Impact of hypovitaminosis D and alfacalcidol therapy on survival of hemodialysis patients: results from the French ARNOS study.

BACKGROUND: In chronic kidney disease and dialysis patients, vitamin D deficiency is associated with mortality. In some observational studies, calcitriol analogue therapy was associated with a better survival rate in hemodialysis (HD) patients. The aim of this study was to determine the relationship between serum 25-hydroxyvitamin D (25-OHD) levels and alfacalcidol therapy with HD patients' outcomes. METHODS: We measured baseline 25-OHD levels using a cross-sectional analysis in 648 HD prevalent patients from the regional ARNOS French cohort. A 42-month survival analysis was applied according to serum 25-OHD level and calcitriol analogue therapy. RESULTS: The prevalence of 25-OHD insufficiency <30 ng/ml was high (73%), with only 22% taking native vitamin D supplementation. A baseline 25-OHD level above the median value (18 ng/ml) was associated with lower all-cause mortality [hazard ratio (HR), 0.73 (0.5-0.96); p = 0.02] after adjustment for age, gender, dialysis vintage, calcemia, phosphatemia, cardiovascular disease, and diabetes. Only in monovariate analysis was low-dose oral alfacalcidol therapy associated with a better survival rate in patients with and without 25-OHD deficiency [HR, 0.7 (0.5-0.92); p = 0.05]. CONCLUSIONS: Our study shows that, among prevalent HD patients, low 25-OHD levels affect mortality. Alfacalcidol therapy, especially in small doses, may provide compensation, but this needs to be further confirmed using prospective controlled studies comparing native and active vitamin D compounds.

Association between very low PTH levels and poor survival rates in haemodialysis patients: results from the French ARNOS cohort.

INTRODUCTION: A very low parathyroid hormone (PTH) level (VLPL) is associated with an increased risk of adynamic bone disease, vascular calcification, and mortality in haemodialysis (HD) patients. The aim of the study was to assess the frequency, the associated factors, and the prognosis of non-surgical VLPL in a cohort of prevalent HD patients. METHODS: In July 2005, a cross-sectional study was performed on the French ARNOS cohort in 1,348 prevalent HD patients from 24 dialysis centres in the Rhône-Alpes area. Patients with a baseline intact PTH level <50 pg/ml (VLPL, Group 1) and ≥ 50 pg/ml (Group 2) were compared and a 42-month survival analysis was performed. Patients with prevalent or incident parathyroidectomy were excluded. RESULTS: We studied 1,138 prevalent HD patients. As compared to patients of Group 2 (n = 1,019), patients with VLPL (Group 1, n = 119) had lower serum albumin levels (34.5 ± 5 vs. 36.4 ± 5 g/l, p < 0.0001), less protein intake (nPCR 0.99 ± 0.28 vs. 1.1 ± 0.28 g/kg/day, p = 0.01), higher calcaemia (2.30 ± 0.2 vs. 2.26 ± 0.2 mmol/l, p = 0.01) and were more frequently treated with calcium carbonate (67 vs. 54%, p < 0.001). Patients with VLPL had a higher mortality rate (HR: 1.4 (1.07-1.8), p = 0.006) after adjustment for age, gender, diabetes, and dialysis vintage. The odds ratios of mortality for patients with VLPL remained higher in all calcaemia and serum albumin quartiles. Only 3/119 patients in Group 1 did not receive any PTH-lowering therapies (i.e. calcium carbonate (67%), alfacalcidol (38%), cinacalcet (10.1%), and dialysate calcium ≥ 1.5 mmol/l (94%)). CONCLUSION: In this observational French cohort, VLPL was observed in 10% of prevalent HD patients and was associated with poor survival rates. An inadequate therapeutic strategy could be responsible for this observation. The real consequences of this iatrogenic adynamic bone disease remain hypothetical, but it may be related to the risk of developing vascular calcification. It is hypothesized that a more adequate strategy, using fewer PTH-lowering therapies in cases of VLPL, may help in improving the poor prognosis.

Changes in blood pressure and renal function following subtotal parathyroidectomy in renal transplant patients presenting with persistent hypercalcemic hyperparathyroidism.

The aims of this retrospective study were to assess renal function and blood pressure after subtotal parathyroidectomy (PTx) performed in renal transplant (RT) patients presenting with persistent hypercalcemic hyperparathyroidism. We identified 34 patients (group A) from our records who had undergone PTx between 1981 and 1994. Group A included 18 women and 16 men with a mean age of 45 +/- 12 years and a mean time on dialysis therapy of 102 +/- 59 months. Thirty of the patients received cyclosporine A (CsA) with or without steroids and/or azathioprine (AZA) and the remaining 4 patients received conventional therapy i.e. AZA and steroids. Twenty-three patients were treated for hypertension and 11 were normotensive. PTx was performed in 21 patients within the first year following renal transplantation and in 13 patients after this period. The study was divided into 3 periods: period 1-pre-PTx; period 2-the month following PTx; period 3-six months after PTx. Parameters were assessed for every patient in each of these periods. Results of group A were compared to those observed in 34 matched (control) RT patients (group B) who did not experience secondary hyperparathyroidism. PTx was associated with a significant decrease in parathyroid hormone (PTH) levels (45 +/- 8 pg/ml vs 338 +/- 54 pg/ml; p = 0.0002) and in calcemia (2.32 +/- 0.18 mmol/l vs 2.75 +/- 0.15 mmol/l; p = 0.0003) during period 3. However, we observed a significant increase in serum creatinine (124 +/- 30 mumol/l vs 110 +/- 25 mumol/l, p = 0.0016) in this group during period 3. Nevertheless, an increase in serum creatinine greater than 30% from baseline which still persisted six months after PTx was only observed in 8 patients (23.5%). There were more hypertensive patients in this latter subgroup (7 out of 8 i.e. 87.5%) than in the rest of the group (16 out of 26 i.e. 64.5%). Renal function impairment in group A was not related to pre-PTx SBP, DBP, MBP, calcemia, creatinine, CsA whole blood trough levels or PTH levels. Conversely, we did not observe significant changes in serum creatinine in the control group during the same periods. During period 2 there was a significant decrease in SBP (134 +/- 16 vs 140 +/- 16 mmHg; p = 0.046), DBP (81 +/- 9 vs 85 +/- 9 mmHg; p = 0.03) and MBP (99.5 +/- 10.5 vs 103.5 +/- 11 mmHg; p = 0.03) of group A. These differences persisted in period 3, with the exception of SBP, although they were no longer statistically significant. Following PTx we were able to discontinue (n = 4) or decrease (n = 4) antihypertensive drugs. In the control group baseline SBP, DBP and MBP were lower than in the PTx group, although the difference was statistically significant only for SBP (132.5 +/- 17 vs 140.5 +/- 16 mmHg; p = 0.05). During the study periods there was no significant changes in SBP, DBP or MBP in the control group. This study shows that RT patients with hypercalcemic hyperparathyroidism are often hypertensive (68%). Subtotal PTx is associated with a significant but transient decrease in SBP, DBP and MBP. Surprisingly we observe a significant and persistent increase in serum creatinine levels in 8 patients (23.5%), particularly in those presenting with hypertension before PTx. These results could reflect a dual effect of parathyroid hormone i.e. a balance between a vasodilating and hypertensive effect.