Haematocrit and the risk of developing end-stage renal disease.

BACKGROUND: Anaemia is common in patients with renal failure; however, it is not known whether haematocrit level in the general population is a predictor for developing end-stage renal disease (ESRD). METHODS: A retrospective analysis was conducted to assess the development of ESRD within a population of 71 802 subjects (37 190 men and 34 612 women), 20-99 years, in Okinawa, Japan. Haematocrit data were collected between April 1983 and March 1984 and the subjects were followed forward to the year 2000 whether they were identified in the Okinawa Dialysis Study registry for identification of ESRD. Multivariate logistic analyses were performed to analyse the influence of haematocrit on the development of ESRD after adjusting for age, sex, blood pressure, body mass index, proteinuria and haematuria. In a subgroup of the cohort, similar analyses were repeated adjusting for estimated creatinine clearance by the method of Cockcroft and Gault. RESULTS: The mean (SD) level of haematocrit at the time of screening was 45.3% (3.3%) for men and 38.8% (3.2%) for women. During the 17-year follow-up, 269 patients (171 men and 98 women) were identified with ESRD. The mean time to onset of ESRD was 130.4 (53.6) months. The adjusted odds ratio and 95% confidence interval (CI) for the influence of haematocrit (%) on the development of ESRD was 0.991 and 0.988-0.995 (P<0.0001), suggesting that the lower haematocrit, the greater was the risk of developing ESRD. This finding was repeated in the subgroup analysis that included calculated creatinine clearance (adjusted odds ratio 0.991 and 95% CI 0.984-0.997, P=0.0057). In women, the adjusted odds ratio for haematocrits of 20.0-34.9% was 3.086 (CI 1.770-5.376, P<0.0001) when compared with the reference haematocrits of 35.0-39.9%. In men, the adjusted odds ratio for haematocrits of 25.0-39.9% was 1.927 (CI 1.418-2.625, P<0.0001) when compared with the reference haematocrits of 45.0-49.9%. CONCLUSIONS: Subjects with low haematocrits, <40% for men and <35% for women, have a significantly increased risk of ESRD.     

Serum cholesterol and risk of end-stage renal disease in a cohort of mass screening

Background To evaluate the relative risk of end-stage renal disease (ESRD), indicated by basal serum cholesterol levels, we examined data from the 1983 community-based, mass screening registry and chronic dialysis program in Okinawa, Japan. Methods Data on serum cholesterol were available for a total of 38,053 subjects (17,859 men and 20,194 women), in addition to dipstick urinalysis and blood pressure data. Between 1983 and the end of 1995, we identified 99 ESRD dialysis patients (62 men and 37 women) among the screening participants. Results The cumulative incidence and risk of ESRD were calculated for the following quartile definitions of serum cholesterol level: ≤167 mg/dL, 168 to 191 mg/dL, 192 to 217 mg/dL, and ≥218 mg/dL. The cumulative incidence of ESRD was 179, 216, 315, and 334 per 100,000 screened subjects in the respective serum cholesterol level quartiles. Logistic regression analysis on the prediction of ESRD by serum cholesterol level quartile was done, and the odds ratio (95% confidence interval) was 1.25 (1.04–1.49). However, the significance was lost when adjusted for the results of urinalysis or blood pressure measurements. Serum cholesterol levels were dependent on the degree of proteinuria by dipstick and blood pressure findings. Conclusion The present study suggests that serum cholesterol may not be an independent predictor of ESRD. Whether the result was due to racial difference or was organ specific remains to be determined.     

