Philippe Morinière

Disappearance of Aluminic Bone Disease in a Long Term Asymptomatic Dialysis Population Restricting Al(OH)3 Intake: Emergence of an Idiopathic Adynamic Bone Disease Not Related to Aluminum

In dialysis centers using reverse osmosis-treated water but not restricting A1(OH)3 administration, a high prevalence of histological aluminum bone disease has been reported. To assess whether this is also the case in our center where A1(OH)3 intake has always been restricted and even completely given up after 1980 thanks to high doses of CaCO3, we reviewed 42 bone biopsies performed between 1975 and 1985 in patients dialyzed for a mean duration of 56 months. Seventeen of these patients had been dialyzed before 1978 with softened water moderately contamined by aluminum, 15 had always been dialyzed with reverse osmosis-treated water and 10 had been exclusively treated by hemofiltration. The prevalence of aluminum bone disease in the whole population was 9.5% (4 patients) and consisted only of adynamic bone disease, osteomalacia being totally absent. When the patients dialyzed with aluminum-contaminated water were excluded as well as 1 diabetic patient who had taken A1(OH)3 for 1.5 years the prevalence of aluminum bone disease was null in this population. When the whole population is considered the prevalence of the other types of bone disease was 76% for osteitis fibrosa and 14.5% for a non-aluminic adynamic bone disease (6 cases). These latter cases differed from the osteitis fibrosa group only by a relative hypoparathyroidism not explained by higher plasma concentrations and higher oral cumulative doses of calcium, magnesium and aluminum or by lower plasma concentrations of phosphate and bicarbonate. None had previous parathyroidectomy, one had an unsuccessful transplantation and one was diabetic. Iron overload was excluded by negative Perls staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of Permcath (Quinton) Catheter in Uraemic Patients in Whom the Creation of Conventional Vascular Access for Haemodialysis Is Difficult

During the last 4 years, the Permcath Quinton double-lumen silicone catheter was inserted into the internal jugular vein of 57 uraemic patients with difficulty for creating conventional vascular access for haemodialysis. In 4 patients, with definitive contraindication of conventional vascular access, this catheter still permits haemodialysis after a duration of 8-25 months. In 25 further patients with terminal uraemia, but poor vein system, it allowed the maturation of an arteriovenous fistula after 2-14 months of use. In 17 patients already on chronic haemodialysis, but who lost abruptly their vascular access (15 grafts and 2 arteriovenous fistulae), it allowed a new arteriovenous fistula to mature in 16 cases after a mean duration of 7.3 +/- months. In 5 patients with short life expectancy because of neoplasia, it allowed to dialyse them until their death which occurred after 6.5 +/- 2.2 months. In 6 patients with acute renal failure and haemostasis problems, it allowed to perform not only dialysis, but also plasmapheresis in 3 and parenteral nutrition in 3 other cases. The complications were the following: sepsis (n = 3); episodes of hypocoagulability due to inadvertent injection of heparin stored in the lumen (n = 2), thrombosis of the lumen (n = 3), and insufficient flow (n = 6). In no case these complications prevented continuation of haemodialysis. The catheter had to be removed in 2 cases because of septis and in 1 case because of insufficient flow. In 3 cases the catheter had to be replaced because of thrombosis and in 1 case because of laceration. These complication rates are, however, fewer than those reported in the literature for arteriovenous shunts or rigid subclavian and femoral catheters. The Permcath catheter seems, therefore to be the method of choice for immediated vascular access in patients in whom the creation of conventional vascular access is difficult.

Evaluation of vascular calcinosis risk factors in patients on chronic hemodialysis: lack of influence of calcium carbonate

