Proteinuria in South Asian children: prevalence and determinants

Proteinuria in children is a marker of kidney disease and atherosclerosis, both which are known predictors of cardiovascular mortality. Recent evidence suggests that migrant South Asian populations living in the West may be at higher risk of kidney disease than native Caucasians. However, the determinants of proteinuria in South Asian children have not been explored. Previously, we reported ethnic variation in the prevalence of proteinuria in the adult population of Pakistan. However, it is not known whether ethnic predisposition to proteinuria appears during childhood or whether it is acquired later in life as a result of prolonged exposure to undiagnosed diabetes and hypertension.Analyses were based on a subset of data for 4977 children aged 5 to less than 15 years collected as part of the broad National Health Survey of Pakistan, conducted between 1990 and 1994. Proteinuria was defined as a dipstick positive for protein on a random urine sample. Ethnicity was reported as mother-tongue, which is specific for each of the five major ethnic subgroups of Pakistan: Muhajir, Punjabi, Sindhi, Pashtun, and Baluchi.The overall prevalence (95% CI) of proteinuria in the children was 3.3% (2.7–3.9%). It was 6.2% in Sindhis, 3.6% in Muhajirs, 2.8% in Punjabis, 2.8% in Baluchis, and 1.0% in Pashtuns (p<0.001). In multivariable analyses, proteinuria was associated with greater height (p=0.007), urban dwelling (p=0.03), lower socioeconomic status (p=0.02), and certain ethnicities (p=0.005).The ethnic variation in proteinuria in South Asian children mirrors variation among ethnic groups in adults. This suggests variations in susceptibility or early exposure to causes of chronic kidney disease, rather than long-term exposure to undiagnosed diabetes or hypertension. Further studies are needed to determine factors in early life that may differentially predispose certain ethnic groups to proteinuria.Supported by grants from Fogarty International Center, NIH RO3 TWO5657–01A1 (Drs. Levey/Jafar//Schmid/Chaturvedi), and NIDDK RO1 DK53869 (Dr. Levey)     

Serum 25-hydroxyvitamin D and bone mineral density among Hispanic men

Summary  There are few data on the skeletal health of Hispanic men. We observed differences in vitamin D deficiency and low BMD between Hispanic ethnic subgroups that persisted with adjustment for risk factors. Our data indicate a substantial burden of low BMD and vitamin D deficiency among Hispanic men. Introduction  Disparities within ethnic groups are generally ignored, but in evolving populations they may have implications for public health. We examined ethnic variation in serum 25-hydroxyvitamin D [25(OH)D] and bone mineral density (BMD) among Hispanic American men. Methods  Three hundred and fifty-eight Hispanic males 30 to 79 years of age were studied. Logistic regression models assessed variation in odds of vitamin D deficiency (<20 ng/mL) and low BMD (T-score<−1) by ethnicity, with and without adjustment for risk factors (age, smoking, occupation, physical activity, body mass index, and sunlight exposure). Results  Vitamin D deficiency was most common among Puerto Rican (26%), compared with Dominican (21%), Central American (11%), and South American (9%) men. Percentages with low BMD were: South American (44%), Puerto Rican (34%), Dominican (29%), and Central American (23%). Adjustment for age and risk factors failed to account for Hispanic subgroup differences in vitamin D deficiency and low BMD. Population estimates indicate a substantial burden of low BMD and vitamin D deficiency among Hispanic men. Conclusions  Our findings underscore the importance of examining the skeletal health of Hispanic subgroups, and suggest that a considerable number of Hispanic men may be at elevated risk of fracture and vitamin D deficiency. Grant Support: The BACH/Bone Survey was supported by grant AG 20727 from the National Institute on Aging (NIA). The parent study (BACH) was supported by grant DK 56842 from the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support from MO RR00533.     

