A prospective controlled study of living kidney donors: three-year follow-up.

BACKGROUND: There have been few prospective controlled studies of kidney donors. Understanding the pathophysiologic effects of kidney donation is important for judging donor safety and improving our understanding of the consequences of reduced kidney function in chronic kidney disease. STUDY DESIGN: Prospective, controlled, observational cohort study. SETTING & PARTICIPANTS: 3-year follow-up of kidney donors and paired controls suitable for donation at their donor's center. PREDICTOR: Kidney donation. OUTCOMES: Medical history, vital signs, glomerular filtration rate, and other measurements at 6, 12, 24, and 36 months after donation. RESULTS: At 36 months, 182 of 203 (89.7%) original donors and 173 of 201 (86.1%) original controls continue to participate in follow-up visits. The linear slope of the glomerular filtration rate measured by plasma iohexol clearance declined 0.36±7.55mL/min per year in 194 controls, but increased 1.47±5.02mL/min per year in 198 donors (P=0.005) between 6 and 36 months. Blood pressure was not different between donors and controls at any visit, and at 36 months, all 24-hour ambulatory blood pressure parameters were similar in 126 controls and 135 donors (mean systolic blood pressure, 120.0±11.2 [SD] vs 120.7±9.7mmHg [P=0.6]; mean diastolic blood pressure, 73.4±7.0 vs 74.5±6.5mmHg [P=0.2]). Mean arterial pressure nocturnal dipping was manifest in 11.2% ± 6.6% of controls and 11.3% ± 6.1% of donors (P=0.9). Urinary protein-creatinine and albumin-creatinine ratios were not increased in donors compared with controls. From 6 to 36 months postdonation, serum parathyroid hormone, uric acid, homocysteine, and potassium levels were higher, whereas hemoglobin levels were lower, in donors compared with controls. LIMITATIONS: Possible bias resulting from an inability to select controls screened to be as healthy as donors, short follow-up duration, and dropouts. CONCLUSIONS: Kidney donors manifest several of the findings of mild chronic kidney disease. However, at 36 months after donation, kidney function continues to improve in donors, whereas controls have expected age-related declines in function.

Effect of niacin on FGF23 concentration in chronic kidney disease.

BACKGROUND: Elevated serum phosphorus and FGF23 are independent cardiovascular risk factors in patients with chronic kidney disease. In a randomized controlled trial of patients with dyslipidemia assigned to either extended release niacin (ERN) alone, ERN combined with the selective prostaglandin D2 receptor subtype 1 inhibitor laropiprant (ERN-L) or placebo, niacin lowered serum phosphorus; however, it is not known if it lowers FGF23 concentrations. METHODS: This is an ancillary study to a multicenter, randomized, double-blind, placebo-controlled trial among patients with dyslipidemia and an estimated glomerular filtration rate (eGFR) of 30-74 ml/min/1.73 m(2). Participants were randomized to ERN-L (n = 162), ERN (n = 97), or placebo (n = 68) in a 3:2:1 ratio for 24 weeks. The primary outcome was a change in serum FGF23 concentrations, and secondary outcomes were changes in other mineral metabolism parameters. RESULTS: Both the ERN and ERN-L groups showed significant declines in serum phosphorus, calcium and calcium·phosphorus product at 24 weeks compared to placebo. A significant decline from baseline (10.9%, p < 0.01) in the serum FGF23 concentration was observed in the ERN group compared to placebo, but not in the ERN-L group compared to placebo (p = 0.36 and 0.97 for ERN-L and placebo, respectively), despite equivalent declines in serum phosphorus. Similarly, the most marked declines in PTH occurred in the ERN-only group versus placebo; no change in PTH was observed in the ERN-L group. CONCLUSIONS: In this ancillary study of hyperlipidemic patients with an eGFR of 30-74 ml/min/1.73 m(2), ERN alone but not in combination with laropiprant lowered FGF23 and PTH concentrations. If confirmed, niacin may provide a novel strategy to decrease phosphorus, FGF23, and PTH concentrations in patients with chronic kidney disease.

Plasma F2-isoprostanes and coronary artery calcification: the CARDIA Study.

