P0898VITAMIN C STATUS MODIFIES PARATHYROID HORMONE SECRETION IN NON-DIALYZED CHRONIC KIDNEY DISEASE PATIENTS

Abstract Background and Aims Among patients with chronic kidney disease (CKD) at predialysis stage, there is a high incidence of secondary hyperparathyroidism. Metabolic changes associated with secondary hyperparathyroidism lead to renal osteodystrophy, including osteitis fibrosa, ectopic calcification, cardiovascular disease, and the risk of death, and serum parathyroid hormone levels are influenced by nutritional variables. Non-dialyzed CKD patients are especially prone to vitamin C deficiency because of dietary restrictions and malnutrition. Vitamin C is an important antioxidant and relates to the development and maintenance of bone tissues. However, the contribution of vitamin C deficiency to parathyroid hormone secretion is unknown. Here, we performed a single-center cross-sectional study in order to assess association of serum vitamin C and parathyroid hormone in non-dialyzed CKD patients. Method We had 280 consecutive patients who underwent serum vitamin C and serum intact parathyroid hormone (iPTH) measurement for screening purposes from January 1st, 2013 to November 30th, 2017. We analysed a total of 128 patients (71.3±11.6 year-old, 80 males) who had an estimated glomerular filtration rate (eGFR) that remained less than 60 mL/min/1.73m2 after 152 patients were excluded because of vitamin C or vitamin D supplementation, age <20 years, dialysis, positive serostatus for HIV, hepatitis B or hepatitis C, chronic infection, or cancer. Results Twenty-three percent of the patients (n=29) had vitamin C levels< 2.0 μg/mL (a range seen in very deficient subjects), 53% (n=68) had levels between 2.0 and 5.5 μg/mL, and 31 patients (24%) had vitamin C levels >5.5 μg/mL, which is considered the upper limit of normal for the healthy population. Log(iPTH) significantly correlated with age (r=-0.238, p=0.00672), log(eGFR) (r=-0.625, p<0.0001), serum calcium (r=-0.609, p<0.0001), and serum phosphate (r=0.41, p<0.0001), and had a tendency to correlate with serum albumin (r=-0.146, p=0.101). Low serum vitamin C was associated with higher serum iPTH (P=0.0005, one-way analysis of variance). In a multiple linear regression model with log(iPTH) as the dependent variable, and age, gender, log(eGFR), serum levels of calcium, phosphate, albumin, and vitamin C as independent variables, the inverse relationship of log(iPTH) and serum vitamin C was confirmed (R2 = 0.568, adjusted R2 = 0.543, P<0.0001), along with other parameters influencing iPTH levels, including age, log(eGFR), serum calcium, and serum phosphate. Low vitamin C levels were also associated with increased serum alkaline phosphatase (r=-0.209, p=0.0179), a further indicator of the impact of vitamin C status on bone metabolism. Conclusion Vitamin C deficiency is prevalent in a significant proportion of non-dialyzed CKD patients. Low vitamin C levels contribute to secondary hyperparathyroidism, leading to increased bone turnover. This novel observation may result from effects of vitamin C on vitamin D metabolism, vitamin D binding in target tissues, and cAMP-linked signalling pathways in bone and parathyroid gland. Therapeutic intervention with supplemental vitamin C for secondary hyperparathyroidism might be a good strategy.

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Secondary and tertiary hyperparathyroidism in chronic kidney disease

Osteoporosis and Bone Diseases ◽

10.14341/osteo2017263-68 ◽

2017 ◽

Vol 20 (2) ◽

pp. 63-68 ◽

Cited By ~ 1

Author(s):

Lilit V. Egshatyan ◽

Natalya G. Mokrisheva ◽

Lyudmila Ya. Rozhinskaya

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Secondary Hyperparathyroidism ◽