Influence of smoking and obesity on the development of proteinuria

BACKGROUND: Proteinuria is a significant risk factor for end-stage renal disease. Previous evidence suggested that smoking and obesity increase the risk of proteinuria. However, it is unclear whether these risk factors predict the development of proteinuria independently of hypertension and diabetes mellitus. The aim of this study was to analyze the effects of obesity and smoking on the development of proteinuria in a screened cohort of subjects with normal kidney function. METHODS: A total of 5403 subjects (3403 men and 2000 women) who participated in the 1997 and 1999 health screening examinations in Okinawa Japan, and who were normal renal function (serum creatinine < or =1.2 mg/dL in men, < or =1.0 mg/dL in women) and negative proteinuria by dipstick examination in 1997 were eligible for study. Logistic analysis was used to examine the relation between the baseline state of smoking or obesity in 1997, and the development of proteinuria in 1999, adjusted for age, sex, and other confounding factors. RESULTS: Proteinuria developed in 5.8% of participants (6.7% in men, 4.4% in women; dipstick score, 1+ in 277, 2+ in 37, and > or =3+ in 4 participants). The incidence of proteinuria was positively associated with the number of cigarettes smoked per day (P = 0.04), and a body mass index (P < 0.0001) at baseline. Analysis showed that the relative risk (95% confidence interval) of developing proteinuria was 1.32 (1.00 to 1.74), P = 0.04 for cigarette smoking, 1.45 (1.13 to 1.86), P = 0.002 for obesity, 1.56 (1.19 to 2.06), P = 0.001 for hypertension, and 2.27 (1.55 to 3.32), P < 0.0001 for diabetes mellitus. Stratified with men and women, the relative risk was 1.28 (0.96 to 1.72), P = 0.09 for smoking, and 1.60 (1.19 to 2.14), P = 0.001 for obesity in men; the relative risk was 1.30 (0.44 to 3.80), P = 0.62 for smoking, and 1.04 (0.63 to 1.72), P = 0.87 for obesity in women. CONCLUSIONS: Hypertension and diabetes mellitus were superior to smoking and obesity in predicting the development of proteinuria in all subjects. Stratified with men and women, obesity was a significant risk factor for the development of proteinuria independently of both hypertension and diabetes mellitus in men. The risk of developing proteinuria also tended to be increased with cigarette smoking in men. Smoking and obesity in women were not significant in this data set.     

The effect of residual neurological deficit on oral glucose tolerance in persons with chronic spinal cord injury

STUDY DESIGN: Oral glucose tolerance testing was performed prospectively in 201 subjects with spinal cord injury (SCI). The dependent variables included the values from the oral glucose tolerance test (glucose and insulin) and diagnostic classification (i.e., diabetes mellitus, impaired glucose tolerance, normal glucose tolerance); the independent variables consisted of study group, gender, ethnic group, age, age at onset of SCI, duration of injury, and anthropometric measurements. OBJECTIVE: To determine the potential effects of level and completeness of SCI on oral glucose tolerance testing. In addition, the effects of gender ethnicity, age, age at onset of SCI, duration of injury, and anthropometric measurements on glucose tolerance were investigated. SETTING: Subjects with chronic SCI were recruited during their annual physical examination at the Comarr Spinal Injury Clinic at Rancho Los Amigos Medical Center, Downey, California. METHODS: An oral 75 g glucose load was administered after an overnight fast. Serum glucose was determined by autoanalyzer and plasma insulin levels, by radioimmunoassay. The results are reported as mean plus or minus standard error of the mean (mean+/-SEM). Analysis of variance (ANOVA) applying a Scheffe' post hoc F ratio was used for the continuous variables. Chi-squared analyses were performed to determine differences between the groups and among the subgroups for per cent distribution. Linear regression analyses were performed between variables of interest. Stepwise regression analyses were used to predict peak serum glucose concentration and peak plasma insulin level from potential determinants. RESULTS: The total group consisted of 169 men with a mean age of 38+/-0.80 (range=20 - 73) years and 32 women with a mean age of 44+/-2.13 (range =20 - 72) years. The distribution by ethnicity for the total group with SCI consisted of 114 (57%) Latino, 54 (27%) white, and 28) 14%) African American individuals. There was no significant difference in ethnic distribution among the subgroups for neurological deficit. Subjects were grouped by tetraplegia (Tetra; n=81) or paraplegia (Para; n=120) and by subgroup for degree of neurological deficit: complete Tetra (n=56), incomplete Tetra (n=25), complete Para (n=84), and incomplete Para (n=36). Of the total group, 27 subjects (13.4%) had diabetes mellitus and 56 (28.8%) had impaired glucose tolerance. Significantly more subjects in the complete Tetra group were classified with a disorder of carbohydrate metabolism than in the other neurological deficit subgroups (73 vs 44%, 24% and 31%, respectively for level of decreasing neurological deficit; X2=36.9, P<0.0001). The complete Tetra group had significantly higher serum glucose concentrations at 60 min, 90 min, and 120 min and serum insulin concentration at 90 and 120 min compared with the other neurological subgroups (P<0.05 for each time point). No differences for plasma glucose were evident between men and women, however, plasma insulin levels were significantly higher for men at the intermediate time points (30 min, 60 min and 90 min), suggesting a relative state of insulin resistance in men. By stepwise regression analyses, higher peak serum glucose concentrations were associated with increased total body %fat, highest level of lesion (complete Tetra vs other neurological subgroups), older age at time of injury, and male gender; higher peak plasma insulin was associated with increased total body %fat and male gender. CONCLUSIONS: This study is the first to report that those individuals with the greatest levels of neurological deficit have increased risk of developing disorders of carbohydrate metabolism. Males with SCI are more insulin resistant than females. Glucose tolerance appears to be independent of the effects of ethnicity.     

