Cardiovascular manifestations of primary hyperparathyroidism: a narrative review

Pepe, Jessica; Cipriani, Cristiana; Sonato, Chiara; Raimo, Orlando; Biamonte, Federica; Minisola, Salvatore

doi:10.1530/eje-17-0485

Cited by 129 publications

(99 citation statements)

References 109 publications

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“…First, it is known that arterial hypertension is highly prevalent in primary hyperparathyroidism, ranging from 40% to 65%, which is much higher than the expected 25%-30% of hypertension in the general adult population. 70 Given our observations, a possible mechanism could be that increased Ca 2+ in the tubular fluid, as occurs in hypercalcemia, stimulates the activity of NCC promoting NaCl reabsorption and, hence, the development of hypertension. Second, it has been recently demonstrated that glucose and other sugars act as type II calcimimetics, enhancing CaSR affinity for Ca 2+ .…”

Section: Discussionmentioning

confidence: 67%

The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK Pathway

Bazúa‐Valenti

Rojas‐Vega

Castañeda‐Bueno

et al. 2018

JASN

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Hypercalciuria can result from activation of the basolateral calcium-sensing receptor (CaSR), which in the thick ascending limb of Henle's loop controls Ca excretion and NaCl reabsorption in response to extracellular Ca However, the function of CaSR in the regulation of NaCl reabsorption in the distal convoluted tubule (DCT) is unknown. We hypothesized that CaSR in this location is involved in activating the thiazide-sensitive NaCl cotransporter (NCC) to prevent NaCl loss. We used a combination of and models to examine the effects of CaSR on NCC activity. Because the KLHL3-WNK4-SPAK pathway is involved in regulating NaCl reabsorption in the DCT, we assessed the involvement of this pathway as well. Thiazide-sensitive Na uptake assays in oocytes revealed that NCC activity increased in a WNK4-dependent manner upon activation of CaSR with Gd In HEK293 cells, treatment with the calcimimetic R-568 stimulated SPAK phosphorylation only in the presence of WNK4. The WNK4 inhibitor WNK463 also prevented this effect. Furthermore, CaSR activation in HEK293 cells led to phosphorylation of KLHL3 and WNK4 and increased WNK4 abundance and activity. Finally, acute oral administration of R-568 in mice led to the phosphorylation of NCC. Activation of CaSR can increase NCC activity the WNK4-SPAK pathway. It is possible that activation of CaSR by Ca in the apical membrane of the DCT increases NaCl reabsorption by NCC, with the consequent, well known decrease of Ca reabsorption, further promoting hypercalciuria.

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Section: Discussionmentioning

confidence: 67%

The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK Pathway

Bazúa‐Valenti

Rojas‐Vega

Castañeda‐Bueno

et al. 2018

JASN

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“…Considering the association of urine KIM‐1/uCr with PTH, a direct action of the hormone may be implicated in the process of kidney injury. Chronic PTH excess is indeed known to be associated with endothelial dysfunction and other atherogenic processes through a direct interaction with its receptor on vessels . This action of PTH on the kidney vasculature and a possible direct effect on the proximal tubule cells could presumably be of importance in the pathogenesis of kidney disease in PHPT.…”

Section: Discussionmentioning

confidence: 99%

Investigating subtle kidney injury in primary hyperparathyroidism by means of sensitive and specific biomarkers

