[Progress in the treatment of some kidney disorders].
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Anemia↗
Biomedical subjects
P Ureña
Publications and source records attributed to P Ureña.
[Calcimimetics, mechanisms of action and therapeutic applications].
The extracellular calcium-sensing receptor (CaR) on the parathyroid cell surface negatively regulates secretion of parathyroid hormone (PTH). Its activation by small changes in the extracellular concentration of ionized calcium (ec[Ca2+]) decreases PTH secretion and secondarily bone turnover. CaR is an ideal target for compounds that may be developed to modulate its activity - activating calcimimetics and inhibiting calcilytics. Calcimimetics can amplify the sensitivity of the CaR to ec(Ca2+), thereby suppressing PTH levels and in turn reducing blood Ca++. They dose-dependently reduce the secretion of PTH in cultured parathyroid cells, in animal models and in humans. In uremic animals, these compounds prevent parathyroid cell hyperplasia when given at the onset of the disease and stop cell proliferation if they are administered afterwards, when the hyperplasia already exists. They normalize plasma PTH levels and bone remodeling. In uremic patients undergoing hemodialysis, calcimimetics reduce plasma PTH concentrations in the short (12 weeks) and long (2 years) terms. They also reduce serum levels of calcium-phosphorus product. Calcimimetics are therefore an alternative for the treatment of secondary hyperparathyroidism, particularly in dialysis patients, when increased serum levels of calcium-phosphorus product, the attendant risk of cardiovascular calcification, and its lack of efficacy limit use of the standard treatment.
Aniline Compounds↗
[The PTH/PTHrP receptor: biological implications].
Since its discovery in 1923, the parathyroid hormone (PTH), was thought to be the sole hormone capable of stimulating bone resorption, renal tubular calcium reabsorption, calcitriol synthesis, and urinary excretion of phosphate. However, in 1987, the PTHrP (PTH-related peptide), was demonstrated to share most of the biological actions of PTH through the activation of the same receptor. This receptor was cloned in 1992 and named PTH/PTHrP receptor or PTH-R1. Both, PTH and PTHrP bind with great affinity to PTH-R1 and stimulate a signal transduction system involving different G-proteins, phospholipase C, and adenylate cyclase. A third member of the PTH family, the TIP-39 (tuberoinfundibular peptide), binds and activates another PTH receptor (PTH-R2). There is evidence for other PTH receptors, a PTH-R3, probably specific for PTHrP in keratinocytes, kidney, placenta and a PTH-R4 specific for C-terminal PTH fragments. Activating mutations in the PTH-R1 gene cause Jansen type metaphyseal chondrodysplasia, whereas inactivating mutations are responsible for Blomstrand type rare chondrodysplasia and enchondromatosis. The renal and bone PTH-R1 expression is upregulated in vitamin D deficient rats and by endotoxin, interleukin-2, dexamethasone, T3, and TGF beta. On the contrary, PTH, PTHrP, angiotensin-II, IGF-1, PGE2, vitamin D, and chronic renal failure decrease its expression. In conclusions, the biological implications of the identification and cloning of different PTH receptors are at their beginning. The almost ubiquitous distribution of PTHrP and PTH-R1, the numerous PTHrP and PTH fragments, let us suppose the existence of other PTH-related receptors, and a great complexity of the bone and mineral metabolism.
Animals↗
Plasma bone-specific alkaline phosphatase changes in hemodialysis patients treated by alfacalcidol.
