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Published ahead of print on March 5, 2008
Clin J Am Soc Nephrol 3: 794-799, 2008
© 2008 American Society of Nephrology
doi: 10.2215/CJN.04150907
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Mineral Metabolism and Bone Disease

Does Vitamin D Receptor and Calcium Receptor Activation Therapy Play a Role in the Histopathologic Alterations of Parathyroid Glands in Refractory Uremic Hyperparathyroidism?

Carlo Lomonte*, Luigi Vernaglione{dagger}, Domenico Chimienti*, Andrea Bruno*, Savino Cocola*, Annalisa Teutonico*, Francesco Cazzato*, and Carlo Basile*

* Division of Nephrology, Miulli General Hospital, Acquaviva delle Fonti, and {dagger} Division of Nephrology, Hospital of Manduria, Manduria, Italy

Correspondence: Dr. Carlo Basile, Via C. Battisti 192, 74100 Taranto, Italy. Phone: +39-80-3054205; Fax: +39-080-762165; E-mail: basile.miulli{at}libero.it


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 Disclosures
 References
 
Background and objectives: Vitamin D receptor activation by vitamin D sterols and calcium-sensing receptor stimulation by cinacalcet are the most powerful treatments of secondary hyperparathyroidism. This study was aimed to assess a possible association between histopathologic changes of parathyroid tissue and treatment modality.

Design, setting, participants, & measurements: Studies were performed on 82 parathyroids of 22 adult white hemodialysis patients undergoing first parathyroidectomy. The type of hyperplasia and the distribution of chief and oxyphil cells, expressed as oxyphil/chief cell ratio, were assessed. Three groups could be studied according to treatment modality: group A consisted of 6 patients who were treated with cinacalcet, intravenous calcitriol, and phosphate binders; group B consisted of 6 patients who were treated with intravenous calcitriol and phosphate binders, and group C consisted of 10 patients who were treated with phosphate binders alone.

Results: Sixty-eight (82.9%) out of 82 glands removed showed nodular hyperplasia. It was more frequent in groups A and B than in group C. A stepwise forward logistic regression model showed that the probability of nodular hyperplasia was higher in patients who were on calcitriol and/or cinacalcet therapy, in female gender and in patients with a higher body mass index. Oxyphil/chief cell ratio also was significantly different among the three groups. Cinacalcet treatment was the only predictor of this ratio.

Conclusions: An association was found between calcitriol and/or cinacalcet therapy and a high prevalence of nodular hyperplasia, and between cinacalcet therapy and high oxyphil/chief cell ratio. The meaning of the observed associations remains uncertain.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusions
 Disclosures
 References
 
A large number of patients with uremia develop secondary hyperparathyroidism (SHPT) (1,2). Receptor therapy is the most adequate treatment of SHPT: Calcitriol and vitamin D analogues act on vitamin D receptors (VDR) in the intestine to increase calcium (Ca) absorption and on VDR in parathyroid cells to inhibit parathyroid hormone (PTH) mRNA synthesis (3); a cell surface receptor located on parathyroid cells, the calcium-sensing receptor (CaR), has been recognized as the primary mechanism that mediates the effects of ionized calcium (Ca2+) on PTH secretion (4,5). The CaR seems to play a key role in the excessive cell proliferation that occurs in parathyroid hyperplasia (5). Drugs that mimic or potentiate the action of Ca2+ at this receptor, calcimimetics, have become available for treatment of dialysis patients who are affected by SHPT (2,6–8); however, in a minority of them, parathyroid overfunction persists, progressively escapes medical control, and eventually becomes extremely severe, requiring surgical parathyroidectomy (PTx). In a time when effective treatment strategies are increasingly available, PTx could be viewed as indicating a medical failure. The reasons for the failure of response of parathyroid glands to the wide and powerful therapeutic armamentarium (namely receptor therapy) that is available must be looked for in several domains, such as intrinsic factors linked to the large volume of the glands themselves with nodular hyperplasia (NH), a reduced density of VDR and CaR, and a persistent hyperphosphatemia (1,2). The main purpose of this study was to assess in hemodialysis patients who were affected by refractory SHPT whether an association exists between the histopathologic alterations of parathyroid glands (NH versus diffuse hyperplasia [DH] and the expression of cell phenotypes) and the treatments with intravenous calcitriol and/or cinacalcet and/or phosphate (P) binders.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusions
 Disclosures
 References
 
