Elevated Urine Albumin/creatinine Ratio Research Articles

Dapagliflozin treatment of patients with chronic kidney disease without diabetes across different albuminuria levels (OPTIMISE-CKD)

Abstract Background We compared kidney and cardiorenal protection in patients without type 2 diabetes across urine albumin-creatinine ratio (UACR) levels after initiation on dapagliflozin for the treatment of chronic kidney disease (CKD). Methods OPTIMISE-CKD is an observational study describing dapagliflozin treatment for CKD. Adult patients with CKD without type 2 diabetes were included in the primary analysis. Baseline UACR was grouped as normal/mildly elevated (0–29 mg/g), low (30–200 mg/g) and high (>200 mg/g). Outcomes were estimated glomerular filtration rate (eGFR) trajectories/slopes, cardiorenal complications and all-cause mortality. Results In total, 1480 patients had low (n = 796) and high (n = 684) UACR. The two groups were similar at baseline, aged 75 and 74 years, and 42% and 39% female, respectively. After dapagliflozin initiation, an acute eGFR dip of 3 mL/min/1.73 m2 was observed, followed by a flat development in both groups. The eGFR slope (95% confidence interval [CI]) for patients with low UACR was 0.79 mL/min/1.73m2 per year (–0.59, 2.56), and similar to patients with high UACR (0.40 mL/min/1.73m2 per year [–0.46, 1.38]). Risks of cardiorenal complications and all-cause mortality were similar, with adjusted hazard ratios of 0.89 [95% CI 0.66, 1.19] and 1.10 [95% CI 0.63, 1.92], respectively. Analogous results were found in those with normal/mildly elevated UACR. Conclusions Dapagliflozin in patients without type 2 diabetes for the treatment of CKD demonstrated similar kidney protection, cardiorenal and all-cause mortality risk across UACR levels. This suggests that the efficacy of dapagliflozin found in clinical trials expands to real-world patients with CKD, regardless of albuminuria levels.

The Fruit and Veggies for Kidney Health Study: A Prospective Randomized Trial

Providing fruits and vegetables (F&Vs) to health care system patients with elevated urine albumin-creatinine ratio (ACR) reduced ACR, slowed chronic kidney disease (CKD) progression and reduced cardiovascular disease (CVD) risk factors in previous studies. This study evaluated a community-based strategy in lower-income populations to identify African Americans with elevated ACR before health care system involvement and sustain them in a 6-month F&V protocol with (F&V+Cook) and without (F&V Only) cooking instructions, with the hypothesis that adjuvant cooking instructions with F&Vs would further reduce ACR. Prospective, randomized, parallel 2-arm design. African American adults with ACR>10mg/g creatinine randomized to 1 of 2 study arms. Two cups/day of F&Vs with or without cooking instructions in participants followed 6 months. Participants sustaining the F&V protocol and between-group indicators of CVD risk, kidney injury, and dietary intake at 6 weeks and 6 months. A total of 142 African American adults (mean age, 57.0 years; ACR, 27.4mg/g; body mass index, 34.4; 24.9% CKD 1; 24.8% CKD 2; 50.4% CKD 3; 55% female) randomized to F&V Only (n=72) or F&V+Cook (n=70), and 71% were retained at 6 months. Participants received 90% of available F&V pick-ups over 6 weeks and 69% over 6 months. In the adjusted model, 6-month ACR was 31% lower for F&V+ Cook than F&V Only (P=0.02). Net 6-week F&V intake significantly increased and biometric variables improved for participants combined into a single group. Small sample size, low-baseline ACR, and potential nonresponse bias for 24-hour dietary recall measure. These data support the feasibility of identifying community-dwelling African Americans with ACR indicating elevated CVD and CKD risk and sustaining a F&V protocol shown to improve kidney outcomes and CVD risk factors and provides preliminary evidence that cooking instructions adjuvant to F&Vs are needed to lower ACR. National Institute on Diabetes, Digestive, and Kidney Diseases grant "Reducing chronic kidney disease burden in an underserved population" (R21DK113440). NCT03832166. African Americans, particularly those in low-income communities, have increased rates of chronic kidney disease (CKD) with worsening outcomes over time. Giving fruits and vegetables to individuals with CKD identified in health care systems was previously shown to reduce kidney damage, measured by urine protein albumin, and slow kidney function decline. We recruited African Americans in low-income communities with increased urine albumin levels. They received fruits and vegetables for 6 months, and we tested whether added cooking instructions further reduced urine albumin levels. Most participants continued to receive fruits and vegetables throughout the 6 months. Those given cooking instructions had lower urine albumin levels after 6 months, indicating decreased kidney damage. Providing cooking instructions with fruits and vegetables appears to lessen kidney damage more than just fruits and vegetables alone.

