A Comparative Study of Serum Phosphate and Related Parameters in Chronic Kidney Disease between the USA and Japan.

INTRODUCTION: Recent studies have suggested a higher incidence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) in the USA than in Japan. Hyperphosphatemia, a possible risk for CVD, may explain this difference; however, international differences in phosphate parameters in CKD have not been well elaborated. METHODS: By using the baseline data from the USA and the Japanese nation-wide, multicenter, CKD cohort studies; the Chronic Renal Insufficiency Cohort Study (CRIC, N = 3,870) and the Chronic Kidney Disease-Japan Cohort Study (CKD-JAC, N = 2,632), we harmonized the measures and compared clinical parameters regarding phosphate metabolism or serum phosphate, fibroblast growth factor-23 (FGF23), and parathyroid hormone (PTH), in the cross-sectional model. RESULTS: Multivariable linear regression analyses revealed that serum phosphate levels were significantly higher in CRIC across all levels of estimated glomerular filtration rate (eGFR) with the greatest difference being observed at lower levels of eGFR. Serum FGF23 and 25-hydroxy vitamin D (25OHD) levels were higher in CRIC, while PTH levels were higher in CKD-JAC at all levels of eGFR. Adjustments for demographics, 25OHD, medications, dietary intake or urinary excretion of phosphate, PTH, and FGF23 did not eliminate the difference in serum phosphate levels between the cohorts (0.43, 0.46, 0.54, 0.64, and 0.78 mg/dL higher in CRIC within eGFR strata of >50, 41-50, 31-40, 21-30, and ≤20 mL/min/1.73 m2, respectively). These findings were consistent when only Asian CRIC participants (N = 105) were included in the analysis. CONCLUSION: Serum phosphate levels in CRIC were significantly higher than those of CKD-JAC across all stages of CKD, which may shed light on the international variations in phosphate parameters and thus in cardiovascular risk among CKD patients. The key mechanisms for the substantial differences in phosphate parameters need to be elucidated.

Combination Treatment with Sodium Nitrite and Isoquercetin on Endothelial Dysfunction among Patients with CKD: A Randomized Phase 2 Pilot Trial.

BACKGROUND AND OBJECTIVES: Endothelial dysfunction is common among patients with CKD. We tested the efficacy and safety of combination treatment with sodium nitrite and isoquercetin on biomarkers of endothelial dysfunction in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This randomized, double-blind, placebo-controlled phase 2 pilot trial enrolled 70 patients with predialysis CKD. Thirty-five were randomly assigned to combination treatment with sodium nitrite (40 mg twice daily) and isoquercetin (225 mg once daily) for 12 weeks, and 35 were randomly assigned to placebo. The primary outcome was mean change in flow-mediated vasodilation over the 12-week intervention. Secondary and safety outcomes included biomarkers of endothelial dysfunction, inflammation, and oxidative stress as well as kidney function, methemoglobin, and adverse events. Intention-to-treat analysis was conducted. RESULTS: Baseline characteristics, including age, sex, race, cigarette smoking, history of hypertension and diabetes, use of renin-angiotensin system blockers, BP, fasting glucose, lipid profile, kidney function, urine albumin-creatinine ratio, and endothelial biomarkers, were comparable between groups. Over the 12-week intervention, flow-mediated vasodilation increased 1.1% (95% confidence interval, -0.1 to 2.3) in the treatment group and 0.3% (95% confidence interval, -0.9 to 1.5) in the placebo group, and net change was 0.8% (95% confidence interval, -0.9 to 2.5). In addition, changes in biomarkers of endothelial dysfunction (vascular adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, vWf, endostatin, and asymmetric dimethylarginine), inflammation (TNF-α, IL-6, C-reactive protein, IL-1 receptor antagonist, and monocyte chemoattractant protein-1), and oxidative stress (oxidized LDL and nitrotyrosines) were not significantly different between the two groups. Furthermore, changes in eGFR, urine albumin-creatinine ratio, methemoglobin, and adverse events were not significantly different between groups. CONCLUSIONS: This randomized phase 2 pilot trial suggests that combination treatment with sodium nitrite and isoquercetin did not significantly improve flow-mediated vasodilation or other endothelial function biomarkers but also did not increase adverse events compared with placebo among patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Nitrite, Isoquercetin, and Endothelial Dysfunction (NICE), NCT02552888.