UNLABELLED Linear calcifications of the abdominal aorta and of the iliac and femoral arteries were measured yearly for 3 years on X rays of 24 patients on chronic hemodialysis taking variable amounts of calcium carbonate and Al(OH)3 but no pharmacological doses of vitamin D or 1 alpha-hydroxylated vitamin D derivatives. The speed of their extension appeared exponential and covariant with the male sex, age only for men and, independently of these two factors, with diastolic blood pressure and blood triglycerides. Plasma concentrations of calcium, phosphate and glucose were covariant with the extension of calcinosis only at a borderline level. The doses of calcium carbonate and the levels of plasma alkaline phosphatase were not at all covariant. CONCLUSIONS (1) The effect of high doses of calcium carbonate is possibly harmful only when supraphysiological levels of plasma calcium are induced, whereas plasma phosphate is not adequately decreased. The doses of calcium carbonate per se have no deleterious effect (2). Since alkaline phosphatase is not covariant with the extension of calcinosis, the degree of hyperparathyroidism per se does not seem to play a causative role in vascular calcinosis (3). The main risk factors of vascular calcinosis are: age, the male sex, diastolic blood pressure and blood triglycerides.

Invasive versus non-invasive diagnosis of renal bone disease.

&NA; At present, bone histomorphometry remains the gold standard for the diagnosis of the various types of renal bone disease. In the search for a non‐invasive method of diagnosis, biochemical serum markers of bone remodelling, in addition to serum intact parathyroid hormone and aluminium determinations, have been proposed as the most reliable tools and are at present widely used in clinical practice. Their respective diagnostic values, as separate items and in combined analysis, are thoroughly discussed in the present review.

Viewpoint: How Do Calcimimetics Fit Into the Management of Parathyroid Hormone, Calcium, and Phosphate Disturbances in Dialysis Patients?

As suggested by its American brand name (Sensipar), the calcimimetic cinacalcet sensitizes the parathyroid cells to the extracellular calcium signal, suppressing parathyroid hormone (PTH) release and synthesis and preventing parathyroid cell proliferation. This primary PTH suppression decreases the release of calcium and phosphate from bone without increasing intestinal absorption of calcium and phosphate. Therefore cinacalcet decreases the risk of hypercalcemia and hyperphosphatemia in contrast to 1α‐OH vitamin D derivatives. Compared with calcium‐containing oral phosphate binder (OPB), it increases the risk of hypocalcemia and may decrease the PTH‐mediated phosphaturia in predialysis patients. This justifies its combined use with calcium‐containing OPB in order to prevent hypocalcemia and enhance the hypophosphatemic effect of the latter, while improving PTH suppression. The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) has recommended restriction of supplemental elemental calcium to 1.5 g/day, a recommendation that we believe should be revised. No pathophysiologic or randomized trial data have yet evidenced the absolute necessity for systematically using 1α‐OH vitamin D derivatives and noncalcium‐containing OPB rather than higher doses of calcium‐containing OPB alone in uremic patients without vitamin D insufficiency. In patients with hyperparathyroidism as severe as in the “Treat to Goal Study,” the Durham study showed that a calcium carbonate dose more than three times the K/DOQI limit could decrease PTH into the recommended range, with the advantage of a lower calcium‐phosphate product compared with the combination of calcitriol and noncalcium OPB. Besides the efficient PTH suppression associated with lower calcium‐phosphate product and a good gastrointestinal tolerance, long‐term data suggest that cinacalcet may decrease the risk of parathyroidectomy and fracture, while high bone turnover lesions are improved. However, no long‐term data on bone mineral density and cardiovascular calcification and complications are yet available. Such studies, along with those comparing cinacalcet and 1α‐OH vitamin D‐based approaches to hyperparathyroidism, are needed.

Comparison of 1α-OH-Vitamin D3 and High Doses of Calcium Carbonate for the Control of Hyperparathyroidism and Hyperaluminemia in Patients on Maintenance Dialysis