Study Population
Twenty-two consecutive adult white hemodialysis patients who were referred for first PTx to our surgery department by six dialysis units of our region in the past 2 yr, from June 2005 to May 2007, were evaluated. The indications for treating or not with calcitriol and/or cinacalcet and the treatment protocols were due exclusively to the different policies of the six dialysis units; furthermore, the indications for PTx had been a matter of debate between the nephrologists of the six dialysis units and the surgeons of our hospital, exclusively. The indications for the surgical correction of SHPT in these patients were the presence of one or more of the following clinical and/or laboratory data: Pruritis not responsive to any treatment (seven patients), persistent hyperphosphatemia (eight patients), persistent serum immunoreactive intact PTH (iPTH) levels >800 pg/ml (22 patients), severe radiologic signs of osteitis fibrosa (12 patients), and parathyroid gland size >1 cm (by means of ultrasound imaging; 18 patients). The patients were subdivided into three groups according to the treatment of SHPT: Group A consisted of six patients who were treated with cinacalcet, intravenous calcitriol and P binders, group B consisted of six patients who were treated with intravenous calcitriol and P binders, and group C consisted of 10 patients who were treated with P binders only.

Body mass index (BMI) was defined as the ratio body weight (kg)/height2 (m). The ranges of a normal BMI are 18 to 24 kg/m2 for women and 19 to 25 kg/m2 for men.

Surgical Procedures
Subtotal PTx (seven eighths) was performed on 11 patients, total PTx with no forearm implantation was performed on five patients, and three glands were detected and removed in six patients; thus, the total number of pathologic glands removed was 82 of the potential 88. All patients had cervical thymectomy.

Histologic Studies of the Parathyroid Glands
Each gland removed was measured with a sterile ruler, and its dimensions were recorded. The weight (g) was estimated as already reported (9). Histologic studies of the parathyroid glands with light microscopy were performed by the same pathologist on seven serial sections of the glands in a blinded manner.

Hyperplasia was classified as DH or NH. DH was defined as an increased number of parenchymal cells with normal lobular structures, and NH was defined as at least one well-circumscribed, encapsulated, and virtually fat cell–free accumulation of parenchymal cells (10). Such nodules are composed of more tightly packed cells featuring larger nuclei and a greater prevalence of cell-cycle markers, oxyphil cells, and acinar cells (9,11,12). Besides defining the type of hyperplasia, a semiquantitative analysis was performed to assess the prevalence of the two major cell populations, chief and oxyphil cells; it was expressed as oxyphil/chief cell ratio (13).

Biochemical Analysis
Serum levels of albumin, immunoreactive iPTH, alkaline phosphatase, Ca, and P were determined at the PTx time point. Serum iPTH levels were measured also on the third post-PTx day. Serum concentrations of albumin, Ca, P, and alkaline phosphatase were measured by routine automated methods. Serum concentrations of iPTH were measured by chemiluminescence immunoassay (Nichols, San Juan Capistrano, CA; normal range 10 to 65 pg/ml).

Statistical Analyses
The comparisons of the continuous variables among groups were made by means of the one-way ANOVA with the Bonferroni post hoc test and by means of the t test for unpaired data, whereas the {chi}2 test was used for the distributions among groups of the categorical variables. A stepwise forward logistic regression model was created, based on the Wald statistics as removal criteria, with histology as dependent variable (DH = 0, NH = 1) and gender (female = 1, male = 2), treatment group (A = 0, B = 1, C = 2), categorized BMI (≤25 kg/m2 = 1, >25 kg/m2 = 2), and categorized gland weight (≤1.5 g = 1, >1.5 = 2) as independent ones. Furthermore, a stepwise multiple regression analysis model was built to evaluate the variables that were significantly related to the oxyphil/chief cell ratio. In this model, the ratio was assumed as a dependent variable, whereas the laboratory values, demographic and clinical parameters, presence/absence of therapy with cinacalcet, intravenous calcitriol, P binders, and the estimated glandular weight were considered as independent variables.

