Effects of Statins on Renal Outcome in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: HMG CoA reductase inhibitors (statins) are known to prevent cardiovascular disease and improve lipid profiles. However, the effects of statins on renal outcomes, including decline in estimated glomerular filtration rate (eGFR) and proteinuria in patients with chronic kidney disease (CKD), are controversial. This meta-analysis evaluated the impact of statins on renal outcomes in patients with CKD. MATERIALS AND METHODS: We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane Databases. The inclusion criteria were published RCT and cohort studies comparing statin therapy to placebo or active controls in patients with CKD (eGFR <60 ml/min/1.73 m(2)) not requiring dialysis. The primary outcome was the differences in the change of eGFR. We also examined change of protein concentration in urine as a secondary outcome. A meta-analysis comparing statin and its control groups and a subgroup analysis examining intensity of statin were performed. RESULTS: From 142 full-text articles, 10 studies were included in the meta-analysis. Overall, there was a significant difference in rate of eGFR change per year favoring statin group (mean difference (MD) = 0.10 ml/min/1.73 m(2), 95% CI: 0.09 to 0.12). In our subgroup analysis, those who received high-intensity statins had a significant difference in eGFR with a MD of 3.35 (95% CI: 0.91 to 5.79) ml/min/1.73 m(2) compared to control. No significant change in eGFR was found with moderate- and low-intensity statin therapy. Compared with the control group, the statin group did not have a difference in reduction of proteinuria with MD in change of proteinuria of 0.19 gm/day (95% CI: -0.02 to 0.40). CONCLUSION: Overall, there was a difference in change of eGFR between the statin and control group. High-intensity statins were found to improve a decline in eGFR in population with CKD not requiring dialysis compared with control, but moderate- and low-intensity statins were not. Statins were not found to decrease proteinuria in patients with CKD.

Non-steroidal anti-inflammatory drugs and risk of venous thromboembolism: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to integrate and examine the association between NSAID use and venous thromboembolism (VTE). METHODS: We conducted a systematic review and meta-analysis of studies that reported odds ratios, relative risks, hazard ratios or standardized incidence ratios for VTE among NSAID users compared with non-users. Pooled risk ratios and 95% CIs were calculated using a random effects generic inverse variance model. RESULTS: Six studies with 21 401 VTE events were identified and included in the data analysis. The pooled risk ratio of VTE in NSAID users was 1.80 (95% CI 1.28, 2.52). CONCLUSION: Our study demonstrated a statistically significant increased risk of VTE among NSAID users. This finding has important public health implications given the prevalence of NSAID use in the general population.

Is the incidence of malignancy increased in patients with sarcoidosis? A systematic review and meta-analysis.

A possible causal relationship between sarcoidosis and malignancy has been the subject of debates for decades. To better understand this association, we conducted a systematic review and meta-analysis of cohort studies that reported relative risk, hazard ratio or standardized incidence ratio with 95% confidence interval (CI) comparing the incidence of malignancy in patients with sarcoidosis versus non-sarcoidosis participants. Pooled risk ratios (RR) and 95% CI were calculated using a random-effect, generic inverse variance methodology. Five studies were identified and included in our data analyses. The pooled RR of malignancy in patients with sarcoidosis was 1.21 (95% CI: 1.04-1.40). However, when we performed a sensitivity analysis that included only studies that compared the incidence of malignancy after the first year of the diagnosis of sarcoidosis with the incidence of malignancy after the first year of index date for non-sarcoidosis controls, the pooled risk ratio decreased and did not reach statistical significance (RR 1.13, 95% CI: 0.97-1.32). Furthermore, analysis for publication bias has suggested that publication bias in favour of positive studies may be present. In conclusion, after accounting for possible detection bias and publication bias, there does not appear be a significant association between sarcoidosis and malignancy.

Risk of malignancy in patients with giant cell arteritis and polymyalgia rheumatica: a systematic review and meta-analysis.

