Hypertension, microalbuminuria and renal dysfunction: the Renal Dysfunction in Hypertension (REDHY) study

AIMS: We assessed the prevalence of kidney dysfunction evaluated by different methods to estimate glomerular filtration rate (GFR) in a wide group of nondiabetic hypertensive patients, without cardiovascular (CV) complications and without known renal disease, participating in the Renal Dysfunction in Hypertension (REDHY) study. METHODS: A total of 1,856 hypertensive individuals (mean age 47 +/- 14 years; men 53%), free from diabetes mellitus and CV complications, and consecutively attending our outpatient hypertension center, were enrolled. Patients with a body mass index >35 (calculated as kg/m(2)) were excluded. The GFR was estimated by the creatinine clearance rate (CrCl), the simplified Modification of Diet in Renal Disease Study prediction equation (MDRD), the Cockcroft-Gault formula (CG) and the Mayo Clinic quadratic equation (Mayo). A 24-hour urine sample was collected to evaluate CrCl and albumin excretion rate (AER). Albuminuria was defined as an AER greater than 20 microg/min. RESULTS: The prevalence of albuminuria was 23.4% (22.7% microalbuminuria and 0.7% macroalbuminuria). Mild renal dysfunction (defined as 24-hour AER >20 microg/min in presence of eGFR > or =60 ml/min per 1.73 m(2)) was found in a proportion of patients ranging from 20.3% using CrCl, to 18.4% using the MDRD equation. The prevalence of overt renal insufficiency (estimated GFR <60 ml/min per 1.73 m(2)) was higher when CrCl (10.8%) or the MDRD equation (10%) was used to estimate the GFR, instead of the CG (7.4%) or Mayo equation (5.4%) (p<0.0001). CONCLUSIONS: Mild renal dysfunction and overt renal insufficiency are highly prevalent among subjects with nonmalignant arterial hypertension without CV complications. However, the prevalence of moderate-to-severe renal function impairment is strongly influenced by the method used to estimate the GFR.     

Albuminuria: marker or target in indigenous populations

BACKGROUND: Australian Aborigines in remote areas are experiencing an epidemic of renal disease, type 2 diabetes, hypertension, and cardiovascular disease. Adult deaths are increased 3- to 6-fold, and renal failure more than 20-fold. Renal disease is marked by albuminuria. We describe its distributions and correlations in two remote communities in the Northern Territory. METHODS: Observations in Community 1 included a screen of 939 adult participants (18+ years, 90% recruitment), a treatment program, and 8 to 11 years of follow-up. In Community 2, a screen of 259 people, or 60% of adults, included HbA1c, homocysteine, C-reactive protein (CRP), CMV serology, and carotid intimal media thickness (CIMT). Albumin/creatinine ratio (ACR) was measured by immunoassay in g/mol on random urine, with microalbuminuria defined as 3.4 to 33, and overt albuminuria as ACR 34+. RESULTS: Dipstick urine protein trace+ correctly classified 76% of people with ACR 3.4+, and dipstick protein 1+ correctly classified 82% of people with ACR 34+. ACR was stable to glucose loading and water diuresis in subsets of people in Community 1. ACR levels rose steeply with age. Rates of micro- and overt albuminuria in Community 1 were 28% and 21%, and in Community B were 31% and 13%. ACR correlated inversely with estimated glomerular filtration rate (GFR). ACR also correlated directly with weight, blood pressure, cholesterol, triglycerides, random glucose, HbA1c, homocysteine, and GGT levels, and inversely with HDL cholesterol. ACR correlated with skin sores, scabies, high titer antibodies to Helicobacter pylori, high-titer CMV antibodies, with CRP over a greatly elevated range and, inversely, with birth weight. Finally, ACR correlated with CIMT. Baseline ACR predicted loss of GFR over time. ACR 3.4+ predicted all-cause and cardiovascular hospitalization, while ACR 34+ predicted all renal failure developing over 11 years and all-cause natural deaths and cardiovascular disease deaths. ACEi treatment for people with ACR 34+ reduced renal failure and natural deaths, but the hierarchical effect of higher ACRs within that group for renal and nonrenal deaths was maintained. CONCLUSION: Random urine ACR is a stable and robust marker of renal disease, which is multideterminant. A broad base of shared risk factors probably explains the simultaneous emergence of the excessive renal and nonrenal chronic disease morbidities from which these populations suffer. Thus, albuminuria is a unifying marker for the harmful effects of the spectrum of chronic disease, and perhaps beyond. Dipstick urine protein is a useful surrogate for ACR when resources are constrained and disease burdens high.     