All statistical inferences were performed with the use of the SPSS software package, version 11.0 (SPSS, Chicago, IL). Data were expressed as means (SD) or percentage of total, and values of P < 0.05 were assumed as statistically significant.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusions
 Disclosures
 References
 
Table 1 shows the demographic, clinical, and biochemical characteristics of the entire group of 22 patients. Table 2 shows the dosage and the duration of treatment with cinacalcet and intravenous calcitriol (group A) and intravenous calcitriol only (group B).


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  		Table 1. Demographic, clinical, and biochemical characteristics of the 22 patientsa

 

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  		Table 2. Dosage and duration of treatment with cinacalcet and intravenous calcitriol (group A) and intravenous calcitriol only (group B)a

 
No statistically significant difference was found when comparing the demographic, clinical, and biochemical characteristics of the three groups of patients (Table 3). The total number of pathologic glands removed was 82: 23 were ablated in the six patients of group A, 22 in the six patients of group B, and 37 in the 10 patients of group C (Table 3). Sixty-eight glands showed NH (82.9%). NH was more frequent in groups A (22 [95.6%] of 23 parathyroids) and B (21 [95.5%] of 22 parathyroids) than in group C (25 [67.6%] of 37 parathyroids; P < 0.05; Table 3).


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  		Table 3. Comparison of histologic and biochemical data among the three groups of patientsa

 
The estimated weight of the parathyroids (expressed as the mean weight of individual parathyroid glands from each patient) was not significantly different when comparing the glands of the three groups (Table 3). Furthermore, the mean weight of the 68 glands showing NH was 1.45 ± 0.3 g, whereas that of the 14 glands showing DH was 1.26 ± 0.4 g. The difference was not statistically significant.

Oxyphil/chief cell ratio was significantly different when comparing the glands of the three groups (0.65 ± 0.3 in group A, 0.36 ± 0.4 in group B, 0.19 ± 0.1 in group C; P < 0.005; Table 3). Furthermore, Bonferroni post hoc test demonstrated that a significant difference existed specifically between groups A and C (P < 0.004; Table 3).

Histopathology of parathyroid glands (NH versus DH) was significantly predicted by BMI (patients with BMI >25 kg/m2 had a probability 5.53 times higher than patients with BMI ≤25 of getting NH; P < 0.047), by the treatment groups (patients of group A had a probability 0.29 times higher than patients of group C and 0.14 times higher than patients of group B of getting NH; P < 0.007), and by gender (female patients had a probability 0.079 times higher than male patients of group C of getting NH; P < 0.031; Table 4).


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  		Table 4. Output of the logistic regression model with parathyroid histology as dependent variable

 
The best fitted stepwise multiple regression analysis model (R2 = 0.515; P = 0.0001) demonstrated that cinacalcet treatment (B = 0.362; SE = 2.586; P = 0.023; 95% confidence interval 0.060 to 0.665) was the only predictor of the oxyphil/chief cell ratio. All of the other variables tested in the regression model resulted in no association with the ratio (Table 5).


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  		Table 5. Output of the multiple regression model with the oxyphil/chief cell ratio as dependent variablea

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusions
 Disclosures
 References
 
As a premise to the discussion, we stress that we had the virtually unique opportunity of examining parathyroid glands of uremic patients who had never been exposed to calcitriol and/or cinacalcet in the attempt to treat SHPT. This opportunity was given by the peculiar type of recruitment of these patients for PTx, as already anticipated in the Materials and Methods section. Thus, patients of group C look like an experimental model of natural history of SHPT not exposed at all to any receptor therapy.

