Effect of nutritional vitamin D preparations on parathyroid hormone in patients with chronic kidney disease

Abstract Background Secondary hyperparathyroidism (SHPT) is a common and major complication in chronic kidney disease (CKD), reflecting the increase of parathyroid hormone (PTH) in response to reduced Vitamin D signaling and hypocalcemia. This meta-analysis evaluated the impact of nutritional vitamin D (NVD) (cholecalciferol or ergocalciferol) on SHPT-related biomarkers. Methods A systematic literature search was performed in PubMed to identify relevant randomized control trials (RCTs) to be included in the meta-analysis. Fixed and random effects models were used to pool study level results. Effects were studied within NVD study arms and relative to control groups (placebo/no treatment); the former in order to identify the effect of actively altering biomarkers levels. Results Reductions in PTH from supplementation with NVD were small when observed within the NVD study arms (pooled reduction: 10.5 pg/ml) and larger when compared to placebo/no treatment (pooled reduction: 49.7 pg/ml). NVD supplementation increased levels of vitamin D (25(OH)D) in both analyses (increase within NVD study arm: 20.6 ng/ml, increase versus placebo/no treatment: 26.9 ng/ml). While small and statistically non-significant changes in phosphate and fibroblast growth factor 23 (FGF23) were observed, NVD supplementation caused calcium levels to increase when compared versus placebo/no treatment (increase: 0.23 mg/dl). Conclusions Our results suggest that supplementation with NVD can be used to increase 25(OH)D to a certain extent, while the potential of NVD to actively reduce PTH in ND-CKD patients with SHPT is limited.

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Serum level vitamin D and parathyroid hormone, and mortality, with or without chronic kidney disease

Journal of Bone and Mineral Metabolism ◽

10.1007/s00774-018-0979-z ◽

2018 ◽

Vol 37 (5) ◽

pp. 825-834

Author(s):

Chang Kyun Choi ◽

Sun-Seog Kweon ◽

Young-Hoon Lee ◽

Hae-Sung Nam ◽

Kyeong-Soo Park ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Serum Level

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

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0898 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Ryuta Fujimura ◽

SHOGO SHIBATA ◽

Takechiyo Tokuda ◽

Ayako Tanaka ◽

Aya Mizumoto ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Vitamin C ◽

Secondary Hyperparathyroidism ◽

Hormone Secretion ◽

Serum Vitamin ◽

Serum Phosphate ◽

Vitamin C Deficiency

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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Relationship between vitamin D status, parathyroid hormone levels and bone mineral density in patients with chronic kidney disease stages 3 and 4

Nephrology ◽

10.1111/j.1440-1797.2007.00860.x ◽

2007 ◽

Vol 0 (0) ◽

pp. 070918212946008-??? ◽

Cited By ~ 3

Author(s):

ARISTEIDIS STAVROULOPOULOS ◽

CHRISTINE J PORTER ◽

SIMON D ROE ◽

DAVID J HOSKING ◽

MICHAEL JD CASSIDY

Keyword(s):

Bone Mineral Density ◽

Chronic Kidney Disease ◽

Vitamin D ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Bone Mineral ◽

Vitamin D Status ◽

Mineral Density ◽

Hormone Levels ◽

Disease Stages

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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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Pathophysiology of chronic kidney disease-mineral and bone disorder

10.1093/med/9780199592548.003.0117 ◽

2015 ◽

Author(s):

Alexandra Voinescu ◽

Nadia Wasi Iqbal ◽

Kevin J. Martin

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Parathyroid Hormone ◽

Kidney Disease ◽

Fibroblast Growth Factor 23 ◽

Serum Levels ◽

Mineral And Bone Disorder ◽

Vitamin D Metabolism ◽

Bone Disorder ◽

Calcium Phosphorus

Chronic kidney disease is associated with the inability to control normal mineral homeostasis, resulting in abnormalities in serum levels of calcium, phosphorus, parathyroid hormone, fibroblast growth factor 23 (FGF23) and vitamin D metabolism. These disturbances lead to the development of secondary hyperparathyroidism, skeletal abnormalities, vascular calcifications, and other systemic manifestations. Traditionally, mineral and bone abnormalities seen in chronic kidney disease were included in the term ‘renal osteodystrophy’. More recently, the term chronic kidney disease-mineral and bone disorder was introduced to define the biochemical abnormalities of phosphorus, parathyroid hormone, FGF23, calcium, or vitamin D metabolism, abnormalities in bone remodelling and mineralization, and vascular or other soft tissue calcifications.