The p53Pro72Arg polymorphism is associated with albuminuria among aboriginal Australians

Albuminuria is a widely recognized marker of renal disease and cardiovascular risk. This is especially true in Aboriginal Australians living in remote communities who suffer high rates of end-stage renal disease and cardiovascular mortality. During a survey of risk factors for renal and cardiovascular disease in one such community, an association between a common polymorphism at codon 72 (Arg/Pro) of the p53 gene and markers of renal disease was sought. A cross-sectional community survey including 217 people was performed. Genotypes of the polymorphism were distributed in Hardy-Weinberg equilibrium, with p53Arg allele frequency of 0.45 (range, 0.41 to 0.50). Overall prevalence of albuminuria was high (31% microalbuminuria; 14% overt albuminuria). Urine albumin/creatinine ratio (ACR) was significantly associated with the number of p53Pro alleles (P = 0.01), and there was an interaction with tobacco smoking (P = 0.04). The p53 genotype was also associated with increasing HbA1c, but the relationship between p53 and ACR was independent of this. This is a previously unreported association. This study does not address the mechanism, but this finding, if confirmed, expands the described effects of p53 in cellular proliferation and apoptosis to include a role in the course of renal and possibly cardiovascular disease in this population.     

Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000

The incidence of kidney failure treatment in the United States increased 57% from 1991 to 2000. Chronic kidney disease (CKD) prevalence was 11% among U.S. adults surveyed in 1988 to 1994. The objective of this study was to estimate awareness of CKD in the U.S. population during 1999 to 2000 and to determine whether the prevalence of CKD in the United States increased compared with 1988 to 1994. Analysis was conducted of nationally representative samples of noninstitutionalized adults, aged 20 yr and older, in two National Health and Nutrition Examination Surveys conducted in 1988 to 1994 (n = 15,488) and 1999 to 2000 (n = 4101) for prevalence +/- SE. Awareness of CKD is self-reported. Kidney function (GFR), kidney damage (microalbuminuria or greater), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine, spot urine albumin to creatinine ratio (ACR), age, gender, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation. Self-reported awareness of weak or failing kidneys in 1999 to 2000 was strongly associated with decreased kidney function and albuminuria but was low even in the presence of both conditions. Only 24.3 +/- 6.4% of patients at GFR 15 to 59 ml/min per 1.73 m(2) and albuminuria were aware of CKD compared with 1.1 +/- 0.3% at GFR of 90 ml/min per 1.73 m(2) or greater and no microalbuminuria. At moderately decreased kidney function (GFR 30 to 59 ml/min per 1.73 m(2)), awareness was much lower among women than men (2.9 +/- 1.6 versus 17.9 +/- 5.9%; P = 0.008). The prevalence of moderately or severely decreased kidney function (GFR 15 to 59 ml/min per 1.73 m(2)) remained stable over the past decade (4.4 +/- 0.3% in 1988 to 1994 and 3.8 +/- 0.4% in 1999 to 2000; P = 0.23). At the same time, the prevalence of albuminuria (ACR >/= 30 mg/g) in single spot urine increased from 8.2 +/- 0.4% to 10.1 +/- 0.7% (P = 0.01). Overall CKD prevalence was similar in both surveys (9% using ACR > 30 mg/g for persistent microalbuminuria; 11% in 1988 to 1994 and 12% in 1999 to 2000 using gender-specific ACR cutoffs). Despite a high prevalence, CKD awareness in the U.S. population is low. In contrast to the dramatic increase in treated kidney failure, overall CKD prevalence in the U.S. population has been relatively stable.     

The natural history of renal disease in Australian Aborigines. Part 2. Albuminuria predicts natural death and renal failure.

