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Biomedical subjects

P Houillier

Publications and source records attributed to P Houillier.

At least 19 recordsLinked to original sources
PubMed2006

Inter-method variability in PTH measurement: implication for the care of CKD patients.

The National Kidney Foundation/Kidney-Dialysis Outcome Quality Initiative guidelines recommend to maintain the serum intact parathyroid hormone (PTH) concentration between 150 and 300 ng/l in chronic kidney disease (CKD) stage 5 patients. As these limits were derived from studies that used the Allegro intact PTH assay, we aimed to evaluate whether they were applicable to other PTH assays. We compared the PTH concentrations measured with 15 commercial immunoassays in 47 serum pools from dialysis patients, using the Allegro intact PTH assay as the reference. We also evaluated the recovery of graded amounts of synthetic 1-84 and 7-84 PTH added separately to a serum pool. Although the assays were highly correlated, the concentrations differed from one assay to another. The median bias between the tested assays and the Allegro intact PTH assay ranged from -44.9 to 123.0%. When the PTH concentrations were 150 or 300 ng/l with the Allegro intact PTH assay, they ranged with other assays from 83 to 323 ng/l and from 160 to 638 ng/l, respectively. The tested assays recognized 7-84 PTH with various cross-reactivities, whereas a given amount of 1-84 PTH was recovered differently by these assays. We found important inter-method variability in PTH results owing to both antibody specificity and standardization reasons. The unacceptable consequence is that opposite therapeutic attitudes may be reached in a single patient depending on the PTH assay used. We propose to use assay-specific decision limits for CKD patients, or to apply a correcting factor to the PTH results obtained with a given assay.

Adult↗
PubMed2006

Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular morbidity and mortality. Arterial stiffness and remodeling have been well documented in patients with end-stage renal disease, but little is known about arterial phenotype in CKD patients with moderate reduction in glomerular filtration rate (GFR). In total, 95 patients (58+/-15 years, mean+/-s.d.) with CKD and GFR measured by renal clearance of (51)Cr-ethylenediaminetetraacetate were compared to 121 hypertensive patients without CKD (59+/-11 years), and 57 normotensive subjects (56+/-6 years). Common carotid artery diameter, intima-media thickness (IMT), distensibility, and Young's elastic modulus were noninvasively determined with a high-definition echotracking system. Patients with CKD had a significantly larger carotid internal diameter than in hypertensives and normotensives (6.32+/-1.05, 5.84+/-0.74, and 5.50+/-0.64 m x 10(-3), respectively; P<0.001), resulting in 25% and 11% increases in circumferential wall stress, respectively, since no significant difference in IMT was observed. Carotid distensibility and elastic modulus did not significantly differ between CKD and hypertensives; normotensives had significantly higher distensibility and lower elastic modulus than CKD and hypertensive patients. Carotid-femoral pulse wave velocity was significantly higher in CKD patients than in hypertensives and normotensives. In multivariate analyses either involving the entire population or restricted to CKD patients, GFR was independently and strongly related to carotid diameter and elastic modulus. Arterial enlargement and increased arterial stiffness occur in parallel with the decline in renal function in patients with mild-to-moderate CKD.

Adult↗
PubMed2001

[Calcium-sensing receptors: physiology and pathology].

The near constancy of extracellular calcium concentration is required for the numerous physiological functions of extra- and intracellular calcium. This implies that any change in extracellular calcium concentration must be detected in order to allow the appropriate correction by the homeostatic systems. The identification and cloning of a calcium-sensing receptor (CaR), which is expressed in the plasma membrane of parathyroid cells as well as many other cell types, has been a major advance in the understanding of the mechanisms involved in the control of extracellular calcium concentration. In addition, it demonstrated that extracellular calcium concentration itself is the first informative hormone-like messenger in this system. CaR belongs to the C subfamily of seven transmembrane-spanning G protein-coupled receptors. Several inherited disorders in extracellular calcium homeostasis are due to both activating or inactivating mutations in CaR gene, strengthening the essential role of CaR in the control of calcium metabolism.

Calcium↗
PubMed2001

Bone status in primary hyperparathyroidism.