Blood Pressure and Risk of Cardiovascular Events in Patients on Chronic Hemodialysis: The CRIC Study (Chronic Renal Insufficiency Cohort).

We recently reported a linear association between higher systolic blood pressure (SBP) and risk of mortality in hemodialysis patients when SBP is measured outside of the dialysis unit (out-of-dialysis-unit-SBP), despite there being a U-shaped association between SBP measured at the dialysis unit (dialysis-unit-SBP) with risk of mortality. Here, we explored the relationship between SBP with cardiovascular events, which has important treatment implications but has not been well elucidated. Among 383 hemodialysis participants enrolled in the prospective CRIC study (Chronic Renal Insufficiency Cohort), multivariable splines and Cox models were used to study the association between SBP and adjudicated cardiovascular events (heart failure, myocardial infarction, ischemic stroke, and peripheral artery disease), controlling for differences in demographics, cardiovascular disease risk factors, and dialysis parameters. Dialysis-unit-SBP and out-of-dialysis-unit-SBP were modestly correlated (r=0.34; P<0.001). We noted a U-shaped association of dialysis-unit-SBP and risk of cardiovascular events, with the nadir risk between 140 and 170 mm Hg. In contrast, there was a linear stepwise association between out-of-dialysis-unit-SBP with risk of cardiovascular events. Participants with out-of-dialysis-unit-SBP ≥128 mm Hg (top 2 quartiles) had >2-fold increased risk of cardiovascular events compared with those with out-of-dialysis-unit-SBP ≤112 mm Hg (3rd SBP quartile: adjusted hazard ratio, 2.08 [95% confidence interval, 1.12-3.87] and fourth SBP quartile: adjusted hazard ratio, 2.76 [95% confidence interval, 1.42-5.33]). In conclusion, among hemodialysis patients, although there is a U-shaped (paradoxical) association of dialysis-unit-SBP and risk of cardiovascular disease, there is a linear association of out-of-dialysis-unit-SBP with risk of cardiovascular disease. Out-of-dialysis-unit blood pressure provides key information and may be an important therapeutic target.

A comparison of three induction therapies on patients with delayed graft function after kidney transplantation.

We compare the outcomes of induction therapies with either methylprednisolone (group 1, n = 58), basiliximab (group 2, n = 56) or alemtuzumab (group 3, n = 98) in primary deceased donor kidney transplants with delayed graft function (DGF). Protocol biopsies were performed. Maintenance was tacrolimus and mycophenolate with steroid (group 1 and 2) or without steroid (group 3). One-year biopsy-confirmed acute rejection (AR) rates were 27.6, 19.6 and 10.2 % in group 1, 2 and 3 (p = 0.007). AR was significantly lower in group 3 (p = 0.002) and group 2 (p = 0.03) than in group 1. One-year graft survival rates were 90, 96 and 100 % in group 1, 2 and 3 (log rank p = 0.006). Group 1 had inferior graft survival than group 2 (p = 0.03) and group 3 (p = 0.002). The patient survival rates were not different (96.6, 98.2 and 100 %, log rank p = 0.81). Multivariable analysis using methylprednisolone induction as control indicated that alemtuzumab (OR 0.31, 95 % CI 0.11-0.82; p = 0.03) and basiliximab (OR 0.60, 95 % CI 0.23-0.98; p = 0.018) were associated with lower risk of AR. Therefore, alemtuzumab or basiliximab induction decreases AR and improves graft survival than methylprednisolone alone in patients with DGF. Alemtuzumab induction might also allow patients with DGF to be maintained with contemporary steroid-withdrawal protocol.

Different components of blood pressure are associated with increased risk of atherosclerotic cardiovascular disease versus heart failure in advanced chronic kidney disease.