OBJECTIVE: To investigate the association between giant cell arteritis (GCA)/polymyalgia rheumatica (PMR) and malignancy risk. METHODS: We conducted a systematic review and meta-analysis of cohort studies that reported relative risk, hazard ratio, or standardized incidence ratio (SIRs) with 95% confidence comparing malignancy risk in patients with GCA/PMR versus non-GCA/PMR participants. Pooled risk ratios and 95% confidence intervals were calculated using a random-effect, generic inverse variance method. RESULT: A total of six studies were identified and included in our data analysis. The pooled risk ratio of malignancy in patients with GCA/PMR was 1.14 (95% CI: 1.05-1.22). The risk was higher in the first 6-12 months after diagnosis with the pooled risk ratio of 2.16 (95% CI: 1.85-2.53). However, when we performed a sensitivity analysis that excluded one study with a potential selection bias, the pooled risk ratio decreased and did not achieve statistical significance. CONCLUSION: Our study demonstrated a low but statistically significant increased malignancy risk among patients with GCA/PMR. However, when we excluded one study with potential selection bias, the new pooled risk ratio did not achieve statistical significance.

Prevalence of cancer in membranous nephropathy: a systematic review and meta-analysis of observational studies.

BACKGROUND: The association between membranous nephropathy (MN) and cancer has been well documented. However, the true prevalence and characteristics of cancer associated with MN have not been well described. METHODS: A systematic review and meta-analysis of cohort studies was conducted to summarize the prevalence of cancer-associated MN as well as patient characteristics and types of cancer in this population. We used a random-effects meta-analysis model to estimate the prevalence of cancer. RESULTS: We included 6 studies (n = 785). The estimated prevalence of cancer was 10.0% (95% CI, 6.1-14.6). The mean age of MN patients with cancer was 67 ± 7 years. The diagnosis of cancer preceded the diagnosis of MN in 20 ± 6.8%. Lung cancer was the most common type of tumor, accounting for 22 cases (26%), followed by prostate cancer (13 cases, 15%), hematologic malignancies (12 cases, 14%), colorectal cancer (9 cases, 11%), breast cancer (6 cases, 7%), and stomach and esophageal cancer (5 cases, 6%). CONCLUSION: The estimated prevalence of cancer in patients with MN is 10% (95% CI, 6.1-14.6). The vast majority of tumors associated with MN are lung and prostate cancer. Hematologic malignancies should also be considered as one of the potential cancers associated with MN. Our study was based on a largely Caucasian population; therefore, the findings might not be applicable to other populations.

Protease inhibitors and avascular necrosis: a systematic review and meta-analysis.

Avascular necrosis (AVN) is a pathological process associated with many medical conditions, including human immunodeficiency virus (HIV) infection. Whether or not the use of protease inhibitors (PIs) confers additional risk for AVN to HIV-infected patients is controversial. Previous epidemiological studies showed an increased risk of AVN among PI users, but these studies did not have enough power to achieve statistical significance. A meta-analysis of case-control studies reporting the odds ratios (ORs) of AVN among HIV-infected patients who were exposed to PIs compared with non-exposed patients was conducted. Pooled ORs and 95% confidence intervals (CIs) were calculated using a fixed-effect Mantel-Haenszel analysis. Four case-control studies were identified and included for data analysis. The meta-analysis demonstrated an increased odds of AVN in participants exposed to PIs, with an OR of 2.09 (95% CI 1.01-4.31; P=0.05). The statistical heterogeneity of this meta-analysis was determined not to be important, with an I(2) of 0%. The meta-analysis revealed a statistically significant increased odds of AVN among PI-exposed, HIV-infected patients. Physician should be aware of this association as it may help guide potential therapeutic options, particularly for patients with other classic risk factors for AVN.

Risk of venous thromboembolism in patients with rheumatoid arthritis: a systematic review and meta-analysis.

We performed this meta-analysis to assess venous thromboembolism risk in patients with rheumatoid arthritis. A comprehensive search was performed in MEDLINE, EMBASE, and the Cochrane databases. Nine observational studies met our inclusion criteria and were included in the data analysis. The pooled risk ratios of deep venous thrombosis, pulmonary embolism, and venous thromboembolism in patients with rheumatoid arthritis (RA) compared with non-RA participants were 2.08 (95% CI 1.75-2.47), 2.17 (95% CI 2.05-2.31), and 1.96 (95% CI 1.81-2.11), respectively. Subgroup analysis demonstrated a consistent increased risk in every study design (cohort, case-control, and cross-sectional). Our results indicate a significant increased risk of venous thromboembolism among patients with rheumatoid arthritis.