Cipriani

Pepe

Colangelo

et al. 2019

Clinical Endocrinology

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Objective Kidney involvement is a common complication in primary hyperparathyroidism (PHPT). No study so far has assessed the prevalence of kidney injury developing before the reduction in glomerular filtration rate (GFR) in PHPT. The study was aimed at establishing the potential role of biomarkers of kidney injury in detecting subtle renal damage in patients with PHPT. Design Cross‐sectional study. Patients A total of 69 postmenopausal patients with PHPT and 41 healthy age‐ and sex‐matched subjects were studied. Exclusion criteria were as follows: GFR < 30 mL/min, chronic inflammatory disease, nephrotic syndrome, infection, malignancy, heart failure, recent exposure to iodinated contrast media or nonsteroidal anti‐inflammatory drugs. Measurements We measured a panel of sensitive biomarkers of kidney injury in PHPT vs controls. Results Mean FGF23 and Klotho were higher in PHPT (72 ± 48 and 811 ± 366 pg/mL, respectively) than controls (53 ± 23.5 and 668.6 ± 17; P < .02 and P < .05). Urine KIM‐1/uCr was significantly higher in PHPT (1.4−6 ± 1.3−6) than controls (9.2−7 ± 7−7; P < .05); this was particularly evident in the CrCl 60‐89 mL/min category (1.36 ± 97 vs 8.2−7 ± 3.6−7; P < .02). Mean values of urine NGAL/uCr were higher in PHPT with (n = 28) compared to those without kidney stones (n = 35; 1.8−5 ± 1.4−5 and 1−5 ± 8−6; P < .0001). We found significant positive associations between urine NGAL/uCr and Ca (R = .292, P < .02) and urine KIM1/uCr and PTH (R = .329, P < .01). Conclusions We propose the utilization of these molecules, particularly urine KIM‐1/uCr and urine NGAL/uCr ratios for the assessment of subtle kidney injury in patients with PHPT. These molecules are elevated in tubular necrosis and have potential role in the development of kidney damage in PHPT, according to the severity of the disease.

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“…Связь между повышением уровня ПТГ, кальция и риском сердечно-сосудистых заболеваний активно обсуждается в настоящее время, однако механизмы остаются не до конца изученными. Имеются предположения о негативном влиянии повышенного уровня ПТГ через активацию ренин-ангиотензиновой системы, также обсуждается прямое влияние ПТГ на кардиомиоциты и эндотелий сосудов [14][15][16]. Кроме этого, низкая концентрация обеспечения витамином D больных ПГПТ, также может играть отрицательную роль и приводить к более частому развитию ССЗ [17].…”

Section: обсуждение основного результата исследованияunclassified

Primary hyperparathyroidism: clinical forms and their features. Retrospective study

Yanevskaya

Геннадьевна²,

Karonova³

et al. 2019

Clin Exp Thyroid

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Background: Primary hyperparathyroidism (PHPT) is a disease characterized by autonomous production of parathyroid hormone (PTH) from one or more parathyroid glands. Over the past 50 years asymptomatic form of the disease have become more prevalent in developed countries. Aims: To evaluate the clinical forms of PHPT presented in recent years and to specify the clinical and laboratory features in patients with symptomatic and asymptomatic forms of the disease. Materials and methods: We reviewed medical records of 449 patients admitted to three Medical Centers (Saint-Petersburg, Russia) between 2011–2018. Anamnesis, anthropometric data, laboratory (PTH, serum total calcium and ionized calcium, phosphorus, alkaline phosphatase, 24-h calciuria level, 25(OH)D) and instrumental (ultrasonography, scintigraphy, CT/MRI scan, DXA) tests were analyzed. Results: Patients’ average age was 59 years, with 93.1% women, and an F:M ratio of 13.5:1. Symptomatic form of PHPT was identified in 310 patients (69%), while 139 were asymptomatic. 4.2% of patients had PHPT as part of MEN syndrome. Almost half of the male population had urolithiasis and 45% of women had osteoporosis. Cardiovascular diseases were present in 64.4% of cases. 25(OH)D level was determined only in 20% of cases and was higher in asymptomatic patients (32.2 & 18.6 ng/ml, p = 0.003). Normocalcemic form of PHPT was diagnosed in 37 patients (8.2%) and was characterized not only by normocalcemia and lower PHT level, but also by smaller adenoma size (p = 0.01) and hypocalcemic syndrome after surgery. Conclusions: Study results showed that symptomatic PHPT is more prevalent in the Russian population, that there are gender distinctions affecting the clinical presentation, and that the frequency of cardiovascular disease is high in this patient population. PHPT as part of MEN syndrome was detected in 4.2% of cases and required molecular genetic testing. Normocalcemic form of PHPT with postoperative hypocalcemia was present in every fourth patient. Rare determination of 25(OH)D level imposes the need of mandatory assessment of vitamin D supplementation and the reduction of its deficiency as part of the preoperative preparation of PHPT patients.

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Cardiovascular manifestations of primary hyperparathyroidism: a narrative review

Cited by 129 publications

References 109 publications

The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK Pathway

The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK Pathway

Investigating subtle kidney injury in primary hyperparathyroidism by means of sensitive and specific biomarkers

Primary hyperparathyroidism: clinical forms and their features. Retrospective study

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