Survival advantage of Hispanic patients initiating dialysis in the United States is modified by race

Differences in survival have been reported among ethnic groups in the general population. Whether these extend to patients with ESRD is unclear. Using national data, mortality risks of ethnic groups who began dialysis treatment in the United States between May 1, 1995, and July 31, 1997, were compared over 2 yr. Patients were classified as Hispanic or non-Hispanic and then subclassified by race forming six race-specific subgroups: Hispanic white, black, and other and non-Hispanic white, black, and other. Mortality rates for Hispanics compared with non-Hispanics were 19.2 versus 26 per 100 patient-years at risk for those with diabetes and were 14.7 versus 22.7 per 100 patient-years at risk for those without diabetes. For those with diabetes, adjusted mortality risks for Hispanics versus non-Hispanics were 30% lower (95% confidence interval [CI], 26 to 34%). In subgroup analysis, mortality risks for Hispanic whites and Hispanic blacks were 35% (95% CI, 31 to 39%) and 33% (95% CI, 12 to 48%) lower than non-Hispanic whites and were similar in magnitude to those of non-Hispanic blacks (32% lower; 95% CI, 29 to 35%) and non-Hispanic other (33% lower; 95% CI, 28 to 39%). Interestingly, mortality risks for Hispanic others were not significantly different from non-Hispanic whites. For those without diabetes, adjusted mortality risks for Hispanics versus non-Hispanics were 17% lower (95% CI, 9 to 23%), and subgroup analysis yielded similar patterns to those of individuals with diabetes. The survival advantage of Hispanic over non-Hispanic patients who receive chronic dialysis treatment in the United States is not consistent across subgroups and is modified by race. Cultural and genetic differences as well as variation in the access and delivery of care before and while on dialysis may account for these differences.     

Proteinuria and the risk of developing end-stage renal disease

BACKGROUND: Dipstick urinalysis for proteinuria and hematuria has been used to screen renal disease, but evidence of the clinical impact of this test on development of end-stage renal disease (ESRD) is lacking. METHODS: We assessed development of ESRD through 2000 in 106,177 screened patients (50,584 men and 55,593 women), 20 to 98 years old, in Okinawa, Japan, who participated in community-based mass screening between April 1983 and March 1984. We used data from the Okinawa Dialysis Study Registry to identify ESRD patients. Multivariate logistic analyses were performed to calculate adjusted odds ratio and 95% confidence interval (95% CI) for the significance of proteinuria and hematuria on the risk of developing ESRD with confounding variables such as age, gender, blood pressure, and body mass index. A similar analysis was repeated in a subgroup of screened patients in whom serum creatinine data existed. RESULTS: During 17 years of follow-up, 420 screened persons (246 men and 174 women) entered the ESRD program. We identified a strong, graded relationship between ESRD and dipstick urinalysis positive for proteinuria; adjusted odds ratio (95% CI) was 2.71 (2.51 to 2.92, P < 0.001). Similar trends were observed after adding serum creatinine data. Compared with dipstick-negative proteinuria, adjusted odds ratio (95% CI) of proteinuria (1+) was 1.93 (1.53 to 2.41, P < 0.001) in men and 2.42 (1.91 to 3.06, P < 0.001) in women. CONCLUSION: Proteinuria was a strong, independent predictor of ESRD in a mass screening setting. Even a slight increase in proteinuria was an independent risk factor for ESRD. Therefore, asymptomatic proteinuria warrants further work-up and intervention.     

Microvascular complications in South African patients with long-duration diabetes mellitus.