Predictors of diabetic end‐stage renal disease in Japan

SUMMARY: Diabetes mellitus (DM) has been the leading cause of incident dialysis in Japan since 1998, according to the Japanese Society for Dialysis Therapy (JSDT). In particular, the number of male DM dialysis patients is increasing. DM is becoming a worldwide epidemic in both developed and developing countries. Strategies to detect individuals at high‐risk of developing CKD and end‐stage renal disease (ESRD) are needed that can be implemented on a population‐basis. Among the commonly measured variables, dipstick urinalysis (proteinuria, haematuria), blood pressure, serum creatinine, body mass index (BMI), and serum uric acid are significant predictors of ESRD. Recently, we evaluated the effect of DM as a risk factor of developing ESRD. DM was diagnosed when the fasting plasma glucose (FPG) was 126 mg/dL or more in participants (n = 78529) of the 1993 screening program in Okinawa. The prevalence of DM was 5.2%. The odds ratio (95% CI) of DM for developing ESRD was 3.098 (1.738–5.525, P = 0.0001) after adjusting for possible confounding variables. Early detection and treatment of DM might prevent DM‐related ESRD. We examined 7125 non‐DM screenees who underwent a 1‐day health check between April 1997 and March 1998. They were followed‐up until March 2000 to determine whether they developed DM. Over the 2 years, the cumulative incidence of DM was 2.3%, 2.9% in men and 1.3% in women. Proteinuria was the most robust predictor of the development of DM; the adjusted relative risk (95% CI) was 1.90 (1.14–3.17). Obesity, per se, is also recognized as a risk factor for developing proteinuria. The higher the BMI, the higher the risk of developing ESRD; the adjusted odds ratio (95% CI) was 1.273 (1.121–1.446, P = 0.0002) for men. Other than being overweight (BMI = 25.0 kg/m²), a smoking habit was a significant predictor of developing proteinuria. The prevalence of obesity and DM is increasing in Japan. It is possible that the impact of obesity and complications of DM are different among races and ethnicities. Public relations regarding the risk of DM and its complications are especially important in Asian countries. Asians have more fat than non‐Asians, even at the same BMI levels. Knowledge of the predictors of DM‐ESRD is crucial as a first step toward prevention. Consistent with this notion, initiatives on the management of CKD and ESRD were recently organized in Japan and internationally.     

Prevalence of high fasting plasma glucose and risk of developing end-stage renal disease in screened subjects in Okinawa,Japan

Background The number of diabetic dialysis patients is increasing worldwide. Only a few studies, however, have examined the effect of diabetes mellitus (DM) as a risk factor for the development of end-stage renal disease (ESRD) in the general population.Methods We examined the cumulative incidence of ESRD based on the results of community-based mass screening in Okinawa, Japan, performed in 1993 by the Okinawa General Health Maintenance Association. Fasting plasma glucose (FPG) data were available for 78529 screenees (37197 men and 41332 women). DM was diagnosed when the FPG was 126mg/dl or more. Screenees who developed ESRD by the end of 2000 were identified through the Dialysis Registry, Okinawa Dialysis Study.Results The mean (SD) FPG was 96.5 (22.8)mg/dl, ranging from 45 to 577mg/dl. The prevalence of DM among the screenees was 4089 (5.2%). A total of 133 screenees (82 men and 51 women) developed ESRD during the 7.75-year study period. The adjusted odds ratio (95% confidence interval [CI]) in the high-FPG group for the risk of developing ESRD was 3.098 (95% CI, 1.738–5.525; P = 0.0001), when adjusted for age, sex, systolic blood pressure, diastolic blood pressure, body mass index, total cholesterol, triglyceride, hematocrit, serum creatinine, hematuria, and proteinuria.Conclusions The results of the present study indicated that FPG is a significant, independent predictor of ESRD. FPG and proteinuria measurements are euqally important in detecting individuals at high risk for developing ESRD.     

Outcome study of renal biopsy patients in Okinawa, Japan

Here we report a community-based epidemiologic study of patients who received renal biopsy in Okinawa, Japan between 1967 and 1994. The total number of cases was 2832 (1395 men and 1437 women), and the mean (SD) age at biopsy was 30.0 (10.0) years (range 1.0 to 88.0 years). The most common clinical indications for renal biopsy were proteinuria/hematuria (46.7%), nephrotic syndrome (21.2%), acute glomerulonephritis (10.1%), and systemic lupus erythematosus (7.5%). Patients who received renal biopsy between 1985 and 1994 (N= 1480) were much less likely to have acute glomerulonephritis than patients treated between 1967 and 1984 (N= 1352); the rates of proteinuria/hematuria, renal failure, and diabetes mellitus were slightly higher in the later period. Okinawa patients who began dialysis between 1971 and 2000 (N= 5246) were also studied. Among them, a total of 468 patients (260 men and 208 women) began dialysis after renal biopsy. The cumulative incidence of end-stage renal disease (ESRD) among these patients was 17% in 17 years. Half of these patients developed ESRD in the 5.8 years after renal biopsy. Among the dialysis patients, the biopsy rate was 12.6% in chronic glomerulonephritis, 1.7% in diabetes mellitus, 2.6% in nephrosclerosis, and 52.1% in systemic lupus erythematosus. The diagnoses of primary renal diseases were primarily made clinically. The survival rate after starting dialysis therapy was slightly better in those with than in those without renal biopsy but this finding was not statistically significant (adjusted hazards ratio 0.855, 95% CI 0.711-1.028, P= 0.095). The clinical significance of renal biopsy, other than its provision of histologic evidence, remains to be shown.     

