A high body mass index and female gender are associated with an increased risk of nodular hyperplasia of parathyroid glands in chronic uraemia.

BACKGROUND: A persistent hyperphosphataemia represents one of the most important factors in the development of secondary hyperparathyroidism (sHPTH). The present prospective study was designed in order to test the hypothesis that a higher body mass index (BMI) may predispose to a larger body burden of phosphate (P), influencing by that way the severity of sHPTH. METHODS: Histological studies were performed on 168 parathyroid glands of 42 consecutive adult Caucasian haemodialysis patients (20 males and 22 females) referred for first parathyroidectomy (PTx): each parathyroid gland was graded as 0, when only or mainly diffuse hyperplasia was found, or as 1, when only or mainly nodular hyperplasia was found. Thus, parathyroid histology was scored on a 5-point scale: 0 = diffuse hyperplasia in the four glands; 1 = nodular hyperplasia in one gland; 2 = nodular hyperplasia in two glands; 3 = nodular hyperplasia in three glands; 4 = nodular hyperplasia in the four glands. For sake of simplicity, the three less severe histological gradings, i.e. scores 0-2 were grouped together and indicated as score group 2. RESULTS: The distribution of the patients was the following: 28.6% were in the score group 2, 23.8% in the score group 3 and 47.6% in the score group 4 (20 patients, 14 of whom were females). The output of the one-way ANOVA with the histological scores as grouping variable and age, dialysis duration, BMI and pre-PTx serum iPTH, alkaline phosphatase (ALP), calcium (Ca) and P as predictors showed that only BMI was different among the three histological scores (P = 0.001). By stratifying the analysis by gender, the relationship between BMI and histological scores was confirmed only in females (P = 0.006). The stratification of the entire cohort into two groups according to the cut-off value of BMI = 25 kg/m(2) showed that: (i) score 4 was more prevalent in the high-BMI group and score 2 in the normal-BMI group (P = 0.01); (ii) female gender was more represented in the high-BMI group (12 out of 18 patients, P = 0.04); and (iii) the pre-PTx serum P levels were significantly higher in the high-BMI group (P = 0.008). The output of the linear multiple regression analysis with pre-PTx serum P as dependent variable and BMI, pre-PTx serum ALP and Ca as independent variables (selected according to the statistical significance in the bivariate correlations) showed that only serum Ca and BMI were statistically significant predictors of serum P levels. CONCLUSIONS: A high BMI and female gender are associated with an increased risk of nodular hyperplasia of parathyroid glands in adult Caucasian haemodialysis patients. The two risk factors, above all if combined in the same patient, appear to predispose to a larger body burden of P, increasing by that way the severity of sHPTH.

Female hemodialysis patients have an increased risk of nodular hyperplasia of parathyroid glands.

BACKGROUND: An association between female gender and more aggressive patterns of secondary hyper-parathyroidism (sHPTH) has been suggested: an increased incidence of refractory sHPTH seems evident in females; therefore, necessitating parathyroidectomy (PTx). METHODS: This study aimed to verify the existence of such an association and secondly to evaluate the impact of female gen-der on parathyroid gland histology. Therefore, a retrospective study was conducted on 67 patients who underwent first PTx (either total or subtotal) in our hospital from 1999-2003. Out of these patients, we selected 55 (28 males, 27 females, mean age 50.8 +/- 14.7 SD yrs, dialysis duration 109.2 +/- 62.4 months) in whom all four parathyroid glands were identified and removed. Serum levels of immunoreactive intact parathyroid hormone (iPTH), alkaline phosphatase, calcium and phosphate were determined at the PTx time point. The same pathologist performed the histological studies of the parathyroid glands on seven serial sections of the glands. Gland hyperplasia was classified as (1) exclusively diffuse (EDH) when only diffuse hyperplasia was found in the four glands; (2) exclusively nodular (ENH) when only nodular hyper-plasia was found in the four glands; (3) diffuse/nodular (D/NH), in which the four glands showed varying degrees of evolution towards both nodular and diffuse hyperplasia. RESULTS: EDH was found in 13 patients with a prevalence of males (11/13; 84.6%); ENH was found in 23 patients with a prevalence of females (15/23; 65.2%); D/NH was found in 19 patients with a similar prevalence between females and males (10 females and 9 males). The difference in the male/female prevalence among the three groups was statistically significant (chi2 test, p=0.015). Serum calcium was significantly higher in the ENH group (one-way analysis of variance, p=0.009). No difference was found among the three groups as far as age, dialysis duration, serum levels of iPTH, alkaline phosphatase and phosphate were concerned. CONCLUSIONS: Female gender is associated with more aggressive histological sHPTH patterns; this association seems to suggest that female gender predisposes to monoclonal proliferation of parathyroid glands in chronic uremia.