Our data show the following:

  1. a statistically significant difference in the prevalence of NH when comparing patients who were treated with P binders only with patients who were treated with the receptor therapy (intravenous calcitriol and cinacalcet, either as monotherapy or in combination); furthermore, a stepwise forward logistic regression model showed that NH was significantly predicted by the treatment groups, the probability of NH being higher in patients who were treated with the receptor therapy (intravenous calcitriol and cinacalcet, either as monotherapy or in combination)
  2. a statistically significant increase of oxyphil/chief cell ratio from 0.19 of the patients who were treated with P binders only to 0.65 of the patients who were treated with the combined therapy intravenous calcitriol and cinacalcet; however, the predominant role in this case is played by cinacalcet, as shown by the stepwise multiple regression analysis model
  3. a statistically significant increase of probability of NH in female gender and in patients with a higher BMI

As far as item 1 is concerned, our data in a new set of patients confirm our previous findings that calcitriol pulse therapy was associated with an increase in the prevalence of NH of parathyroid glands (11). Our data show that also cinacalcet therapy is associated with a very high prevalence of NH when combined with intravenous calcitriol; however, when trying to determine the possible contribution of cinacalcet and/or calcitriol in the high prevalence of NH, a logical reasoning leads us to argue that the main role should be played only by intravenous calcitriol for the following reasons: (1) The latter is associated with a prevalence of NH of 95.5% (group B), whereas the addition of cinacalcet to calcitriol treatment does not seem to modify this prevalence (95.6%, group A); (2) calcitriol treatment preceded by many months the prescription of cinacalcet in all patients of group A; consequently, it is logical to think that the high prevalence of NH observed in group B (calcitriol treatment) would be observed also in group A at the moment of adding cinacalcet to calcitriol. It is obvious to say that logical evidence does not constitute scientific evidence. Thus, it is possible that also cinacalcet treatment per se might be associated with a high prevalence of NH. The only way to demonstrate the latter issue is to study patients who are treated with cinacalcet only. As well known, calcitriol has an antiproliferative action on many target tissues, including parathyroid glands; however, a secondary adverse effect at the pharmacologic doses used could be produced because of the antiproliferative action of calcitriol: The development of cell clones having functional autonomy in hyperplastic parathyroid gland. In that way, the prevalence of NH increases from 67.6% of group C to 95.5% of group B. The reasons for this paradoxic adverse effect could be looked for in the frequently occurring delay in starting calcitriol treatment, in a discontinuous instead of a continuous strategy of treatment, and in the use of pharmacologic instead of physiologic doses, as it should occur in every endocrinologic substitution therapy; however, two other possibilities should be considered for explaining the different prevalence of NH among the three groups: (a) A selection process could have occurred in groups A and B, which received calcitriol, in which calcitriol-sensitive parathyroid glands responded to treatment and less responsive glands affected by NH did not respond, resulting in a preponderance of glands with NH at the time of PTx. In this scenario, calcitriol treatment could not induce NH but could select for the presence of NH because of the decreased responsiveness to calcitriol associated with NH; and (b) the hypothesis cannot be excluded, despite that the three groups were similar at the time of surgery as far as serum Ca, P, and iPTH were similar, that group A patients were affected by the most severe form of SHPT (association of three drugs) when compared with group C patients (one-drug regimen). In other words, patients who were treated unsuccessfully with calcitriol could be those who presented the most aggressive histopathologic patterns of parathyroid hyperplasia already before starting calcitriol treatment.