Factors influencing access to cardiovascular procedures in patients with chronic kidney disease: race, sex, and insurance.

Blacks and women are less likely to undergo invasive cardiac procedures than whites and men in patients with chronic renal disease. We determined the relationship between ethnic and sex differences in access to cardiac procedures as patients progress to ESRD and acquire Medicare insurance. We performed a cohort study of a nationwide random sample of 4,987 patients who progressed to ESRD in 1986 to 1987 and were followed up for 7 years was used. Data were collected from medical charts and Medicare administrative records. Pre-ESRD, the odds of cardiac procedure use were much lower for white women (adjusted odds 0.67 [95% confidence interval (CI) 0.49-0.92]), black men (adjusted odds 0.32 [95% CI 0.20-0.49]), and black women (adjusted odds 0.30 [95%CI 0.18-0.50]) compared with white men. After initiating dialysis therapy, the ethnic and sex differences decreased with odds of receiving a cardiac procedure compared with white men 0.88 (95% CI 0.63-1.21) for white women, 0.66 (95% CI 0.47-0.92) for black men, and 0.75 (95% CI 0.53-1.08) for black women. Patients uninsured pre-ESRD had the largest increase in procedure rates at follow-up. The wide pre-ESRD disparities in cardiac procedure use between white women, black men, and black women compared with white men narrowed substantially with acquisition of Medicare and entry into comprehensive dialysis care. Health insurance contributed to the narrowing of differences. Procedure use for black men still lagged behind the other groups, suggesting the need for closer examination of health needs in this potentially vulnerable group.     

Outcome of subjects with elevated serum creatinine in a community-based mass screening

Background The outcome and prognosis of screened subjects with elevated levels of serum creatinine (>-176.8 μmol/L [≥2.0 mg/dL]) in a community-based mass health screening were examined in Okinawa, Japan. Methods From 1983 to 1992, a total of more than 1.24 million people had received at least 1 screening by the Okinawa General Health Maintenance Association. The status of 250,091 individuals for whom data on serum creatine levels was available, as of January 1, 1996, was examined by using information from the Okinawa Dialysis Study registry, which included data on the end-stage renal disease (ESRD) program, and by reviewing the medical charts. Results A total of 289 screened subjects (187 men and 102 women) were investigated in this study. The total duration of observation was 1081.8 person-years. Clinical demographics and the incidence of ESRD, and the death of patients with ESRD before starting dialysis therapy (ESRD+death) were compared in 2 consecutive periods: A (1983 to 1987) and B (1988 to 1992). The incidence of ESRD and ESRD+death was 122.4 (161.5) per 1000 person-years in period A, whereas that of period B was 143.8 (170.2) per 1000 person-years. In the period 1988 to 1992, the hazards ratio for ESRD and ESRD+death was 1.50 and 1.38, respectively. The 95% confidence interval was 1.05 to 2.15 and 0.99 to 1.91, respectively, when compared to the period of 1983 to 1987. Conclusion This study shows that the risk of ESRD and ESRD+death is not decreasing, therefore the current strategy for the prevention of ESRD is not satistactory. Further study is needed to determine the underlying causes and mechanisms of the progression of renal disease.     