OBJECTIVE: To determine the prevalence of microvascular complications in South African black and Indian patients with long-duration diabetes mellitus (DM). DESIGN: A retrospective analysis was undertaken of clinical records of 219 DM patients (132 black, 87 Indian) with long-duration DM (over 10 years) attending a diabetes clinic in Durban. Data recorded on each subject included demographic details (age, gender, ethnic group, type of diabetes, age of onset and duration of diabetes), presence of retinopathy, markers of nephropathy and biochemical variables. The prevalence of complications and the clinical and biochemical parameters were evaluated for type 1 and type 2 diabetes and for each ethnic group. RESULTS: Of the 219 patients, 47 had type 1 DM (36 blacks, 11 Indians) and 172 were classified as type 2 DM (96 blacks, 76 Indians). The mean age of onset of DM was later in blacks than Indians, both for type 1 (P < 0.05) and type 2 DM (P < 0.01). In patients with type 1 DM, the prevalence of retinopathy was 53.2% (blacks 55.6%, Indians 45.5%), persistent proteinuria was found in 23.4% (blacks 25%, Indians 18.2%) and hypertension in 34%. No ethnic difference was found except for the prevalence of hypertension which was higher in blacks than Indians (41.7% v. 9.1%, P < 0.5). Onset of retinopathy from time of diabetes diagnosis occurred earlier in blacks than Indians (13.0 +/- 4.6 yrs v. 18.0 +/- 4.6 yrs, P < 0.05). For the type 2 DM group, retinopathy was found in 64.5% (black v. Indian 68.8 v. 59.2%) and persistent proteinuria in 25% (black v. Indian 30.2 v. 18.4%). Hypertension was observed in 68% and was more prevalent in blacks (84.4 v. 47.4%, P < 0.01) There was an earlier onset of retinopathy (P < 0.05) and hypertension (P < 0.01) from time of diabetes diagnosis in blacks than Indians. In the type 1 DM group retinopathy was associated with a significantly longer duration of diabetes (P < 0.05) and higher glycated haemoglobin (HbA1) (P < 0.05). For type 2 DM subjects there was a significant association between retinopathy and longer duration of diabetes (P < 0.05) and higher systolic blood pressure (P < 0.05). CONCLUSION: This study has shown that there is a high prevalence of microvascular complications in South African patients with long-duration diabetes mellitus.     

The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population

Proteinuria, high serum creatinine, and reduced glomerular filtration rate (GFR) have been associated with increased mortality from cardiovascular disease (CVD) and all causes. However, the combined effect of proteinuria with serum creatinine and GFR on CVD or all-cause mortality has not been well investigated. We conducted a 10-year prospective cohort study of 30,764 men and 60,668 women aged 40-79 years who participated in annual health checkups in 1993. The Cox proportional hazards model was used to estimate the relative risk (RR) after adjusting for age, smoking, and other cardiovascular risk factors. The multivariable RR (95% confidence interval (CI)) of CVD death for positive vs negative proteinuria was 1.38 (1.05-1.79) among men and 2.15 (1.64-2.81) among women. The respective RR for the highest vs lowest creatinine groups (> or = 1.3 vs < or = 0.8 mg/dl for men and > or = 1.1 vs < or = 0.6 mg/dl for women) was 1.56 (1.19-2.04) among men and 2.15 (1.58-2.93) among women. The respective RR for GFR < 60 vs > r = 100 ml/min/1.73 m2 was 1.65 (1.25-2.18) among men and 1.81 (1.39-2.36) among women. For individuals with proteinuria combined by hypercreatininemia or reduced GFR, the risk of CVD death was two-fold higher in men and 4-6-fold higher in women compared to those without proteinuria and with normal creatinine level or GFR. Similar associations were observed for stroke, coronary heart disease, and all-cause mortality. Proteinuria, and hypercreatininemia or reduced GFR and their combination were significant predictors of CVD and all-cause mortality.     

Chronic proteinuric nephropathies. II. Outcomes and response to treatment in a prospective cohort of 352 patients: differences between women and men in relation to the ACE gene polymorphism. Gruppo Italiano di Studi Epidemologici in Nefrologia (Gisen)

In the Ramipril Efficacy in Nephropathy study, ramipril decreased the rate of GFR decline (deltaGFR) and progression to end-stage renal disease (ESRD) in 352 patients with proteinuric chronic nephropathies. This study investigated whether in these patients disease outcome and response to treatment were affected by gender or insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene. deltaGFR (0.43 +/- 0.05 versus 0.48 +/- 0.08 ml/min per 1.73 m2) and incidence of ESRD (23 and 22%, respectively) were comparable in male and female patients. However, compared to conventional treatment, ramipril decreased deltaGFR (-52% versus -19%) and progression to ESRD (-74% versus -40%) more effectively in women than in men. Thus, the relative risk (95% confidence interval [CI]) of events (ESRD) between conventional and ramipril treatment was 5.52 (1.59 to 19.17, P = 0.003) in women, but only 1.80 (1.08 to 2.97, P = 0.02) in men. This gender-related effect of ramipril was associated with more reduction in proteinuria (-7.8 +/- 4.2% versus -21.9 +/- 5.7%, P = 0.05) and was still evident even after correction for potentially confounding factors such as baseline GFR, daily sodium intake, ramipril dose, BP control, and concomitant treatment with diuretics or dihydropyridinic calcium channel blockers (adjusted RR [95% CI]: women, 5.07 [1.26 to 20.38], P = 0.02; men, 1.44 [0.85 to 2.44], P = 0.17). Ramipril uniformly decreased deltaGFR and incidence of ESRD in women with either DD (-39% and - 100%) or II + ID (-71% and -82%) genotype, and in men (-25% and -50%) with the DD genotype, but had no beneficial effect in men with the II + ID genotype (+18% and +34%). Thus, the relative risk of events (ESRD) between conventional and ramipril-treated men was higher in subjects with the DD genotype (1.85; 0.69 to 4.94) and lower in those with the II +/- ID genotype (0.71; 0.28 to 1.80). Again, in parallel with deltaGFR and events, proteinuria decreased in women with DD (-23.3 +/-8.0%) or II + ID (-16.0 +/- 9.5%) genotype and in men with the DD genotype (-14.8 +/- 7.0%), but did not change in men with II + ID genotype (+ 1.0 +/- 7.8%). Of note, the ACE genotype-related effect of ramipril was still evident even after correction for the above potentially confounding factors (adjusted RR [95% CI]: DD, 2.52 [0.83 to 7.63], P = 0.10; II + ID, 0.35 [0.12 to 1.01], P = 0.05). Thus, among patients with chronic proteinuric nephropathies, men are at increased risk of progression due to their lower response to ACE inhibitor treatment. ACE inhibition is uniformly renoprotective in women regardless of the ACE polymorphism, and in men with the DD genotype, but is virtually devoid of beneficial effects in men with the II or ID genotype. This information may help to guide therapeutic interventions in clinical practice and to interpret the results of prospective trials in chronic renal disease.     

