Cell Biology of Parathyroid Gland Hyperplasia in Chronic Renal Failure

Drüeke, Tilman B.

doi:10.1681/asn.v1161141

Cited by 149 publications

(11 citation statements)

References 89 publications

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“…The observed gender difference can partially be accounted for at the molecular level by various regulators of monoclonal proliferation and mitosis of parathyroid tissue. Despite being characterized by a low rate of cell turnover and division, 15 mitosis of parathyroid cells can be stimulated by conditions of functional demand such as a hypocalcemic state 16 . Although the precise molecular mechanisms involved in this process have yet to be defined, various growth factors and cell‐cycle regulators have been implied 17 .…”

Section: Discussionmentioning

confidence: 99%

Female Gender as a Risk Factor for Transient Post‐Thyroidectomy Hypocalcemia

Sands

Payne

Côté

et al. 2011

Otolaryngol.--head neck surg.

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Section: Discussionmentioning

confidence: 99%

Female Gender as a Risk Factor for Transient Post‐Thyroidectomy Hypocalcemia

Sands

Payne

Côté

et al. 2011

Otolaryngol.--head neck surg.

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“…Second, we evaluated weight loss for up to 12 months, which is a relatively short period. However, given the observed increasing magnitude of weight loss during the 12 month period and the progressive nature of SHPT, 15 we expect that the association of SHPT with weight loss will be yet more pronounced over longer follow‐up. Third, we did not account for changes in PTH levels during longitudinal follow‐up.…”

Section: Discussionmentioning

confidence: 94%

“… 13 , 14 Secondary hyperparathyroidism (SHPT) is a common complication in haemodialysis patients. 15 , 16 , 17 However, few studies have examined the potential link between SHPT and wasting in haemodialysis patients. 18 , 19 , 20 Furthermore, SHPT has been shown to be associated with increased risk of death, 16 , 17 but the causal effect of SHPT on mortality is uncertain and underlying mechanisms not well understood.…”

Section: Introductionmentioning

confidence: 99%

Secondary hyperparathyroidism, weight loss, and longer term mortality in haemodialysis patients: results from the DOPPS

Komaba

Zhao

Yamamoto

et al. 2021

J cachexia sarcopenia muscle

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Background Wasting is a common complication of kidney failure that leads to weight loss and poor outcomes. Recent experimental data identified parathyroid hormone (PTH) as a driver of adipose tissue browning and wasting, but little is known about the relations among secondary hyperparathyroidism, weight loss, and risk of mortality in dialysis patients. Methods We included 42,319 chronic in-centre haemodialysis patients from the Dialysis Outcomes and Practice Patterns Study phases 2-6 (2002-2018). Linear mixed models were used to estimate the association between baseline PTH and percent weight change over 12 months, adjusting for country, demographics, comorbidities, and labs. Accelerated failure time models were used to assess 12 month weight loss as a mediator between baseline high PTH and mortality after 12 months. Results Baseline PTH was inversely associated with 12 month weight change: 12 month weight loss >5% was observed in 21%, 18%, 18%, 17%, 15%, and 14% of patients for PTH ≥600 pg/mL, 450-600, 300-450, 150-300, 50-150, and <50 pg/mL, respectively. In adjusted analyses, 12 month weight change compared with PTH 150-299 pg/mL was À0.60%, À0.12%, À0.10%, +0.15%, and +0.35% for PTH ≥600, 450-600, 300-450, 50-150, and <50 pg/mL, respectively. This relationship was robust regardless of recent hospitalization and was more pronounced in persons with preserved appetite. During follow-up after the 12 month weight measure [median, 1.0 (interquartile range, 0.6-1.7) years; 6125 deaths], patients with baseline PTH ≥600 pg/mL had 11% [95% confidence interval (CI), 9-13%] shorter lifespan, and 18% (95% CI, 14-23%) of this effect was mediated through weight loss ≥2.5%. Conclusions Secondary hyperparathyroidism may be a novel mechanism of wasting, corroborating experimental data, and, among chronic dialysis patients, this pathway may be a mediator between elevated PTH levels and mortality. Future research should determine whether PTH-lowering therapy can limit weight loss and improve longer term dialysis outcomes.

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“…The main factors responsible for parathyroid hyperplasia are similar to those that increase PTH biosynthesis and secretion. High phosphate, hypocalcemia and 1,25D deficiency in CKD all contribute to the development of hyperplasia [87].The studies on parathyroid cell proliferation in experimental SHP of renal failure mainly rely on either 5/6 nephrectomy performed by removing one kidney and 2/3 of the contralateral kidney or an adenine diet. SHP is further increased when the rodents in these models are fed a high phosphorus diet [7,17,18,[88][89][90][91].…”

Section: Parathyroid Cell Proliferation In Secondary Hyperparathyroidismmentioning

confidence: 99%

Molecular Mechanisms of Parathyroid Disorders in Chronic Kidney Disease

et al. 2022

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Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that induces morbidity and mortality in patients. How CKD stimulates the parathyroid to increase parathyroid hormone (PTH) secretion, gene expression and cell proliferation remains an open question. In experimental SHP, the increased PTH gene expression is post-transcriptional and mediated by PTH mRNA–protein interactions that promote PTH mRNA stability. These interactions are orchestrated by the isomerase Pin1. Pin1 participates in conformational change-based regulation of target proteins, including mRNA-binding proteins. In SHP, Pin1 isomerase activity is decreased, and thus, the Pin1 target and PTH mRNA destabilizing protein KSRP fails to bind PTH mRNA, increasing PTH mRNA stability and levels. An additional level of post-transcriptional regulation is mediated by microRNA (miRNA). Mice with parathyroid-specific knockout of Dicer, which facilitates the final step in miRNA maturation, lack parathyroid miRNAs but have normal PTH and calcium levels. Surprisingly, these mice fail to increase serum PTH in response to hypocalcemia or uremia, indicating a role for miRNAs in parathyroid stimulation. SHP often leads to parathyroid hyperplasia. Reduced expressions of parathyroid regulating receptors, activation of transforming growth factor α-epidermal growth factor receptor, cyclooxygenase 2-prostaglandin E2 and mTOR signaling all contribute to the enhanced parathyroid cell proliferation. Inhibition of mTOR by rapamycin prevents and corrects the increased parathyroid cell proliferation of SHP. This review summarizes the current knowledge on the mechanisms that stimulate the parathyroid cell at multiple levels in SHP.

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Cell Biology of Parathyroid Gland Hyperplasia in Chronic Renal Failure

Cited by 149 publications

References 89 publications

Female Gender as a Risk Factor for Transient Post‐Thyroidectomy Hypocalcemia

Female Gender as a Risk Factor for Transient Post‐Thyroidectomy Hypocalcemia

Secondary hyperparathyroidism, weight loss, and longer term mortality in haemodialysis patients: results from the DOPPS

Molecular Mechanisms of Parathyroid Disorders in Chronic Kidney Disease

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