Detecting high-risk chronic kidney disease-mineral bone disorder phenotypes among patients on dialysis: a historical cohort study.

BACKGROUND: The clinical management of chronic kidney disease-mineral bone disorder (CKD-MBD) remains extremely challenging, partially due to difficulties in defining high-risk phenotypes based on serum biomarkers. We evaluated the prevalence and outcomes of 27 mutually exclusive CKD-MBD phenotypes in a large, multi-national cohort of chronic dialysis patients over a 5-year follow-up study. METHODS: In this historical cohort study, we enrolled all haemodialysis patients registered in EuCliD® on 1 July 2011 across 28 Europe, the Middle East and Africa (EMEA) and South American countries. We created 27 mutually exclusive phenotypes based on combinations of serum parathyroid hormone (PTH), phosphorus (P) and calcium (Ca) 6-month averages (L, low; T, target; H, high). We tested the association between CKD-MBD phenotypes and 5-year mortality and hospitalization risk by outcome risk score-adjusted proportional hazard regression. RESULTS: We enrolled 35 721 eligible patients. Eastern European and South American countries generally achieved poorer CKD-MBD control when compared with Western European countries (prevalence ratio: 0.79; P < 0.001). There were 15 795 deaths [126.7 deaths/1000 person-years; 95% confidence interval (CI) 124.7-128.7]; 18 014 had at least one hospitalization (203.9 hospitalizations/1000 person-years; 95% CI 201.0-206.9); the incidence of the composite endpoint was 280.0 events/1000 person-years (95% CI 276.6-283.5). In the fully adjusted model, relative mortality risk ranged from hazard ratio (HR) = 1.07 (PTH/Ca/P: TLT) to HR = 1.59 (PTH/Ca/P: LTL), whereas the relative composite endpoint risk ranged from HR = 1.07 (PTH/Ca/P: TTH) to HR = 1.36 (PTH/Ca/P: LTL). CONCLUSION: We identified several CKD-MBD phenotypes associated with reduced hospitalization-free survival and increased mortality. Ranking of relative risk estimates or excess events concurs in informing healthcare priority setting.

Hemodynamic and metabolic responses to valsartan and atenolol in obese hypertensive patients.

OBJECTIVE: None of the current hypertension guidelines provides specific guidance regarding pharmacological management of obese hypertensive patients. Treatment recommendations for lean hypertensives may not be simply extrapolated to obese hypertensive persons. DESIGN: Randomized, double-blind, parallel-group study with a 13-week treatment period. SETTING: Multicenter study in Germany. PATIENTS: Obese patients with mild to moderate uncomplicated essential hypertension. INTERVENTION: Patients were treated with valsartan at a maximal dose of 160 mg/day or with atenolol at a maximal dose of 100 mg/day. Hydrochlorothiazide at doses of 12.5-25 mg was added in patients with blood pressure > 140/90 mmHg on monotherapy. MAIN OUTCOME MEASURES: Blood pressure, lipid and glucose metabolism, and highly sensitive C-reactive protein (hsCRP) were monitored. RESULTS: Sixty-seven patients were randomized to valsartan and 65 patients to atenolol. With valsartan, systolic blood pressure (SBP) decreased from 160.8 +/- 8.9 to 140.5 +/- 13.3 mmHg and diastolic blood pressure (DBP) from 96.1 +/- 7.0 to 85.1 +/- 8.1 mmHg by the end of the study. With atenolol, SBP decreased from 159.3 +/- 6.8 to 139.8 +/- 14.5 mmHg and DBP from 95.0 +/- 6.8 to 83.5 +/- 7.5 mmHg (P = 0.91 for SBP and P = 0.34 for DBP between interventions). Body weight did not change with either treatment. We did not see a significant difference in the response of lipid levels or hsCRP between interventions. To assess the cumulative effect of each intervention on glucose metabolism over the trial duration, we calculated individual areas under the curve for homeostasis model assessment for insulin resistance (HOMA-IR) over time. The resulting area under the curve was significantly smaller with valsartan compared with atenolol (P = 0.02). CONCLUSIONS: Beta-adrenoreceptor blockers and AT1-receptor blockers, particularly in combination with low-dose diuretics, effectively lower blood pressure in obese hypertensives. However, metabolic responses differ between both treatment strategies, with beneficial effects of AT1-receptor blockers. AT1-receptor blockers are a good choice in obese hypertensives, given the profoundly increased diabetes risk in this population.

Adipose tissue metabolism and CD11b expression on monocytes in obese hypertensives.

At a given degree of adiposity, metabolic and cardiovascular risk varies markedly between individuals. Animal studies suggest that differentially expressed systemic activation of monocytes contributes to the obesity-associated risk variability. We tested the hypothesis that systemic monocyte activation is associated with changes in adipose tissue and skeletal muscle metabolism. In 17 obese hypertensive patients, we assessed CD11b expression on circulating monocytes, gene expression in adipose tissue biopsies, and obtained blood samples and adipose tissue and skeletal muscle microdialysis samples in the fasted state and during a glucose load. Patients were stratified into groups with higher and lower CD11b expression on monocytes. Expression of the macrophage marker CD68 was increased markedly in adipose tissue of subjects with higher CD11b expression. Although no differences in systemic insulin sensitivity were found between both groups, patients with higher peripheral CD11b expression showed a markedly augmented increase in dialysate glucose in adipose tissue during oral glucose tolerance testing and increased adipose tissue lipolysis as well. Our data demonstrate that human monocyte activation is associated with tissue-specific changes in glucose and lipid metabolism. These findings may be explained in part by monocyte/macrophage infiltration of adipose tissue, which appears to interfere with insulin responsiveness.