We previously reported an increased risk of all-cause and AIDS mortality among HIV-infected women with albuminuria (proteinuria or microalbuminuria) enrolled in the Women’s Interagency HIV Study (WIHS) prior to the introduction of highly active antiretroviral therapy (HAART).
The current analysis includes 1,073 WIHS participants who subsequently initiated HAART. Urinalysis for proteinuria and semi-quantitative testing for microalbuminuria from two consecutive study visits prior to HAART initiation were categorized as follows: confirmed proteinuria (both specimens positive for protein), confirmed microalbuminuria (both specimens positive with at least one microalbuminuria), unconfirmed albuminuria (one specimen positive for proteinuria or microalbuminuria), or negative (both specimens negative). Time from HAART initiation to death was modeled using proportional hazards analysis.
Compared to the reference group of women with two negative specimens, the hazard ratio (HR) for all-cause mortality was significantly elevated for women with confirmed microalbuminuria (HR 1.9; 95% CI 1.2–2.9). Confirmed microalbuminuria was also independently associated with AIDS death (HR 2.3; 95% CI 1.3–4.3), while women with confirmed proteinuria were at increased risk for non-AIDS death (HR 2.4; 95% CI 1.2–4.6).
In women initiating HAART, pre-existing microalbuminuria independently predicted increased AIDS mortality, while pre-existing proteinuria predicted increased risk of non-AIDS death. Urine testing may identify HIV-infected individuals at increased risk for mortality even after the initiation of HAART. Future studies should consider whether these widely available tests can identify individuals who would benefit from more aggressive management of HIV infection and comorbid conditions associated with mortality in this population.
HIV; microalbuminuria; proteinuria; mortality; non-AIDS death
Microalbuminuria is associated with increased risk of cardiovascular disease and mortality. The objective of the study was to evaluate if HIV infection was an independent risk factor for microalbuminuria.
The relationship between HIV infection and microalbuminuria was assessed using subjects enrolled in the study of Fat Redistribution and Metabolic Change in HIV Infection, which consists of HIV-positive and control men and women. Participants with proteinuria (dipstick ≥1+) were excluded.
Microalbuminuria (urinary albumin/creatinine ratio, ACR>30 mg/g) was present in 11% of HIV infected, and 2% of control participants (P<0.001); a fivefold odds after multivariate adjustment (odds ratio, 5.11; 95% confidence interval, 1.97–13.31; P=0.0008). Several cardiovascular risk factors were associated with higher ACR in HIV participants: insulin resistance (HOMA>4; 32%, P<0.0001), systolic blood pressure (21%, P=0.01 for 120–140 versus <120 mmHg, and 43%, P <0.06 for >140 versus <120 mmHg), and family history of hypertension (17%, P=0.03). Higher CD4 cell count was associated with lower albumin/creatinine ratio (−24%, P=0.009 for 200–400 versus <200 cells/ml and −26%, P=0.005 for >400 versus <200 cells/ml).
HIV infection had a strong and independent association with microalbuminuria, the severity of which was predicted by markers of insulin resistance, hypertension, and advanced HIV infection. These associations warrant further investigation, as the increased prevalence of microalbuminuria in HIV infection may be a harbinger of future risk of cardiovascular and kidney diseases.
Microalbuminuria; kidney; urine protein; insulin resistance; lipodystrophy
To examine the sex-specific contributions of the metabolic syndrome and microalbuminuria to cardiovascular disease (CVD) and coronary heart disease (CHD) mortality in community-dwelling older adults, between 1992–1995, 869 women and 575 men aged 40–96 years (mean 71) completed questionnaires, physical examinations, and fasting laboratory tests. Participants were followed over an average of 8 years. CVD and CHD mortality were analyzed using Cox proportional hazards models. At baseline, 267 participants had the Adult Treatment Panel III metabolic syndrome, 151 had microalbuminuria, and 34 had both. During follow up, there were 180 CVD deaths, including 83 CHD deaths. In women, microalbuminuria was associated with a 2-fold increased risk of CVD and CHD mortality (p ≤ 0.01). Women with both microalbuminuria and the metabolic syndrome (n = 18) had a 3-fold increased risk of CVD mortality and a 5-fold increased risk of CHD mortality compared with women without either (n = 657). A significant interaction existed between microalbuminuria and the metabolic syndrome in the prediction of both CVD and CHD (p = 0.021). In men, neither the combination of the metabolic syndrome and microalbuminuria (n = 16), nor either alone, significantly increased the risk of CVD or CHD mortality. In conclusion, in this cohort, microalbuminuria and the metabolic syndrome together were a more powerful predictor of CVD mortality than either alone in women but not in men. Screening for microalbuminuria in older women may identify women at high risk for CVD mortality, beyond that conferred by risk factors included in the metabolic syndrome.