Blood pressure is a modifiable risk for cardiovascular disease (CVD). Among hemodialysis patients, there is a U-shaped association between blood pressure and risk of death. However, few studies have examined the association between blood pressure and CVD in patients with stage 4 and 5 chronic kidney disease. Here we studied 1795 Chronic Renal Insufficiency Cohort (CRIC) Study participants with estimated glomerular filtration rate <30 ml/min per 1.73 m2 and not on dialysis. The association of systolic (SBP), diastolic (DBP), and pulse pressure with the risk of physician-adjudicated atherosclerotic CVD (stroke, myocardial infarction, or peripheral arterial disease) and heart failure was tested using Cox regression adjusted for demographics, comorbidity and medications. There was a significant association with higher SBP (adjusted hazard ratio 2.04 [95% confidence interval: 1.46-2.84]) for SBP over 140 vs under 120 mmHg, higher DBP (2.52 [1.54-4.11]) for DBP >90 mm Hg versus <80 mm Hg and higher pulse pressure (2.67 [1.82-3.92]) for pulse pressure >68 mm Hg versus <51 mm Hg with atherosclerotic CVD. For heart failure, there was a significant association with higher pulse pressure only (1.42 [1.05-1.92]) for pulse pressure >68 mm Hg versus <51 mmHg, but not for SBP or DBP. Thus, among participants with stage 4 and 5 chronic kidney disease, there was an independent association between higher SBP, DBP, and pulse pressure with the risk of atherosclerotic CVD, whereas only higher pulse pressure was independently associated with a greater risk of heart failure. Further trials are needed to determine whether aggressive reduction of blood pressure decreases the risk of CVD events in patients with stage 4 and 5 chronic kidney disease.

Sodium Excretion and the Risk of Cardiovascular Disease in Patients With Chronic Kidney Disease.

IMPORTANCE: Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular disease (CVD) compared with the general population. Prior studies have produced contradictory results on the association of dietary sodium intake with risk of CVD, and this relationship has not been investigated in patients with CKD. OBJECTIVE: To evaluate the association between urinary sodium excretion and clinical CVD events among patients with CKD. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of patients with CKD from 7 locations in the United States enrolled in the Chronic Renal Insufficiency Cohort Study and followed up from May 2003 to March 2013. EXPOSURES: The cumulative mean of urinary sodium excretion from three 24-hour urinary measurements and calibrated to sex-specific mean 24-hour urinary creatinine excretion. MAIN OUTCOMES AND MEASURES: A composite of CVD events defined as congestive heart failure, stroke, or myocardial infarction. Events were reported every 6 months and confirmed by medical record adjudication. RESULTS: Among 3757 participants (mean age, 58 years; 45% women), 804 composite CVD events (575 heart failure, 305 myocardial infarction, and 148 stroke) occurred during a median 6.8 years of follow-up. From lowest (<2894 mg/24 hours) to highest (≥4548 mg/24 hours) quartile of calibrated sodium excretion, 174, 159, 198, and 273 composite CVD events occurred, and the cumulative incidence was 18.4%, 16.5%, 20.6%, and 29.8% at median follow-up. In addition, the cumulative incidence of CVD events in the highest quartile of calibrated sodium excretion compared with the lowest was 23.2% vs 13.3% for heart failure, 10.9% vs 7.8% for myocardial infarction, and 6.4% vs 2.7% for stroke at median follow-up. Hazard ratios of the highest quartile compared with the lowest quartile were 1.36 (95% CI, 1.09-1.70; P = .007) for composite CVD events, 1.34 (95% CI, 1.03-1.74; P = .03) for heart failure, and 1.81 (95% CI, 1.08-3.02; P = .02) for stroke after multivariable adjustment. Restricted cubic spline analyses of the association between sodium excretion and composite CVD provided no evidence of a nonlinear association (P = .11) and indicated a significant linear association (P < .001). CONCLUSIONS AND RELEVANCE: Among patients with CKD, higher urinary sodium excretion was associated with increased risk of CVD.

Masked Hypertension and Elevated Nighttime Blood Pressure in CKD: Prevalence and Association with Target Organ Damage.