Medical Therapy ◽

Receptor Activation ◽

Mineral Density ◽

Tertiary Hyperparathyroidism ◽

End Stage

In the treatment of secondary hyperparathyroidism of end-stage chronic kidney disease, vitamin D receptor activation and allosteric modulators of the calcium-sensing receptor – inhibit glandular hyperplasia, reduce parathyroid hormone levels, impact on bone turnover and mineral density. But the use of calcimimetic and vitamin D analogs or mimetics did not reduce the need for parathyroidectomy for refractory hyperparathyroidism. The enlarged parathyroid gland and gland nodular transformation became refractory to medical therapy and patient need for parathyroidectomy. Tertiary hyperparathyroidism is a state of excessive secretion of parathyroid hormone after a long period of secondary hyperparathyroidism and renal transplantation. In this article, we present the case of a Caucasian male with chronic kidney disease (end-stage on chronic hemodialysis and after kidney transplantation) and different forms of hyperparathyroidism (secondary and tertiary). Our case study shows that only a multi-interventional strategy is likely to be more effective treatment in cases of severe and refractory to medical therapy hyperparathyroidism.

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Secondary hyperparathyroidism in patient with type 2 diabetes and stages 3–4 chronic kidney disease

Diabetes Mellitus ◽

10.14341/dm9458 ◽

2018 ◽

Vol 21 (2) ◽

pp. 128-134

Author(s):

Lilit V. Egshatyan ◽

Natalya G. Mokrisheva

Keyword(s):

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Vitamin D ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Secondary Hyperparathyroidism ◽

Vitamin D Receptor ◽

Receptor Activation ◽

Mineral Density

Secondary hyperparathyroidism is an early complication of chronic kidney disease, with increasing severity as the glomerular filtration rate decreases and characterized by a progressive increase in parathyroid hormone and growth of the parathyroid glands. It is generally accepted that a deficiency in active form of vitamin D or calcitriol levels seems to play a relevant role in its development and progression of secondary hyperparathyroidism. A reduction in plasma calcitriol levels occurs early in renal disease. Major renal guidelines recommend use of vitamin D for secondary hyperparathyroidism in chronic kidney disease. In the treatment vitamin D receptor activation inhibit glandular hyperplasia; reduce parathyroid hormone levels impact on bone turnover and mineral density. Treatment with calcitriol can occasionally result in hypercalcemia and hyperphosphatemia in renal patients due promotes intestinal calcium and phosphorus absorption. This limits its suitability for the treatment. But next generation vitamin-D analogs such as paricalcitol have lower intestinal absorption of calcium, phosphorous and significantly lowers renin levels, albuminuria and blood pressure. In this article, we present the case of a Caucasian male with type 2 diabetes and secondary hyperparathyroidism in stages 34 chronic kidney disease. Our case study shows that in treating for secondary hyperparathyroidisms selective vitamin D receptor activation with paricalcitol reduction of levels parathyroid hormone, albuminuria, offering low chance hypercalcemia, hyperphosphatemia and other side effects.

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Vitamin D Level in Predialysis Chronic Kidney Disease Patients Stage 3 to 5 and Predictors of its Deficiency

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2021/v33i1831055 ◽

2021 ◽

pp. 64-72

Author(s):