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Erratum to: Con: Nutritional vitamin D replacement in chronic kidney disease and end-stage renal disease

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa172 ◽

2020 ◽

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Kidney Disease ◽

Renal Disease ◽

End Stage Renal Disease ◽

Stage Renal Disease ◽

End Stage ◽

Nutritional Vitamin

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P0891META-ANALYSIS OF NUTRITIONAL VITAMIN D FOR THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM IN PATIENTS WITH NON-DIALYSIS CHRONIC KIDNEY DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0891 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Joel Gunnarsson ◽

Rosa Lauppe ◽

Edelgard Kaiser ◽

Marco Soro ◽

Philipp Csomor

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Kidney Disease ◽

Secondary Hyperparathyroidism ◽

Fixed Effects ◽

Untreated Patient ◽

Critical Role ◽

Vitamin D Levels ◽

Patient Groups ◽

Nutritional Vitamin

Abstract Background and Aims Chronic kidney disease (CKD) is commonly associated with mineral and bone disorder (CKD-MBD). Secondary hyperparathyroidism (SHPT) is a critical component of CKD-MBD characterized by excessive PTH secretion and parathyroid hyperplasia. SHPT develops in CKD because of disturbances in CKD-MBD parameters such as increases in serum phosphate and fibroblast growth factor 23, and reductions in 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and serum calcium. Low vitamin D levels play a critical role in the development and progression of SHPT. Nutritional vitamin D (NVD) supplements are being frequently used to address SHPT, especially in early CKD. The objective of this meta-analysis (MA) was to evaluate the effectiveness of the NVDs cholecalciferol and ergocalciferol in reducing PTH and increasing 25(OH)D in patients with non-dialysis CKD (ND-CKD). Method A systematic literature search was performed in PubMed to identify relevant randomized control trials (RCTs) to be included in the MA. All analyses were performed using both random and fixed effects models with inverted-variance weighting. Comparisons were made between the effects of NVDs relative to placebo-treated or untreated patients and between the baseline and end-of-study values of the patients treated with the NVDs, i.e. the effects in treated patients only. Results A total of 14 RCTs comprising 974 patients were included in the analyses. Overall reductions in PTH were small when compared to baseline (reduction of 10.95 pg/ml, 95 % confidence interval (CI): -15.99 to -5.91 pg/ml), while reductions in PTH were approximately three times larger when compared to placebo-treated or untreated patient groups (reduction of 34.35 pg/ml, 95 % CI:-47.47 to -21.24 pg/ml). This indicated a limited potential to actively lower PTH with NVDs as the relative effect on PTH when compared to placebo-treated or untreated patient groups was driven to a large degree by increases in PTH in the comparator arms. Treatment with NVDs tended to increase levels of 25(OH)D both when compared to placebo-treated or untreated patients (increase of 26.54 ng/ml, 95 % CI: 24.62 to 28.46 ng/ml) and when only the changes in treated patients were considered (increase of 21.49 ng/ml, 95 % CI: 20.54 to 22.44 ng/ml). However, large variations in effect sizes on levels of 25(OH)D were observed, making judgements about the size of any true treatment effect difficult. Average levels of 25(OH)D in treated patients at the end of the study period were >30 ng/ml in all but two RCTs and >50 ng/ml in only five of the included RCTs. No clear relationship was observed between study length (range: 4 to 144 weeks) or doses administered (range: 14 000 to 75 000 UI weekly average) and effects on 25(OH)D or PTH. Conclusion Our results suggest that treatment with NVDs is not efficacious to reliably and consistently lower PTH in ND-CKD patients with SHPT. Although treatment with NVDs can potentially be used to correct vitamin D insufficiency, our results suggest that the potential of NVD treatment to raise 25(OH)D levels to >50 ng/ml, a level needed to reduce PTH, is limited.

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