Cardiovascular disease; Elderly; Metabolic syndrome; Microalbuminuria
Background. The survival of human immunodeficiency virus (HIV)-infected patients has increased significantly since the introduction of combination antiretroviral therapy, leading to the development of important long-term complications including cardiovascular disease (CVD) and renal disease. Microalbuminuria, an indicator of glomerular injury, is associated with an increased risk of progressive renal deterioration, CVD and mortality. However, the prevalence of microalbuminuria has barely been investigated in HIV-infected individuals.
Methods. Based on three prospective urine samples in an unselected nonhypertensive, nondiabetic HIV-positive cohort (n = 495), we analysed the prevalence of microalbuminuria and compared the Caucasian share with that of a nonhypertensive, nondiabetic population-based control group (n = 2091). Significant predictors for microalbuminuria were analysed within the HIV-positive cohort.
Results. The prevalence of microalbuminuria was 8.7% in the HIV-infected cohort, which is three to five times higher than that in the general population. HIV-infected patients with microalbuminuria were older, and had higher blood pressure, longer duration of HIV infection, higher serum beta 2-microglobulin, higher serum creatinine and a reduced glomerular filtration rate of ≤90 mL/min, compared with those with normal albumin excretion. In multivariate analysis, systolic blood pressure, serum beta 2-microglobulin and duration of HIV infection were found to be independent predictors of microalbuminuria.
Conclusions. Our findings indicate that in addition to haemodynamic effects, inflammatory activity may be implicated as a cause of the development of microalbuminuria. With respect to the increasing risk of developing CVD or renal diseases and mortality, the high prevalence of microalbuminuria in HIV-infected individuals warrants special attention.
beta 2-microglobulin; blood pressure; combination antiretroviral treatment; HIV; microalbuminuria
Microalbuminuria is a common condition associated with increased incidence of cardiovascular events and mortality. Abdominal obesity is associated with microalbuminuria, but studies linking visceral adipose tissue (VAT) and microalbuminuria are limited. Our objective was to determine the associations of albuminuria with VAT and subcutaneous adipose tissue (SAT). We performed a cross-sectional study in the Framingham Multi-detector Computed Tomography cohort (n = 3099, 48.2% women, mean age 53 years). VAT and SAT volumes were measured using computed tomography. Urinary albumin-to-creatinine ratio (UACR) was calculated from spot urine samples. Microalbuminuria was defined as a UACR >25 mg/g in women or >17 mg/g in men. Overall, 7.9% (n = 244) of the sample had microalbuminuria. Among men, VAT (Odds ratio [OR] 1.48 per standard deviation [SD], p<0.0001) and SAT (OR 1.37 per SD, p=0.0002) were associated with microalbuminuria in minimally-adjusted models, which remained significant after multivariable adjustment (VAT OR 1.34 per SD, p=0.001; SAT OR 1.28 per SD, p=0.005). Additionally, when considered jointly, VAT (p=0.002) but not SAT (p=0.2) was associated with microalbuminuria. In women, VAT was associated with microalbuminuria after minimal adjustment (OR 1.28, p=0.01), but not after multivariable adjustment (OR 1.03, p=0.8). In multivariable models in women, SAT was associated with a decreased odds of having microalbuminuria (OR 0.75 per SD, p=0.03). In conclusion, VAT is associated with microalbuminuria in men but not women. Albuminuria may be a manifestation of visceral adiposity.
Abdominal obesity; Microalbuminuria; Computed Tomography
This study examines the association between microalbuminuria and the development of proteinuria among HIV-infected persons.
948 subjects provided urine samples for albumin, protein, and creatinine measurements semiannually. Microalbuminuria was an albumin-to-creatinine ratio of >30 mg/gm. Proteinuria was a protein-to-creatinine ratio of ≥0.350 mg/mg. The progression from microalbuminuria to proteinuria was described.
At baseline, 69.4% had no detectable proteinuria, 20.2% had microalbuminuria, and 10.4% had proteinuria. Subjects with microalbuminuria and proteinuria were more likely to be black (p=0.03), have lower CD4+ counts (p=0.02,0.0001 compared to subjects without abnormal proteinuria, respectively), and have a higher HIV RNA level (p=0.08,0.04). Among 658 subjects with normal urine protein, 82.7% continued to have no abnormality, 14.3% developed microalbuminuria, and 3.0% developed proteinuria. Subjects without baseline proteinuria (i.e. either normal protein excretion or microalbuminuria) who developed proteinuria were more likely to have microalbuminuria (p=0.001), a lower CD4+ count (p=0.06), and a higher plasma HIV RNA (p=0.03) than those who did not progress to proteinuria. In multivariate analysis, only microalbuminuria remained associated with the development of proteinuria (OR=2.9; 95% CI 1.5, 5.5; p=0.001).