BACKGROUND AND OBJECTIVES: Masked hypertension and elevated nighttime BP are associated with increased risk of hypertensive target organ damage and adverse cardiovascular and renal outcomes in patients with normal kidney function. The significance of masked hypertension for these risks in patients with CKD is less well defined. The objective of this study was to evaluate the association between masked hypertension and kidney function and markers of cardiovascular target organ damage, and to determine whether this relationship was consistent among those with and without elevated nighttime BP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cross-sectional study. We performed 24-hour ambulatory BP in 1492 men and women with CKD enrolled in the Chronic Renal Insufficiency Cohort Study. We categorized participants into controlled BP, white-coat, masked, and sustained hypertension on the basis of clinic and 24-hour ambulatory BP. We obtained echocardiograms and measured pulse wave velocity in 1278 and 1394 participants, respectively. RESULTS: The percentages of participants with controlled BP, white-coat, masked, and sustained hypertension were 49.3%, 4.1%, 27.8%, and 18.8%, respectively. Compared with controlled BP, masked hypertension independently associated with low eGFR (-3.2 ml/min per 1.73 m(2); 95% confidence interval, -5.5 to -0.9), higher proteinuria (+0.9 unit higher in log2 urine protein; 95% confidence interval, 0.7 to 1.1), and higher left ventricular mass index (+2.52 g/m(2.7); 95% confidence interval, 0.9 to 4.1), and pulse wave velocity (+0.92 m/s; 95% confidence interval, 0.5 to 1.3). Participants with masked hypertension had lower eGFR only in the presence of elevated nighttime BP (-3.6 ml/min per 1.73 m(2); 95% confidence interval, -6.1 to -1.1; versus -1.4 ml/min per 1.73 m(2); 95% confidence interval, -6.9 to 4.0, among those with nighttime BP <120/70 mmHg; P value for interaction with nighttime systolic BP 0.002). CONCLUSIONS: Masked hypertension is common in patients with CKD and associated with lower eGFR, proteinuria, and cardiovascular target organ damage. In patients with CKD, ambulatory BP characterizes the relationship between BP and target organ damage better than BP measured in the clinic alone.

Influence of Nephrologist Care on Management and Outcomes in Adults with Chronic Kidney Disease.

BACKGROUND: Predialysis nephrology care for adults with late stage chronic kidney disease (CKD) is associated with improved outcomes. Less is known about the effects of nephrology care in earlier stages of CKD. OBJECTIVE: We aimed to evaluate the effect of nephrology care on management of CKD risk factors and complications, CKD progression, incident cardiovascular disease (CVD), and death. DESIGN: This was a prospective cohort study. PARTICIPANTS: Participants included 3855 men and women aged 21 to 74 years enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study with a mean (SD) estimated glomerular filtration rate (eGFR) at entry of 45 (17) ml/min/1.73 m(2), followed for a median of 6.6 years. MAIN MEASURES: The main predictor was self-reported prior contact with a nephrologist at study enrollment. Outcomes evaluated included CKD progression (≥ 50 % eGFR loss or end-stage renal disease), incident CVD, and death. RESULTS: Two-thirds (67 %) of the participants reported prior contact with a nephrologist at study enrollment. They were younger, more likely to be male, non-Hispanic white, and had lower eGFR and higher urine protein (p < 0.05). A subgroup with eGFR 30- < 60 ml/min/1.73 m(2) and prior contact with a nephrologist were more likely to receive pharmacologic treatment for CKD-related complications and to report angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB) use. After propensity score matching (for reporting prior contact with a nephrologist vs. not) and adjusting for demographic and clinical variables, prior contact with a nephrologist was not significantly associated with CKD progression, incident CVD or death (p > 0.05). CONCLUSIONS: One-third of CRIC participants had not seen a nephrologist before enrollment, and this prior contact was subject to age, sex, and ethnic-related disparities. While prior nephrology care was associated with more frequent treatment of CKD complications and use of ACEi/ARB medications, there was neither an association between this care and achievement of guideline-recommended intermediate measures, nor long-term adverse outcomes.