Traditional bone involvement, such as osteoitis fibrosa, has become very rare (< 1%) in primary hyperparathyroidism (PHPT); nevertheless, fractures seem more frequent than in controls, with a predilection for fractures of the distal extremity of the radius, pelvis, ribs and vertebrae, and a relative modest incidence of fractures of the upper extremity of the femur. Histo-morphometric studies have stressed a discrepancy between cortical and trabecular bone with an increase of bone remodeling. The cortical width is constantly diminished and the cortical porosity is increased whereas trabecular volume is normal and micro-architecture preserved. Bone mineral density (BMD) allows an early diagnosis of bone disease and takes a growing place in the management of patients. Since the consensus conference in 1991, the measurement of BMD has been incorporated in the surgical decision with a threshold: Z-score < -2. The demineralisation predominates on sites rich in cortical bone (1/3 proximal of the distal radius); the radius, which was the first site evaluated for technical reasons, is also the most discriminating one. Spine demineralisation is met in more severe forms and BMD measurement of the whole body is promising but requires more studies. In the absence of a radical processing, moderate forms remain stable, whereas more severe forms have a tendency to deteriorate. The evaluation of spine and femoral BMD is useful for the follow-up because the bone gain after parathyroidectomy is significant early on at these sites (rich in trabecular bone with high bone turnover), whereas the BMD of radius is relatively stable.

Bone Density↗
PubMed2001

Paracellin-1 is critical for magnesium and calcium reabsorption in the human thick ascending limb of Henle.

BACKGROUND: A new protein, named paracellin 1 (PCLN-1), expressed in human thick ascending limb (TAL) tight junctions, possibly plays a critical role in the control of magnesium and calcium reabsorption, since mutations of PCLN-1 are present in the hypomagnesemia hypercalciuria syndrome (HHS). However, no functional experiments have demonstrated that TAL magnesium and calcium reabsorption were actually impaired in patients with HHS. METHODS: Genetic studies were performed in the kindred of two unrelated patients with HHS. Renal magnesium and calcium reabsorption in TAL were analyzed in one homozygous affected patient of each family, one patient with extrarenal hypomagnesemia (ERH), and two control subjects (CSs). RESULTS: We found two yet undescribed mutations of PCLN-1 (Gly 162 Val, Ala 139 Val). In patients with HHS, renal magnesium and calcium reabsorptions were impaired as expected; NaCl renal conservation during NaCl deprivation and NaCl tubular reabsorption in diluting segment were intact. Furosemide infusion in CS markedly increased NaCl, Mg, and Ca urinary excretion rates. In HHS patients, furosemide similarly increased NaCl excretion, but failed to increase Mg and Ca excretion. Acute MgCl(2) infusion in CS and ERH patient provoked a dramatic increase in urinary calcium excretion without change in NaCl excretion. When combined with MgCl(2) infusion, furosemide infusion remained able to induce normal natriuretic response, but was unable to increase urinary magnesium and calcium excretion further. In HHS patients, calciuric response to MgCl(2) infusion was blunted. CONCLUSION: This study is the first to our knowledge to demonstrate that homozygous mutations of PCLN-1 result in a selective defect in paracellular Mg and Ca reabsorption in the TAL, with intact NaCl reabsorption ability at this site. In addition, the study supports a selective physiological effect of basolateral Mg(2+) and Ca(2+) concentration on TAL divalent cation paracellular permeability, that is, PCLN-1 activity.

Adolescent↗
PubMed2001

No evidence for point mutations of the calcium-sensing receptor in familial idiopathic hypercalciuria.

BACKGROUND: Idiopathic hypercalciuria (IH) is frequently associated with nephrolithiasis. As 40% of patients have a positive familial history of IH, an autosomal dominant mode of inheritance has been suggested. Numerous genes have been studied in this regard but none have been found to be linked to IH. Mutation of the calcium-sensing receptor (CaR) has never been studied. Therefore, we conducted a study to detect such mutations. METHODS: Seven families with IH and nephrolithiasis were recruited in a prospective study. Forty-two family members underwent 24-h urine calcium measurement. Twenty-five of them with 24-h hypercalciuria also underwent extensive metabolic evaluation. Blood samples were collected in one or two affected family members in each family and exons 2-7 of the CaR gene were sequenced. RESULTS: In the seven families, at least one parent and more than half of the children had hypercalciuria (21/30), consistent with autosomal dominant inheritance. Among the nine affected family members whose CaR gene has been studied, all nine had absorptive hypercalciuria, three also had fasting hypercalciuria, and one had renal phosphorous leak. No mutation of the CaR gene was detected in these seven families. Two previously reported polymorphisms were detected, each of them in five families: A986S and C-to-T change at -60 in intron 5. CONCLUSION: In these seven families, IH is not related to the CaR gene mutation. Although we cannot exclude that point mutations can be found in other families, familial IH does not seem to be generally associated with CaR mutation.