BACKGROUND: The purpose of this study was to describe the relationship of albuminuria and glomerular filtration rate (GFR) with natural death and renal failure in an Australian Aboriginal community with high rates of renal disease. METHODS: Study subjects were 825 adults (18+ years, mean 33.6 years) or 88% of adults in a remote community who participated in a health screening program offered between 1990 and 1997. The urinary albumin:creatinine ratio (ACR; g/mol) was used as the renal disease marker. Participants were followed for 1.0 to 9.8 years (mean 5.8 years) until renal failure, death, the start of systematic antihypertensive/renal-protective treatment or June 30, 2000. RESULTS: Sixty-five people reached a terminal end point of renal failure or natural death. Sixteen people developed terminal renal failure, all of whom had an ACR of 34+ at baseline exam. There were 49 other natural deaths, which were also strongly correlated with increasing ACR and decreasing GFR over a wide range. This was observed in people without diabetes and in people with normal and elevated blood pressures. It applied to deaths associated with cardiovascular disease and to deaths without an assigned primary or underlying cardiovascular or renal cause. With adjustment for age, the association with death was more robust with ACR than GFR. When compared with people with an ACR <3.4, the hazard ratio (HR; 95% CI) for nonrenal natural death of persons with an ACR 3.4 to 33 was 3.0 (1.1 to 8.4), with an ACR 34 to 99, it was 5.4 (1.8 to 15.9), and with an ACR 100+, it was 6.5 (2.0 to 21). Regression equations predicted that each tenfold increase in the ACR was associated with a 3.7-fold increase in all-cause natural death: a> 400-fold increase in renal deaths, a 4-fold increase in cardiovascular deaths, and a 2.2-fold increase in nonrenal noncardiovascular deaths. Eighty-four percent of all-cause natural death was associated with pathologic albuminuria. CONCLUSION: All renal failure develops out of a background of persistent albuminuria in this population. More important, albuminuria and, inversely, GFR are powerful markers of risk for nonrenal natural death, including, but not restricted to, cardiovascular deaths. Most of the risk for premature death can be assessed by a simple urine test, and interventions that prevent development and progression of albuminuria and loss of GFR should not only prevent renal insufficiency, but powerfully reduce mortality from natural causes as well.     

Towards an epidemiologic definition of renal disease: Rates and associations of albuminuria in a high-risk Australian Aboriginal community

Summary: An epidemic of renal failure is accompanying the rising rates of hypertension, type 2 diabetes and cardiovascular disease among Aborigines in the Northern Territory of Australia. the rates and associations of the underlying renal disease were studied in a remote Aboriginal community whose renal failure rates are among the highest reported in the world. More than 90% of school-age children and adults participated in a health screen, in which the urinary albumin/creatinine ratio (ACR) was used as the primary renal disease marker. Albuminuria was evident in early childhood and increased dramatically with age; 26% of adults had microalbuminuria and 24% had overt albuminuria. Most hypertension segregated in persons with albuminuria and all renal failure developed out of a background of overt albuminuria. ACR levels correlated with the presence of scabies at screening, with a history of post-streptococcal glomerulonephritis, with increasing bodyweight or its surrogates, with increasing blood pressure, glucose, insulin and lipid levels, and with evidence of heavy drinking. ACR also correlated inversely with birthweight. Finally, increasing ACR correlated with an increasing cardiovascular risk factor score. Thus many factors contribute to renal disease in this community; most are the features and consequences of lifestyle change, poverty and disadvantage. Renal disease shares risk factors, including low birthweight, with Syndrome X, which supports the inclusion of renal disease in that syndrome, and explains the excess cardiovascular morbidity in people with chronic renal disease. There is an urgent need for effective programs to modify recognized risk factors, and to identify and treat people with established renal disease to retard the progression of renal insufficiency.     

Albuminuria as a predictor of cardiovascular and renal outcomes in people with known atherosclerotic cardiovascular disease