Association of single measurements of dipstick proteinuria, estimated glomerular filtration rate, and hematocrit with 25-year incidence of end-stage renal disease in the multiple risk factor intervention trial

The incidence of ESRD is increasing rapidly. Limited information exists regarding early markers for the development of ESRD. This study aimed to determine over 25 yr the risk for ESRD associated with proteinuria, estimated GFR (eGFR), and hematocrit in men who did not have identified kidney disease and were randomly assigned into the Multiple Risk Factor Intervention Study (MRFIT). A total of 12,866 men who were at high risk for heart disease were enrolled (1973 to 1975) and followed through 1999. Renal replacement therapy was ascertained by matching identifiers with the United States Renal Data System's data; vital status was from the National Death Index. Men who initiated renal replacement therapy or died as a result of kidney disease were deemed to have developed ESRD. Dipstick urine for proteinuria, eGFR, and hematocrit were related to development of ESRD. During 25 yr, 213 (1.7%) men developed ESRD. Predictors of ESRD were dipstick proteinuria of 1+ or > or =2+ (hazard ratio [HR] 3.1 [95% confidence interval (CI) 1.8 to 5.4] and 15.7 [95% CI 10.3 to 23.9] respectively) and an eGFR of <60 ml/min per 1.73 m(2) (HR 2.4; 95% CI 1.5 to 3.8). Correlation between eGFR and serum creatinine was 0.9; the risk for ESRD with a 1-SD difference of each was identical (HR 1.21). Bivariate analysis demonstrated a 41-fold increase in ESRD risk in those with an eGFR <60 ml/min per 1.73 m(2) and > or =2+ proteinuria (95% CI 15.2 to 71.1). There was no association between hematocrit and ESRD. Other baseline measures that independently predicted ESRD included age, cigarette smoking, BP, low HDL cholesterol, and fasting glucose. Among middle-aged men who were at high risk for cardiovascular disease but had no clinical evidence of cardiovascular disease or significant kidney disease, dipstick proteinuria and an eGFR value <60 ml/min per 1.73 m(2) were strong predictors of long-term development of ESRD. It remains unknown whether intervention for proteinuria or early identification of those with chronic kidney disease reduces the risk for ESRD.     

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 conundrum of increased burden of end-stage renal disease in Asians

BACKGROUND: Few cohort studies have examined the risk of end-stage renal disease (ESRD) among Asians compared with whites and blacks. METHODS: To compare the incidence of ESRD in Asians, whites, and blacks in Northern California, we examined sociodemographic and clinical data on 299,168 adults who underwent a screening health checkup at Kaiser Permanente between 1964 and 1985. Incident cases of ESRD were ascertained by matching patient identifiers with the nationally comprehensive United States Renal Data System ESRD registry. RESULTS: Overall, 1346 cases of ESRD occurred during 7,837,310 person-years of follow-up. The age-adjusted rate of ESRD (per 100,000 person-years) was 14.0 [95% confidence interval (CI) 10.5-18.5] among Asians, 7.9 (95% CI 6.5-9.5) among whites, and 43.4 (95% CI 36.6-51.4)] among blacks. Controlling for age, gender, educational attainment, diabetes, prior myocardial infarction, serum creatinine, systolic and diastolic blood pressure, proteinuria, hematuria, cigarette smoking, serum total cholesterol, and body mass index increased the risk of ESRD in Asians relative to whites from 1.69 to 2.08 (95% CI 1.61-2.67). By contrast, adjustment for the same covariates decreased the risk of ESRD in blacks relative to whites from 5.30 to 3.28 (95% CI 2.91-3.69). CONCLUSION: Factors contributing to the excess ESRD risk in Asians relative to whites extend beyond usually considered sociodemographic and comorbidity disparities. Strategies aimed at examining novel risk factors for kidney disease and efforts to increase awareness of kidney disease among Asians may reduce ESRD incidence in this high-risk group.     

Decreased body mass index as an independent risk factor for developing chronic kidney disease