Elevated urine albumin creatinine ratio increases cardiovascular mortality in coronary artery disease patients with or without type 2 diabetes mellitus: a multicenter retrospective study

BackgroundAlbuminuria has been suggested as an atherosclerotic risk factor among the general population. However, whether this association will be amplified in patients with coronary artery disease (CAD) is unknown. It is also unknown whether diabetes mellitus confounds the association. We aim to analyse the prognosis of elevated urine albumin creatinine ratio (uACR) in the CAD population with or without type 2 diabetes mellitus (T2DM).MethodsThis multi-center registry cohort study included 5,960 patients with CAD. Patients were divided into T2DM and non-T2DM group, and baseline uACR levels were assessed on three grades (low: uACR < 10 mg/g, middle: 10 mg/g ≤ uACR < 30 mg/g, and high: uACR ≥ 30 mg/g). The study endpoints were cardiovascular mortality and all-cause mortality.ResultsDuring the median follow-up of 2.2 [1.2–3.1] years, 310 (5.2%) patients died, of which 236 (4.0%) patients died of cardiovascular disease. CAD patients with elevated uACR had a higher risk of cardiovascular mortality (middle: HR, 2.32; high: HR, 3.22) than those with low uACR, as well as all-cause mortality. Elevated uACR increased nearly 1.5-fold risk of cardiovascular mortality (middle: HR, 2.33; high: HR, 2.34) among patients without T2DM, and increased 1.5- fold to 3- fold risk of cardiovascular mortality in T2DM patients (middle: HR, 2.49; high: HR, 3.98).ConclusionsEven mildly increased uACR could increase the risk of cardiovascular mortality in patients with CAD, especially when combined with T2DM.

Simple predictive score for nocturnal hypertension and masked nocturnal hypertension using home blood pressure monitoring in clinical practice.

The decision whether to measure night-time blood pressure (BP) is challenging as these values cannot be easily evaluated because of problems with measurement devices and related stress. Using the nationwide, practice-based Japan Morning Surge-Home BP Nocturnal BP study data, we developed a simple predictive score that physicians can use to diagnose nocturnal hypertension. We divided 2765 outpatients (mean age 63 years; hypertensive patients 92%) with cardiovascular risks who underwent morning, evening, and night-time home BP (HBP) measurements (0200, 0300, and 0400 h) into a calibration group ( n = 2212) and validation group ( n = 553). We used logistic-regression models in the calibration group to identify the predictive score for nocturnal hypertension (night-time HBP ≥120/70 mmHg) and then evaluated the score's predictive ability in the validation group. In the logistic-regression model, male sex, increased BMI) (≥25 kg/m 2 ), diabetes, elevated urine-albumin creatinine ratio (UACR) (≥30 mg/g Cr), elevated office BP (≥140/90 mmHg) and home (average of morning and evening) BP (≥135/85 mmHg) had positive relationships with nocturnal hypertension. The predictive scores for nocturnal hypertension were 1 point (male, BMI, and UACR); 2 points (diabetes); 3 points (office BP ≥140/90 mmHg); 6 points (home BP ≥135/85 mmHg); total 14 points. Over 75% of the nocturnal hypertension cases in the validation group showed at least 10 points [AUC 0.691, 95% CI (0.647-0.735)]. We also developed a score for masked nocturnal hypertension, that is, nocturnal hypertension despite controlled daytime HBP. We developed a simple predictive score for nocturnal hypertension that can be used in clinical settings and for diagnoses.

Risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis and diabetic nephropathy: A 3-year follow-up study.

This study aimed to explore the risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis (DFO) and diabetic nephropathy (DN). This is a prospective cohort study. Between May 2018 and May 2021, we selected 120 inpatients with comorbid severe diabetic foot infection (PEDIS Grade 3 or above) and DN for inclusion in our study. All cases were followed up for 36 months. The study outcomes were whether foot ulcer recurred and the time to recurrence. The risk factors of ulcer recurrence were analysed by comparing the data of the three groups. According to the recurrence of foot ulcer, the participants were divided into three groups: Group A (no foot ulcer recurrence, n=89), Group B (foot ulcer recurrence within 12-36 months, n=19) and Group C (foot ulcer recurrence within 6-12 months, n=12). The multivariate Cox regression analysis showed that urine albumin-creatinine ratio (UACR) (HR: 1.008, 95% CI: 1.005-1.011, P < .001) and vibration perception threshold (VPT) (HR: 1.064, 95% CI: 1.032-1.096, P < .001) were identified as independent risk factors. Kaplan-Meier curves showed a significant positive association between UACR or VPT and the risk of foot ulcer recurrence (log rank, all P < .05). Areas under the ROC curves for UACR, VPT and the combination of UACR and VPT were 0.802, 0.799 and 0.842, respectively. The best cut-off values of UACR and VPT were 281.51 mg/g and 25.12 V, respectively. In summary, elevated UACR and VPT were independent risk factors. The best clinical cut-off values of UACR and VPT for prediction of foot ulcer recurrence were 281.51 mg/g and 25.12 V, respectively. Besides, our results suggested that microcirculation disorders rather than macrovascular complications play a major role in the recurrence of foot ulcer in patients with comorbid DFO and DN.

The Lower Limit of Reference of Urinary Albumin/Creatinine Ratio and the Risk of Chronic Kidney Disease Progression in Patients With Type 2 Diabetes Mellitus.

A urine albumin/creatinine ratio (UACR) <30 mg/g is considered to be normal, while increased risk of incident hypertension and cardiovascular disease mortality in subjects with high normal UACR level had been observed. However, a mild elevated but normal UACR level was associated with the risk of initiating chronic kidney disease (CKD) is uncertain. We investigated whether higher normal UACR is associated with the risk of developing CKD. A total of 4821 subjects with type 2 diabetes mellitus (T2DM), an estimated glomerular filtration rate >60 ml/min/1.73 m2 and UACR <30 mg/g enrolled in a diabetes disease management program between 2006 and 2020 were studied. The optimal cutoff point for baseline UACR as a predictor for progression to CKD according to the 2012 KDIGO definition was calculated using receiving operating characteristic curve analysis. After a mean of 4.9 years follow-up, the CKD risk progression increased in parallel with the quartiles of baseline UACR <30 mg/g (p for trend <0.0001). UACR cutoff points of 8.44 mg/g overall, 10.59 mg/g in males and 8.15 mg/g in females were associated with the risk of CKD progression. In multivariate Cox regression analysis, the hazard ratios for the association between UACR (>8.44 mg/g, >10.9 mg/g, >8.15 mg/g in overall, male, and female patients, respectively) and the risk of CKD progression were significant. This study demonstrated that a cutoff UACR value of >10 mg/g could significantly predict the cumulative incidence and progression of CKD in patients with T2DM.

SIMPLE PREDICTIVE SCORE FOR NOCTURNAL HYPERTENSION AND MASKED NOCTURNAL HYPERTENSION USING HOME BLOOD PRESSURE MONITORING IN CLINICAL PRACTICE

