Introduction: Emerging therapies derived from the molecular pathogenesis of secondary hyperparathyroidism in ESRD patients

2002 ◽  
Vol 9 (3) ◽  
pp. 153-158 ◽  
Author(s):  
L. Darryl Quarles
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Molecular Pathogenesis ◽  
Emerging Therapies ◽  
Esrd Patients

scholarly journals Use of Percutaneous Ethanol Injection Therapy for Recurrent Secondary Hyperparathyroidism after Subtotal Parathyroidectomy

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Walter G. Douthat ◽  
Gabriela Cardozo ◽  
Gabriela Garay ◽  
Santiago Orozco ◽  
Carlos Chiurchiu ◽  
...  
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Therapeutic Option ◽  
Percutaneous Ethanol Injection ◽  
Injection Therapy ◽  
Subtotal Parathyroidectomy ◽  
Ethanol Injection ◽  
Percutaneous Ethanol Injection Therapy ◽  
Calcium Phosphorus ◽  
Ethanol Injection Therapy ◽  
Esrd Patients

We evaluated the efficacy of percutaneous ethanol injection therapy (PEIT) as a therapeutic option for recurrence of secondary hyperparathyroidism after subtotal parathyroidectomy in ESRD patients. Six patients underwent PEIT. A mean of 1.3 ± 0.8 ethanol injections was performed. Nodular volume was 1.5 ± 1.7 cm3, and 2.8 ± 2.8 cm3of ethanol was injected per patient. After ethanol injection PTH decreased significantly (1897 ± 754 to 549 ± 863 pg/mL (P<.01)). There was also a reduction in serum calcium, phosphorus and calcium-phosphorus product. A positive and significant correlation was found between nodular volume with ethanol injected and time from parathyroidectomy. Only one patient required hospitalization due to severe hypocalcaemia. In other two cases, local discomfort and temporary mild dysphonia were registered. PEIT is an effective treatment to control recurrences of secondary hyperparathyroidism postsubtotal parathyroidectomy.

Use of 2MD, a Novel Oral Calcitriol Analog, in Hemodialysis Patients with Secondary Hyperparathyroidism

2016 ◽  
Vol 43 (3) ◽  
pp. 213-220 ◽  
Author(s):  
Richa Pandey ◽  
Julia Zella ◽  
Margaret Clagett-Dame ◽  
Lori A. Plum ◽  
Hector F. DeLuca ◽  
...  
Keyword(s):  
Secondary Hyperparathyroidism ◽  
No Reduction ◽  
Hemodialysis Patients ◽  
Dihydroxyvitamin D3 ◽  
Future Studies ◽  
Receptor Activator ◽  
Dose Levels ◽  
Oral Doses ◽  
Esrd Patients

Background: Use of existing therapies for secondary hyperparathyroidism (SHPT), such as calcitriol or paricalcitol, is frequently limited by the development of hypercalcemia. 2-Methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD; DP001) is a novel and a more potent vitamin D receptor activator (VDRA) that more selectively localizes in the parathyroid gland, and has a wider therapeutic margin in the uremic rat model than calcitriol and paricalcitol. Design, Setting, Participants, and Measurements: Hemodialysis patients were enrolled and dosed with 110, 220, 330, 440, or 550 ng of 2MD orally thrice weekly for 4 weeks. Responders were defined as patients having a ≥30% reduction in parathyroid hormone (PTH) from baseline, and were assessed at weeks 2 and 4. Results: Of 31 patients recruited, 24 completed the 4-week treatment. There was little or no reduction in PTH in the 110 and 220 ng dose cohorts. Higher dose cohorts had greater PTH suppression with more than half the patients in the 440 and 550 ng dose cohorts considered responders (≥30% PTH reduction from baseline). None had oversuppression of PTH or hypercalcemia (corrected serum calcium >10.6 mg/dl). Plasma drug concentration increased with increasing dose, and all responders achieved a 2MD concentration of ≥1.5 pg/ml. All dose levels of 2MD were well tolerated without safety concerns. Conclusions: In hemodialysis patients with SHPT, 2MD, at thrice weekly oral doses of 440 and 550 ng, is well tolerated and effectively suppresses PTH without hypercalcemia. Future studies are needed to study the long-term implications of treating ESRD patients with this novel VDRA.

scholarly journals Molecular patterns of diffuse and nodular parathyroid hyperplasia in long-term hemodialysis