Vitamin D derivatives correct high bone remodeling by decreasing plasma iPTH concentration in uremic patients with secondary hyperparathyroidism. However, without bone biopsy, plasma iPTH alone might not provide sufficient information regarding vitamin D-induced bone changes. Plasma bone-specific alkaline phosphatase (bAP) seems more sensitive than iPTH in assessing the degree of bone remodeling. We prospectively studied the evolution of iPTH and bAP in 14 adult hemodialysis patients treated for 1 year by i.v. alfacalcidol pulses. The mean total alfacalcidol dose was 0.08 +/- 0.02 g/kg/week. Ten patients completed the study, 2 patients had to be parathyroidectomized before week 24 because of hypercalcemia and uncontrolled hyperphosphatemia, and 2 other patients died before week 36. Mean iPTH levels diminished from 826 +/- 300 pg/ml (range 507 - 1,500 pg/ml) at baseline to 436 +/- 371 pg/ml (range 18 - 1,095 pg/ml) after 52 weeks of treatment (48% of decrease). Only 2 patients normalized plasma iPTH levels while 8/10 normalized bAP. Five patients remained with plasma iPTH concentrations higher than 5-fold the normal value. In contrast, plasma bAP levels declined from 47.6 +/- 32.2 ng/ml (range 15.4 - 130.0 ng/ml) at baseline to 17.8 +/- 9.9 ng/ml (range 8.0 +/- 38.0 ng/ml) at week 52 (63% of decrease). Bone histomorphometry was available in 6 patients after 15.8 +/- 5.1 months of alfacalcidol treatment. None of them met the criteria of adynamic bone disease as they had increased bone resorption and marrow bone fibrosis. Bone formation rate was normal in 2 patients and unmeasurable in the other 4. Two patients showed signs of osteomalacia. In conclusion, alfacalcidol preferentially reduced bone formation rate rather than the other histological parameters of secondary hyperparathyroidism. It reduced plasma bAP more efficiently than iPTH.
Adjuvants, Immunologic↗
[Parathyroid gland, calcium receptor and calcimimetics].
Parathyroid glands, bones, intestines and kidneys closely regulate ionized extracellular calcium concentration and thereby bone mineral density. This regulation is accomplished by a membrane associated receptor that responds to small changes in the extracellular calcium concentration (Ca2+)ec. The activation of this receptor regulates the secretion of PTH and the urinary excretion of calcium. The cloning of this calcium sensing receptor (RCa) in 1993 has allowed the identification of several hereditary disorders characterized by either a hyperparathyroidism or a hypoparathyroidism, as well as the development of pharmaceutical compounds potentially of interest for the treatment of these diseases. The calcimimetics are able either to directly stimulate the RCa or to make the RCa more sensitive to the effects of (Ca2+)ec. By this way, they decrease the secretion of PTH, but they also stimulate the secretion of calcitonin. The first clinical studies with a first-generation calcimimetic have demonstrated their efficacy lowering plasma intact PTH concentration in uremic patients with secondary hyperparathyroidism. However, the low biodisponibility of these first calcimimetics predict a difficult clinical utilization. The preliminary results obtained with a second-generation calcimimetic, the AMG-073, are very promising and await long term evaluation. The goal of this manuscript is to review the physiological, biological and clinical bases for the development of calcimimetic. Moreover, to try to replace the potential use of these drugs in the context of chronic renal failure and in the treatment of secondary hyperparathyroidism.
Animals↗
[Arterial hypotension in dialysis].
Arterial hypotension, defined as a systolic blood pressure < 100 mmHg, is the most frequent complication in dialysis patients. Four types of hypotension can be identified: chronic, per-dialytic, hypotensive shock and the hypotension due to an unexpected cause. The pathophysiology is relatively well known when the hypotension is secondary to a decrease in the intravascular volume provoked by a sustained ultrafiltration rate during the dialysis session. However, new mechanisms also appear to play an-important role, namely, the dysfunction of the autonomic nervous system and the plasmatic accumulation of vasoactive substances such as adrenomedullin, nitric oxide, and asymmetric dimethyl arginine. Hypotensive episodes can be responsible of acute vascular complications such as myocardial ischemia, ischemic cerebro-vascular accidents, venous thrombosis (retina vein), intestinal ischemia and the aggravation of lower member arteritis. In the long-term, pre-dialysis hypotension has been found associated with an increased mortality rate. The goal of this article is to review the pathophysiological mechanisms involved in the arterial hypotension of dialysis patients, its treatment and the potential preventive measures.