Microalbuminuria predicts the development of proteinuria among HIV-infected persons. Because proteinuria has been linked to poorer outcomes, strategies to affect microalbuminuria should be tested.
HIV-1; microalbuminuria; proteinuria; HIVAN; urine
Background. Human immunodeficiency virus associated nephropathy (HIVAN) is a rapidly progressive chronic renal parenchymal disease that occurs in HIV-infected individuals and manifests commonly as proteinuria, which is preceded by microalbuminuria (MA). This clinical entity is defined as a spot urine albumin of 20–200 mg/L. Objectives. To determine the prevalence of microalbuminuria in HIV positive children in UNTH, Enugu and compare it with that of HIV-negative children. Methods. A total of 154 HIV positive children aged 18 months to 14 years and 154 HIV-negative children of corresponding attributes were screened for microalbuminuria, using Micral test II strip which has a sensitivity of 90–99%. Results. No child among the groups (HIV positive and negative) had microalbuminuria. Majority (96.0%) of HIV-positive children had nonadvanced HIV disease at the time of the study (P = 0.00). About 77.3% were using HAART (P < 0.0001), the mean CD4 cell count of the subjects was 709.2 ± 443.9 cells/mm3; while 78.0% had nonsevere immunosuppression (P = 0.00). Furthermore, HIV-positive children with severe immunosuppression were younger and had shorter duration of treatment. Conclusion. Microalbuminuria may not be very common in Nigerian children irrespective of their HIV status.
BACKGROUND. Microalbuminuria may predict proteinuria and increased mortality in non-insulin dependent diabetic patients. Early detection of microalbuminuria may therefore be essential. AIM. The primary objective of this study was to describe the association between the presence of albuminuria in diabetic patients as detected by general practitioners using conventional reagent strip dipstick tests for albumin, and the urinary albumin concentration as measured in a hospital laboratory. METHOD. A total of 675 newly diagnosed diabetic patients aged 40 years or over were included in the Danish study, diabetes care in general practice. Data for urinary albumin concentration from a morning urine sample and the results of three consecutive dipstick tests for albumin were collected for 417 patients. RESULTS. When defining elevated urinary albumin concentration as 200 mg l-1 or more (proteinuria) the finding of at least one positive test out of the three dipstick tests for albumin had a diagnostic sensitivity of 73% and a specificity of 89%. When the microalbuminuric range (15.0 to 199.9 mg l-1) was added to the definition of renal involvement, the sensitivity of the dipstick test became as low as 28% with a specificity of 96%. CONCLUSION. It is essential for general practitioners to be able to identify proteinuric patients. To achieve this by means of the conventional dipstick test, general practice procedures need to be improved. As it is becoming increasingly well-documented that microalbuminuric non-insulin dependent diabetic patients may benefit from pharmacological treatment of even slight arterial hypertension and heart failure, it seems reasonable to suggest that the use of dipsticks for albumin in general practice be replaced by laboratory quantitative determination of urinary albumin concentration in a morning urine sample.
Our study evaluates the long-term effect of microalbuminuria on mortality among patients with acute myocardial infarction. We followed 151 patients from 1996 to 2007 to investigate if microalbuminuria is a risk factor in coronary heart disease. All patients admitted with acute myocardial infarction in 1996 were included. At baseline, we recorded urinary albumin/creatinine concentration ratio, body mass index, blood pressure, left ventricle ejection fraction by echocardiography, smoking status, medication, diabetes, age, and gender. Deaths were traced in 2007 by means of the Danish Personal Identification Register. Microalbuminuria, defined as a urinary albumin/creatinine concentration ratio above 0.65 mg/mmoL, occurred in 50% of the patients and was associated with increased all-cause mortality. Thus, 68% of the patients with microalbuminuria versus 48% of the patients without microalbuminuria had died during the 10 years of follow-up (P=0.04). The crude hazard ratio for death associated with microalbuminuria was 1.78 (CI: 1.18–2.68) (P=0.006), whereas the gender- and age-adjusted hazard ratio was 1.71 (CI: 1.03–2.83) (P=0.04). We concluded that microalbuminuria in hospitalized patients with acute myocardial infarction is prognostic for increased long-term mortality. We recommend measurement of microalbuminuria to be included as a baseline risk factor in patients with acute myocardial infarction and in future trials in patients with coronary heart disease.
acute myocardial infarction; microalbuminuria; risk factors; atherosclerosis; cardiovascular disease.