Blood pressure and risk of all-cause mortality in advanced chronic kidney disease and hemodialysis: the chronic renal insufficiency cohort study.

Studies of hemodialysis patients have shown a U-shaped association between systolic blood pressure (SBP) and mortality. These studies have largely relied on dialysis-unit SBP measures and have not evaluated whether this U-shape also exists in advanced chronic kidney disease, before starting hemodialysis. We determined the association between SBP and mortality at advanced chronic kidney disease and again after initiation of hemodialysis. This was a prospective study of Chronic Renal Insufficiency Cohort participants with advanced chronic kidney disease followed through initiation of hemodialysis. We studied the association between SBP and mortality when participants (1) had an estimated glomerular filtration rate <30 mL/min/1.73 m2 (n=1705), (2) initiated hemodialysis and had dialysis-unit SBP measures (n=403), and (3) initiated hemodialysis and had out-of-dialysis-unit SBP measured at a Chronic Renal Insufficiency Cohort study visit (n=326). Cox models were adjusted for demographics, cardiovascular risk factors, and dialysis parameters. A quadratic term for SBP was included to test for a U-shaped association. At advanced chronic kidney disease, there was no association between SBP and mortality (hazard ratio, 1.02 [95% confidence interval, 0.98-1.07] per every 10 mm Hg increase). Among participants who started hemodialysis, a U-shaped association between dialysis-unit SBP and mortality was observed. In contrast, there was a linear association between out-of-dialysis-unit SBP and mortality (hazard ratio, 1.26 [95% confidence interval, 1.14-1.40] per every 10 mm Hg increase). In conclusion, more efforts should be made to obtain out-of-dialysis-unit SBP, which may merit more consideration as a target for clinical management and in interventional trials.

Relation of serum lipids and lipoproteins with progression of CKD: The CRIC study.

BACKGROUND AND OBJECTIVES: Hyperlipidemia is common in patients with CKD. The objective of this study was to evaluate whether measures of plasma lipids and lipoproteins predict progression of kidney disease in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prospective cohort study in adults (n=3939) with CKD aged 21-74 years recruited between 2003 and 2008 and followed for a median of 4.1 years. At baseline, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), apoA-I , apoB, and lipoprotein(a) [Lp(a)] were measured. The outcomes were composite end point of ESRD or 50% decline in eGFR from baseline (rate of change of GFR). RESULTS: Mean age of the study population was 58.2 years, and the mean GFR was 44.9 ml/min per 1.73 m(2); 48% of patients had diabetes. None of the lipid or lipoprotein measures was independently associated with risk of the composite end point or rate of change in GFR. However, there were significant (P=0.01) interactions by level of proteinuria. In participants with proteinuria<0.2 g/d, 1-SD higher LDL-C was associated with a 26% lower risk of the renal end point (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.59 to 0.92; P=0.01), and 1-SD higher total cholesterol was associated with a 23% lower risk of the renal end point (HR, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In participants with proteinuria>0.2 g/d, neither LDL-C (HR, 0.98; 95% CI, 0.98 to 1.05) nor total cholesterol levels were associated with renal outcomes. Treatment with statins was reported in 55% of patients and was differential across lipid categories. CONCLUSIONS: In this large cohort of patients with CKD, total cholesterol, triglycerides, VLDL-C, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) were not independently associated with progression of kidney disease. There was an inverse relationship between LDL-C and total cholesterol levels and kidney disease outcomes in patients with low levels of proteinuria.

Successful transplantation of HIV patients: the Louisiana experience.

Human immunodeficiency virus (HIV) seropositivity has historically been an absolute contraindication for solid organ transplantation. However, the successful application of HAART (highly active anti-retroviral therapy) drug regimens has greatly prolonged the life expectancy of HIV-positive patients. Therefore, it has become appropriate to consider this patient population for transplantation. HIV positive transplants are being performed around the country in controlled settings, usually as part of a research protocol. The aim of our study is to describe the Louisiana experience with organ transplantation into HIV-positive patients. We identified seven HIV-positive patients who underwent kidney or kidney/pancreas transplantation at our center between 2007 and 2010. We performed a retrospective chart review to ascertain graft function, as well as virologic and immunologic status post-transplant. Renal function (glomerular filtration rate and serum creatinine concentrations) improved in all subjects post-transplant, and six of seven (85.8%) subjects remained virologically suppressed with no progression to Acquired Immunodeficiency Syndrome (AIDS). Overall, two-year graft and patient survival rates were 85.5%. HIV seropositive End Stage Renal Disease (ESRD) patients represent a new population of patients that can be successfully transplanted. This offers a new dimension in care for successful HAART therapy to prolong the life of HIV-infected patients.