U-shaped association between body mass index and proteinuria in a large Japanese general population sample

Background

There is little data on the association between body mass index (BMI) and proteinuria.

Methods

This was a cross-sectional cohort study assessing the association between BMI and proteinuria in a large Japanese population. Using a nationwide health check-up database of 212,251 Japanese aged >20 years with no pre-existing cardiovascular diseases (185,183 men, median age 66 years; 127,068 women, median age 65 years), we examined the association between BMI and proteinuria (≥1+ on dipstick).

Results

Subjects were divided into 11 subgroups by BMI grading in 1 kg/m² intervals from 18.5?27.5 kg/m². A BMI of approximately 22 ± 0.5 kg/m² was considered optimal for Japanese; therefore, this subgroup was set as a reference when logistic analysis was applied. Age, waist circumference, height, weight, smoking and drinking habits, use of medications such as antihypertensive, antidiabetic, or antihyperlipidemic, as well as proteinuria, estimated glomerular filtration rate (eGFR), chemistry data, and blood pressure levels were significantly different between subgroups in both genders. The odds ratio for proteinuria showed a U-shape in men and women, even after adjustment for significant covariates such as age, waist circumference, systolic blood pressure, eGFR, fasting plasma glucose, triglyceride, low-density lipoprotein, antihypertensive use, antidiabetic use, antihyperlipidemic use, and lifestyle factors (smoking and drinking). Gender differences were also prominent—a BMI <20.4 kg/m² was significantly associated with proteinuria in men compared to a BMI <18.4 kg/m² in women. On the other hand, a BMI ≥ 25.5 kg/m² was also significantly associated with proteinuria in men compared to a BMI ≥ 22.5 kg/m² in women.

Conclusions

We found that BMI levels were associated with proteinuria in a U-shaped manner and showed marked gender differences. Health guidance should not only focus on higher BMI subjects, but also on thin subjects, in terms of the prevention of chronic kidney disease.     

Proteinuria on dipstick urine analysis after sexual intercourse

OBJECTIVE: To examine the role of sexual intercourse as a cause of proteinuria, and establishes its duration, as a knowledge of benign causes of proteinuria is required to avoid unnecessary testing. SUBJECTS AND METHODS: Twenty-four married couples were instructed to produce a urine sample before and after sexual intercourse; their urine was tested for proteinuria by dipstick analysis. RESULTS: Samples were assayed from 22 men and 11 women. Whereas none of the 24 men originally assessed for the study had proteinuria before sexual intercourse, six of the 22 who were eventually enrolled had proteinuria after intercourse (27.3%, 95% confidence interval, 10-50%; P = 0.008). None of the women had proteinuria after sexual intercourse (95% confidence interval, 70-100%). The time to disappearance of proteinuria was <12 h. CONCLUSION: Sexual intercourse is confirmed as a benign cause of proteinuria in men. Whenever possible, it is wise to avoid sexual intercourse at least 12 h before urinary dipstick testing.     