Lifetime nonnarcotic analgesic use and decline in renal function in women.

BACKGROUND: Analgesics are commonly used and may impair kidney function. However, limited prospective information is available on the long-term effects of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen on renal function. METHODS: A total of 1697 women participating in the Nurses' Health Study provided information on a mailed questionnaire in 1999 about lifetime use of acetaminophen, aspirin, and NSAIDs and provided blood samples in 1989 and 2000. The main outcome was change in estimated glomerular filtration rate (GFR) in 11 years. Multivariate logistic regression was used to determine the odds of developing the outcome according to lifetime analgesic intake. RESULTS: The mean +/- SD estimated GFR decreased from 88 +/- 17 to 79 +/- 17 mL/min per 1.73 m(2). There were no substantial differences in the unadjusted or estimated GFR levels among the categories of lifetime intake for the 3 analgesic groups at baseline or after 11 years. Acetaminophen use was associated with an increased risk of a GFR decline of at least 30 mL/min per 1.73 m(2) (P trend =.01) and a GFR decline of 30% or greater (P trend<.001), but aspirin and NSAID use were not. Compared with women consuming less than 100 g of acetaminophen, multivariate-adjusted odds ratio (95% confidence intervals) for a decline in GFR of at least 30 mL/min per 1.73 m(2) for women consuming more than 3000 g was 2.04 (1.28-3.24). CONCLUSIONS: Higher lifetime use of aspirin and NSAIDs is not associated with renal function decline, but high acetaminophen use may increase the risk of loss of renal function. The absolute risk of renal function decline due to even high lifetime analgesic intake seems to be modest.

Kidney dysfunction, inflammation, and coronary events: a prospective study.

Kidney dysfunction and high C-reactive protein (CRP) levels are independently associated with coronary events. However, it is unclear whether the risk of coronary events associated with decreased kidney function is at least partially mediated by inflammation and whether the association between inflammatory biomarkers and coronary events is influenced by level of kidney function. With the use of a prospective, nested, case-control study design, the association among kidney function, inflammatory biomarker levels, and coronary events was studied. A total of 244 women who were participants in the Nurses' Health Study and had no history of cardiovascular disease received a diagnosis of an incident coronary event (defined as nonfatal myocardial infarction or death as a result of coronary disease) during the follow-up period from 1990 to 1998 and were matched to 486 control subjects. Serum creatinine and inflammatory biomarker levels were measured in blood samples collected in 1989. Creatinine clearance (CrCl) was estimated using creatinine, age, weight, and height. In multivariate analyses, the odds ratio (OR) for a coronary event in women with an estimated CrCl <60 ml/min was 2.33 (95% confidence interval [CI], 1.01 to 5.38) compared with those with a CrCl > or =90 ml/min. When soluble tumor necrosis factor receptor (sTNFR) I and II levels were added into this model individually, the observed OR for women with CrCl <60 ml/min was attenuated. In analyses stratified by estimated CrCl, higher high-sensitivity CRP (hs-CRP), IL-6, and sTNFR I and II levels each were significantly associated with an increased odds of coronary events in women with an estimated CrCl < or =74 ml/min but not in women with an estimated CrCl > or =75 ml/min. The OR per 5-mg/L unit increase in hs-CRP was 1.68 (95% CI, 1.13 to 2.52) for women with an estimated CrCl < or =74 ml/min, compared with 1.23 (95% CI, 0.86 to 1.76) and 0.99 (95% CI, 0.76 to 1.29) for women with an estimated CrCl 75 to 89 and > or =90 ml/min, respectively (P = 0.004 for interaction). In conclusion, kidney dysfunction is associated with an increased odds of coronary events, and inflammation, as assessed by higher sTNFR I and II levels, may mediate some of this risk. Higher inflammatory biomarkers levels, specifically, hs-CRP, IL-6, and sTNFR I and II, were significantly associated with coronary events only in women with reduced kidney function. These findings warrant further investigation in other populations.

The quality of pharmacologic care for vulnerable older patients.