Autonomic Nervous System Diseases↗
Unilateral surgery for primary hyperparathyroidism on the basis of technetium Tc 99m sestamibi and iodine 123 subtraction scanning.
HYPOTHESIS: Parathyroid scanning, based on simultaneous recording of technetium Tc 99m sestamibi and iodine 123 images, is able to identify patients with multiple parathyroid gland disease and is a safe imaging technique for unilateral parathyroid surgery. DESIGN: Scintigraphic criteria of eligibility for unilateral surgery were prospectively tested against findings of conventional bilateral surgery. SETTING: Patients referred to an endocrine surgeon in a university hospital. PATIENTS: Seventy consecutive patients with primary hyperparathyroidism had dual-isotope scanning before conventional surgery. Forty-one patients had scan findings compatible with unilateral surgery, with a single focus of high intensity seen on the anterior and lateral views. The remaining 29 patients had 1 or more criteria of ineligibility: (1) scan findings pointing to multiple gland disease, (2) no well-identified focus, (3) contralateral thyroid nodule requiring surgical management, or (4) family history of hyperparathyroidism or multiple endocrine disease. MAIN OUTCOME MEASURES: Number of enlarged parathyroid glands at surgical inspection and calcemia follow-up. RESULTS: None of the 41 patients, with a single well-defined focus on the scan image, showed evidence of multiple parathyroid involvement. Each parathyroid adenoma was resected from the precise site predicted by the subtraction scan. Nine patients (13%) had surgical findings of multiple parathyroid gland disease. All 9 were ineligible based on preoperative image findings. CONCLUSIONS: Unilateral surgery can be safely offered to 60% of patients with primary hyperparathyroidism, on the basis of simultaneous (99m)Tc-sestamibi and (123)I scanning. This may reduce the length of the operation, anesthesia requirements, and hospital stay, and the risks of hypoparathyroidism and injury to the recurrent laryngeal nerve.
Adult↗
Vitamin D receptor as a candidate tumor-suppressor gene in severe hyperparathyroidism of uremia.
Most chronic renal failure patients with severe refractory hyperparathyroidism harbor at least one monoclonal parathyroid tumor, but the specific acquired genetic defects that confer this clonal selective advantage remain poorly understood. Somatic inactivation of the vitamin D receptor (VDR) gene could contribute to clonal outgrowth, because a parathyroid cell containing this lesion would have an impaired response to the antiproliferative influence of 1,25-dihydroxyvitamin D3. Furthermore, diminished expression of VDR protein has been described in uremia-associated parathyroid tumors. Therefore, to assess VDR gene inactivation's potential pathogenetic role in this disease, we rigorously analyzed the VDR gene in 59 parathyroid tumors surgically resected from uremic patients. First, Southern blotting and/or PCR analyses of 29 tumor samples from 14 genetically informative patients revealed no allelic losses at the VDR locus. Next, direct DNA sequencing of all VDR splice junctions, associated intronic sequences, and virtually the entire VDR-coding region for all 59 tumors revealed no acquired mutations. Last, 37 tumor DNA samples were subjected to comparative genomic hybridization, and no chromosomal losses in the VDR region (12cen-q12) were observed. These observations suggest that inactivating defects within the VDR gene do not commonly contribute to the primary pathogenesis of severe refractory hyperparathyroidism in uremia.
Adult↗
Circulating biochemical markers of bone remodeling in uremic patients.