Diabetic nephropathy is the main cause of the increased morbidity and mortality in patients with insulin dependent diabetes. The prevalence of microalbuminuria was determined in adults with insulin dependent diabetes of five or more years' duration that had started before the age of 41. All eligible patients (n=982) attending a diabetes clinic were asked to collect a 24 hour urine sample for analysis of albumin excretion by radio-immunoassay; 957 patients complied. Normoalbuminuria was defined as urinary albumin excretion of ≤30 mg/24 h (n=562), microalbuminuria as 31-299 mg/24 h (n=215), and macroalbuminuria as ≥300 mg/24 h (n=180). The prevalence of microalbuminuria and macroalbuminuria was significantly higher in patients whose diabetes had developed before rather than after the age of 20. The prevalence of arterial hypertension increased with increased albuminuria, being 19%, 30%, and 65% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. The prevalence of proliferative retinopathy and blindness rose with increasing albuminuria, being 12% and 1·4%, respectively, in patients with normoalbuminuria, 28% and 5·6% in those with microalbuminuria and 58% and 10·6% in those with macroalbuminuria. An abnormal vibratory perception threshold was more common in patients with microalbuminuria (31%) and macroalbuminuria (50%) than in those with normoalbuminuria (21%).
This study found a high prevalence (22%) of microalbuminuria, which is predictive of the later development of diabetic nephropathy. Microalbuminuria is also characterised by an increased prevalence of arterial hypertension, proliferative retinopathy, blindness, and peripheral neuropathy. Thus, urinary excretion of albumin should be monitored routinely in patients with insulin dependent diabetes.
Microalbuminuria (defined as urinary albumin excretion of 30-300 mg/day, or 20-200 µg/min) is an earlier sign of vascular damage. It is a marker of general vascular dysfunction and nowadays is considered a predictor of worse outcomes for both kidney and heart patients. There is a significant correlation between blood pressure and microalbuminuria. Even high normal blood pressure is associated with significant higher frequency of microalbuminuria and this way may be a biomarker of increased cardiovascular risk. Microalbuminuria could be taken also, as an indicator of insulin resistance and of the increased renal and cardiovascular risk associated with metabolic syndrome. Renal involvement is a pivotal development in diabetes and microalbuminuria is generally the first clinical sign of renal dysfunction in diabetics. It is demonstrated that cardiovascular and renal risk is elevated even in the high normal range of microalbuminuria (below 30 mg/day). There is no doubt that therapies that prevent or delay the development of microalbuminuria and all measures that reduce it, may help to prevent or delay end organ damage.
microalbuminuria; cardiovascular risk; high blood pressure; diabetic nephropathy
In the early highly active antiretroviral therapy (HAART) era, kidney dysfunction was strongly associated with death among HIV-infected individuals. We re-examined this association in the later HAART period to determine whether chronic kidney disease (CKD) remains a predictor of death after HAART-initiation.
To evaluate the effect of kidney function at the time of HAART initiation on time to all-cause mortality, we evaluated 1415 HIV-infected women initiating HAART in the Women’s Interagency HIV Study (WIHS). Multivariable proportional hazards models with survival times calculated from HAART initiation to death were constructed; participants were censored at the time of the last available visit or December 31, 2006.
CKD (eGFR <60 ml/min/1.73 m2) at HAART initiation was associated with higher mortality risk adjusting for age, race, hepatitis C serostatus, AIDS history and CD4+ cell count (hazard ratio [HR]=2.23, 95% confidence interval [CI]: 1.45–3.43). Adjustment for hypertension and diabetes history attenuated this association (HR=1.89, CI: 0.94–3.80). Lower kidney function at HAART initiation was weakly associated with increased mortality risk in women with prior AIDS (HR=1.09, CI: 1.00–1.19, per 20% decrease in eGFR).
Kidney function at HAART initiation remains an independent predictor of death in HIV-infected individuals, especially in those with a history of AIDS. Our study emphasizes the necessity of monitoring kidney function in this population. Additional studies are needed to determine mechanisms underlying the increased mortality risk associated with CKD in HIV-infected persons.
kidney disease; mortality; HIV; WIHS; antiretroviral therapy
Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC).
This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30).
Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306).
Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure.