Risk factors for renal glomerular and vascular changes in an autopsy-based population survey: the Hisayama study

BACKGROUND: Information of the effect of cardiovascular risk factors on renal glomerular and vascular changes is scarce in the general population. METHOD: Between 1962 and 1994, 1394 autopsies were performed in Hisayama, for a total autopsy rate of 80%. Of these, 839 individuals who preserved adequate renal tissues and had recent health examinations data before death were eligible for the present study. We examined the degree of glomerular sclerosis, renal arteriolar hyalinosis, and arteriosclerosis, and evaluated their risk factors by means of a logistic regression model. RESULTS: The development of glomerular sclerosis, arteriolar hyalinosis, and arteriosclerosis were 16%, 16%, and 18% in men, respectively, and 27%, 15%, and 24% in women, respectively. All these frequencies increased linearly with advancing age. In the multivariate analysis, both age and systolic blood pressure were significant independent risk factors for almost all these glomerular and vascular changes. In addition, glucose intolerance and proteinuria for men were found to be significant risk factors for glomerular sclerosis. Elevated total cholesterol levels significantly increased the risk of arteriolar hyalinosis in men. Electrocardiogram (ECG) abnormalities were an independent risk factor for arteriosclerosis in both men and women, and proteinuria was an additional risk factor in women. Alcohol intake tended to have a protective effect on glomerular sclerosis and arteriosclerosis in women. CONCLUSION: Our data confirmed that age and systolic blood pressure are common risk factors for all glomerular and renal vascular changes in the general population. In addition, glucose intolerance, total cholesterol, ECG abnormalities, and proteinuria affect either glomerular or vascular changes.     

The impact of sex in primary glomerulonephritis.

BACKGROUND: Studies comparing the impact of sex in primary glomerular disease have reported conflicting results. METHODS: We analysed 395 membranous (MGN), 370 focal and segmental glomerulosclerosis (FSGS) and 542 IgA nephropathy patients to determine the impact of the patients' sex on outcome. We assessed initial and follow-up blood pressure, proteinuria, anti-hypertensive and immunosuppressive therapy, rate of renal function decline and survival from renal failure or a 50% decrease in creatinine clearance (combined event). RESULTS: Women accounted for one-third of the cohort. At presentation they were on average 2 years younger than men, and over follow-up received no more immunosuppression or anti-hypertensive agents than their male counterpart. Their mean arterial pressure (MAP) overall was 2 mmHg lower. Proteinuria at presentation and during follow-up in women compared to men was 50% and 30% lower in MGN and FSGS, while no differences were seen in IgA nephropathy. The rate of renal function decline and outcome favoured women over men in MGN (hazard ratios of a combined event of 0.63, 95% CI 0.40-1.00, P = 0.05) and in FSGS (HR 0.67, 95% CI 0.48-0.95, P = 0.02) but not in IgA nephropathy. These differences were not independent of blood pressure and proteinuria, indicating that these sex-dependent risk factors accounted for most of the hazards seen in men. However, the quantitative effect of proteinuria on the rate of progression was distinct and modified by sex in MGN and FSGS with higher proteinuria levels having less impact on progression rate in women. This interaction was independent of blood pressure. CONCLUSIONS: Women have a better outcome than men in MGN and FSGS but not in IgA nephropathy. These benefits are mostly mediated through both lower proteinuria and blood pressure at presentation and throughout follow-up, although females did have an independent advantage at higher levels of proteinuria.     

Birth weight and risk of renal cell cancer

BACKGROUND: The prenatal period has been suggested to be important for future cancer risk. Conditions in utero are also important for the development of the kidney, and birth weight, a marker of fetal nutrition and growth, is linearly correlated with the number of nephrons and the structural and functional unit of the kidney. An association between birth weight and renal cell cancer, the major form of kidney cancer, is biologically plausible, but has never been studied. METHODS: We conducted a population-based, case-controlled study in Sweden of men and women aged 20 to 79 years. We collected self-reported information on categories of birth weight from 648 patients with newly diagnosed renal cell cancer and from 900 frequency-matched control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the relative risks. RESULTS: An increased risk of renal cell cancer was observed among men with a birth weight of > or =3500 g (adjusted OR = 1.3, 95% CI, 1.0 to 1.8) compared with men with a birth weight between 3000 and 3499 g, especially in the subgroup without hypertension or diabetes (adjusted OR = 1.8, 95% CI, 1.2 to 2.6). No clear association among men with a birth weight <3000 g or among women was found. CONCLUSIONS: Our study shows that conditions in utero, reflected by birth weight, might affect the risk of renal cell cancer in adulthood. It is unclear why no association was found among women. Further studies, based on weight from birth certificates, are needed to clarify this relationship.     