Objective: The decision whether to measure nighttime blood pressure (BP) is challenging because these values cannot be easily evaluated due to problems with measurement devices and related stress. Using the nationwide, practice-based Japan Morning Surge-Home BP Nocturnal BP study data, we developed a simple predictive score that physicians can use to diagnose nocturnal hypertension. Design and method: We divided 2,765 outpatients (mean age 63 years; hypertensives 92%) with cardiovascular risks who underwent morning, evening, and nighttime home BP (HBP) measurements (2:00, 3:00, and 4:00 a.m.) into a calibration group (n = 2,212) and validation group (n = 553). We used logistic-regression models in the calibration group to identify the predictive score for nocturnal hypertension (nighttime HBP &gt; = 120/70 mmHg) and then evaluated the score's predictive ability in the validation group. Results: In the logistic-regression model, male sex, increased body mass index (BMI) (&gt; = 25 kg/m2), diabetes, elevated urine-albumin creatinine ratio (UACR) (&gt; = 30 mg/g Cr), elevated office BP (&gt; = 140/90 mmHg), and elevated morning and evening HBP (&gt; = 135/85 mmHg) had positive relationships with nocturnal hypertension. The predictive scores for nocturnal hypertension were 1-point (male, BMI, diabetes, and UACR); 2-points (office BP &gt; = 140/90 mmHg); 3-points (evening HBP &gt; = 135/85 mmHg); 4-points (morning HBP &gt; = 135/85 mmHg); total 13 points. Over 80% of the nocturnal hypertension cases in the validation group showed &gt; = 10-points (AUC = 0.705, 95%CI: 0.661–0.748). We also developed a score for masked nocturnal hypertension, i.e., nocturnal hypertension despite controlled daytime HBP. Conclusions: We developed a simple predictive score for nocturnal hypertension that can be used in clinical settings and for diagnoses.

Urine Albumin-Creatinine ratio is associated with prognosis in patients with diabetic foot osteomyelitis

AimsWe aimed to explore the association between albuminuria and clinical outcomes in patients with diabetic foot osteomyelitis (DFO). MethodsThis is an observational retrospective study and a total of 202 inpatients with DFO were eligible for inclusion in our study. Based on urine albumin-creatinine ratio (UACR), the patients were divided into three groups: normoalbuminuria group, microalbuminuria group and macroalbuminuria group. The data collected include demographics data, laboratory data, clinical diagnostic data, diabetic foot examination and clinical visit data. The association was then evaluated between albuminuria and all-cause mortality, major cardiovascular adverse events (MACE) and mixed endpoint events. ResultsThe mean age was 60.3 years, 62.9% were male and 45.05% were urinary protein-positive. The incidence rates of all-cause mortality, MACE and mixed endpoint events related to elevated UACR were significantly increased in patients with DFO (all P for trend < 0.01). After adjusting for confounders, compared with normoalbuminuria group, the risk of all-cause mortality, MACE and mixed endpoint events in the microalbuminuria group increased by 81.8%, 135.4% and 136.4%, respectively. The risk of all-cause mortality, MACE and mixed endpoint events in the macroalbuminuria group increased by 246.2%, 145.1% and 252.3%, respectively. The population attributable risk percentage (PAR%) suggested that 50.16% of all-cause mortality, 47.85% of MACE and 59.11% of mixed endpoint events could be attributed to the elevated UACR. Meanwhile, compared with normoalbuminuria, those with microalbuminuria or macroalbuminuria have lower apoA1 and ABI, higher SCr and higher incidence rate of CHD, hindfoot infection and severe infection (all P < 0.05). ConclusionsIn patients with DFO, the UACR level is associated with all-cause mortality, MACE and mixed endpoint events and elevated UACR levels increase the risk of all-cause mortality, MACE and mixed endpoint events.

Long-term exposure to ambient air pollution and renal function in African Americans: the Jackson Heart Study.

Renal dysfunction is prevalent in the US among African Americans. Air pollution is associated with renal dysfunction in mostly white American populations, but not among African Americans. We evaluated cross-sectional associations between 1-year and 3-year fine particulate matter (PM2.5) and ozone (O3) concentrations and renal function among 5090 African American participants in the Jackson Heart Study. We used mixed-effect linear regression to estimate associations between 1-year and 3-year PM2.5 and O3 and estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio (UACR), serum creatinine, and serum cystatin C, adjusting for: sociodemographic factors, health behaviors, and medical history and accounting for clustering by census tract. At baseline, JHS participants had mean age 55.4 years, and 63.8% were female; mean 1-year and 3-year PM2.5 concentrations were 12.2 and 12.4 μg/m3, and mean 1-year and 3-year O3 concentrations were 40.2 and 40.7 ppb, respectively. Approximately 6.5% of participants had reduced eGFR (<60 mL/min/1.73m2) and 12.7% had elevated UACR (>30 μg/g), both indicating impaired renal function. Annual and 3-year O3 concentrations were inversely associated with eGFR and positively associated with serum creatinine; annual and 3year PM2.5 concentrations were inversely associated with UACR. We observed impaired renal function associated with increased O3 but not PM2.5 exposure among African Americans.