Increased urinary excretion of angiotensinogen is associated with risk of chronic kidney disease.

BACKGROUND: The effect of intrarenal renin-angiotensin system (RAS) activity on risk of chronic kidney disease (CKD) has not been well studied in human subjects. METHODS: We investigated the association between urinary angiotensinogen, a reliable biomarker of intrarenal RAS activity, and risk of CKD in 201 patients and 201 controls. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) or presence of albuminuria ( ≥ 30 mg/24 h). RESULTS: Compared to controls, median urinary angiotensinogen excretion (45.4 versus 7.4 µg/24 h, P < 0.0001) and angiotensinogen-to-creatinine ratio (26.3 versus 4.4 µg/g, P < 0.0001) were significantly higher in patients with CKD. Log-transformed urinary angiotensinogen excretion and angiotensinogen-to-creatinine ratio were inversely correlated with eGFR (r = -0.59 and -0.57, both P < 0.0001) and positively correlated with log-transformed urinary albumin excretion (r = 0.89 and 0.87, both P < 0.0001). After adjusting for multiple covariables, including the use of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, diuretics and statins, the odds ratios (95% confidence interval) for CKD comparing the highest tertile to the lowest two tertiles of urinary angiotensinogen excretion and angiotensinogen-to-creatinine ratio were 6.70 (3.43, 13.1; P < 0.0001) and 6.45 (3.34, 12.4; P < 0.0001), respectively. CONCLUSIONS: These data indicate the intrarenal RAS may play an important role in the etiology of CKD, and urinary angiotensinogen may be a useful clinical biomarker for the identification of patients at a high risk for CKD.

Performance of estimated glomerular filtration rate prediction equations in preeclamptic patients.

Accurate estimation of the glomerular filtration rate (GFR) in patients with preeclampsia requires the collection of a 24-hour urine and can have important therapeutic and diagnostic implications. This procedure is often difficult or impossible to accomplish in this patient group. In this study, the Cockcroft-Gault, the Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were evaluated for their accuracy in determining GFR in the setting of preeclampsia. The estimated GFRs calculated from the above formulas were compared with the creatinine clearance values obtained from a 24-hour urine collections in 543 preeclamptic patients recruited from several large hospitals. Additionally, a set of new equations, preeclampsia GFR (PGFR), based on ethnicity, was created. The Cockcroft-Gault, MDRD, and CKD-EPI formulas were inaccurate in predicting GFR and both were significantly less accurate than PGFR. The latter formula provided an estimated GFR that was much closer to the creatinine clearance. Current GFR estimation equations based on serum creatinine values in nonpregnant patients are not reliable measures of renal function in patients with preeclampsia. The use of a new formula (PGFR) is recommended.

Association of serum intact parathyroid hormone with lower estimated glomerular filtration rate.

