Parathyroid hormone, vitamin D, and cardiovascular disease in chronic renal failure

Immunometric assays claiming to determine intact parathyroid hormone (PTH) generally cross-react with N-truncated forms such as PTH(7-84). Laboratories need to examine the relevance of new assays with probable PTH(1-84) specificity. It is logical that assays should measure what they state they do. However, it seems unlikely that use of older 'intact' PTH assays will affect the clinical interpretation of results in primary hyperparathyroidism or vitamin D deficiency. It is plausible that appropriate application of new PTH assays could improve outcome in chronic renal failure. However, it has never been suggested that straightforward replacement of existing assays with new PTH(1-84) assays will lead to this improved outcome. A better understanding of PTH fragments and their interaction with PTH receptors may shed light on the relevance of different PTH assays. In the meantime, older technologies will continue to work well for the vast majority of patients.

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Clinical evaluation of two parathyroid hormone assays in the context of vitamin D supply in chronic kidney disease

Orvosi Hetilap ◽

10.1556/oh.2013.29784 ◽

2013 ◽

Vol 154 (51) ◽

pp. 2025-2036

Author(s):

László Kovács ◽

Éva Virágh ◽

Dóra Balogh ◽

Bernadette Kálmán ◽

Zoltán Lőcsei ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Vitamin D ◽

Renal Failure ◽

Peritoneal Dialysis ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Vitamin D Deficiency ◽

Intact Parathyroid Hormone ◽

Hormone Levels ◽

The Difference

Introduction: Parathyroid hormone levels provide important information in chronic renal failure. Aim: To compare parathyroid hormone levels measured by two assays in correlation with vitamin D supply. Method: Parathyroid hormone and 25-hydroxi-vitamin-D were determined in 104 patients (31 patients with chronic renal failure without renal replacement therapy, 36 patients treated with peritoneal dialysis and 37 patients treated with hemodialysis). Results: Good correlation was found between results of the two parathyroid hormone methods, but the intact parathyroid hormone levels were higher than the biointact values. 87% and 13% of the patients had vitamin-D deficiency and insufficiency, respectively. The frequency of serious vitamin-D deficiency was higher in the peritoneal dialysis than in the hemodialysis group. Intact parathyroid hormone levels were different in dialysed patients having vitamin-D-deficiency and insufficiency, and the difference was higher for the biointact than intact values. Negative correlation was detected between biointact parathyroid hormone and 25-hydroxivitamin-D in the hemodialysis group. Conclusions: Biointact parathyroid hormone levels better reflect the vitamin D supply and bone metabolism than intact levels, especially in hemodialysed patients. Orv. Hetil., 2013, 154(51), 2025–2036.

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Distribution of Circulating Immunoreactive Components of Parathyroid Hormone in Normal Subjects and in Patients with Primary and Secondary Hyperparathyroidism: The Role of the Kidney and of the Serum Calcium Concentration

Clinical Science ◽

10.1042/cs0570435 ◽

1979 ◽

Vol 57 (5) ◽

pp. 435-443 ◽

Cited By ~ 28

Author(s):

M. A. Dambacher ◽

J. A. Fischer ◽

W. H. Hunziker ◽

W. Born ◽

J. Moran ◽

...

Keyword(s):

Vitamin D ◽

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Primary Hyperparathyroidism ◽

Vitamin D Deficiency ◽

Normal Subjects ◽

Dependent Manner ◽

Intact Pth ◽

Calcium Dependent

1. The distribution of intact parathyroid hormone-(1–84) [PTH-(1–84)] and of its COOH-terminal fragments was determined in human serum by column chromatography. In addition to PTH-(1–84) (peak I), COOH-terminal fragments having molecular weights of approximately 4000–7000 (peak II) and immunoreactive components co-eluting with human PTH-(1–12) (peak III) were observed. 2. Mean concentrations of intact PTH-(1–84) and of its COOH-terminal fragments were significantly raised in chronic renal failure as compared with those of normal subjects. Mean amounts of peak II were higher in patients with chronic renal insufficiency than in nutritional vitamin D deficiency, in pseudohypoparathyroidism and in primary hyperparathyroidism, despite comparable amounts of PTH-(1–84). 3. In chronic renal failure as well as in a group of patients with vitamin D deficiency, pseudohypoparathyroidism and primary hyperparathyroidism and in controls, significant linear relations were found between the serum concentrations of calcium and log (peak II/peak I). Our findings suggest that the conversion of intact PTH-(1–84) into COOH-terminal fragments by the parathyroid glands (resulting in a raised secretion of fragments) and/or in peripheral organs may be directly related to the serum concentration of calcium. However, the degradation of the fragments may also be suppressed in a calcium-dependent manner.

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Serum Phosphate, Parathyroid Hormone and Vitamin D Metabolites in Patients with Chronic Renal Failure: Effect of Aluminum Hydroxide Administration

Nephron ◽

10.1159/000183480 ◽

1985 ◽

Vol 40 (3) ◽

pp. 286-291 ◽

Cited By ~ 10

Author(s):

Shoshi Takamoto ◽

Toshio Onishi ◽

Shigeto Morimoto ◽

Shunji Imanaka ◽

Hiroyasu Tsuchiya ◽

...