BACKGROUND: Microalbuminuria predicts elevated cardiovascular risk in those with and without diabetes. In diabetes, microalbuminuria also heralds overt diabetic nephropathy. The predictive value of albuminuria below the microalbuminuria cutoff, and the development of overt nephropathy in nondiabetics with microalbuminuria, have not been well studied. We review findings of the HOPE Study. METHODS: The HOPE Study database includes data on first morning urine albumin/creatinine ratio (ACR) in 9043 participants at baseline, and in 7674 participants at baseline and at last follow-up. Inclusion criteria were known vascular disease or diabetes, plus one other cardiovascular risk factor; exclusion criteria included heart failure or known impaired left ventricular function, dipstick-positive proteinuria (> 1+), and serum-creatinine > 2.3 mg/dL (200 micromol/L). Microalbuminuria was defined as an ACR > or = 2 mg/mmol. RESULTS: Microalbuminuria at baseline approximately doubled the relative risk (RR) of the primary outcome (myocardial infarction, stroke, or CV death). For every 1 mg/mmol rise of ACR, even below the level of microalbuminuria, the adjusted hazard of the primary outcome increased by about 15%. Baseline microalbuminuria predicted subsequent clinical proteinuria, RR 17.5, similarly in participants without and with diabetes. New microalbuminuria developed in 1542 participants, and clinical proteinuria in 317. CONCLUSION: Albuminuria is a continuous risk factor for CV events even below the level of microalbuminuria. Microalbuminuria predicts clinical proteinuria in nondiabetics.     

The natural history of renal disease in Australian Aborigines. Part 1. Changes in albuminuria and glomerular filtration rate over time.

BACKGROUND: The purpose of this study was to describe changes over time in albuminuria and glomerular filtration rate (GFR) in a cohort of Australian Aborigines from a community with high rates of renal disease and renal failure. METHODS: Participants were 486 adult community members (20+ years at first exam) who were screened for renal disease and related factors on at least two occasions (mean 2.7 occasions), at least a year apart, between 1990 and 1997. Renal function was assessed by the albumin:creatinine ratio (ACR; g/mol) on a random urine specimen and by the GFR estimated from the Cockcroft-Gault formula. Evolution over time was expressed as the average annual changes in these parameters. RESULTS: On baseline examination, 70% of participants had albuminuria (ACR 1.1+ g/mol) There was a significant net increase in ACR and a fall in GFR in the cohort over time. Among individuals, however, changes were strongly correlated with ACR levels at baseline. There was no loss of GFR in persons with normal renal parameters at baseline and a rapid loss of GFR in those with substantial levels of albuminuria at baseline. Other factors significantly correlated with progression of ACR included age, baseline body mass index and systolic blood pressure, the presence of diabetes (or levels of fasting glucose), and elevated levels of serum gamma glutamyl transferase. Factors significantly associated with loss of GFR included body mass index, diabetes, systolic and diastolic blood pressures, microscopic hematuria, and marginally high cholesterol levels. CONCLUSION: Albuminuria progresses and GFR is lost over time in individuals in this community, at rates that are strongly dependent on levels of pre-existing albuminuria. Much loss of GFR and all renal failure should be avoided by preventing the development of albuminuria and minimizing its progression. This depends on improving the weight, blood pressure, and metabolic profile of the entire community and reducing infections. Modification of the course in people with established disease depends on vigorous control of blood pressure and the metabolic profile and the specific use of angiotensin-converting enzyme inhibitors.     

上海城市社区成年人群慢性肾脏病流行病学研究

目的 获取上海城市社区成年人群慢性肾脏病流行病学及其高危人群数据，有助于慢性肾脏病的早期发现、早期诊断、早期治疗及有助于国家卫生政策的制定。 方法 采用多阶段整群随机抽样法对上海市长宁区江苏街道中2596名18岁以上常住居民进行问卷调查并检测肾脏损伤指标及相关危险因素，包括体格检查、尿常规+沉渣镜检、尿白蛋白/肌酐比值（ACR）、Scr、BUN、血尿酸、血糖、血胆固醇（Cho）、血三酰甘油（TG）、血红蛋白（Hb）及肾脏B超等。调查员均经过培训及接受技术指导，同时培训社区居委会有关人员，以便与居民的沟通与联络。3个月后对ACR试纸半定量检查阳性者进行复查。 结果 在2554例资料完整的居民中，白蛋白尿患病率为6.3%；肾功能下降为5.8%；镜下血尿为1.2%。该人群中CKD患病率11.8%，知晓率8.2%。多因素Logistic回归提示，CKD的最强烈危险因素为高尿酸血症，其余依次为肾结石、贫血、糖尿病、腹型肥胖、高血压、年龄。 结论 在上海城市社区人群中，CKD患病率为11.8%，知晓率仅为8.2%。CKD的危险因素为高尿酸血症、肾结石、贫血、糖尿病、腹型肥胖、高血压、年龄。     

A new dimension to the Barker hypothesis: low birthweight and susceptibility to renal disease.