Are low plasma levels of 25-(OH)vitamin D a major risk factor for hyperparathyroidism independent of calcitriol in renal transplant patients?

BACKGROUND: Recently, some studies have emphasized the role of plasma 25-(OH)vitamin D (25OHD) levels in mineral metabolism dysregulation in chronic kidney diseases (CKDs). However, to date little attention has been paid to 25OHD metabolism abnormalities after renal transplantation (Tx). This cross-sectional study aimed to focus on its role in mineral metabolism dysregulation in functioning Tx. METHODS: Twenty-eight out of 75 Caucasian Tx patients were selected following strict inclusion and exclusion criteria. Two blood samples were effected at the end of the winter for the measurements of plasma 25OHD and calcitriol levels. Serum creatinine (Cr), alkaline phosphatase (SAP), immunoreactive intact parathyroid hormone (PTH), electrolytes and 24-hr proteinuria were also determined. The Kolmogorov-Smirnov test was used to evaluate the data distribution: serum Cr, Cr clearance, dialysis duration and PTH levels were non-normally distributed and were log-transformed. Values of p<=0.01 were assumed as statistically significant. RESULTS: Median serum Cr and PTH levels were, respectively, 1.0 mg/dL and 90.0 pg/mL (range 27-420; normal range 10-65); most of our Tx patients (78.5%) had serum PTH levels above the upper limit of normal values. Mean plasma 25OHD concentration was 19.6 +/- 8.9 SD ng/mL (range: 6-36). None had levels <5 ng/mL (severe deficiency); 10 patients (35.7%) had mild deficiency (5-15 ng/mL); 14 patients (50%) had vitamin D insufficiency (16-30 ng/mL); and only four patients (14.3%) had target levels (>30 ng/mL). Mean plasma calcitriol levels were 69.7 +/- 19.0 pg/mL (range 47-105; normal range 35-85). They were not significantly correlated to plasma 25OHD levels. Proteinuria (292.6 +/- 147.0 mg/24 hr) inversely correlated to plasma 25OHD levels (r=-0.480; p<0.01). The bivariate correlation analysis between logPTH and the other parameters showed a significant correlation for SAP (r=0.494; p=0.008), plasma 25OHD levels (r=-0.442; p=0.01), proteinuria (r=0.452; p=0.01), log serum Cr (r=0.551; p=0.002) and log Cr clearance (r=-0.534; p=0.003). The other parameters did not correlate significantly with logPTH, notably plasma calcitriol and serum phosphate levels. Only the parameters significantly correlated to logPTH in the bivariate correlation analysis were included in the back stepwise multiple linear regression analysis as independent variables (model: p<0.0001; R2=0.54): among them, only plasma 25OHD levels (Beta=-0.486; p=0.001) and log serum Cr levels (Beta=0.589; p=0.0002) were the dependent variable logPTH predictors. CONCLUSIONS: This cross-sectional study demonstrated that plasma calcitriol levels in a highly selected group of Tx patients were normal and not significantly correlated to either plasma 25OHD or serum PTH levels. Most patients (85.7%) had plasma 25OHD levels below the target value of 30 ng/mL; the latter were inversely correlated with serum PTH levels. Therefore, our study strengthens the suggestion that low plasma 25OHD levels are a major risk factor for secondary hyperparathyroidism (sHPTH) in Tx patients and stresses the importance of monitoring these patients.