Persistent proteinuria is strongly associated with increased mortality in insulin dependent diabetes, and risk of this condition can be predicted many years in advance by subclinical increases in albumin excretion rate (microalbuminuria). Eight normotensive insulin dependent diabetics with microalbuminuria who had overnight albumin excretion rates of between 15 and 200 micrograms/min underwent a three week randomised crossover study of their normal protein diet (median 92 (range 55-117) g/day) and a low protein diet (47 (38-57) g/day). Both diets were isoenergetic, and the low protein diet was supplemented with calcium and phosphate. Median overnight albumin excretion rate fell from 23.0 (15.0-170.1) micrograms/min during the normal diet to 15.4 (4.1-97.8) micrograms/min during the low protein diet. No consistent change was found in urinary excretion of beta 2 microglobulin during the two diets. The reduction in albumin excretion rate was accompanied by a significant fall in median glomerular filtration rate and fractional renal clearance of albumin. Kidney volume remained unchanged. There were no significant changes in glycaemic control or arterial blood pressure. In these few patients restriction of dietary protein had a beneficial effect on microalbuminuria, independent of changes in glucose concentrations and arterial blood pressure.
To evaluate the predictive values of urinary calcium creatinine ratio (CCR) and microalbuminuria for preeclampsia.
Urinary calcium creatinine ratio and microalbuminuria were determined in a spot urine sample in 200 asymptomatic pregnant women between 20–24 weeks of gestation, who attended the antenatal OPD at St John’s Medical College and Hospital. The results were analyzed by Chi square test and Fisher Exact test to find the significant association of findings of preeclampsia and CCR and microalbuminuria. Area under Receiver Operator Curve (ROC) was used to find the predictive values of CCR at less than or equal to 0.04 and microalbuminuria for preeclampsia.
It was found that CCR had a sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of 69.2%, 98.2%, 85.7% and 95.8% respectively with a statistical accuracy of 87% and p value of <0.001 (strongly significant). It was found to be a good test for prediction of preeclampsia. Microalbuminuria had sensitivity, specificity, PPV and NPV of 53.6%, 86%, 36% and 95% and was found to be only a fair test for prediction of preeclampsia.
CCR at 0.04 in spot urine sample being a good test for prediction of preeclampsia can be recommended as a screening test in all asymptomatic pregnant women, for preeclampsia. Microalbuminuria does not seem to be effective as a screening tool for preeclampsia at present.
calcium creatinine ratio; microalbuminuria; prediction of preeclampsia
HIV-associated immune injury is hypothesized to increase the risk of preclinical disability and frailty via inflammatory pathways. We investigated the role of CD4+ T cell depletion and clinical AIDS on preclinical disability and frailty in HIV-positive women with a history of combination antiretroviral therapy (cART) and HIV-negative women.
This was a cross-sectional study nested within the Women's Interagency HIV Study (WIHS), a prospective cohort study initiated in 1994 across five U.S. cities. Questionnaires and tests were performed by 573 HIV-negative and 1206 HIV-positive women. Prevalence ratios were computed using regression models.
Severe CD4+ cell depletion was an independent predictor of slowness, weakness, and frailty in HIV-positive women compared with HIV-negative women. Women with CD4+ counts <100 cells/mm3 were 0.13 seconds slower to complete 4 meters (95% CI 0.06-0.21), 1.25 kg weaker (95% CI −2.31-−0.19), and had 2.7 times higher prevalence of frailty (95% CI 1.46-5.01).
This study is one of the largest studies to administer performance-based tests to investigate disability and frailty in HIV-positive women. HIV-positive women with intact immune systems and without a history of clinical AIDS were no different from HIV-negative women on tests of slowness, weakness, and frailty phenotype.