BACKGROUND: There is an epidemic of renal failure among Aborigines in the Australia's Northern Territory. The incidence is more than 1000 per million, and is doubling every three to four years. We evaluated the relationship of birthweight to renal disease in adults in one high-risk community. METHODS: We screened more than 80% of people in the community for renal disease, using the urine albumin/creatinine ratio (ACR, g/mol) as the marker, and reviewed records for birthweights. RESULTS: Birthweights were available with increasing frequency for people born after 1956. In 317 adults aged 20 to 38 years at screening, the mean birthweight (SD) was 2.712+/-0.4 kg, and 35% had been low birthweight (LBW, less than 2.5 kg). Birthweight was positively correlated with body mass index (BMI), blood pressure, and diabetes rates, but was inversely correlated with ACR. The odds ratio for overt albuminuria in LBW persons compared with those of higher birthweights was 2.82 (CI, 1.26 to 6.31) after adjusting for other factors, and LBW contributed to an estimated 27% (CI, 3 to 45%) of the population-based prevalence of overt albuminuria. Multivariate models suggest that increasing BMI and blood pressure and decreasing birthweight act in concert to amplify the increases in ACR that accompany increasing age. CONCLUSIONS: LBW contributes to renal disease in this high-risk population. The association might be mediated through impaired nephrogenesis caused by intrauterine malnutrition. The renal disease epidemic in Aborigines may partly be the legacy of greatly improved survival of LBW babies over the last four decades. Disease rates should eventually plateau as birthweights continue to improve, if postnatal risk factors can also be contained.     

Albuminuria and renal insufficiency prevalence guides population screening: results from the NHANES III

BACKGROUND: A number of screening criteria, applied either at a single point in time or serially, can be used for the purpose of identifying individuals at risk of end-stage renal disease (ESRD). This study focused on two such criteria measured on a single occasion, proteinuria and renal insufficiency, and examined their prevalence in a sample representative of the adult U.S. non-institutionalized population. Such knowledge guides the utility of population screening to prevent ESRD. METHODS: The prevalence of albuminuria (microalbuminuria and macroalbuminuria from a random urine albumin-to-creatinine ratio) and renal insufficiency [glomerular filtration rate (GFR) estimated from serum creatinine] was determined in different age categories in various adult screening groups in the cross-sectional Third National Health and Nutrition Examination Survey (NHANES III). RESULTS: A total of 14,622 adult participants were included in the analysis. In the general population, 8.3% and 1.0% of participants demonstrated microalbuminuria and macroalbuminuria, respectively. To identify one case of albuminuria, one would need to screen three persons with diabetes mellitus, seven non-diabetic hypertensive persons, or six persons over the age of 60. When albuminuria and renal insufficiency were considered together, it was clear that these tests were identifying different segments of the population; 37% of participants with a GFR less than 30 mL/min/1.73 m2 demonstrated no albuminuria. Non-albuminuric renal insufficiency was most evident in the ages of 60 to 79; 34% of diabetics, and 63% of non-diabetic hypertensives with a GFR less than 30 mL/min/1.73 m2 demonstrated no albuminuria. CONCLUSIONS: Albuminuria is prevalent, and when considered together, screening tests of albuminuria and renal insufficiency measured on a single occasion identify different segments of the population. The prevalence of albuminuria and renal insufficiency in populations of interest should be considered, as this knowledge has implications for the effectiveness of screening.     

云南省西双版纳地区成人慢性肾脏病流行病学调查

目的 了解我国云南省西双版纳少数民族地区成人慢性肾脏病(CKD)患病率及危险因素.方法 对该地区20岁以上常住居民进行随机分层抽样,留取晨尿,分别采用尿白蛋白,肌酐比值方法检测白蛋白尿发生率(≥30 mg/g为阳性);干化学法结合尿离心后显微镜检查法检测血尿发生率(≥3红细胞/高倍视野为阳性);以中国人简化MDRD公式计算估计肾小球滤过率(eGFR)[低于60 ml·min-1·(1.73m2)-1者为eGFR异常].检测CKD相关危险因素指标.结果 符合入选条件的被调查者共5566例,白蛋白尿阳性率为8.06%;血尿阳性率为4.01%;eGFR低于60 ml·min-1(1.73 m2)-1者为2.89%;去除白蛋白尿、血尿及eGFR下降共同存在造成的重复.该地区CKD患病率为12.53%.性别、年龄、民族以及相关危险因素分层后比较结果与多因素Logistic回归分析结果一致,年龄增加、血压升高、空腹血糖升高及三酰甘油升高与白蛋白尿独立相关;年龄增加、收缩压升高与肾功能下降独立相关;年龄增加与血尿独立相关.结论 云南省西双版纳地区成人CKD患病率为12.53%,相关危险因素包括年龄增加、高血压、血糖及血脂异常.     