Keyword(s):

Vitamin D ◽

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Aluminum Hydroxide ◽

Serum Phosphate ◽

Vitamin D Metabolites

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Role of parathyroid hormone in the glucose intolerance of chronic renal failure.

Journal of Clinical Investigation ◽

10.1172/jci111765 ◽

1985 ◽

Vol 75 (3) ◽

pp. 1037-1044 ◽

Cited By ~ 99

Author(s):

M Akmal ◽

S G Massry ◽

D A Goldstein ◽

P Fanti ◽

A Weisz ◽

...

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Glucose Intolerance

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Parathyroid hormone secretion in chronic renal failure

Kidney International ◽

10.1038/ki.1996.488 ◽

1996 ◽

Vol 50 (5) ◽

pp. 1700-1705 ◽

Cited By ~ 2

Author(s):

Jesper C. Madsen ◽

Anne Q. Rasmussen ◽

Søren D. Ladefoged ◽

Peter Schwarz

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Hormone Secretion

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Endothelium-dependent vasodilation and oxidative stress in chronic renal failure: Impact on cardiovascular disease

Kidney International ◽

10.1046/j.1523-1755.63.s84.2.x ◽

2003 ◽

Vol 63 ◽

pp. S50-S53 ◽

Cited By ~ 48

Author(s):

Margus Annuk ◽

Mihkel Zilmer ◽

Bengt Fellström

Keyword(s):

Oxidative Stress ◽

Cardiovascular Disease ◽

Renal Failure ◽

Chronic Renal Failure ◽

And Oxidative Stress

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Parathyroid hormone metabolism and its potential as a uremic toxin

AJP Renal Physiology ◽

10.1152/ajprenal.1980.239.1.f1 ◽

1980 ◽

Vol 239 (1) ◽

pp. F1-F12 ◽

Cited By ~ 3

Author(s):

E. Slatopolsky ◽

K. Martin ◽

K. Hruska

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Biological Effects ◽

Uremic Toxin ◽

Terminal Portion ◽

Single Chain ◽

Biochemical Alterations ◽

Amino Terminal ◽

Carboxy Terminal

Secondary hyperparathyroidism is a universal complication of chronic renal failure. It has been proposed that the markedly elevated levels of immunoreactive parathyroid hormone (i-PTH) in uremia may represent a “uremic toxin” responsible for many of the abnormalities of the uremic state. Plasma i-PTH consists of a mixture of intact hormone, a single-chain polypeptide of 84 amino acids, and smaller molecular weight hormonal fragments from both the carboxy- and amino-terminal portion of the PTH molecule. The hormonal fragments arise from metabolism of intact PTH by peripheral organs as well as from secretion of fragments from the parathyroid glands. The structural requirements for the known biological actions of PTH reside in the amino-terminal portion of the PTH molecule. Carboxy-terminal fragments, biologically inactive at least in terms of adenylate cyclase activation, hypercalcemia, or phosphaturia, depend on the kidney for their removal from plasma, and thus accumulate in the circulation in chronic renal failure. It is unknown at the present time if other biological effects of these carboxy-terminal fragments may contribute to some of the biochemical alterations observed in uremia. The most significant consequence of increased PTH levels in uremia is the development of bone disease characterized by osteitis fibrosa. In addition, it would appear that PTH plays an important role in some of the abnormal electroencephalographic patterns observed in uremia. This may be due to a potential role of PTH in increasing calcium content of brain. Parathyroid hormone also has been implicated as a pathogenetic factor in many other alterations present in uremia, i.e., peripheral neuropathy, carbohydrate intolerance, hyperlipidemia, and other alterations. Unfortunately, outstanding clinical research is lacking in this field and conclusive experimental data are practically nonexistent. Further studies are necessary if one is to accept the concept of PTH being a significant “uremic toxin.”

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Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic renal failure

Clinical Science ◽

10.1042/cs0960427 ◽

1999 ◽

Vol 96 (4) ◽

pp. 427-430 ◽

Cited By ~ 4

Author(s):

M. BLUM ◽

Y. WEISMAN ◽

S. TURGEMAN ◽

S. CABILI ◽

Y. WOLLMAN ◽

...

Keyword(s):

Renal Failure ◽

Parathyroid Hormone ◽

Chronic Renal Failure ◽

Virgin Female ◽

Normal Pregnancy ◽

High Serum ◽

Female Rats ◽

Pregnant Rats ◽

Serum Ipth ◽

Immunoreactive Parathyroid Hormone

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20–21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100±18 pg/ml) and low calcitriol levels (10.6±4.3 pg/ml) compared with normal rats [N1: 14±2.5 pg/ml (P< 0.001) and 18.2±4.2 pg/ml (P< 0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2±5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4±8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87±17 pg/ml) and low calcitriol levels (9.3±1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.

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