Adult↗
PubMed2000

[Primary hyperparathyroidism].

Primary hyperparathyroidism is the third most frequent endocrine disorder. The condition required for diagnosis is inappropriately elevated secretion of parathyroid hormone (PTH) with respect to calcemia. Most often, the disease is due to a parathyroid adenoma, i.e. a monoclonal benign parathyroid tumor, less often to a parathyroid hyperplasia. The main tumorogenic mechanisms currently proposed are a DNA rearrangement in the PTH locus (transposition of the PTH promoter upstream to Cyclin D1/PRAD 1 gene) and a mutation of the gene responsible for multiple endocrine neoplasia type I. The clinical presentation has strikingly evolved towards a milder, asymptomatic form, frequently diagnosed on systematic screenings. Though the mechanism of hypercalcemia is better understood, several hypothesis are still being considered about the regulation of tumoral PTH secretion: the role of the expression of calcium-receptor in parathyroid gland cells, vitamin D receptor and estrogen receptor polymorphisms, etc. Surgery is still advised for symptomatic forms of the disease, either because of a bone involvement, or because of an evolutive nephrolithiasis. In the near future, the new calcium-receptor agonists could be a relevant therapeutic approach.

Humans↗
PubMed1998

[Hypercalciuria].

Hypercalciuria is a very frequent disorder that is defined by a daily calcium excretion rate in excess of 0.1 mmol/kg. Whatever its mechanism, it always expresses an increased input of calcium in extracellular fluid, from intestine and (or) bone. In few instances, hypercalciuria is secondary to an underlying disease that needs to be identified (primary hyperparathyroidism, cancer, granulomatosis...). However, in most cases, it is a primary (idiopathic) disorder that reveals an abnormal handling of calcium by intestinal and renal tubular epithelia. It is then treated by a restricted dietary supply in sodium and animal proteins, and by the use of thiazide diuretics.

Absorption↗
PubMed1997

[Extraparathyroid hypercalcemias. Physiopathological and therapeutic aspects].

An increase in plasma calcium concentration is always the consequence of at least one of the following events: an increase in the net calcium input in extracellular fluid, a decrease in glomerular filtration rate, and an increase in the tubular reabsorption of the filtered calcium. In parathyroid hormone-related hypercalcemia, that is typically stable with time, the main determinant is the rise in parathyroid hormone-induced tubular calcium reabsorption. By contrast, in parathyroid hormone-independent hypercalcemia, usually steadily progressive (the main cause being hypercalcemia of cancer), the primary event is almost always a rapid increase in the net calcium input in extracellular fluid. The attendant hypercalcemia is commonly poorly tolerated and induces a renal sodium leak and a decrease in extracellular fluid volume. The latter leads to a fall in glomerular filtration rate and a rise in tubular calcium reabsorption which, in turn, worsen hypercalcemia. Treatment includes a reexpansion of extracellular fluid volume and the inhibition of bone calcium release.

Calcium↗
PubMed1997

Pregnancy in women with impaired renal function.

The outcome and consequences of pregnancy in women with impaired renal function are still debated. To assess the benefit of recent advances in coordinated obstetrical and nephrologic management, we analyzed fetal and maternal outcome of 43 pregnancies in 30 women with various types of primary renal disease and moderate to severe renal failure at conception defined by serum creatinine concentration (Scr) ranging from 0.11 to 0.49 mmol/l. All pregnancies took place during the 20-year period from 1975 through 1994 and were prospectively followed jointly by our Nephrology Unit and Obstetric and Neonatology Units of University Hospitals. Of the 43 pregnancies (45 fetuses), 13 ended in fetal death (including 5 first-trimester abortions and 8 fetal deaths beyond the 20th gestational week). There were 32 live births, a success rate of 82% not considering first-trimester abortions. Successful pregnancies were significantly more frequent in the last decade than in the preceding one (91 vs 65%, p = 0.05). Overall live birth rate was higher in pregnancies started with Scr < 0.20 mmol/l than in those with Scr > 0.20 mmol/l (80% vs 53%, p = 0.02). The upper preconception Scr value associated with a successful fetal outcome was 0.27 mmol/l. Hypertension was the major factor of fetal prognosis, as the relative risk of fetal loss was 10.6 times higher when hypertension was present at conception or early in pregnancy than when blood pressure was spontaneously normal or well-controlled by therapy. An accelerated course toward end-stage renal failure was observed in 7 patients (23%), all of whom had severe hypertension and heavy proteinuria at conception. We conclude that fetal outcome in patients with impaired renal function has been improved in recent years, due to advances in obstetrics and neonatology, improved blood pressure control and close co-operation between nephrologists and obstetricians, but that a risk of fetal loss and of accelerated deterioration of maternal renal disease still persists when Ccr at conception is lower than 25-30 ml/ min/1.73 m2.