BACKGROUND: Although pharmacotherapy is critical to the medical care of older patients, medications can have considerable toxicity in this age group. To date, research has focused on inappropriate prescribing and policy efforts have aimed at access, but no comprehensive measurement of the quality of pharmacologic management using explicit criteria has been performed. OBJECTIVE: To evaluate the broad range of pharmacologic care processes for vulnerable older patients. DESIGN: Observational cohort study. SETTING: 2 managed care organizations enrolling older persons. PATIENTS: Community-dwelling high-risk patients 65 years of age or older continuously enrolled in the managed care organizations from 1 July 1998 to 31 July 1999. MEASUREMENTS: Patients' receipt of care as specified in 43 quality indicators covering 4 domains of pharmacologic care: 1) prescribing indicated medications; 2) avoiding inappropriate medications; 3) education, continuity, and documentation; and 4) medication monitoring. RESULTS: Of 475 vulnerable older patients, 372 (78%) consented to participate and had medical records that could be abstracted. The percentage of appropriate pharmacologic management ranged from 10% for documentation of risks of nonsteroidal anti-inflammatory drugs to 100% for avoiding short-acting calcium-channel blockers in patients with heart failure and avoiding beta-blockers in patients with asthma. Pass rates for quality indicators in the "avoiding inappropriate medications" domain (97% [95% CI, 96% to 98%]) were significantly higher than pass rates for "prescribing indicated medications" (50% [CI, 45% to 55%]); "education, continuity, and documentation" (81% [CI, 79% to 84%]); and "medication monitoring" (64% [CI, 60% to 68%]). LIMITATIONS: Fewer than 10 patients were eligible for many of the quality indicators measured, and the generalizability of these findings in 2 managed care organizations to the general geriatric population is uncertain. CONCLUSIONS: Failures to prescribe indicated medications, monitor medications appropriately, document necessary information, educate patients, and maintain continuity are more common prescribing problems than use of inappropriate drugs in older patients.

Dietary factors and the risk of incident kidney stones in younger women: Nurses' Health Study II.

BACKGROUND: In older women and men, greater intakes of dietary calcium, potassium, and total fluid reduce the risk of kidney stone formation, while supplemental calcium, sodium, animal protein, and sucrose may increase the risk. Recently, phytate has been suggested to play a role in stone formation. To our knowledge, no prospective information on the role of dietary factors and risk of kidney stone formation is available in younger women. METHODS: We prospectively examined, during an 8-year period, the association between dietary factors and the risk of incident symptomatic kidney stones among 96 245 female participants in the Nurses' Health Study II; the participants were aged 27 to 44 years and had no history of kidney stones. Self-administered food frequency questionnaires were used to assess diet in 1991 and 1995. The main outcome measure was an incident symptomatic kidney stone. Cox proportional hazards regression models were used to adjust simultaneously for various risk factors. RESULTS: We documented 1223 incident symptomatic kidney stones during 685 973 person-years of follow-up. After adjusting for relevant risk factors, a higher dietary calcium intake was associated with a reduced risk of kidney stones (P =.007 for trend). The multivariate relative risk among women in the highest quintile of intake of dietary calcium compared with women in the lowest quintile was 0.73 (95% confidence interval, 0.59-0.90). Supplemental calcium intake was not associated with risk of stone formation. Phytate intake was associated with a reduced risk of stone formation. Compared with women in the lowest quintile of phytate intake, the relative risk for those in the highest quintile was 0.63 (95% confidence interval, 0.51-0.78). Other dietary factors showed the following relative risks (95% confidence intervals) among women in the highest quintile of intake compared with those in the lowest quintile: animal protein, 0.84 (0.68-1.04); fluid, 0.68 (0.56-0.83); and sucrose, 1.31 (1.07-1.60). The intakes of sodium, potassium, and magnesium were not independently associated with risk after adjusting for other dietary factors. CONCLUSIONS: A higher intake of dietary calcium decreases the risk of kidney stone formation in younger women, but supplemental calcium is not associated with risk. This study also suggests that some dietary risk factors may differ by age and sex. Finally, dietary phytate may be a new, important, and safe addition to our options for stone prevention.

Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement.