BACKGROUND: Obesity and metabolic syndrome are risk factors for the development of chronic kidney disease (CKD). Few studies have examined the effect of change in body mass index (DeltaBMI) on CKD incidence in a general screening setting. METHODS: Subjects of this study were screenees that participated in the screening program of the Okinawa General Health Maintenance Association in 1993 and 2003 in Okinawa, Japan. Using identification number, birth date, sex, and other recorded identifiers, we identified 33,389 subjects among the 1993 screening participants (N = 143,948) who also participated in the 2003 screening. CKD was defined as estimated glomerular filtration rate <60 ml/min/1.73 m(2), according to the modification of diet in renal disease study equation. Obesity was defined as BMI > or = 25 kg/m(2). RESULTS: CKD prevalence was 13.8% in 1993 and 22.4% in 2003. The incidence of developing CKD in 10 years was 15.5%. The effect of DeltaBMI on CKD incidence was evaluated after considering other confounding factors such as age, sex, blood pressure, BMI, fasting plasma glucose, and proteinuria. Median DeltaBMI was 1.0%. The adjusted odds ratio (95% CI) for the effect of DeltaBMI on CKD incidence was 1.111 (1.026-1.204, P < 0.01; entire study population), 1.271 (1.116-1.448, P = 0.0030; men), and 1.030 (0.931-1.139, NS; women), when DeltaBMI > or = 1% was taken as a reference. DeltaBMI was an independent predictor of CKD incidence. CONCLUSIONS: The present results suggest that there was an inverse relationship between DeltaBMI and CKD incidence among screened subjects. The reasons for this observation are not clear, but careful follow-up for DeltaBMI is necessary, particularly in obese men with proteinuria.     

Ethnic differences and determinants of proteinuria among South Asian subgroups in Pakistan

BACKGROUND: Hypertension, diabetes, increasing age, and smoking are known risk factors for proteinuria. Prevalence of proteinuria is high in South Asians. However, ethnic subgroup differences and determinants of proteinuria within the South Asian population have not been explored. METHODS: The National Health Survey of Pakistan conducted between 1990 and 1994 was used to explore ethnic subgroup variation in proteinuria. Distinct ethnic subgroups, the Muhajir, the Punjabi, the Sindhi, the Pashtun, and the Baluchi, were defined by mother tongue. We report results in individuals aged >or=15 years (N = 9442). Proteinuria was defined as dipstick positive for protein on random urine sample. RESULTS: Increasing age, high consumption of meat, and presence of hypertension and diabetes were each independently associated with proteinuria. The age-standardized prevalence of proteinuria was 4.6% (4.2% to 5.1%) and varied among ethnic subgroups (P < 0.001). The highest was among the Sindhi (men 9.5%, women 10.3%), then the Muhajir (men 8.2%, women 4.7%), the Punjabi (men 3.2% women 3.5%), and lowest among the Baluchi (men 2.4%, women 4.2%) and the Pashtun (men 2.7%, women 1.2%). The ethnic differences persisted after adjusting for the above-mentioned sociodemographic, dietary, and clinical risk factors [adjusted odds ratio (OR) (95% CI)] were 6.42 (3.97 to 10.38) for the Sindhis, 3.58 (2.22 to 5.79) for the Muhajirs, 2.03 (1.25 to 3.29) for the Punjabis, and 1.75 (0.79 to 3.88) for the Baluchis compared to the Pashtuns). CONCLUSION: We conclude that unmeasured environmental or genetic factors account for ethnic variations in proteinuria, and deserve further study.     

Sodium intake, ACE inhibition, and progression to ESRD

High sodium intake limits the antihypertensive and antiproteinuric effects of angiotensin-converting enzyme (ACE) inhibitors in patients with CKD; however, whether dietary sodium also associates with progression to ESRD is unknown. We conducted a post hoc analysis of the first and second Ramipril Efficacy in Nephropathy trials to evaluate the association of sodium intake with proteinuria and progression to ESRD among 500 CKD patients without diabetes who were treated with ramipril (5 mg/d) and monitored with serial 24-hour urinary sodium and creatinine measurements. Urinary sodium/creatinine excretion defined low (<100 mEq/g), medium (100 to <200 mEq/g), and high (≥200 mEq/g) sodium intake. During a follow-up of >4.25 years, 92 individuals (18.4%) developed ESRD. Among those with low, medium, and high sodium intakes, the incidence of ESRD was 6.1 (95% confidence interval [95% CI], 3.8-9.7), 7.9 (95% CI, 6.1-10.2), and 18.2 (95% CI, 11.3-29.3) per 100 patient-years, respectively (P<0.001). Patients with high dietary sodium exhibited a blunted antiproteinuric effect of ACE inhibition despite similar BP among groups. Each 100-mEq/g increase in urinary sodium/creatinine excretion associated with a 1.61-fold (95% CI, 1.15-2.24) higher risk for ESRD; adjusting for baseline proteinuria attenuated this association to 1.38-fold (95% CI, 0.95-2.00). This association was independent from BP but was lost after adjusting for changes in proteinuria. In summary, among patients with CKD but without diabetes, high dietary salt (>14 g daily) seems to blunt the antiproteinuric effect of ACE inhibitor therapy and increase the risk for ESRD, independent of BP control.     