Urinary protein excretion and renal function in young people with diabetes mellitus.

To detect early renal involvement in young diabetic patients (IDDM), urinary protein excretion and renal function were examined in 110 patients aged 5.9-25.0 years. Clearances of inulin and PAH were determined as well as albumin (Alb), IgG, N-acetyl-beta-D-glucosaminidase (NAG) and creatinine (Cr) excretion rates (UV). The patients were grouped according to IDDM duration (2- less than 5, 5-10 and greater than 10 years) and albumin excretion rate (non-albuminuria less than 20, microalbuminuria 20-200, and albuminuria greater than 200 micrograms/min per 1.73 m2). Four patients had overt albuminuria, 17 microalbuminuria (equally distributed among the duration groups). Grouped according to albumin excretion rate, the mean GFR was increased in those without albuminuria but 'normalized' in patients with microalbuminuria/albuminuria. Grouped according to albumin excretion rate and the duration of the disease, the non-albuminuric patients with IDDM for greater than 10 years had a lower GFR than those with a shorter duration of IDDM. The patients with microalbuminuria/albuminuria and IDDM for less than 5 years had a reduced GFR. Patients with increased NAG excretion rate had lower Na excretion rate, lower fractional Na excretion and greater creatinine excretion than those with normal NAG excretion. Albumin excretion correlated with IgG excretion, but also with NAG excretion. Our results suggest that early albuminuria in IDDM is of both glomerular and tubular origin. The hyperfiltration declines with increasing albumin excretion but also with the duration of the disease.     

The effects of highly active antiretroviral therapy on albuminuria in HIV-infected persons: results from a randomized trial.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) regimens, especially those containing protease inhibitors (PIs), are at increased risk for cardiovascular events. Albuminuria is a known independent predictor for the development of cardiovascular disease and may potentially increase in patients receiving PIs. Alternatively, albuminuria may improve with HAART as a result of treating renal parenchymal HIV infection. Longitudinal studies have not been performed previously addressing the effects of HAART on albuminuria. METHODS: We evaluated the effects of HAART on albumin to creatinine ratios (ACRs) during the initial 64 weeks of therapy in 68 previously untreated HIV-infected subjects, without pre-existing diagnosed diabetes or hypertension, enrolled in a randomized trial comparing PI-based (n = 32) with non-PI-based (n = 36) HAART regimens. We also estimated the prevalence of albuminuria, defined as an ACR > or =3.4 mg/mmol, in these subjects prior to initiation of HAART. RESULTS: The changes in ACR over the initial 64 weeks of therapy in those receiving PIs [0.0 mg/mmol (-0.4, 0.3)] and in those not receiving PIs [0.0 mg/mmol (-0.5, 0.3)] were not significantly different. There was also no significant difference in the change in the ACR in the group as a whole. However, albuminuria at baseline was found in seven (10%) subjects. Five of these seven subjects had substantial improvements in ACR, ranging from 45 to 95%, with HAART use; three subjects had resolution of albuminuria. ACR at baseline significantly correlated with the baseline HIV-1 RNA level (r = 0.25; P = 0.04) and negatively with CD4 cell count (r = -0.25; P = 0.04). CONCLUSION: Albuminuria in HIV-infected, treatment-na?ve patients was found more frequently than expected and may be influenced by baseline immune status. Although we did not observe an effect of HAART on ACR during the first 64 weeks of therapy, we cannot exclude the possibility that HAART may be beneficial in those patients with significant albuminuria prior to treatment. Research in larger cohorts is required to investigate more definitively the associations between immune status, antiretroviral therapies and renal function in HIV-infected patients.     