BACKGROUND: It is well known that serum creatinine may be used as a marker of renal function only if taking into account factors that influence creatinine production, such as age, gender, and weight. Serum cystatin C has been proposed as a potentially superior marker than serum creatinine, because serum cystatin C level is believed to be produced at a constant rate and not to be affected by such factors. However, there are limited data on factors that may influence serum cystatin C levels, and there are limited data comparing cystatin C-based estimates of renal function with creatinine-based estimates that adjust for such factors, especially in individuals with normal, or mildly reduced, renal function. METHODS: This was a cross-sectional study of 8058 inhabitants of the city of Groningen, The Netherlands, 28 to 75 years of age. Serum cystatin C and serum creatinine levels were measured, and creatinine clearance was determined from the average of two separate 24-hour urine collections. We performed multivariate analyses to identify factors independently associated with serum cystatin C levels after adjusting for creatinine clearance. Then, partial Spearman correlations were obtained after adjusting for factors that may influence serum cystatin C and creatinine levels. We also compared the goodness-of-fit (R(2)) of different multivariate linear regression models including serum cystatin C level and serum creatinine level for the outcome of creatinine clearance. RESULTS: Older age, male gender, greater weight, greater height, current cigarette smoking, and higher serum C-reactive protein (CRP) levels were independently associated with higher serum cystatin C levels after adjusting for creatinine clearance. After adjusting for age, weight, and gender, the partial Spearman correlations between creatinine and, respectively, serum cystatin C level and serum creatinine level were -0.29 (P < 0.001) and -0.42 (P < 0.001), respectively. The R(2) values for serum cystatin C level and serum creatinine level adjusted for age, weight, and gender were 0.38 and 0.42, respectively. The addition of cigarette smoking and serum CRP levels did not improve the R(2) value for the multivariate serum cystatin C-based model. CONCLUSION: Serum cystatin C appears to be influenced by factors other than renal function alone. In addition, we found no evidence that multivariate serum cystatin C-based estimates of renal function are superior to multivariate serum creatinine-based estimates.

A comparison of prediction equations for estimating glomerular filtration rate in adults without kidney disease.

The ability of the Modification of Renal Disease (MDRD) equation to predict GFR when compared with multiple other prediction equations in healthy subjects without known kidney disease was analyzed. Between May 1995 and December 2001, a total of 117 healthy individuals underwent (125)I-iothalamate or (99m)Tc-diethylenetriamine-pentaacetic acid (DTPA) renal studies as part of a routine kidney donor evaluation at either Brigham and Women's Hospital or Boston Children's Hospital. On chart review, 100 individuals had sufficient data for analysis. The MDRD 1, MDRD 2 (simplified MDRD equation), Cockcroft-Gault (CG), Cockcroft-Gault corrected for GFR (CG-GFR), and other equations were tested. The median absolute difference in ml/min per 1.73 m(2) between calculated and measured GFR was 28.7 for MDRD 1, 18.5 for MDRD 2, 33.1 for CG, and 28.6 for CG-GFR in the (125)I-iothalamate group and was 31.1 for MDRD 1, 38.2 for MDRD 2, 22.0 for CG, and 31.1 for CG-GFR in the (99m)Tc-DTPA group. Bias was -0.5, -3.3, 25.6, and 5.0 for MDRD 1, MDRD 2, CG, and CG-GFR, respectively, in subjects who received (125)I-iothalamate and -33.2, -36.5, 6.0, and -15.0 for MDRD 1, MDRD 2, CG, and CG-GFR, respectively, in those who received (99m)Tc-DTPA studies. Precision testing, as measured by linear regression, yielded R(2) values of 0.04 for CG, 0.05 for CG-GFR, 0.15 for MDRD 1, and 0.14 for MDRD in those who underwent (125)I-iothalamate studies and 0.18 for CG, 0.21 for CG-GFR, 0.40 for MDRD 1, and 0.38 for MDRD 2 for those who underwent (99m)Tc-DTPA studies. The MDRD equations were more accurate within 30 and 50% of the measured GFR compared with the CG and CG-GFR equations. When compared with the CG equation, the MDRD equations are more precise and more accurate for predicting GFR in healthy adults. The MDRD equations, however, consistently underestimate GFR, whereas the CG equations consistently overestimate measured GFR in people with normal renal function. In potential kidney donors, prediction equations may not be sufficient for estimating GFR; radioisotope studies may be needed for a better assessment of GFR. Further studies are needed to derive and assess GFR prediction equations in people with normal or mildly impaired renal function.

Moderate alcohol intake and renal function decline in women: a prospective study.