Metabolic syndrome and chronic kidney disease in Okinawa, Japan

We assessed the prevalence of chronic kidney disease (CKD) in a hospital-based screening program in Okinawa, Japan. The significance of metabolic syndrome as a determinant of CKD was examined using multivariate logistic regression analysis. A total of 6980 participants, aged 30-79 years, participated in a screening program in Tomishiro Chuo Hospital. Metabolic syndrome was defined according to the criteria of the Adult Treatment Panel III (ATP III). Data were also analyzed according to the modified criteria of the National Cholesterol Education Program (NCEP) that defines abdominal obesity as a waist circumference of > oe =85 cm in men and > or =90 cm in women. CKD was defined as dipstick proteinuria (> or =1+) or a reduced glomerular filtration rate (GFR). GFR was estimated using the abbreviated Modification of Diet in Renal Disease (MDRD) formula. The prevalence of metabolic syndrome and CKD was 12.8 and 13.7%, respectively. Metabolic syndrome was a significant determinant of CKD (adjusted odds ratio (OR) 1.537 and 95% confidence interval (CI) 1.277-1.850, P<0.0001). The adjusted OR (95% CI) was 1.770 (1.215-2.579, P=0.0029) for those with four metabolic syndrome risk factors compared to those with no metabolic syndrome risk factors. Metabolic syndrome was a significant determinant for younger participants (<60 years; OR 1.686, 95% CI 1.348-2.107, P<0.0001), but not for older participants (> or =60 years; OR 1.254, 95% CI 0.906-1.735, NS). The relationship between the number of metabolic syndrome risk factors and the prevalence of CKD was linear using the modified criteria. The results suggest that metabolic syndrome is a significant determinant of CKD in men under 60 years of age, in Okinawa, Japan.     

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.     

Relationship between dyslipidemia and the risk of developing end-stage renal disease in a screened cohort

Background Disturbances in lipid metabolism are often observed in patients with renal failure and could be a risk factor for end-stage renal disease (ESRD). However, few studies have examined abnormal lipid metabolism as a risk factor for the development of ESRD in the general population.Methods We examined the cumulative incidence of ESRD based on the results of a community-based mass screening in Okinawa, Japan, which was conducted in 1993 by the Okinawa General Health Maintenance Association. Screenees who developed ESRD by the end of 2000 were identified through the Okinawa Dialysis Study registry.Results Total cholesterol (TC) data were available for 133338 (92.6%) of the total 143948 screenees) and triglyceride (TG) data were available for 132094 (91.8%). Dyslipidemia was defined as TC 220mg/dl or TG 150mg/dl. The cumulative incidences of ESRD, per 1000 screenees, were 1.12 for those without dyslipidemia and 2.53 for those with dyslipidemia. The adjusted hazard ratio (95% confidence interval) for dyslipidemia was 0.856 (0.484–1.516) for men and 1.260 (0.661–2.400) for women; neither was significant when adjustment was made for age, systolic blood pressure, diastolic blood pressure, body mass index, creatinine clearance, diabetes mellitus, and proteinuria.Conclusions The present study showed dyslipidemia to be an insignificant predictor of development of ESRD in the general Okinawa population.     

Smoking, gender and rheumatoid arthritis-epidemiological clues to etiology. Results from the behavioral risk factor surveillance system

OBJECTIVES: This study was undertaken to confirm and extend our earlier observation that gender is a biological effect modifier of smoking-rheumatoid arthritis (RA) relationship in a diverse national survey sample in the United States. METHODS: Smoking history of 644 cases of RA and 1509 geographically matched general population controls were compared using weighted logistic regression. RESULTS: There were 644 respondents with RA (cases) and 1509 geographically matched controls. Cases were significantly younger, less educated, more likely to be single and female than controls. Among cases 57% were smokers while among controls 49% smoked. Among women, after adjusting for age, hysterectomy had an age adjusted odds ratio 1.45, (95% CI 0.99-2.10) and menopause an adjusted odds ratio 1.18 (95% CI 0.99-2.10) were associated with smoking. In univariable analysis ever-smoking was associated with increased risk of RA (odds ratio 1.34, 95% CI 1.0-1.81). Among the strata of smokers, there was an increasing gradient of risk with increasing exposure to smoking (P = 0.041). In separate multivariable models, smoking increased the risk in men (odds ratio 2.29, 95% CI 1.35-3.90) while in women the risk was not elevated (odds ratio 0.98, 95% CI 0.67-1.42). After adjusting for the statistically significant interaction both female gender (odds ratio 2.30, 95% CI 1.39-3.83) and having ever smoked (odds ratio 2.31, 95% CI 1.36-3.94) emerged as significant risk factors for RA. CONCLUSIONS: Gender interacts with smoking in by an unknown mechanism to lead to differential risk of RA.     