2016 ◽  
Vol 311 (4) ◽  
pp. E720-E729 ◽  
Author(s):  
Irena Týcová ◽  
Sylvie Dusilová Sulková ◽  
Jitka Štěpánková ◽  
Zdeněk Krejčík ◽  
Michaela Dostálová Merkerová ◽  
...  
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Molecular Mechanisms ◽  
Gene Annotation ◽  
Parathyroid Tissue ◽  
Enrichment Analysis ◽  
Hemodialysis Patients ◽  
Parathyroid Hyperplasia ◽  
Rt Pcr ◽  
Nodular Hyperplasia ◽  
Esrd Patients

Secondary hyperparathyroidism is a well-known complication of end-stage renal disease (ESRD). Both nodular and diffuse parathyroid hyperplasia occur in ESRD patients. However, their distinct molecular mechanisms remain poorly understood. Parathyroid tissue obtained from ESRD patients who had undergone parathyroidectomy was used for Illumina transcriptome screening and subsequently for discriminatory gene analysis, pathway mapping, and gene annotation enrichment analysis. Results were further validated using quantitative RT-PCR on the independent larger cohort. Microarray screening proved homogeneity of gene transcripts in hemodialysis patients compared with the transplant cohort and primary hyperparathyroidism; therefore, further experiments were performed in hemodialysis patients only. Enrichment analysis conducted on 485 differentially expressed genes between nodular and diffuse parathyroid hyperplasia revealed highly significant differences in Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genomes database in ribosome structure ( P = 3.70 × 10−18). Next, quantitative RT-PCR validation of the top differently expressed genes from microarray analysis proved higher expression of RAN guanine nucleotide release factor (RANGRF; P < 0.001), calcyclin-binding protein ( CACYBP; P < 0.05), and exocyst complex component 8 ( EXOC8; P < 0.05) and lower expression of peptidylprolyl cis/ trans-isomerase and NIMA-interacting 1 (PIN1; P < 0.01) mRNA in nodular hyperplasia. Multivariate analysis revealed higher RANGRF and lower PIN1 expression along with parathyroid weight to be associated with nodular hyperplasia. In conclusion, our study suggests the RANGRF transcript, which controls RNA metabolism, to be likely involved in pathways associated with the switch to nodular parathyroid growth. This transcript, along with PIN1 transcript, which influences parathyroid hormone secretion, may represent new therapeutical targets to cure secondary hyperparathyroidism.

scholarly journals Race Is a Major Determinant of Secondary Hyperparathyroidism in Uremic Patients

2000 ◽  
Vol 11 (2) ◽  
pp. 330-334
Author(s):  
AJAY GUPTA ◽  
LEE R. KALLENBACH ◽  
GERARD ZASUWA ◽  
GEORGE W. DIVINE
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Serum Calcium ◽  
Bone Disease ◽  
Odds Ratio ◽  
Adynamic Bone Disease ◽  
Diabetic Status ◽  
Increased Risk ◽  
Adynamic Bone ◽  
Incident Cases ◽  
Esrd Patients

In the general population, blacks have higher parathyroid gland mass and circulating parathyroid hormone (PTH) levels than whites. This may predispose black patients to more severe parathyroid disease when renal failure develops. Therefore, racial differences in the severity of uremic hyperparathyroidism were examined in a population of patients with endstage renal disease (ESRD). Among ESRD patients receiving hemodialysis or peritoneal dialysis, two or more values of intact PTH (immunoradiometric assay, pg/ml) obtained at least 90 d apart were available in 1270 prevalent cases (61.1% blacks, 51% males, and 31.1% diabetic), including 466 incident cases with onset of ESRD after 1993. Maximum PTH levels were analyzed as a function of race, gender, age, diabetic status, and levels of serum calcium, phosphorus, alkaline phosphatase, and aluminum. Using a stepwise multiple regression model, the determinants of maximum PTH in the order of their importance were black race, serum phosphorus, absence of diabetes, younger age, serum calcium, and female gender. The maximum PTH levels averaged 641.7 in blacks and 346.0 in whites after adjusting for age, gender, diabetic status, serum calcium, and phosphorus (P < 0.0001). In blacks compared with whites, the odds ratio (95% confidence interval) for adynamic bone disease (maximum PTH < 150 pg/ml) was 0.26 (0.17 to 0.41), whereas the odds ratio for hyperparathyroid bone disease (mean PTH > 500 pg/ml) was 4.4 (2.10 to 9.25). Race is a major independent determinant of uremic secondary hyperparathyroidism. Among ESRD patients, blacks may be at an increased risk for hyperparathyroid bone disease and whites for adynamic bone disease.

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