BACKGROUND AND OBJECTIVES: The prevalence of mineral metabolism abnormalities is almost universal in stage 5 chronic kidney disease (CKD), but the presence of abnormalities in milder CKD is not well characterized. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data on adults > or =20 yr of age from the National Health and Nutrition Examination Survey 2003-2004 (N = 3949) were analyzed to determine the association between moderate declines in estimated GFR (eGFR), calculated using the Modfication of Diet in Renal Disease formula, and serum intact parathyroid hormone (iPTH) > or = 70 pg/ml. RESULTS: The geometric mean iPTH level was 39.3 pg/ml. The age-standardized prevalence of elevated iPTH was 8.2%, 19.3%, and 38.3% for participants with eGFR > or = 60, 45 to 59, and 30 to 44 ml/min/1.73 m(2), respectively (P-trend < 0.001). After adjustment for age; race/ethnicity; sex; menopausal status; education; income; cigarette smoking; alcohol consumption; body mass index; hypertension; diabetes mellitus; vitamin D supplement use; total calorie and calcium intake; and serum calcium, phosphorus, and 25-hydroxyvitamin D levels-and compared with their counterparts with an eGFR > or = 60 ml/min/1.73 m(2)-the prevalence ratios of elevated iPTH were 2.30 and 4.69 for participants with an eGFR of 45 to 59 and 30 to 44 ml/min/1.73 m(2), respectively (P-trend < 0.001). Serum phosphorus > or = 4.2 mg/dl and 25-hydroxyvitamin D < 17.6 ng/ml were more common at lower eGFR levels. No association was present between lower eGFR and serum calcium < 9.4 mg/dl. CONCLUSIONS: This study indicates that elevated iPTH levels are common among patients with moderate CKD.

Psychosocial status of hemodialysis patients one year after Hurricane Katrina.

BACKGROUND: Hemodialysis patients experience a high degree of psychosocial impairment. METHODS: The psychosocial status of hemodialysis patients after Hurricane Katrina was evaluated using the Hurricane Coping Self-Efficacy (HCSE) measure, the Short Form-12 Health Survey (physical component summary [PCS] and mental component summary [MCS]), and the Center for Epidemiologic Studies Short Depression Scale (CES-D). These scales were administered to 391 hemodialysis patients (86% participation rate), 7 to 14 months after Hurricane Katrina. RESULTS: The mean score (standard deviation) was 36.2 (9.6) for the HCSE scale, 37.1 (10.9) and 46.7 (12.7) for the PCS and MCS, respectively, and 10.0 (6.5) on the CES-D. Symptoms of depression (CES-D scores > or =10) were present in 45.5% of patients. After age, race, and gender adjustment, evacuating less than 2 days before Hurricane Katrina making landfall and more fear of dying were associated with less favorable scores on the HCSE, MCS, and CES-D scales. Patients placed in a shelter and with a longer displacement had significantly lower MCS scores and more depressive symptoms. More depressive symptoms were observed among patients hospitalized in the month after the storm. Those who evacuated to a hotel, with more fear of dying and who were hospitalized in the month after Hurricane Katrina had lower scores on the PCS. CONCLUSIONS: Impaired psychosocial status was common among dialysis patients surviving Hurricane Katrina and associated with reduced coping. These data demonstrate the need for screening and management of psychosocial issues in hemodialysis patients after disasters.

Estimation of glomerular filtration rate in preeclamptic patients.

Accurate estimation of the glomerular filtration rate (GFR) in patients with preeclampsia is often difficult or impossible to accomplish. In this study, the Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and MDRD2 formulas were evaluated for their accuracy in determining GFR in the setting of preeclampsia. The estimated GFR calculated from these formulas was compared with the creatinine clearance values obtained from a 24-hour urine collection in 209 preeclamptic patients recruited from five large hospitals. Additionally, a set of new equations that more accurately estimate GFR in preeclamptic patients based on ethnicity, preeclampsia GFR (PGFR), was created. Both the CG and MDRD formulas were inaccurate in predicting GFR in preeclamptic patients, and both were significantly less accurate than PGFR. In conclusion, current GFR estimation equations based on serum creatinine values in nonpregnant patients are not reliable measures of renal function in patients with preeclampsia. The use of a new (PGFR) formula is recommended.

Prevalence and predictors of posttraumatic stress disorder among hemodialysis patients following Hurricane Katrina.