Chronic renal failure is often associated with bone disorders, including secondary hyperparathyroidism, aluminum-related low-turnover bone disease, osteomalacia, adynamic osteopathy, osteoporosis, and skeletal beta2-microglobulin amyloid deposits. In spite of the enormous progress made during the last few years in the search of noninvasive methods to assess bone metabolism, the distinction between high- and low-turnover bone diseases in these patients still frequently requires invasive and/or costly procedures such as bone biopsy after double tetracycline labeling, scintigraphic-scan studies, computed tomography, and densitometry. This review is focused on the diagnostic value of several new serum markers of bone metabolism, including bone-specific alkaline phosphatase (bAP), procollagen type I carboxy-terminal extension peptide (PICP), procollagen type I cross-linked carboxy-terminal telopeptide (ICTP), pyridinoline (PYD), osteocalcin, and tartrate-resistant acid phosphatase (TRAP) in patients with chronic renal failure. Most of the observations made by several groups converge to the conclusion that serum bAP is the most sensitive and specific marker to evaluate the degree of bone remodeling in uremic patients. Nonetheless, PYD and osteocalcin, in spite of their retention and accumulation in the serum of renal insufficient patients, are also excellent markers of bone turnover. The future generalized use of these markers, individually or in combination with other methods, will undoubtedly improve the diagnosis and the treatment of the complex renal osteodystrophy.
Acid Phosphatase↗
Evolutive aortic stenosis in hemodialysis patients: analysis of risk factors.
Cardiovascular diseases represent the major cause of death in hemodialysis patients. However, little information is available about the repercussion of uremia on cardiac valves. We retrospectively investigated the incidence rate of aortic stenosis (AS), from 1991 to 1996, in 110 hemodialysis patients followed by Doppler-echocardiography. Progressive AS was diagnosed in 16 patients who had a decrease in their indexed aortic valve area from 1.24 +/- 0.09 to 0.66 +/- 0.21 cm2/m2 of BSA in 16.8 +/- 1.9 months. The mean incidence of AS per year was of 3.3%, ranging from 1.5 to 8.0%. Eight patients died in less than 3 years after the diagnosis of AS with a mean survival time of 23.0 +/- 9.5 months. Survival curves using Kaplan-Meier estimates showed a statistically significant decrease in the survival rate of patients with AS compared with patients without valvulopathy (p < 0.001). They were older than patients with normal valve, 68.6 +/- 11.1 versus 56.7 +/- 16.0 years, respectively. Men were 4 times more affected than women and showed a significantly more rapid progression to AS than women. The calcium-phosphorus product was higher in AS patients, 5.43 +/- 0.98 than in patients without AS, 3.95 +/- 0.50 mM. It was mainly due to hyperphosphatemia without hypercalcemia and the hyperphosphatemia was associated with biological signs of hypoparathyroidism or adynamic bone disease in 62% of the cases. Plasma vitamin D3 was also higher in patients with AS, 20.5 +/- 13.5 ng/ml than in those with normal valves, 9.6 +/- 6.3 ng/ml. Logistic regression showed that age, vitamin D3 and hyperphosphatemia correctly predicted 56% of the AS cases. In conclusion, AS is frequent and of poor outcome in hemodialysis patients. Age, relatively high plasma vitamin D3 levels, and hyperphosphatemia, mostly due to hypoparathyroidism, must be considered as risk factors.
Adult↗
Estrogen stimulates PTHrP but not PTH/PTHrP receptor gene expression in the kidney of ovariectomized rat.
The aim of the present study was to test the hypothesis that the decreased renal tubular reabsorption of calcium observed in estrogen deficiency is associated with a local regulation of either PTHrP or PTH/PTHrP receptor genes in the kidney. Rats were randomly sham-operated (S) or ovariectomized receiving either vehicle (OVX) or 4 microg E2/kg/day (OVX+E4) or 40 microg E2/kg/d (OVX+E40) during 14 days using alzet minipumps. Plasma PTH and calcium levels were lower in untreated OVX animals than in all other groups (P < 0.01). Plasma PTH was higher in OVX+E40 than in OVX+E4 (P < 0.05). PTHrP mRNA expression in the kidney was unaffected by ovariectomy but was increased in OVX+E40 (0.984 +/- 0.452 for PTHrP/GAPDH mRNAs expression vs. 0.213 +/- 0.078 in sham, P < 0.01). PTH/PTHrP receptor mRNA expression and the cAMP response of renal membranes to PTH were unaffected by ovariectomy and estrogen substitution. In conclusion, renal PTHrP and PTH/PTHrP receptor mRNAs are not modified by ovariectomy. However, 17beta-estradiol increases renal expression of PTHrP mRNA without evident changes in its receptor expression and function. This may help to explain the pharmacological action of estrogen in the kidney, especially how it prevents the renal leak of calcium in postmenopausal women.