Mohamed G. Mohamed ◽

Hanaa I. Okda ◽

Hossam A. Hodeib ◽

Mostafa T. Gabr

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Vitamin D Deficiency ◽

Serum Vitamin ◽

Cross Sectional ◽

Serum Vitamin D ◽

Ckd Stage ◽

Significant Difference

Background: Vitamin D deficiency is commonly encountered in patients with chronic kidney disease (CKD) with or without undergoing dialysis. This study was conducted to assess vitamin D level in patients diagnosed with predialysis CKD stage 3 – 5, and to determine the predictors of its deficiency in such patients. Materials and Methods: This cross-sectional study included 75 patients who were divided into three equal groups of CKD-3, CKD-4 and CKD-5. All cases were subjected to detailed history taking, physical examination and measurement of estimated glomerular filtration rate (eGFR) according to Cockcroft-Gault formula. In addition, laboratory investigations included CBC, renal function tests, serum ferritin, intact parathyroid hormone (iPTH) and vitamin D level. Results: Patient demographics and other co-morbidities were comparable among the three groups. Serum vitamin D had mean values of 24.84, 20.52 and 11.24 ng/ml in patients with stages III, IV and V respectively, with significant difference between the three groups. Vitamin D deficiency was more common in CKD-5 cases. On the contrary, serum parathyroid hormone and ferritin were significantly higher levels, in patients with higher stages. There was statistically significant positive correlation of serumvitamin D with eGFR, Hb, calcium and albumin. On the other hand, serum vitamin D was negatively correlated with phosphate, PTH, urea andcreatinine. Conclusion: It is evident that higher stages of CKD are associated with more vitamin D deficiency.

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Extended-release calcifediol in stage 3–4 chronic kidney disease: a new therapy for the treatment of secondary hyperparathyroidism associated with hypovitaminosis D

Journal of Nephrology ◽

10.1007/s40620-021-01152-5 ◽

2021 ◽

Author(s):

Mario Cozzolino ◽

Paola Minghetti ◽

Pierluigi Navarra

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Secondary Hyperparathyroidism ◽

Extended Release ◽

Hypovitaminosis D ◽

Active Vitamin ◽

Vitamin D Levels ◽

25 Oh Vitamin D

AbstractA high percentage of patients with chronic kidney disease have hypovitaminosis D, which is a driver of secondary hyperparathyroidism and an important factor in chronic kidney disease-mineral and bone disorder. Vitamin D deficiency (serum total 25-OH vitamin D levels < 30 ng/mL) occurs early in the course of chronic kidney disease and treatment guidelines recommend early intervention to restore 25-OH vitamin D levels as a first step to prevent/delay the onset/progression of secondary hyperparathyroidism. The vitamin D forms administered to replace 25-OH vitamin D include cholecalciferol, ergocalciferol, and immediate- or extended-release formulations of calcifediol. Most patients with intermediate-stage chronic kidney disease will develop secondary hyperparathyroidism before dialysis is required. Control of parathyroid hormone levels becomes a major focus of therapy in these patients. This article focuses on the position of extended-release calcifediol in the treatment of patients with stage 3–4 chronic kidney disease and secondary hyperparathyroidism with hypovitaminosis D. Several characteristics of extended-release calcifediol support its use in the intermediate stages of chronic kidney disease. The pharmacokinetics of extended-release calcifediol make it effective for replenishing 25-OH vitamin D levels, with minimal impact on vitamin D catabolism from fibroblast-growth factor-23 and CYP24A1 upregulation. Extended-release calcifediol increases circulating 25-OH vitamin D levels in a dose-dependent manner and lowers parathyroid hormone levels by a clinically relevant extent, comparable to what can be achieved by administering active vitamin D analogues, though with a lower risk of hypercalcaemia and hyperphosphataemia. Active vitamin D analogues are reserved for patients undergoing dialysis or pre-dialysis patients with severe progressive secondary hyperparathyroidism. Graphic abstract

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Selective Vitamin D Receptor Activation as Anti-Inflammatory Target in Chronic Kidney Disease

Mediators of Inflammation ◽

10.1155/2014/670475 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 12

Author(s):

J. Donate-Correa ◽

V. Domínguez-Pimentel ◽

M. L. Méndez-Pérez ◽

M. Muros-de-Fuentes ◽

C. Mora-Fernández ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Secondary Hyperparathyroidism ◽

Vitamin D Receptor ◽

Mononuclear Cells ◽

Receptor Activation ◽

Control Group ◽

Pth Level

Paricalcitol, a selective vitamin D receptor (VDR) activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD), has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m2and an intact parathyroid hormone (PTH) level higher than 110 pg/mL received oral paricalcitol (1 μg/48 hours) as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%,P<0.01), TNF-α(11.9%,P=0.01), and IL-6 (7%,P<0.05), with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFαand IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P=0.01) and 35.4% (P=0.01), respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD.

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