (SBP) and diastolic blood pressure (DBP) measurements during 24 h, daytime, and nighttime were calculated. Three early morning urinary albumin-to-creatinine ratios (ACRs), A1C, and anthropometric parameters were available for the offspring.
All paternal ABP parameters, except for nighttime SBP, were independently related to the offspring's ABP (24-h SBP β = 0.18, 24-h DBP β = 0.22, daytime SBP β = 0.25, daytime DBP β = 0.23, and nighttime DBP β = 0.18; all P < 0.01). Maternal 24-h DBP (β = 0.19, P = 0.004), daytime DBP (β = 0.09, P = 0.04), and nighttime SBP (β = 0.24 P = 0.001) were related to the corresponding ABP parameter in the offspring. Significant associations were found between the offspring's logACR and maternal ABP. The association with 24-h DBP (β = 0.16, P = 0.02), daytime DBP (β = 0.16 P = 0.02), and nighttime DBP (β = 0.15 P = 0.03) persisted even after adjustment for the offspring's ABP. Mothers of offspring with microalbuminuria had higher ABP than mothers of offspring without microalbuminuria (all P < 0.05).
In this cohort, parental ABP significantly influenced offspring blood pressure, therefore confirming familial influences on this trait. In addition, maternal ABP, particularly DBP, was closely related to ACR in the offspring, suggesting a dominant effect of maternal genes or an effect of the intrauterine environment on microalbuminuria risk.
Glycemic exposure activates 12-lipoxygenase (12LO) expression and formation of arachidonic acid-derived products. These products can induce cell hypertrophy, cell proliferation and extracellular matrix deposition, potentially leading to diabetic nephropathy (DN).
Settings & Participants
955 European American siblings from 369 Diabetes Heart Study families. Participants were categorized as: non-diabetic, diabetic with hemoglobin A1c < 6.5%, and diabetic with hemoglobin A1c > 6.5% (uncontrolled T2DM).
Four haplotype-tagging variants in the arachidonate 12LO gene (ALOX12), glycemic control, and other covariates.
Outcomes & Measurements
Albuminuria measured by urinary albumin:creatinine ratio (ACR).
The median ACR was 11.9 mg/g (interquartile range, 5.6–39.1). The overall test of the Arg261Gln genotypic association with ACR was significant (p=0.009). Compared to the 261Arg allele carriers, adjusted mean ACR was 42% higher among the 189 carriers of two 261Gln alleles (95% confidence interval, 10% to 83%; p = 0.007). This association was confined to the uncontrolled T2DM group (N=623) with the highest ACR values (P<0.001). Adjustments for additional determinants of ACR yielded similar results.
Urine ACR was measured in duplicate on only a single occasion. This study was limited to European Americans.
Consistent with animal and cellular studies, these results provide further evidence of the importance of the 12LO pathway in the pathogenesis of human DN.
lipoxygenase; ALOX12 gene; albuminuria; diabetic nephropathy; genetics; type 2 diabetes mellitus
Albumin and enzymes-N-acetyl-beta-glucosaminidase (NAG) and gamma glutamyl transferase (GGT) were estimated in the morning random urine samples of 196 albustix negative diabetic patients to evaluate the clinical utility of these urinary enzymes as early markers of diabetic nephropathy. Albumin was estimated by immunoturbidimetric method and enzymes by linetic essay within six hours of voiding of urine. The urinary albumin and urinary enzyme concentration was calculated in terms of ratio with respect to urinary creatinine. Correlation coefficient (r) bewween urinary albumin and urinary enzymes in normoalbuminuric, microalbuminuric and overall diabetic cases was 0.23, 0.32 and 0.40 respectively for NAG, and 0.08, 0.06 and 0.18 respectively for GGT. NAG excretion was found increased in 34%, 63.7% and 49.5% of normoalbuminuric, microalbuminuric and overall diabetic cases respectively while GGT in 6.4%, 24.5% and 15.8%. The correlation coefficient between urinary albumin and NAG in normoalbuminuric, microalbuminuric, and overall diabetic patients with increased NAG excretion was found only 0.31, 0.27 and 0.35 respectively. No correlation was found between duration of diabetes and enzyme excretion. The study suggests that urinary NAG or GGT or both together do not have any clinical significance as an early marker of diabetic nephropathy.
Microalbuminuria; Diabetic nephropathy; N-acetyl-beta-glucosaminidase; Gamma glutamyl transferase