BACKGROUND: The impact of moderate alcohol consumption on renal function has important public health implications given the high prevalence of alcohol use. Experimentally, alcohol may adversely affect renal function, but clinical data are limited and no large, prospective studies have examined this issue. METHODS: In a prospective study of 1658 nurses enrolled in the Nurses' Health Study, we sought to determine if there was an association between moderate alcohol consumption and rate of decline in renal function. Daily alcohol intake was measured in 1990, 1994 and 1998 using a detailed questionnaire. Maximum daily alcohol intake was measured in 1988. Creatinine, measured from blood samples provided in 1989 and 2000, was used to estimate glomerular filtration rate (GFR) and creatinine clearance (CCr). RESULTS: Compared to individuals with no alcohol intake, the odds ratios (ORs) for developing a >or=25% estimated GFR decline were: 0.98 (95% CI: 0.72-1.32) for 0.1-4.9 g/day, 0.83 (95% CI: 0.56-1.21) for 5-14.9 g/day and 0.81 (95% CI: 0.50-1.31) for 15-59.9 g/day. For women with hypertension (n = 726), the ORs for a >or=25% estimated GFR decline were: 0.98 (95% CI: 0.53-1.21) for 0.1-4.9 g/day, 0.62 (95% CI: 0.34-1.12) for 5-14.9 g/day and 0.53 (95% CI: 0.25-1.12) for 15-59.9 g/day. CONCLUSIONS: Moderate alcohol consumption had no substantial adverse effect on renal function in women over an 11 year follow-up period.

The association between mental health, physical function, and hemodialysis mortality.

BACKGROUND: Mortality rates for individuals on chronic hemodialysis remain very high; therefore, strategies are needed to identify individuals at greatest risk for mortality so preventive strategies can be implemented. One such approach is to stratify individuals by self-reported mental health and physical function. Examining these parameters at baseline, and over time, may help identify individuals at greater risk for mortality. METHODS: We enrolled 14,815 individuals with end-stage renal disease (ESRD) and followed these individuals for up to 2 years. The mean age was 61.0 +/- 15.4 years (range, 20 to 96 years) and 31% were African Americans. The SF-36 Health Survey was administered 1 to 3 months after hemodialysis initiation and 6 months later. We examined the associations between the initial SF-36 Health Survey mental component summary (MCS) and physical component summary (PCS) scores and mortality during the follow-up period, and examined the associations between 6-month decline in PCS and MCS scores and subsequent mortality. We also examined the interactions between age and MCS and PCS scores. The general population-based mean of each of these scores was 50 with a standard deviation of 10. The main outcome measurement was death. RESULTS: Self-reported baseline mental health (MCS score) and physical function (PCS score) were both independently associated with increased mortality, and 6-month decline in these parameters was also associated with increased mortality. The multivariate hazard ratios for 1-year mortality for MCS scores of less than 30, 30 to 39, and 40 to 49 were 1.48 (95% CI, 1.32 to 1.64), 1.23 (95% CI, 1.14 to 1.32) and 1.18 (95% CI, 1.10 to 1.26) compared with a MCS score of 50 or more. The hazard ratios for PCS scores of less than 20, 20 to 29, and 30 to 39 were 1.97 (95% CI, 1.64 to 2.36), 1.62 (95% CI, 1.36 to 1.92), and 1.32 (95% CI, 1.11 to 1.57) compared with a PCS score of 50 or more. Six-month decline in self-reported mental health (hazard ratio, 1.07; 95% CI, 1.02 to 1.12, per 10-point decline in MCS score) and physical function (hazard ratio, 1.25; 95% CI, 1.18 to 1.33, per 10-point decline in PCS score) were also both significantly associated with an additional increase in mortality beyond baseline risk. We also found a significant interaction between age and physical function (P = 0.02). Specifically, there was a graded response between the PCS score category and mortality in most age strata, but this relationship was not observed in the oldest age (85 years old or older). CONCLUSION: In individuals newly initiated on chronic hemodialysis, self-reported baseline mental health and physical function are important, independent predictors of mortality, and there is a graded relationship between these parameters and mortality risk. Following these parameters over time provides additional information on mortality risk. One must also consider age when interpreting the relationship between physical function and mortality.

High-normal blood pressure and microalbuminuria.