Adenylyl Cyclases↗
Pamidronate corrects the down-regulation of the renal parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor mRNA in rats bearing Walker tumors.
Human hypercalcemia of malignancy (HHM) is generally due to the release into the circulation of parathyroid hormone-related peptide (PTHrP). PTHrP stimulates osteoclastic bone resorption and renal calcium reabsorption through the activation of a receptor similar to that of PTH (PTH-R). However, there is scarce information about the PTH-R regulation in the setting of the hypercalcemia. In the present study, we assessed the molecular basis of renal PTH-R regulation in Walker tumor-bearing rats either treated or not by a bisphosphonate, pamidronate. Twenty-seven 6-week-old rats were randomly divided into three experimental groups: WC- APD- (9 control rats), WC+ APD- (9 Walker tumor-bearing rats), and WC+ APD+ (9 Walker tumor-bearing rats receiving 15 mg/kg/day of sodium pamidronate every day for seven days). Pamidronate induced a significant decrease in the mean tumor weight (9.3+/-0.8 vs 6.3+/-0.6 g). Seven days after the subcutaneous implantation of the Walker cells, plasma total calcium was 10.8+/-0.4, 16.8+/-0.6, and 12.9+/-0.6 mg/dl in WC- APD-, WC+ APD-, and WC+ APD+, respectively. Plasma PTHrP concentration was undetectable, 15.9+/-2.6, and 7.2+/-1.4 pmol/l, respectively. Bone histomorphometric results showed high resorption in WC+ APD-, which returned below the basal level of the WC- APD- with pamidronate treatment. Densitometric analysis of Northern blots revealed that the renal PTH-R mRNA expression in WC+ WPD- rats was a quarter of the levels in the WC- APD- and WC+ APD+ groups. WC+ APD- also had a decreased PTH-stimulated cAMP production in renal membranes. The PTH-R was expressed in the Walker tumor and it was not modified by pamidronate treatment. In conclusion, the expression of PTH-R receptor mRNA is significantly reduced in the kidney of rats bearing Walker carcinoma tumor. Its regulation is tissue-specific: pamidronate, which partially corrected the hypercalcemia and elevated circulating PTHrP, normalized the PTH-R mRNA expression in the kidney but not in the tumor.
Adenylyl Cyclases↗
Secondary hyperparathyroidism: detection with I-123-Tc-99m-Sestamibi subtraction scintigraphy versus US.
PURPOSE: To compare iodine-123-technetium-99m-sestamibi subtraction scintigraphy with ultrasonography (US) for detection of parathyroid abnormalities in uremic patients with secondary hyperparathyroidism. MATERIALS AND METHODS: Fourteen adult uremic patients with severe secondary hyperparathyroidism underwent subtraction scintigraphy before total or subtotal parathyroidectomy. Subtraction scintigrams were acquired with a double-energy-window technique. US was performed with high-frequency transducers and standard methods. RESULTS: 1-123-Tc-99m-sestamibi subtraction scintigraphy correctly demonstrated 41 of 50 surgically confirmed enlarged parathyroids; US demonstrated 27. Sensitivity for detection of hyperplastic glands was 82% for scintigraphy and 54% for US. Scintigrams were correct in seven patients, and US scans were correct in five. Scintigraphy demonstrated all four enlarged parathyroids in six of 12 patients who were to undergo first surgery, whereas US demonstrated all four enlarged glands in three of the 12 patients. Gland weight was correlated with likelihood of detection with either method. Glands undetected at scintigraphy were significantly (P < .01) smaller (mean weight, 257 mg) than those undetected at US (mean weight, 467 mg). CONCLUSION: I-123-Tc-99m-sestamibi subtraction scintigraphy is efficient for detection of enlarged parathyroid glands in uremic patients with secondary hyperparathyroidism and is more sensitive than US.