The novel finding shown by item 2 is that cinacalcet is associated with a statistically significant increase in the oxyphil/chief cell ratio. Also in this case, when trying to determine the possible contribution of cinacalcet and/or calcitriol to the high oxyphil/chief cell ratio shown by group A patients, a logical reasoning leads us to argue that the main role should be played only by cinacalcet for the following reason: Calcitriol treatment preceded by many months the prescription of cinacalcet in all patients of group A; consequently, it is logical to think that the ratio of 0.36 observed in group B patients (calcitriol treatment) would be observed also in group A patients at the moment of addition of cinacalcet to calcitriol; this ratio went up to 0.65 after the introduction of cinacalcet therapy. Furthermore, a stepwise multiple regression analysis showed unequivocally that the predominant role was played by cinacalcet. We have to keep in mind three background points: (a) We and others have shown that oxyphil cells are well represented in NH (9,11). Recently, it was shown that oxyphil cells produce actively PTH-related protein and that oxyphil cells have a level of proliferation lower than that of chief cells (14); PTH-related protein could act through an autocrine/paracrine mechanism to regulate proliferation and differentiation of parathyroid cells (14), favoring their metaplastic change into the oxyphil phenotype (14,15); (b) CaR are expressed in many tissues, with the highest density being found in the chief cells of the parathyroid glands (2); (c) furthermore, very recently, it was also shown that CaR activation by the calcimimetic R-568 accelerates chief cell death, probably through an apoptotic mechanism in uremic rats in vitro (16). Thus, the hypothesis could be made that cinacalcet counteracts SHPT mainly through two synergistically operating mechanisms: An antiproliferative and a proapoptotic action on chief cells. In this way, the oxyphil/chief cell ratio increases, probably because of a more significant decrease in the absolute number of chief cells than because of an increase in the absolute number of oxyphil cells. The paradox that a seemingly beneficial effect, such as the increase in the oxyphil/chief cell ratio in the cinacalcet treatment group, was not able to preserve these patients from PTx could be explained by the short cinacalcet treatment time (3.3 ± 1.8 mo; range 2 to 7 mo) with a probably inadequate dosage titration in some cases and/or by the fact that the start of cinacalcet treatment was too delayed.

As far as item 3 is concerned, our data expand previous findings of other authors that female gender favors the development of refractory SHPT and the need for PTx (17–19). They also confirm our previous findings that female gender (10,20) and BMI were associated with an increased risk for NH of parathyroid glands (10). We demonstrated in that prospective study that a higher BMI was associated with a larger body burden of P in female hemodialysis patients, influencing by that way the severity of SHPT (10). Why female hemodialysis patients with high BMI may have a larger P body burden is a matter of speculation that we largely discussed in that article (10).


   Conclusions
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
Disclosures
 References
 
The development of a refractory SHPT continues to represent an important problem because of the frequent need for PTx. We found an association between calcitriol and/or cinacalcet therapy and a high prevalence of nodular type parathyroid hyperplasia and between cinacalcet therapy and high oxyphil/chief cell ratio. The meaning of the observed association between treatment modality and histopathologic changes of parathyroid tissue in refractory SHPT remains uncertain. Further prospective studies are required to confirm these findings and understand the underlying mechanisms.


   Disclosures
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 Disclosures
References
 
None.


   Footnotes
 
Published online ahead of print. Publication date available at www.cjasn.org.

Received September 28, 2007. Accepted January 10, 2008.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 Disclosures
 References
 