BACKGROUND: High-normal blood pressure (BP) is associated with increased cardiovascular risk compared with optimal BP, but no study has specifically examined the association between high-normal BP and microalbuminuria, an established predictor of future cardiovascular events. METHODS: This was a cross-sectional study of normotensive (systolic BP [SBP] < 140 mm Hg, diastolic BP [DBP] < 90 mm Hg) individuals without diabetes with no hypertension history enrolled in the Third National Health and Nutrition Examination Survey. BP was categorized as high normal (SBP, 130 to 139 mm Hg or DBP, 85 to 89 mm Hg), normal (SBP, 120 to 129 mm Hg or DBP, 80 to 84 mm Hg), and optimal (SBP < 120 mm Hg and DBP < 80 mm Hg). We also separately examined SBP, DBP, mean arterial pressure (MAP), and pulse pressure. Microalbuminuria was defined using sex-specific cutoff values (urine albumin-creatinine ratio > or = 17 and < or = 250 microg/mg [> or =1.0 and < or =28 mg/mmol] for men and > or = 25 and < or = 355 microg/mg for women [> or =3 and < or =40 mg/mmol]). We used multivariate logistic regression to analyze the association between different BP measurements and microalbuminuria. RESULTS: Compared with optimal BP, high-normal BP was significantly associated with increased odds of microalbuminuria (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.51 to 3.01). Similarly, MAP (OR, 1.41; 95% CI, 1.15 to 1.74 per 10-mm Hg increment), SBP (OR, 1.27; 95% CI, 1.09 to 1.48 per 10-mm Hg increment), and DBP (OR, 1.29; 95% CI, 1.06 to 1.57 per 10-mm Hg increment) were significantly associated with microalbuminuria. CONCLUSION: High-normal BP is significantly associated with microalbuminuria compared with optimal BP and may be a biomarker of the increased cardiovascular risk observed in this population.

The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency.

BACKGROUND: In individuals with moderate to severe renal insufficiency, low protein intake may slow renal function decline. However, the long-term impact of protein intake on renal function in persons with normal renal function or mild renal insufficiency is unknown. OBJECTIVE: To determine whether protein intake influences the rate of renal function change in women over an 11-year period. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. PARTICIPANTS: 1624 women enrolled in the Nurses' Health Study who were 42 to 68 years of age in 1989 and gave blood samples in 1989 and 2000. Ninety-eight percent of women were white, and 1% were African American. MEASUREMENTS: Protein intake was measured in 1990 and 1994 by using a semi-quantitative food-frequency questionnaire. Creatinine concentration was used to estimate glomerular filtration rate (GFR) and creatinine clearance. RESULTS: In multivariate linear regression analyses, high protein intake was not significantly associated with change in estimated GFR in women with normal renal function (defined as an estimated GFR > or = 80 mL/min per 1.73 m2). Change in estimated GFR in this subgroup over the 11-year period was 0.25 mL/min per 1.73 m2 (95% CI, -0.78 to 1.28 mL/min per 1.73 m2) per 10-g increase in protein intake; the change in estimated GFR was 1.14 mL/min per 1.73 m2 (CI, -3.63 to 5.92 mL/min per 1.73 m2) after measurement-error adjustment for protein intake. In women with mild renal insufficiency (defined as an estimated GFR > 55 mL/min per 1.73 m2 but <80 mL/min per 1.73 m2), protein intake was significantly associated with a change in estimated GFR of -1.69 mL/min per 1.73 m2 (CI, -2.93 to -0.45 mL/min per 1.73 m2) per 10-g increase in protein intake. After measurement-error adjustment, the change in estimated GFR was -7.72 mL/min per 1.73 m2 (CI, -15.52 to 0.08 mL/min per 1.73 m2) per 10-g increase in protein intake, an association of borderline statistical significance. High intake of nondairy animal protein in women with mild renal insufficiency was associated with a significantly greater change in estimated GFR (-1.21 mL/min per 1.73 m2 [CI, -2.34 to -0.33 mL/min per 1.73 m2] per 10-g increase in nondairy animal protein intake). CONCLUSIONS: High protein intake was not associated with renal function decline in women with normal renal function. However, high total protein intake, particularly high intake of nondairy animal protein, may accelerate renal function decline in women with mild renal insufficiency.