BACKGROUND: Oxidation of lipids in lipoproteins and cells may initiate and enhance the early development of cardiovascular disease. METHOD AND RESULTS: We assayed F(2)-isoprostanes, oxidation products of arachidonic acid, by gas chromatography-mass spectrometry in a biracial cohort of 2850 young healthy adult men and women. Coronary artery calcification (CAC), a component of coronary artery atherosclerosis, was detectable in 10% of the cohort and appeared to be in its initial stages (Agatston scores <20 in 47% and <100 in 83% of CAC-positive participants). After adjusting for sex, clinical site, age, and race, the presence of any CAC was 24% more likely among those with high vs low concentrations of F(2)-isoprostanes [odds ratio (OR) = 1.24 per 92.2 pmol/L (32.7 ng/L; 1 SD of F(2)-isoprostanes); 95% confidence interval (CI), 1.09-1.41]. The OR was only slightly attenuated [1.18 per 92.2 pmol/L (32.7 ng/L); CI, 1.02-1.38] after further adjustment for body mass index, smoking, serum lipids, C-reactive protein, antioxidant supplementation use, diabetes, and blood pressure. As a continuous variable, the Agatston score increased by 6.9% per 92.2 pmol/L (32.7 ng/L) of F(2)-isoprostane concentration (P <0.01). Whereas CAC prevalence was lower in women than men, mean (SD), F(2)-isoprostanes were higher in women {190 (108.9) pmol/L [67.4 (38.6) ng/L]} than in men {140.4 (55.6) pmol/L [49.8 (19.7) ng/L]}. Nevertheless, F(2)-isoprostanes were associated with an increased risk of CAC in both sexes. CONCLUSION: This association between increased concentrations of circulating F(2)-isoprostanes and CAC in young healthy adults supports the hypothesis that oxidative damage is involved in the early development of atherosclerosis.

Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial.

CONTEXT: Hormone replacement therapy (HRT) and antioxidant vitamins are widely used for secondary prevention in postmenopausal women with coronary disease, but no clinical trials have demonstrated benefit to support their use. OBJECTIVE: To determine whether HRT or antioxidant vitamin supplements, alone or in combination, influence the progression of coronary artery disease in postmenopausal women, as measured by serial quantitative coronary angiography. DESIGN, SETTING, AND PATIENTS: The Women's Angiographic Vitamin and Estrogen (WAVE) Trial, a randomized, double-blind trial of 423 postmenopausal women with at least one 15% to 75% coronary stenosis at baseline coronary angiography. The trial was conducted from July 1997 to January 2002 in 7 clinical centers in the United States and Canada. INTERVENTIONS: Patients were randomly assigned in a 2 x 2 factorial design to receive either 0.625 mg/d of conjugated equine estrogen (plus 2.5 mg/d of medroxyprogesterone acetate for women who had not had a hysterectomy), or matching placebo, and 400 IU of vitamin E twice daily plus 500 mg of vitamin C twice daily, or placebo. MAIN OUTCOME MEASURE: Annualized mean (SD) change in minimum lumen diameter (MLD) from baseline to concluding angiogram of all qualifying coronary lesions averaged for each patient. Patients with intercurrent death or myocardial infarction (MI) were imputed the worst rank of angiographic outcome. RESULTS: The mean (SD) interval between angiograms was 2.8 (0.9) years. Coronary progression, measured in mean (SD) change, worsened with HRT by 0.047 (0.15) mm/y and by 0.024 (0.15) mm/y with HRT placebo (P =.17); and for antioxidant vitamins by 0.044 (0.15) mm/y and with vitamin placebo by 0.028 (0.15) mm/y (P =.32). When patients with intercurrent death or MI were included, the primary outcome showed an increased risk for women in the active HRT group (P =.045), and suggested an increased risk in the active vitamin group (P =.09). Fourteen patients died in the HRT group and 8 in the HRT placebo group (hazard ratio [HR], 1.8; 95% confidence interval [CI], 0.75-4.3), and 16 in the vitamin group and 6 in the vitamin placebo group (HR, 2.8; 95% CI, 1.1-7.2). Death, nonfatal MI, or stroke occurred in 26 HRT patients vs 15 HRT controls (HR, 1.9; 95% CI, 0.97-3.6) and in 26 vitamin patients and 18 vitamin controls (HR, 1.5; 95% CI, 0.80-2.9). There was no interaction between the 2 treatment interventions. CONCLUSION: In postmenopausal women with coronary disease, neither HRT nor antioxidant vitamin supplements provide cardiovascular benefit. Instead, a potential for harm was suggested with each treatment.