Microalbuminuria independently predicts the development of nephropathy and increased cardiovascular morbidity and mortality in diabetic patients, but it may be an indicator of the acute phase response. This study examined microalbuminuria as a marker of the acute phase response in patients with inflammatory bowel disease and correlated it with the disease activity in 95 patients with inflammatory bowel disease (ulcerative colitis (n = 52), Crohn's disease (n = 43)) determined by the simple index of Harvey and Bradshaw. Fifty patients were in complete clinical remission and 45 patients had active disease. Microalbuminuria was detected in all patients with inflammatory bowel disease (147 (17) v 18 (2) microgram/min, inflammatory bowel disease v controls mean (SEM), p < 0.007). Patients with active inflammatory bowel disease had higher concentrations of microalbuminuria compared with patients in remission (206 (19) v 65 (8) microgram/min, mean (SEM), p < 0.0001). Eight patients with active inflammatory bowel disease who were sequentially followed up with measurements of microalbuminuria had significantly lower values, when the disease was inactive (active inflammatory bowel disease 192 (44) v inactive inflammatory bowel disease 64 (14) microgram/min, p < 0.03). There was a significant correlation with the simple index of Harvey and Bradshaw (r = 0.818, p < 0.0001). Microalbuminuria values were significantly lower in inflammatory bowel disease patients in remission, maintained with olsalazine compared with those patients maintained with mesalazine and salazopyrine, but no significant difference was seen in values of microalbuminuria in active inflammatory bowel disease patients receiving different salicylates. This study also measured serum amyloid-A as an indicator of the acute phase response in the same patients. Serum amyloid-A was significantly increased in active disease compared with inactive disease (151 (43) v 33 (7) or controls 11 (2) micrograms/ml, p < 0.05). In conclusion microalbuminuria is present in abnormal amounts in all patients with active inflammatory bowel disease, and values fall when the disease is quiescent. Microalbuminuria is probably a consequence of an acute phase response and provides a simple, rapid, and inexpensive test, which has the potential to monitor inflammatory bowel disease activity and response to treatment.
Although cardiovascular disease (CVD) is the leading cause of mortality in patients with chronic kidney disease (CKD), the pathophysiology is not thoroughly understood. Given that elevated albuminuria or circulating angiopoietin-2 associates with CVD and mortality in CKD patients, we were intrigued by the relationship between albuminuria and angiopoietin-2. A total of 416 patients with CKD stages 3 to 5 were stratified by urine albumin-creatinine ratio as normoalbuminuria (<30 mg/g), microalbuminuria (30–300 mg/g), or macroalbuminuria (>300 mg/g). The levels of plasma angiopoietin-2 and vascular endothelial growth factor (VEGF) increased, and soluble Tie-2 decreased in the subgroups of albuminuria; whereas angiopoietin-1 did not change. Linear regression showed a positive correlation between urine albumin-creatinine ratio (ACR) and plasma angiopoietin-2 (correlation coefficient r = 0.301, 95% confidence interval 0.211–0.386, P<0.0001), but not between ACR and VEGF or soluble Tie-2. Multivariate linear regression analysis showed that plasma angiopoietin-2 was independently associated with ACR (P = 0.025). Furthermore, plasma angiopoietin-2 was positively correlated with high sensitive C-reactive protein (r = 0.114, 95% confidence interval 0.018–0.208, P = 0.020). In conclusion, plasma angiopoietin-2 was associated with albuminuria and markers of systemic microinflammation in CKD patients. Although previous evidence has shown that angiopoietin-2 destabilizes vasculature and induces inflammation in different scenarios, further study will be required to delineate the role of angiopoietin-2 in albuminuria and microinflammation in CKD patients.
Microalbuminuria is associated with diabetes and is an independent risk factor for developing diabetic nephropathy. We have previously reported the overall prevalence of normoalbuminuria, microalbuminuria, and macroalbuminuria to be 51, 39, and 9.8%, respectively, in an unselected population of patients with type 2 diabetes. Renal dysfunction was present in a large proportion of these patients without proteinuria, assessed by a single random albumin-to-creatinine ratio (ACR). We therefore undertook to characterize the nature of this association of non-proteinuric renal dysfunction in type 2 diabetes.
In the DEMAND (Developing Education on Microalbuminuria for Awareness of Renal and Cardiovascular Risk in Diabetes) study, a global, cross-sectional study which described the prevalence and risk factors for albuminuria in a clinic-based cohort, kidney function was assessed in 11,573 patients; ACR was measured using the Bayer reagent strip Multistix® 10SG. Normoalbuminuria was defined as ACR <30 mg/g, microalbuminuria as 30–299 mg/g, and macroalbuminuria as >300 mg/g.
Among the patients with estimated kidney function determined, chronic kidney disease was noted in 17% of those with normoalbuminuria (stage 3–5), and significant kidney dysfunction was found in 27% of those with microalbuminuria and 31% of those with overt proteinuria. CrCl was <60 ml/min in 20.5% of normoalbuminurics, 30.7% of microalbuminurics, and 35.0% of macroalbuminurics (p < 0.0001).
A large proportion of diabetic patients with completely normal urinary albumin excretion or microalbuminuria presented with significant kidney dysfunction. Therefore, further investigation is warranted.
Albuminuria; Chronic kidney disease; Diabetes; Diabetic nephropathy; Normoalbuminuria; Proteinuria
Continuous increase in the number of patients with end-stage renal disease demands early detection of chronic kidney disease (CKD). The aim of the present study was to diagnose CKD in its earliest stages in a randomly selected population using a diagnostic algorithm developed by the working group.