Unmet need for bariatric surgery

IntroductionWith the rising prevalence of severe obesity and type 2 diabetes (T2D), bariatric surgery offers a clinical and cost-effective treatment for carefully selected patients. Despite this, the provision of surgical services varies significantly between countries. ObjectiveTo inform health service planning by estimating the number of people who would potentially benefit from bariatric surgery. SettingNationally representative sample of community-dwelling older adults. MethodsWe applied two separate evidence-based criteria sets for eligibility for bariatric surgery. For the first set of criteria, we considered those with body mass index≥40 kg/m2 or≥35 kg/m2 and one or more of the following: T2D, hypertension, previous myocardial infarction, or sleep apnea. For the second set of criteria, we considered patients with T2D and body mass index≥35 kg/m2, with one or more of the following: previous myocardial infarction, elevated urine albumin-creatinine ratio, retinopathy, neuropathy, or peripheral vascular disease. Prevalence estimates were applied to census figures for 2011, estimating absolute numbers meeting the criteria. ResultsAmong adults aged≥50 years, 7.97% (95% confidence interval [CI]: 7.23, 8.78), representing 92,573 people (95% CI: 83,978, 101,981), met criteria one and 0.97% (95% CI: 0.73, 1.28), representing 11,231 people (95% CI: 8471, 14,890), met criteria two. With fewer than 1/100,000 population publicly funded surgeries taking place annually, current service provision meets much less than 0.1% of the need. ConclusionsWhile many adults who fulfill the eligibility criteria for bariatric surgery may not want or require it, the current level of need for bariatric surgical services is not being met. A strategy to develop and expand the provision of bariatric care is urgently needed.

Albuminuria, Cerebrovascular Disease and Cortical Atrophy: among Cognitively Normal Elderly Individuals.

We tested the hypothesis that decreased glomerular filtration rate and albuminuria have different roles in brain structure alterations. We enrolled 1,215 cognitively normal individuals, all of whom underwent high-resolution T1-weighted volumetric magnetic resonance imaging scans. The cerebral small vessel disease burdens were assessed with white matter hyperintensities (WMH), lacunes, and microbleeds. Subjects were considered to have an abnormally elevated urine albumin creatinine ratio if the value was ≥17 mg/g for men and ≥25 mg/g for women. Albuminuria, but not estimated glomerular filtration rate (eGFR), was associated with increased WMH burdens (p = 0.002). The data was analyzed after adjusting for age, sex, education, history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, total cholesterol level, body mass index, status of smoking and alcohol drinking, and intracranial volume. Albuminuria was also associated with cortical thinning, predominantly in the frontal and occipital regions (both p < 0.01) in multiple linear regression analysis. However, eGFR was not associated with cortical thickness. Furthermore, path analysis for cortical thickness showed that albuminuria was associated with frontal thinning partially mediated by WMH burdens. The assessment of albuminuria is needed to improve our ability to identify individuals with high risk for cognitive impairments, and further institute appropriate preventive measures.

Effective risk stratification in patients with moderate cardiovascular risk using albuminuria and atherosclerotic plaques in the carotid arteries.