Aortic pulse wave velocity and albuminuria in patients with type 2 diabetes

Development of microalbuminuria increases the risk for cardiovascular disease (CVD) in type 2 diabetes. The nature of this relationship is unclear but may involve arterial stiffness, an independent risk marker for CVD mortality. Aortic pulse wave velocity (Ao-PWV) and albumin creatinine ratio (ACR) were measured in 134 consecutive patients with type 2 diabetes without overt renal impairment (serum creatinine <150 micromol/L). ACR ranged from 0.2 to 153 mg/mmol. Patients with raised ACR (>/=3 mg/mmol) had higher Ao-PWV, poorer diabetic control, and higher pulse pressure (PP) and systolic BP (SBP) (all P < 0.05) than those with normal ACR. The closest univariate associations of Ao-PWV were positively with age, duration of diabetes, SBP, PP, ACR, and insulin treatment and negatively with GFR and weight (all P < 0.01). In a multiple linear step-down regression analysis, the significant predictors of Ao-PWV were age, SBP or PP, duration of diabetes, gender, number of antihypertensive medications, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, which together explained 55% of the variance of Ao-PWV. When ACR was offered in place of arterial pressure to a separate model, ACR emerged as a significant predictor of Ao-PWV. After age adjustment, patients with lower, below median GFR had higher Ao-PWV than those with GFR above the median (P = 0.043). In patients with type 2 diabetes without overt renal impairment, raised ACR is associated with higher Ao-PWV, a relationship most likely mediated by raised BP. The association of Ao-PWV with reduced GFR suggests that even modest renal dysfunction may affect the viscoelastic properties of large arteries.     

Use of the albumin/creatinine ratio to detect microalbuminuria: implications of sex and race

The recommended albumin (microg)/creatinine (mg) ratio (ACR) (30 microg/mg) to detect microalbuminuria does not account for sex or racial differences in creatinine excretion. In a nationally representative sample of subjects, the distribution of urine albumin and creatinine concentrations was examined by using one ACR value (> or =30 microg/mg) and sex-specific cutpoints (> or =17 microg/mg in men and > or =25 microg/mg in women) measured in spot urine specimens. Mean urine albumin concentrations were not significantly different between men and women, but urine creatinine concentrations were significantly higher (P < 0.0001). Compared with non-Hispanic whites, urine creatinine concentrations were significantly higher in non-Hispanic blacks (NHB) and Mexican Americans, whereas urine albumin concentrations were significantly higher in NHB (P < 0.0001) but not Mexican Americans. When a single ACR is used, the prevalence of microalbuminuria was significantly lower among the men compared with women (6.0 versus 9.2%; P < 0.0001) and among non-Hispanic whites compared with NHB (7.2 versus 10.2%; P < 0.0001). No significant difference in the prevalence of microalbuminuria between men and women was noted when sex-specific ACR cutpoints were used. In the multivariate adjusted model, female sex (odds ratio, 1.62; 95% confidence interval, 1.29 to 2.05) and NHB race/ethnicity (odds ratio, 1.34; 95% confidence interval, 1.12 to 1.61) were independently associated with microalbuminuria when a single ACR threshold was used. When a sex-specific ACR was used, NHB race/ethnicity remained significantly associated with microalbuminuria but sex did not. The use of one ACR value to define microalbuminuria may underestimate microalbuminuria in subjects with higher muscle mass (men) and possibly members of certain racial/ethnic groups.     

Association between renal damage markers and carotid atherosclerosis in Afro-descendants with hypertension belonging to a minority ethnic group from Brazil

Ethnicity appears to play an important role in the prevalence and severity of hypertension, renal disease, and atherosclerosis. A cross-sectional study was conducted, including 206 Afro-descendants with hypertension, living in the remaining quilombo communities. These subjects underwent a carotid intima-media thickness (CIMT) assessment. The presence of renal injury was assessed by: (1) The glomerular filtration rate (GFR) estimated by the formula CKD-EPI using creatinine and cystatin C and (2) Albuminuria (ACR ≥30?mg/g). The Poisson distribution model was set with robust variance to identify factors associated with carotid atherosclerosis. The statistical analysis was performed using the Stata 12.0 software, adopting a significance level of 5%. Most subjects were women (61.65%); the average age was 61.32 (±12.44) years. Subjects (12.62%) were identified with GFR <60?mL/min/1.73?m² and 22.8% with albuminuria. Patients (59.22%) presented with a high CIMT. In the adjusted regression model, age ≥60?years (PR: 1.232 [CI 95%:1.091–1.390], p value?=?.001), ACR ≥30?mg/g (PR: 1.176 [CI 95%: 1.007–1.373], p?=?.040), and GFR/CKD-EPI using cystatin C (PR: 1.250 [CI 95%: 1.004–1.557], p?=?.045) were independently associated with carotid atherosclerosis. The occurrence of atherosclerotic lesions was high in the studied group. Age, albuminuria, and GFR (estimated by the formula CKD-EPI using cystatin C) influenced the prevalence of carotid atherosclerosis.     