Adult↗
Calcitriol may directly suppress bone turnover.
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Adult↗
[Alkaline phosphatase of bone origin in hemodialyzed patients. 110 assays].
OBJECTIVES: To evaluate the value of plasma bone-specific alkaline phosphatase (bAP) in the diagnosis and the prediction of the type of renal osteodystrophy in hemodialysis patients. To examine whether bAP correlated with the two classical biochemical markers of bone turnover in dialysis patients which are total alkaline phosphatases (tAP) and intact PTH (iPTH). METHODS: One hundred adult uremic patients undergoing regular hemodialysis therapy were included in the study. Plasma bAP was determined using a radioimmunometric assay. Intact PTH (1-84) was measured using a radioimmunometric assay, Allegro Intact PTH, Nichols Institute, CA, USA. Other laboratory tests including calcium, phosphorus, and tAP were performed by automated methods. RESULTS: Based on previous biochemical and histological data obtained in the same type of patients, we arbitrarily divided plasma bAP levels in normal (10-20 ng/ml), low (< 10 ng/ml), and high (> 20 ng/ml). We found here that bAP levels were normal in 27 patients, high in 36, and low in 37. In the group with normal bAP, 8/27 patients had iPTH levels higher than 200 pg/ml, the other 19 patients had an iPTH within the normal range. In the 36 patients with high bAP, 10 showed markedly high iPTH and clinical signs of severe hyperparathyroidism leading to the indication of a surgical parathyroidectomy in 7 patients and i.v. calcitriol therapy in the other 3. However, 9 of these 36 patients had an iPTH lower than 200 pg/ml and 17 between 200-500 pg/ml. In the 37 patients with low bAP, iPTH levels were also low in 15 of them, but 12 patients had iPTH levels higher than 200 pg/ml. There was a good correlation between bAP, tAP, and iPTH. However, bAP correlated better with iPTH than tAP. A bAP > 20 ng/ml had a sensitivity of 56%, specificity of 92% and positive predictive value of 80% in the prediction of an PTH higher than > 400 pg/ml and therefore of the biological diagnosis of hyperparathyroidism. A bAP < 10 ng/ml had a sensitivity of 70%, specificity of 56% and a positive predictive value of 48% in predicting a normal-low iPTH (< 100 pg/ml). CONCLUSION: In the absence of bone biopsy, plasma bAP self provides useful information about bone remodeling in hemodialysis patients. The combination of bAP and iPTH measurements further define the type of bone turnover. either elevated plasma bAP or iPTH alone are no always anonymous with secondary hyperparathyroidism.
Adult↗
PTH/PTHrP receptor mRNA is down-regulated in epiphyseal cartilage growth plate of uraemic rats.