The aim of this study was to investigate whether subclinical vascular damage improved traditional risk prediction, reclassifying individuals with regard to primary prevention. Two thousand and fifty-nine healthy individuals aged 41, 51, 61, and 71 years were divided into age, Systematic COronary Risk Evaluation (SCORE), and Framingham risk score (FRS) groups. Subclinical vascular damage was defined as carotid-femoral pulse wave velocity at least 12 m/s, and carotid atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 90th percentile of 0.73/1.06 mg/mmol in men/women. The composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for ischemic heart disease was recorded (n = 229). Both elevated UACR (P = 0.002) and atherosclerotic plaques (P < 0.0001) identified a subgroup of moderate SCORE risk patients and high-intermediate FRS risk patients with high risk (P = 0.04 and P = 0.001, respectively), whereas elevated carotid-femoral pulse wave velocity did not. Elevated UACR or presence of atherosclerotic plaques reclassified patients from moderate to high SCORE risk [net reclassification improvement of 6.4%; P = 0.025), or from high intermediate to high FRS risk (net reclassification improvement 8.8%; P = 0.002). Assuming primary prevention could reduce the relative cardiovascular risk by 24-27%, on the basis of actual levels of blood pressure and cholesterol, one composite endpoint could be avoided by giving primary prevention to 19 or 24 reclassified patients found by screening 52 or 104 patients with high-intermediate FRS or moderate SCORE risk, respectively. Elevated UACR and presence of atherosclerotic plaques could in a potentially cost-effective manner identify patients with moderate SCORE risk or high-intermediate FRS with actual high cardiovascular risk who will benefit from primary prevention.

Prevalence of microalbuminuria and associated risk factors among adult Korean hypertensive patients in a primary care setting

Microalbuminuria is an early sign of nephropathy and an independent predictor of end-stage renal disease. The purpose of this study was to assess microalbuminuria prevalence and its contributing factors in Korean hypertensive patients. This cross-sectional study enrolled male and female patients of ≥35 years old with an essential hypertension diagnosis as made by 841 physicians in primary care clinics and 17 in general hospitals in the Republic of Korea between November 2008 and July 2009. To assess microalbuminuria prevalence, urine albumin/creatinine ratio (UACR) was measured in patients with a positive dipstick test. Of the 40,473 enrolled patients, 5713 (14.1%) had a positive dipstick test. Of 5393 patients with a positive dipstick test and valid UACR values, 2657 (6.6%) had significantly elevated UACR (≥30 μg mg(-1)), 2158 (5.4%) had microalbuminuria (30 μg mg(-1)≤UACR <300 μg mg(-1)) and 499 (1.2%) had macroalbuminuria (UACR ≥300 μg mg(-1)). Based on multivariate analysis, independent factors associated with elevated UACR included low adherence to antihypertensive medication (23% higher; P=0.042), poorly controlled blood pressure (BP; 38% higher for systolic BP/diastolic BP ≥130 mm Hg/≥80 mm Hg; P<0.001), obesity (47% higher for body mass index (BMI) ≥25.0 kg m(-2); P<0.001), age (17% lower and 58% higher for age categories 35-44 years (P=0.043) and >75 years (P<0.001), respectively) and a prior history of diabetes (151% higher; P<0.001) and kidney-related disease (71% higher; P<0.001). The prevalences of elevated UACR and microalbuminuria were 6.6% and 5.4%, respectively. Age, increased BMI, presence of comorbidities, poor medication adherence and inadequately controlled BP were independent predictors of elevated UACR after controlling for potential confounders.

Anaemia and type 2 diabetes: implications from a retrospectively studied primary care case series