Microalbuminuria and urinary albumin excretion: clinical practice guidelines

Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hours-urine sample. Values defining microalbuminuria are: 24 hour-urine sample: 30-300 mg/24 hours; morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mol (women). Timed urine sample: 20-200 microg/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been shown in humans. IN DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is also a marker of CV and renal risk in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. IN NO DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of the renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence or elevation of UAE overtime is associated with deleterious outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive subjects with one or two CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome as it is in diabetic or hypertensive subjects. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is annually recommended in all subjects with microalbuminuria. MANAGEMENT: In patients with microalbuminuria, weight reduction, sodium restriction (<6 g/day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of ACEI or ARB are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non diabetic subjects, any of the five classes of antihypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or betablockers) can be used.     

Microalbuminuria and hypertension in long-term renal donors

In order to determine whether the proteinuria observed in some renal donors was glomerular or tubular in origin, and to determine whether creatinine clearance was an accurate index of glomerular filtration rate (GFR) in subjects with reduced nephron mass, 29 donors were evaluated 9-18 years after uninephrectomy. Results were compared with those in 31 age-, sex-, and race-matched controls evaluated at the same time. Mean creatinine clearance (Ccreat) in donor was 78% that of controls, which was similar to the 85% ratio of inulin clearance (Cin) in donors compared with that of controls. Furthermore, the ratio of Ccreat/Cin was similar in both donors and controls. One third of the renal donors had an elevated albumin excretion compared with controls (microalbuminuria [12-220 mg/24 hr] in seven patients; 301 and 1084 mg/24 hr in two patients). There was no correlation between albuminuria and blood pressure, nor was there a demonstrable clinical cause for the albuminuria in most patients. In contrast to these results, excretion of beta-2 microglobulin, an index of tubular proteinuria, was normal in all but one patient. The prevalence of hypertension was higher in donors compared with the expected prevalence adjusted for age, sex, and race. These results verify that creatinine clearance is a reliable measure of GFR in long-term renal donors. They also demonstrate an increased frequency of glomerular proteinuria and hypertension in renal donors. Despite these mild abnormalities, GFR is well preserved for up to 18 years postuninephrectomy.     

Prevention and treatment of diabetic nephropathy with blood pressure lowering drugs

Summary: Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria (>300 mg/24 h), a relentless decline in glomerular filtration rate (GFR), and raised arterial blood pressure. the prevalence of abnormal elevated albumin excretion rate (>30 mg/24 h) is approximately 40% in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) patients. Diabetes has become the leading cause of end-stage renal failure in the United States of America and Japan and it remains the second leading cause in Europe. Patients suffering from diabetic nephropathy have an enormous increase in morbidity and mortality from cardiovascular disease in addition to renal death. Elevated blood pressure is an early and frequent phenomenon and furthermore accelerates the course of diabetic nephropathy. Studies in humans suggest that angiotensin-converting enzyme (ACE) inhibitors postpone and may even prevent progression to clinical overt diabetic nephropathy in normotensive IDDM and NIDDM patients with persistent microalbuminuria. Conventional antihypertensive therapy and ACE inhibition usually combined with a diuretic reduces albuminuria and postpones renal insufficiency in hypertensive IDDM patients with overt nephropathy. A more beneficial effect on the rate of decline in glomerular filtration rate has been demonstrated by ACE inhibitors compared to conventional antihypertensive treatment in IDDM patients with diabetic nephropathy and reduced kidney function (serum creatinine >133 mmol/L). These findings suggest that ACE inhibition causes renal protection (i.e. a beneficial effect on kidney function [structure] above and beyond what would be expected from blood pressure lowering effect alone). Finally, it should be stressed that ACE inhibition and conventional antihypertensive treatment postpone end-stage renal failure and improve survival in diabetic nephropathy.