Racial differences in early-onset renal disease among young adults: the coronary artery risk development in young adults (CARDIA) study

Although 11 million people in the United States have chronic renal insufficiency, little is known about ethnic/racial disparities for early-onset renal impairment. This study sought to determine whether there is an independent association between race/ethnicity and early-onset renal impairment and to identify other risk factors that might account for observed disparities. All Coronary Artery Risk Development in Young Adults subjects in which serum creatinine was measured at the year 15 examination were identified (n = 3554), excluding those who were pregnant at year 15. Potential risk factors at study entry (ages 18 to 30 yr, 1985 to 1986) included age, weight, gender, race/ethnicity, glucose, uric acid, and systolic BP. Renal impairment was defined as creatinine > or =1.5 mg/dl for men and > or = 1.2 mg/dl for women at year 15 (ages 33 to 45 yr). Fifty-two (2.7%) women and 39 (2.4%) men had renal impairment at the year 15 examination. In bivariate analyses, the odds of renal impairment among black women was estimated to be 2.4-fold that of white women, and among black men, the odds of renal impairment were 9.0-fold that of white men. In multivariate analysis, the odds of an elevated creatinine among black women compared with white women reduced to a nonsignificant 1.5-fold, whereas among men, the odds of an elevated creatinine among blacks was 11.4-fold that of whites. Although adjustment for baseline glucose levels accounted for much of the association between ethnicity and elevated creatinine among women, adjustment for weight, systolic BP, uric acid, glucose, and socioeconomic status did not account for the association between ethnicity and renal impairment among men. The data suggest that there are ethnic differences in the development of early-onset renal dysfunction. Among women, these differences are modest and largely accounted for by differences in glucose levels early in adult life. Differences in race/ethnicity related risk of early-onset renal impairment are particularly large among men and are not accounted for by the metabolic or socioeconomic factors evaluated.     

Racial differences in prostate cancer growth: apoptosis and cell proliferation in Caucasian and African-American patients

BACKGROUND: Epidemiologic evidence reveals striking racial differences in incidence and clinical behavior of prostate cancer among American men. In this study, we assessed the incidence of apoptosis and cell proliferation in prostate cancer specimens from African-American and Caucasian patients in an attempt to identify potential differences in tumor growth determinants between the two ethnic groups. METHODS: Apoptosis and cell proliferation were analyzed in archival paraffin-embedded prostatic tumors from 44 African-American and 35 Caucasian age-matched men who underwent radical prostatectomy for localized prostate cancer. Both groups had comparable preoperative prostate-specific antigen (PSA) levels, clinical stage, and Gleason scores, and neither group of patients received neoadjuvant therapy prior to surgery. Apoptotic status in prostate tumors was evaluated in situ, using the transferase deoxyuridine end labeling (TUNEL) assay, and the expression profile of two apoptotic proteins, bcl-2 and bax. The proliferative index was determined on the basis of Ki-67 antigen immunoreactivity. RESULTS: Apoptosis in malignant prostate cells was significantly higher in African American than Caucasian men (11.6% vs. 4.2%, P < 0. 001). Interestingly, the rate of cell proliferation of prostate tumor cells was similar in the two ethnic groups (4.5% and 4.2%). The antiapoptotic protein bcl-2 was detected at significantly higher levels in tumors from Caucasian than African-American patients (40. 8% vs. 31.6%, P < 0.05). Expression of bax, the apoptosis promoter, was consistently high among tumor epithelial cells in specimens from both racial groups (68%). CONCLUSIONS: These findings provide a novel insight into the molecular determinants of tumor growth that may underlie the ethnic differences in prostate cancer incidence and clinical behavior. Downregulation of bcl-2 expression may be potentially responsible for the loss of apoptotic control in prostate tumors from African-American men. This study may have significant clinical implications in the development of novel diagnostic approaches for biologically aggressive prostate cancer from diverse racial origin.     

Impact of post-ejaculatory pain in men with category III chronic prostatitis/chronic pelvic pain syndrome

PURPOSE: Chronic Pelvic Pain Syndrome (CPPS) is a common debilitating condition in which ejaculation relieves symptoms for some but exacerbates them in others. We studied ejaculatory pain in a cohort with CPPS to investigate associations with symptoms, quality of life and risk factors. MATERIALS AND METHODS: The 486 men in the National Institutes of Health Chronic Prostatitis Cohort study were stratified into 4 subgroups according to the presence of ejaculatory pain at baseline visit and at each of 3 monthly followup contacts. Subgroups were based on answers and labeled NO (always "no"), Nvar ("no" at baseline but "yes" or missing at least once), Yvar ("yes" at baseline but "no" or missing at least once) and YES (always "yes"). Demographic and quality of life data were obtained at baseline, together with medical and sexual history, symptoms, and cultures and microscopy of urine and seminal fluids. Associations among selected baseline risk factors, symptoms and post-ejaculatory pain were analyzed. RESULTS: Overall 128 men were classified as NO, 106 as Nvar, 137 as Yvar and 115 as YES. There was a progressive increase in baseline National Institutes of Health-Chronic Prostatitis Symptom Index total score (modified to exclude post-ejaculatory pain) from 18.5 for the NO subgroup to 25.5 for the YES subgroup (p <0.0001). Mental and physical quality of life were also progressively lower from the NO to the YES subgroup (p <0.001). There were no significant differences in white blood cell count or bacterial growth in urine, prostate fluid or semen among subgroups. Men in the YES subgroup were younger, more likely to live alone, had lower income and a greater variety of sexual practices than those without ejaculatory pain (NO subgroup). CONCLUSIONS: Patients with CPPS and persistent ejaculatory pain have more severe symptoms, are less likely to improve with time, and have differences in demographic and sexual history compared to other patients with CPPS.     