OBJECTIVES. To identify the prevalence of anaemia in Chinese type 2 diabetic patients managed in a primary care setting and to explore its associations with cardiovascular complications and kidney disease. DESIGN. Retrospective case series study. SETTING. General Out-patient Clinic of Hospital Authority, Hong Kong. PATIENTS. Chinese type 2 diabetic patients who had annual assessments between 1 January 2010 and 31 December 2011 were recruited. Their complete blood picture, serum creatinine, estimated glomerular filtration rate (calculated by Modification of Diet in Renal Disease method), haemoglobin A1c, and urine albumin-creatinine ratio were retrieved. Anaemia was defined as a haemoglobin level of <130 g/L in men and <120 g/L in women (World Health Organization criteria). Student's t test and analysis of variance were used to analyse continuous variables and the Chi squared test for categorical data. Pearson's correlation coefficient and multivariate logistic regression were used to examine associations between haemoglobin level and different variables including age, gender, serum creatinine level, estimated glomerular filtration rate, and urine albumin-creatinine ratio. All statistical tests were two-sided, and a P value of <0.05 was considered significant. RESULTS. Among 6325 Chinese type 2 diabetic patients fulfilling the inclusion criteria, 1441 were found to have anaemia with a period prevalence of 22.8%. The prevalence of anaemia increased significantly with deterioration of renal function. Compared with diabetic patients with normal haemoglobin levels, anaemic diabetic patients had a higher co-morbidity rate for stroke, ischaemic heart disease, hypertension, and chronic kidney disease (P<0.001). Independent predictors for haemoglobin level among diabetic patients were age, gender, serum creatinine level, estimated glomerular filtration rate, haemoglobin A1c, and urine albumin-creatinine ratio (P<0.001). Multivariate analysis showed that male gender, old age, increased serum creatinine level, decreased estimated glomerular filtration rate, elevated urine albumin-creatinine ratio, and co-morbidity with stroke or ischaemic heart disease were associated with greater odds for the presence of anaemia. CONCLUSION. Anaemia is common among Chinese type 2 diabetic patients, particularly those with impaired renal function or established cardiovascular disease. Early detection of anaemia and prompt referral to specialist care for optimal treatment, if associated with severe renal impairment or high-risk proteinuria at the primary care settings, is recommended.

Effect of Cilnidipine on Normal to Marginally Elevated Urine Albumin-Creatinine Ratio in Asymptomatic Non-Diabetic Hypertensive Patients

High-normal urinary albumin excretion has been reported to have clinical significance with respect to progression of proteinuria and hypertension. We analysed the effect of cilnidipine (10 mg/day) on morning systolic blood pressure (SBP) and urine albumin-creatinine ratio (UACR) in 16 non-diabetic hypertensive patients with a normal to marginally elevated UACR (mean +/- SD 29.4 +/- 21.7; range 7.5-72.9 mg/g creatinine). Sequential home BP and UACR data were fitted to a simple exponential function as follows: where y is SBP (mmHg) or UACR (mg/g creatinine); alpha is the extent of the SBP (mmHg)- or UACR (mg/g creatinine)-lowering effect; beta (days) is the time-constant for SBP or UACR decrease; t is the number of days after the start of cilnidipine administration; and gamma is the finally stabilized SBP (mmHg) or UACR (mg/g creatinine). Mean +/- SD morning SBP and UACR decreased by 20.4 +/- 11.4 mmHg and 15.2 +/- 13.1 mg/g creatinine, respectively, as determined by coefficient alpha. The mean +/- SD time-constant for UACR decrease was significantly longer than that for BP decrease (43.5 +/- 22.9 vs 15.4 +/- 7.1 days). UACR reduction correlated with pre-treatment UACR values (correlation coefficient [R] = 0.88, p < 0.01) but not with BP decrease. The present study demonstrated that cilnidipine reduced UACR in hypertensive patients with normal to marginally elevated UACR independent of its BP-lowering effect.

Associations of microalbuminuria with brain atrophy and white matter hyperintensities in hypertensive sibships

Because of similarities between brain and kidney microvascular disease, there may be a relationship between measures of renal microvascular disease and brain structural changes in middle aged or elderly individuals. To determine whether the urine albumin/creatinine ratio (UACR), a measure of renal microvascular disease, is associated with brain atrophy and white matter hyperintensities. As part of a larger study of the genetics of hypertension, we performed brain imaging and assessed microalbuminuria and other vascular risk factors including diabetes, hypertension, hyperlipidemia and hyperhomocysteinemia in 1253 individuals from hypertensive sibships (age mean 63.8 years, range 50 to 91; 65% women; 49% African-American; 78% hypertensive). Semi-automated quantitative measurements of brain atrophy (BA) ventricular volume, and white matter hyperintensities (WMH) were carried out on the brain MR scans. In logistic regression models, elevated UACR was associated with greater BA (odds ratio (OR)=1.70 (95% CI 1.14, 2.54) and burden of WMH (OR=2.06 (95% CI 1.37, 3.10) after controlling for demographic factors, blood glucose, hypertension severity, duration of smoking and serum homocysteine. In contrast to elevated UACR, the associations with elevated creatinine or reduced glomerular filtration rate and WMH were not significant in the fully adjusted models. In this cohort with an overrepresentation of hypertensives, elevated UACR was independently associated with both brain atrophy and white matter hyperintensities. Brain volume loss and WMH burden might represent expressions of microvascular disease that share common mechanisms with nephrosclerosis.