PTH/PTHrP receptor mRNA is down-regulated in epiphyseal cartilage growth plate of uraemic rats. Growth retardation, hypocalcaemia, hyperphosphataemia, and skeletal resistance to the action of PTH are well known features of advanced chronic renal failure (CRF). It has been suggested that the downregulation of renal and skeletal PTH receptors (PTH/PTHrP-R) could play an important role in the occurrence of these abnormalities. In the present study, four uraemic (4 weeks after 5/6 nephrectomy) and four control (sham-operated) rats were analysed for PTH/PTHrP-R mRNA expression at the proximal femoral and tibial growth plates by in situ hybridization. Uraemic rats had plasma biochemical abnormalities of advanced CRF including high creatinine, phosphate, and PTH, and low calcium and calcitriol levels. The femoral and tibial bones of uraemic animals were shorter in length than those of control rats, and had reduced width and cellularity of the epiphyseal cartilage growth plate. Mean (+/- SD) tibia growth plate width was 152 +/- 30 microns in uraemic rats, compared with 170 +/- 35 microns in control rats. The difference was mostly due to a marked reduction of the zone expressing PTH/PTHrP-R (mature chondrocytes) which was 30 +/- 5 microns in tibias from uraemic versus 44 +/- 10 microns in tibias from control rats. The hybridization signals of PTH/PTHrP-R per individual cell were quantified on dark field images using a computer-assisted image analysis system. The number of grains in PTH/PTHrP-R positive cells was also decreased in uraemic rats, 103 +/- 13 compared with 123 +/- 14 arbitrary units (dark pixel density)/cell in control rats (P < 0.005). In conclusion, these data indicate that rats with severe CRF and secondary hyperparathyroidism have reduced epiphyseal cartilage PTH/PTHrP-R mRNA expression. This alteration may be relevant in the pathogenesis of growth retardation in uraemia.
Animals↗
Localization of parathyroid hormone/parathyroid hormone-related peptide receptor mRNA in kidney.
In kidney, parathyroid hormone (PTH) exerts differential distal effects along the nephron. To define cells expressing receptors for PTH in kidney, we localized PTH/ PTH-related peptide (PTH/PTHrP) receptor mRNA in rat kidney by in situ hybridization. PTH/PTHrP receptor mRNA is localized to glomerular podocytes, convoluted and straight proximal tubules, the cortical portion of thick ascending limbs, and distal convoluted tubules, but was not detected in the thin limb of Henle's loop or in collecting ducts. Northern blot analysis showed that cultured human glomerular podocytes express a unique 4.0-kb PTH/PTHrP receptor transcript but do not express detectable levels of the common approximately 2.4-kb transcript found in whole kidney and in many other tissues. Whereas the tubular localization of PTH/PTHrP receptor mRNA coincides well with previously known sites of PTH action, the intense expression and the unique size of the PTH/PTHrP receptor transcript in glomerular podocytes suggest that PTH and/or PTHrP may play a role(s) in glomerular function.
Autoradiography↗
Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients.
Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients. Plasma bone-specific alkaline phosphatase (bAP) has been demonstrated to be more reliable than total alkaline phosphatases (tAP) in providing information about bone turnover in patients with metabolic bone diseases. This study surveyed 42 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Plasma bAP was determined by using a new immunoassay (Tandem-R Ostase, Hybritech, Liège, Belgium). Plasma bAP values were compared with those of two other plasma markers of bone metabolism, namely tAP and intact parathyroid hormone (iPTH), for the correlations with bone histomorphometric parameters. Patients with high-turnover bone disease (HTBD) (N = 32) had significantly higher plasma bAP levels than patients with normal or low bone turnover (N/LTBD) (N = 10) (66.9 +/- 63.5 ng/mL versus 10.8 +/- 4.2 ng/mL, respectively). Bone formation and resorption were highly correlated in these patients, and plasma bAP levels were positively correlated with bone resorption parameters, including osteoclast surface (r = 0.39, P < 0.0001) and osteoclast number/mm2 (r = 0.36, P < 0.001), and with bone formation parameters, osteoblast surface (r = 0.50, P < 0.005), and bone formation rate (r = 0.91, P < 0.0001). The bone formation rate was better correlated with plasma bAP levels than with either plasma tAP or iPTH concentrations. Plasma bAP level equal or higher than 20 ng/mL, either alone or combined with plasma iPTH of 200 pg/mL, had the highest sensitivity, specificity, and predictability values for the diagnosis of high-turnover bone disease, and formally excluded patients with normal or LTBD. In conclusion, plasma bAP can be measured with a reliable immunoassay in hemodialysis patients. It represents a highly sensitive and specific biochemical marker of skeletal remodeling in these patients. Therefore, both serum iPTH and bAP are complementary in diagnoses of the type of renal osteodystrophy.
Alkaline Phosphatase↗