An algorithm for the diagnostic procedure was created to identify patients with CKD requiring further nephrological care. Randomly chosen adult inhabitants of a city with a population of 60,000 were invited to participate in this study. Screening procedures included a microalbuminuria dipstick test accompanied by blood pressure measurement and medical questionnaire. In further diagnosis of CKD, estimated glomerular filtration rate (eGFR), albumin concentration in urine, urinalysis and ultrasound examination were used according to the algorithm. Multivariate logistic regression was performed to identify associations between participants’ characteristics and albuminuria.
Out of 9,700 invited subjects, 2,471 individuals participated in the PolNef study. Albuminuria was detected in 15.6% of the investigated population using the dipstick test and thereafter confirmed in 11.9% by the turbidimetric method. The modeling of multivariate logistic regression indicated the following independent predictors of albuminuria: male sex, diabetes, nocturia and hypertension. For people without diabetes and without hypertension, nocturia independently predicted detection of albuminuria. 481 people received a consultation with a nephrologist, and 96% of them were recognized as having CKD. At least 9% of patients with CKD had eGFR by MDRD <60 ml/min/1.73 m2. Six persons were referred for further treatment because of newly diagnosed kidney tumor.
CKD in early stages occurs frequently in the studied population. The proposed diagnostic algorithm seems to be a powerful tool to identify subjects at risk of CKD. The role of nocturia as an independent predictor of albuminuria, both in the general population and in people without diabetes or hypertension, should be further examined.
Albuminuria; Chronic kidney disease; Diagnostic algorithm; Nocturia
To evaluate the effects of longitudinal patterns and types of non-injection drug use (NIDU) on HIV progression in the highly active antiretroviral therapy (HAART) era.
Women’s Interagency HIV Study (WIHS), a prospective cohort study conducted at six US sites.
Data were collected semi-annually from 1994 to 2002 on 1046 HIV+ women. Multivariate Cox proportional hazards modeling was used to estimate relative hazards for developing AIDS and for death by pattern and type of NIDU.
During follow-up, 285 AIDS events and 287 deaths, of which 177 were AIDS-related, were reported. At baseline, consistent and former NIDU was associated with CD4+ counts of < 200 cells/μl (43% and 46%, respectively) and viral load > 40 000 copies/ml (53% and 55%, respectively). Consistent NIDU reported less HAART use (53%) compared with other NIDU patterns. Stimulant use was associated with CD4+ cell counts of < 200 cells/μl (53%) and lower HAART initiation (63%) compared with other NIDU types. In multivariate analyses, progression to AIDS was significantly higher among consistent (RH = 2.52), inconsistent (RH = 1.63) and former (RH = 1.56) users compared with never users; and for stimulant (RH = 2.04) and polydrug (RH = 1.65) users compared with non-users. Progression to all-cause death was higher only among former users (RH = 1.48) compared with never users in multivariate analysis. NIDU behaviors were not associated with progression to AIDS-related death.
In this study, pattern and type of NIDU were associated with HIV progression to AIDS and all-cause mortality. These differences were associated with lower HAART utilization among consistent NIDU and use of stimulants, and poor baseline immunological and virological status among former users.
Acquired immunodeficiency syndrome; highly active anti-retroviral therapy; human immunodeficiency virus; mortality; non-injection drug use
HIV associated nephropathy (HIVAN) is the most common form of chronic kidney disease resulting directly from HIV infection. The true prevalence of HIVAN in the paediatric population of West Africa is unknown, largely due to lack of surveillance and reporting of kidney disease in HIV positive patients.
This was a prospective study over a six month period( July to December 2008) conducted in the Infectious Disease Unit of the Department of Paediatrics, University of Uyo Teaching Hospital, Uyo, Nigeria involving all confirmed cases of paediatric HIV infection. Urine microalbuminuria using calculated urine albumin – creatinine ratio was determined and repeated in 4 weeks interval. CD4 count and renal ultrasonography was done for all the patients. The correlation of urine albumin – creatinine ratio with CD4 count, duration of treatment with highly active antiretroviral therapy (HAART) and association with clinical staging of the disease was also examined.
Fifty – nine (60.2%) were males, thirty – nine (39.8%) were females with male to female ratio of 1.5:1. The prevalence rate of 31.6% HIVAN was found, out of which 3.1% had abnormal ultrasound findings. There was a significant correlation between CD4 count and urine albumin – creatinine ratio (r=−0.22, p=0.03). There was no correlation between urine albumin – creatinine ratio and duration on HAART (r=−0.10, p=0.31).