Association of CC chemokine ligand 5 genotype with urinary albumin excretion in the non-diabetic Japanese general population: the Takahata study

Albuminuria is an early marker of vascular damage, and its development in diabetic nephropathy is associated with genotype of inflammatory CC chemokine ligand 5 (CCL5). This study investigated whether the association of CCL5 and albuminuria is a general phenomenon. We characterized a Japanese population consisting of 2,749 non-diabetic individuals over 40 years in Takahata, Japan. The urine albumin-creatinine ratio (UACR) was obtained from morning spot urine. We genotyped SNPs within the CCL5 gene that displayed frequent minor allele frequencies in Japanese (i.e., rs2107538, rs2280789, rs3817655 and rs9909416). Assessment of possible association and linkage disequilibrium (LD) revealed that all four SNP genotypes are correlated significantly with UACR (P = 0.004-0.005), and these four SNPs variations showed an obvious consistency of genotypes by detecting almost complete linkage disequilibrium (D' = 1 and r (2) > 0.95). We found two exclusive haplotypes in the CCL5 gene (haplotype1: rs2107538G/rs2280789T/rs3817655T/rs9909416G, frequency 0.64 and haplotype2: rs2107538A/rs2280789C/rs3817655A/rs9909416A, frequency 0.35) among the population. A significant association with elevated UACR was identified with haplotype1 (P = 0.002). Homozygotes for haplotype1 displayed strikingly-elevated UACR (48.5 +/- 6.6 mg/g, n = 1,116) compared to the rest (28.6 +/- 1.6 mg/g, n = 1,530) (P = 0.001). In conclusion, these results suggested that genetic variation of CCL5 might be an important risk factor for albuminuria in the non-diabetic Japanese general population.

Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and high sensitivity C-reactive protein is affected by age and sex

Previous studies have shown that the urine albumin/creatinine ratio (UACR), high sensitivity C-reactive protein (hsCRP) and N-terminal pro brain natriuretic peptide (Nt-proBNP) predict cardiovascular events in a general population aged 41, 51, 61 or 71 years. This study investigated the impact of age and sex on their prognostic performance in a subgroup of 1994 apparently healthy individuals without diabetes, previous stroke or myocardial infarction, who did not receive any cardiovascular, antidiabetic or lipid-lowering medication. In 1993-1994 we recorded cardiovascular risk factors, UACR, hsCRP and Nt-proBNP. The composite cardiovascular endpoint (CEP) of cardiovascular death and non-fatal stroke or myocardial infarction was assessed after 9.5 years. In Cox regression analyses predicting CEP, the effects of log(hsCRP) and log(Nt-proBNP) were modulated by sex (P < 0.05) and age (P < 0.05), respectively. The effect of logUACR was not significantly modulated by age or sex. Log(hsCRP)/SD did not predict CEP in women, but did predict CEP in 41 plus 51-year-old men [hazard ratio (HR) 1.71; 95% confidence interval, 1.1-2.6; P < 0.05] and 61 plus 71-year-old men (HR 1.64; 1.3-2.2; P < 0.001). Log(Nt-proBNP)/SD predicted CEP in 61 plus 71-year-old women (HR 1.74; 1.2-2.5; P < 0.01) and in 61 plus 71-year-old men (HR 1.58; 1.3-2.0; P < 0.001). Elevated hsCRP, reflecting early atherosclerosis, predicted CEP even in 41 plus 51-year-old men. Elevated Nt-proBNP, reflecting subclinical cardiovascular damage, predicted CEP in 61 plus 71-year-old subjects. Elevated UACR, reflecting endothelial dysfunction as well as microvascular damage, predicted events independently of age and sex, but primarily in 61 plus 71-year-old subjects.