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.     

Proteinuria and decreased body mass index as a significant risk factor in developing end-stage renal disease

Background  Body mass index (BMI) is a significant predictor of developing end-stage renal disease (ESRD). The relation between a change in BMI (ΔBMI) and the incidence of ESRD has not been examined in any large epidemiologic studies. Methods  We determined the ΔBMI in subjects who participated in the Okinawa General Health Maintenance Association (OGHMA) screenings in 1983 and again in 1993. Screenees were free of ESRD at the 1993 screening and were then monitored until the end of 2000 to determine whether they developed ESRD. Participants were identified using ID numbers, birthdates, and other identifiers. Details of every ESRD patient treated in Okinawa are maintained in an independent community-based dialysis registry. Multivariate logistic analyses were performed to determine the significance of a ΔBMI on the incidence of ESRD using SAS. The ethics committee of the OGHMA approved the study protocol. Only coded data were used for this study. Results  Among the 92,364 subjects aged 30–89 years screened in 1983, 29,011 (31.4%) returned for the 1993 screening. The median ΔBMI was 2.1%, and the subjects were divided into two groups: ΔBMI < 2.1% (G1) and ΔBMI ≥ 2.1% (G2). The cumulative incidence of ESRD was 0.31% in G1 (ESRD in 44) and 0.14% in G2 (ESRD in 21). The odds ratio (95% confidence interval) of developing ESRD based on a ΔBMI was 2.268 (1.284–4.000, P < 0.01) after adjusting for age, sex, systolic blood pressure, BMI in 1983, and proteinuria. Conclusion  The findings of the present study suggest that a ΔBMI is an independent risk factor for the incidence of ESRD, especially for those with proteinuria. The reasons for the BMI change were not recorded in this study. Unintentional weight loss, however, might warrant evaluation for the presence or progression of chronic kidney disease.     

Modest serum creatinine elevation affects adverse outcome after general surgery

BACKGROUND: Modest preoperative serum creatinine elevation (1.5 to 3.0 mg/dL) has been recently shown to be independently associated with morbidity and mortality after cardiac surgery. It is important to know if this association can be applied more broadly to general surgery cases. METHODS: Multivariable logistic regression analyses of 46 risk variables in 49,081 cases from the Veterans Affairs National Surgical Quality Improvement Program, undergoing major general surgery from 10/1/96 through 9/30/98. RESULTS: Thirty day mortality and several cardiac, respiratory, infectious and hemorrhagic morbidities were significantly (P < 0.001) higher in patients with a serum creatinine>1.5 mg/dL. With multivariable analysis, the adjusted odds ratio for mortality for patients with a serum creatinine of 1.5 to 3.0 mg/dL was 1.44 [95% confidence interval (95% CI) 1.22 to 1.71] and for creatinine>3.0 mg/dL was 1.93 (95% CI 1.51 to 2.46). The adjusted odds ratio for morbidity (one or more postoperative complications) for patients with a serum creatinine of 1.5 to 3.0 mg/dL was 1.18 (95% CI 1.06 to 1.32) and for creatinine>3.0 mg/dL was 1.19 (95% CI 0.99 to 1.43). Further stratification and recursive partitioning of creatinine levels revealed that a serum creatinine level>1.5 mg/dL was the approximate threshold for both increased morbidity and mortality. CONCLUSIONS: Modest preoperative serum creatinine elevation (>1.5 mg/dL) is a significant predictor of risk-adjusted morbidity and mortality after general surgery. A preoperative serum creatinine of 1.5 mg/dL or higher is a readily available marker for potential adverse outcomes after general surgery.