BACKGROUND: Patients with end-stage renal disease reliant on maintenance hemodialysis therapy may be particularly susceptible to developing post-traumatic stress disorder (PTSD) after natural disasters. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Patients who received treatment at 9 New Orleans, LA, metropolitan area hemodialysis units before Hurricane Katrina made landfall on August 29, 2005, were recruited for the study. Overall, 391 patients completed the interview between April and October 2006 (participation rate, 85.6%). PREDICTORS: Demographic, dialysis-related, and evacuation characteristics. OUTCOMES & MEASUREMENTS: PTSD was assessed by using the 17-item PTSD Checklist and defined using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. RESULTS: Overall, 23.8% of hemodialysis patients reported symptoms consistent with PTSD. After adjustment for age and sex, black patients were 1.92 (95% confidence interval, 1.31 to 2.83) times more likely than whites to have PTSD. After age, race, and sex adjustment, PTSD was more common in hemodialysis patients who were in their first 2 years of treatment, were evacuated fewer than 2 days before the hurricane made landfall, were evacuated initially to a shelter, and missed 3 or more dialysis treatments because of Hurricane Katrina and its aftermath. Additionally, patients who remained displaced for 3 or more months were more likely to have PTSD. LIMITATIONS: Data were not available to distinguish between the presence of acute, chronic, or delayed-onset PTSD. CONCLUSIONS: A substantial proportion of hemodialysis patients had PTSD symptoms approximately 1 year after Hurricane Katrina. Emergency planning for hemodialysis patients should include the identification and treatment of PTSD after future disasters.

Phenotypic characteristics shared by preeclamptic patients and an animal model of the syndrome: report of a pilot study.

BACKGROUND: Preeclampsia is a disorder that affects between 3% and 10% of all pregnancies. Progress in the understanding of the etiology (or etiologies) of this disorder has been impeded by the lack of suitable animal models of its early pathogenesis. Etiologic possibilities abound, and there are a number of considerations that suggest that preeclampsia is not one disease but rather a group of diseases with similar phenotypic characteristics. A rat model of this syndrome has been developed by inducing excessive volume expansion using desoxycorticosterone acetate and by replacing the drinking water with 0.9% saline. These animals develop hypertension, proteinuria, and intrauterine growth restriction (IUGR). However, they do not develop glomerular endotheliosis or a reduced glomerular filtration rate (GFR). We therefore surveyed the charts of patients with a discharge diagnosis of preeclampsia. We addressed the question of whether there was a group of such patients with the characteristics of our rat model. These include hypertension, proteinuria, IUGR, and either normal or only mildly abnormal GFR. METHODS: We performed a retrospective chart review of 630 consecutive patients discharged with a diagnosis of preeclampsia. Of the patients, 1290 had all data available to allow appropriate analysis. RESULTS: A total of 29 patients demonstrated hypertension (>140/90 mm Hg), proteinuria (>300 mg/ 24 h), and IUGR and did not have any confounding comorbid conditions. Of these 29 patients, 18 had GFR that were within the range expected for gestational age or only slightly reduced. CONCLUSIONS: There is a group of patients that mirror the characteristics of our animal model. Accordingly, at least one etiology of preeclampsia is related to excessive expansion of the extracellular fluid volume.

Effects of the selective cyclooxygenase-2 inhibitor analgesic celecoxib on renal carbonic anhydrase enzyme activity: a randomized, controlled trial.

Rofecoxib and celecoxib were the first cyclooxygenase-2 (COX-2)-specific inhibitors to be marketed as effective anti inflammatory agents. The results of several recent trials and a meta analysis of currently available studies all demonstrate a greater incidence of increased blood pressure, edema, and cardiovascular events in subjects treated with rofecoxib compared with celecoxib. As an approach to the assessment of molecular mechanisms that may contribute to these cardiorenal differences, this study investigated the inhibitory effects of celecoxib on renal carbonic anhydrase enzyme activity in human hypertensive subjects because in vitro enzyme studies demonstrate such an effect. Ten subjects with stable, treated hypertension were randomized to 1 of 3 treatment sequences, which included, in differing order, 200 mg celecoxib twice a day, 250 mg acetazolamide twice a day, or placebo twice a day. Whereas acetazolamide caused a bicarbonate diuresis and a hyperchloremic metabolic acidosis, celecoxib appeared to have no detectable effect on renal carbonic anhydrase or acid-base homeostasis. Thus, in this short-term study of human subjects, therapeutic doses of celecoxib did not appear to have a clinically significant inhibitory action on renal carbonic anhydrase.