Conventional coronary artery bypass grafting: why women take longer to recover

BACKGROUND: Recovery following successful coronary artery bypass grafting (CABG) has been dramatically improved with the use of fast-track methods. Although data exist that demonstrate a significant gender difference in survival following CABG, little is known about factors influencing gender-specific recovery. This report describes a series of consecutive patients undergoing isolated CABG to determine gender-associated factors that may impact outcomes and recovery. METHODS: Five hundred and seventeen consecutive patients underwent isolated CABG utilizing cardiopulmonary bypass and were retrospectively reviewed. The outcomes of 351 men in the study were compared to the group of 160 women. A rapid recovery protocol focused on reduced cardiopulmonary bypass time, aggressive preoperative intra-aortic balloon pump use, early extubation, perioperative administration of corticosteroids and thyroid hormone, aggressive diuresis and atrial fibrillation prevention was applied to all patients. RESULTS: The 30-day mortality rate for the women was 4.2% (Parsonnet risk 16.3+/-9.0) compared with 3.4% (Parsonnet risk 9.9+/-7.5) for the men. There were no statistically significant differences in the 30-day mortality rates or postoperative complication rates between the women and men. The women, however, were found to be older (71+/- years versus 65+/- years, p<0.001), and to have a higher incidence of acute myocardial infarction (31% versus 20%, p<0.05), obesity (23% versus 10%, p <0.05), diabetes (31% versus 22%, p<0.05), hypertension (65% versus 48%, p<0.001), and symptomatic vascular disease (20% versus 12%, p<0.05). The women required fewer bypass grafts (2.9 versus 3.5 grafts, p<0.001), and consequently, had shorter cross and cardiopulmonary bypass times. Rapid recovery with discharge before the fifth postoperative day was achieved in 30% of the women, in comparison to 44% of the men (p<0.01). The postoperative hospital length of stay was longer for the women in comparison to the men (7.2+/-7.1 versus 5.8+/-5.2 days, p<0.05). CONCLUSIONS: Women had similar operative mortality and postoperative complication rates to men under a rapid recovery protocol. However, women have a longer recovery interval compared to men, which may be a reflection of their higher preoperative risk profile.     

Serum creatinine levels in the US population: third National Health and Nutrition Examination Survey

This report describes the distribution of serum creatinine levels by sex, age, and ethnic group in a representative sample of the US population. Serum creatinine level was evaluated in the third National Health and Nutrition Examination Survey (NHANES III) in 18,723 participants aged 12 years and older who were examined between 1988 and 1994. Differences in mean serum creatinine levels were compared for subgroups defined by sex, age, and ethnicity (non-Hispanic white, non-Hispanic black, and Mexican-American). The mean serum creatinine value was 0.96 mg/dL for women in the United States and 1.16 mg/dL for men. Overall mean creatinine levels were highest in non-Hispanic blacks (women, 1.01 mg/dL; men, 1.25 mg/dL), lower in non-Hispanic whites (women, 0.97 mg/dL; men, 1.16 mg/dL), and lowest in Mexican-Americans (women, 0.86 mg/dL; men, 1.07 mg/dL). Mean serum creatinine levels increased with age among both men and women in all three ethnic groups, with total US mean levels ranging from 0.88 to 1.10 mg/dL in women and 1.00 to 1.29 mg/dL in men. The highest mean creatinine level was seen in non-Hispanic black men aged 60+ years. In the total US population, creatinine levels of 1.5 mg/dL or greater were seen in 9.74% of men and 1.78% of women. Overall, among the US noninstitutionalized population, 10.9 million people are estimated to have creatinine values of 1.5 mg/dL or greater, 3.0 million have values of 1.7 mg/dL or greater, and 0.8 million have serum creatinine levels of 2.0 mg/dL or greater. Mean serum creatinine values are higher in men, non-Hispanic blacks, and older persons and are lower in Mexican-Americans. In the absence of information on glomerular filtration rate (GFR) or lean body mass, it is not clear to what extent the variability by sex, ethnicity, and age reflects normal physiological differences rather than the presence of kidney disease. Until this information is known, the use of a single cutpoint to define elevated serum creatinine values may be misleading.