Adult↗
PubMed1996

Pregnancy in women with reflux nephropathy.

Reflux nephropathy is one of the most prevalent renal diseases and a leading cause of chronic renal failure in women-of childbearing age. To evaluate the issue and possible complications of pregnancy in women with reflux nephropathy, we retrospectively analyzed fetal and maternal outcome in 158 women who had 375 pregnancies between 1965 and 1994. The overall fetal death rate was 10.2% and tended to decrease in the 1985 to 1994 decade as compared to the preceding period (8.4% vs. 12.6%). The relative risk of fetal death was 4.8 times greater hypertension was present at conception than in normotensive patients. Fetal death rate was also higher in patients with impaired renal function that in those with serum creatinine < 0.11 mmol/liter at conception (36.7% vs. 7.7%, P < 0.0001). Urinary tract infection accounted for frequent morbidity but seldom resulted in fetal mortality. Maternal renal disease was unaffected by pregnancy, excepted for 4 of the 21 patients with pre-existing renal failure who exhibited an irreversibly accelerated course after pregnancy. We conclude that pregnancy is essentially successful and uneventful in patients diagnosed with reflux nephropathy who have normal blood pressure and preserved renal function, whereas the fetal prognosis is more compromised and there is a risk of accelerated progression of maternal renal disease when serum creatinine concentration is in excess of 0.22 mmol/ liter. This suggests that women with reflux nephropathy should preferably conceive before having reached that stage of renal failure.

Adolescent↗
PubMed1996

Calciuric response to an acute acid load in healthy subjects and hypercalciuric calcium stone formers.

Excessive animal protein consumption is associated with a greater risk of occurrence of renal calcium stone, presumably because of the attendant endogenous acid production. Indeed, chronic acid load enhances urinary calcium excretion possibly through an increased bone calcium release. Because acute studies are best designed to elucidate the mechanism, renal or extra renal, underlying hypercalciuria in the setting of enhanced acid load, we examined the response of 9 healthy adults (8 males, 1 female, aged 38 +/- 3 years, weight 67 +/- 2 kg) and 34 hypercalciuric recurrent calcium stone formers (31 males, 3 females, aged 44 +/- 2 years, weight 72 +/- 2 kg), without any associated disease, to an oral acid load (NH4Cl 2 mmol/kg body wt). After an overnight fast, each patient and control was studied during one one-hour period before and three two-hour periods after their intake of the acid load. An additional group of four time-control subjects (4 males, aged 33 +/- 2 years, weight 66 +/- 2 kg) was studied as the experimental groups except that they did not receive the acid load. On baseline, the three groups exhibited similar glomerular filtration rates, net acid excretions, and plasma calcium and magnesium concentrations. However, fasting urine calcium and magnesium excretions were higher in hypercalciuric calcium stone formers than in healthy control or time-control subjects. In time-control subjects, plasma acid base status, net acid excretion, filtered loads of calcium and magnesium, and urinary calcium and magnesium excretions remained unchanged all over the study. By contrast, after the oral acute acid load, net acid excretion increased and urinary pH decreased similarly in patient and control groups; glomerular filtration rate did not change, as well as plasma calcium and magnesium concentrations. Nevertheless, urinary calcium and magnesium excretions markedly increased, in both groups, independently of changes in tubular sodium handling and in plasma parathyroid hormone concentration. The increase in urinary calcium and magnesium excretions that occurred in the absence of any change in the filtered load of calcium and magnesium was therefore mediated by a decrease in tubular calcium and magnesium reabsorption, independent of PTH, but dependent on changes in net acid excretion. A positive linear relationship between urinary calcium and magnesium excretions suggested that the target tubular site for acid load was the thick ascending limb of Henle's loop. Finally, a negative linear relationship was demonstrated between the acid load-induced increase in urinary calcium excretion and fasting urinary calcium excretion; indeed, the lowest calciuric responses were observed in patients with the highest fasting urinary calcium excretion. Thus there was no additional effect of the acid load-induced inhibition on intrinsic defect in tubular calcium reabsorption which suggests that the tubular target site for acid load and the site of calcium transport defect in idiopathic hypercalciuria may be the same.

Acidosis↗