Screening for microalbuminuria is essential for the early diagnosis and treatment of HIVAN in this age group.
HIVAN; microalbuminuria; HIV; HAART; proteinuria; paediatrics; Nigeria
Hazardous alcohol consumption among women with human immunodeficiency virus (HIV) infection is associated with several adverse health and behavioral outcomes, but the proportion of HIV-positive women who engage in hazardous drinking over time is unclear. The authors sought to determine rates of hazardous alcohol consumption among these women over time and to identify factors associated with this behavior. Subjects were 2,770 HIV-positive women recruited from 6 US cities who participated in semiannual follow-up visits in the Women's Interagency HIV Study from 1995 to 2006. Hazardous alcohol consumption was defined as exceeding daily (≥4 drinks) or weekly (>7 drinks) consumption recommendations. Over the 11-year follow-up period, 14%–24% of the women reported past-year hazardous drinking, with a slight decrease in hazardous drinking over time. Women were significantly more likely to report hazardous drinking if they were unemployed, were not high school graduates, had been enrolled in the original cohort (1994–1995), had a CD4 cell count of 200–500 cells/mL, were hepatitis C-seropositive, or had symptoms of depression. Approximately 1 in 5 of the women met criteria for hazardous drinking. Interventions to identify and address hazardous drinking among HIV-positive women are urgently needed.
alcohol drinking; HIV; longitudinal studies; women
Diabetic nephropathy is becoming an increasingly important cause of morbidity and mortality worldwide owing to the increasing prevalence of type 2 diabetes, largely driven by increasing obesity. There is considerable evidence that obesity, hypertension and other elements of the metabolic syndrome also contribute to the progression of renal disease independent of diabetes. How they interact and contribute to diabetic nephropathy, however, is not completely understood. Clinical diabetic nephropathy is preceded by an increase in glomerular filtration rate (GFR), microalbuminuria and glomerular hypertrophy. Poor glycemic control and elevated systolic blood pressure exacerbate proteinuria and renal injury that may culminate in end-stage renal disease. A similar sequence of events may lead to obesity-related renal disease even in the absence of diabetes. This article compares and contrasts factors involved in the development of glomerular hemodynamic and kidney pathological processes associated with diabetes and obesity.
Cross-sectional studies found less microalbuminuria in type 2 diabetic patients with the Ala12 allele of the peroxisome proliferator–activated receptor-γ2 (PPAR-γ2) Pro12Ala polymorphism. We prospectively evaluated the association between Pro12Ala polymorphism (rs1801282) and new-onset microalbuminuria.
RESEARCH DESIGN AND METHODS
Pro12Ala polymorphism was genotyped by TaqMan-based assay in genomic DNA of 1,119 consenting patients from BErgamo NEphrologic DIabetic Complications Trial (BENEDICT)—a prospective, randomized trial evaluating ACE inhibition effect on new-onset microalbuminuria (albuminuria 20–200 μg/min in at least two of three consecutive overnight urine collections in two consecutive visits) in hypertensive type 2 diabetes with albuminuria <20 μg/min at inclusion.
Baseline characteristics of Ala (Ala/Ala or Ala/Pro) carriers and Pro/Pro homozygotes were similar, with a nonsignificant trend to lower albuminuria (P = 0.1107) in the 177 Ala carriers. Over a median (interquartile range) of 44.0 (17.1–51.9) months, 7 (4%) Ala carriers and 86 (9.1%) Pro/Pro homozygotes developed microalbuminuria (hazard ratio [HR] 0.45 [95% CI 0.21–0.97]; P = 0.042). Final albuminuria was significantly lower in Ala carriers than Pro/Pro homozygotes (7.3 ± 9.1 vs. 10.5 ± 24.9 μg/min, respectively), even after adjustment for baseline albuminuria (P = 0.048). Baseline and follow-up blood pressure and metabolic control were similar in both groups. Incidence of microalbuminuria was significantly decreased by ACE versus non-ACE inhibitor therapy in Pro/Pro homozygotes (6.3 vs. 11.9%, respectively, HR 0.46 [0.29–0.72]; P < 0.001).
In type 2 diabetes, the Ala allele protects from worsening albuminuria and new-onset microalbuminuria, and ACE inhibition blunts the excess risk of microalbuminuria associated with the Pro/Pro genotype. Evaluating Pro12Ala polymorphism may help identifying patients at risk who may benefit the most from early renoprotective therapy.