  1. Rodriguez M, Canalejo A, Garfia B, Aguilera E, Almaden Y: Pathogenesis of refractory secondary hyperparathyroidism. Kidney Int61 :S155 –S160,2002[CrossRef]
  2. Drüeke T, Martin D, Rodriguez M: Can calcimimetics inhibit parathyroid hyperplasia? Evidence from preclinical studies. Nephrol Dial Transplant22 :1828 –1839,2007[Free Full Text]
  3. Dusso AS, Brown AJ, Slatopolsky E: Vitamin D. Am J Physiol Renal Physiol289 :F8 –F28,2005[Abstract/Free Full Text]
  4. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC: Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature366 :575 –580,1993[CrossRef][Medline]
  5. Brown EM, Mac Leod RJ: Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev81 :239 –297,2001[Abstract/Free Full Text]
  6. de Francisco AL: Cinacalcet HCl: A novel therapeutic for hyperparathyroidism. Expert Opin Pharmacother6 :441 –452,2005[CrossRef][Medline]
  7. Lomonte C, Antonelli M, Losurdo N, Marchio G, Giammaria B, Basile C: Cinacalcet is effective in relapses of secondary hyperparathyroidism after parathyroidectomy. Nephrol Dial Transplant22 :2056 –2062,2007[Abstract/Free Full Text]
  8. Rodriguez M, Nemeth E, Martin D: The calcium-sensing receptor: A key factor in the pathogenesis of secondary hyperparathyroidism. Am J Physiol Renal Physiol288 :F253 –F264,2005[Abstract/Free Full Text]
  9. Custódio MR, Montenegro F, Costa AF, dos Reis LM, Buchpiguel CA, Oliveira SG, Noronha IL, Moysés RM, Jorgetti V: MIBI scintigraphy, indicators of cell proliferation and histology of parathyroid glands in uraemic patients. Nephrol Dial Transplant20 :1898 –1903,2005[Abstract/Free Full Text]
  10. Basile C, Lomonte C, Vernaglione L, Casucci F, Chimienti D, Bruno A, Cocola S, Verrelli EA, Cazzato F: A high body mass index and female gender are associated with an increased risk of nodular hyperplasia of parathyroid glands in chronic uremia. Nephrol Dial Transplant21 :968 –974,2006[Abstract/Free Full Text]
  11. Lomonte C, Martino R, Selvaggiolo M, Bona RM, Cazzato F, Milano R, Chiarulli G, Basile C: Calcitriol pulse therapy and histology of parathyroid glands in hemodialysis patients. J Nephrol16 :716 –720,2003[Medline]
  12. Drüeke TB: Cell biology of parathyroid gland hyperplasia in chronic renal failure. J Am Soc Nephrol11 :1141 –1152,2000[Free Full Text]
  13. Szende B, Farid P, Végsõ G, Perner F, Kopper L: Apoptosis and P53, Bcl-2 and Bax gene expression in parathyroid glands of patients with hyperparathyroidism. Pathol Oncol Res10 :98 –103,2004[Medline]
  14. Matsushita H, Hara M, Endo Y, Shishiba Y, Hara S, Ubara Y, Nakazawa H, Suzuki N, Kawaminami K, Kido T, Li Q, Grimelius L: Proliferation of parathyroid cells negatively correlates with expression of parathyroid hormone-related protein in secondary parathyroid hyperplasia. Kidney Int55 :130 –138,1999[CrossRef][Medline]
  15. Kitazawa R, Kitazawa S, Maeda S, Kobayashi A: Expression of parathyroid hormone-related protein (PTHrP) in parathyroid tissue under normal and pathological conditions. Histol Histopathol17 :179 –184,2002[Medline]
  16. Mizobuchi M, Ogata H, Hatamura I, Saji F, Koiwa F, Kinugasa E, Koshikawa S, Akizawa T: Activation of calcium-sensing receptor accelerates apoptosis in hyperplastic parathyroid glands. Biochem Biophys Res Commun362 :11 –16,2007[CrossRef][Medline]
  17. Almaden Y, Felsenfeld AJ, Rodriguez M, Cañadillas S, Luque F, Bas A, Bravo J, Torregrosa V, Palma A, Ramos B, Sanchez C, Martin-Malo A, Canalejo A: Proliferation in hyperplastic human and normal rat parathyroid glands: Role of phosphate, calcitriol, and gender. Kidney Int64 :2311 –2317,2003[CrossRef][Medline]
  18. Malberti F, Marcelli D, Conte F, Limido A, Spotti D, Locatelli F: Parathyroidectomy in patients on renal replacement therapy: An epidemiologic study. J Am Soc Nephrol12 :1242 –1248,2001[Abstract/Free Full Text]
  19. Foley RN, Li S, Liu J, Gilbertson DT, Chen S-C, Collins AJ: The fall and rise of parathyroidectomy in U.S. hemodialysis patients, 1992 to 2002. J Am Soc Nephrol16 :210 –218,2005[Abstract/Free Full Text]
  20. Lomonte C, Cazzato F, Casucci F, Chimienti D, Bruno A, Cocola S, Antonicelli Verrelli E, Basile C: Female hemodialysis patients have an increased risk of nodular hyperplasia of parathyroid glands. J Nephrol18 :92 –95,2005[Medline]



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