27 patients on hemodialysis (dialysate aluminium less than 0.7 mumol/l for 2 years, and 2 mumol/l before) whose plasma Ca and PO4 were adequately controlled for already 6 months by high doses of CaCO3 alone (mean +/- SD: 9 +/- 5 g/day), were randomly divided into 2 groups, a control group (c group) which was kept on the same treatment, and a group in which CaCO3 was reduced to 3 g/day but in which plasma Ca was kept normal due to 1 alpha-OH-vitamin D3 administration (1 microgram/day at the beginning, 0.3 microgram/day after 6 months; 1 alpha group) whereas plasma phosphate was kept below 6.0 mg/dl because of Al(OH)3 (2.7-5 g/day). Initially, the 2 groups were comparable as regards the plasma concentrations of total and ionized Ca, phosphate, alkaline phosphatases, medium and C-terminal parathyroid hormone (PTH) and aluminium, but the control group had lower plasma 25-OH-vitamin D (25-OHD.) After 6 months, the same difference in plasma 25-OHD was found with comparable plasma concentrations of total and ionized calcium as well as of medium and C-terminal PTH (beta error 1%). However, plasma concentration of phosphate and the plasma Ca phosphate product, as well as the plasma aluminium were higher in the 1 alpha group whereas their PCO3H- was lower. Although the alkaline phosphatase values were not significantly different between the 2 groups, they increased only in the control group because of 1 patient who developed a vitamin-D-deficient osteomalacia (plasma 25-OHD 3 ng/ml), which was subsequently cured by physiological doses of 25-OHD3. The incidence of transient hypercalcemia (15 vs. 21 episodes) and worsening of soft tissue calcifications (3 in each group) was the same in the 2 groups.

Reappraisal of 2003 NKF-K/DOQI guidelines for management of hyperparathyroidism in chronic kidney disease patients

The 2003 guidelines for the management of hyperparathyroidism in chronic kidney disease compiled by the Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation (NKF-K/DOQI) were formulated on the basis of work published up until 2001. Since then, new drugs (e.g. calcimimetics and lanthanum carbonate) have become available, and others (e.g. sevelamer, nicotinamide and paricalcitol) have been more stringently clinically evaluated. Because of these advancements, a reappraisal of the 2003 guidelines is justified. In this article we critically review the following recommendations of the NKF-K/DOQI: (i) routine use of 1.25 mmol/l (5.0 mg/dl) dialysate calcium and 1αOH-vitamin D derivatives; (ii) limitation of the maximal daily dose of calcium-based oral phosphate binders to 1.5 g of elemental calcium; and (iii) not correcting vitamin D insufficiency in dialysis patients.

Drug Insight: renal indications of calcimimetics

Calcimimetics suppress the secretion of parathyroid hormone by sensitizing the parathyroid calcium receptor to serum calcium. Cinacalcet (Sensipar®/Mimpara®, Amgen Inc., Thousand Oaks, CA), the first-in-class calcimimetic agent approved for treatment of secondary hyperparathyroidism in dialysis patients, is, in association with higher dose of a calcium-based oral phosphate binder, a well-tolerated and effective alternative to standard treatments such as vitamin D derivatives in association with a non-calcium-based oral phosphate binder. Here, we present an overview of evidence in support of this assertion. We extend our discussion to encompass other indications for calcimimetics—secondary hyperparathyroidism in predialysis chronic kidney disease patients, hypercalcemic hyperparathyroidism in renal transplant recipients, primary hyperparathyroidism, and hypercalcemia associated with parathyroid carcinoma—as well as providing guidance on optimal usage of this drug.

A comparison of bicarbonate kinetics and acid-base status in high flux hemodialysis and on-line post-dilution hemodiafiltration

Objectives: To compare bicarbonate kinetics and acid base status in HD and HDF for the same patient; and to investigate the effect of patient physiologic parameters on these kinetics. Methods: In order to monitor HCO3- kinetics during dialysis, acid-base parameters, pH, blood gases partial pressures, and HCO3- concentrations were recorded during 3 regular dialysis (HD) and 3 on-line post-dilution HDF sessions performed on 12 patients, using same dialysis fluid with a 38 mmol/l HCO3-concentration. HCO3- mass transfers through the hemodialyzers membranes and into the patients were continuously calculated during the sessions from HCO3- concentrations, together with HCO3-dialysance. The “apparent” HCO3-gain was calculated by integrating over time the instantaneous mass transfer from dialyzer and re-infusion fluid to the patient. A second method consisted in calculating the patient apparent bicarbonate space (ABS) and HCO3- mass (ABS times plasma concentration) at beginning and end of session. Results: No significant differences were observed between acid base parameters at the end of HD and HDF sessions. In contrast to urea clearances, HCO3- dialysances decayed with time during sessions from 110 to 140 ml/min to about 40 ml/min after one hour. The net HCO3- gain was taken as the difference between final and initial HCO3-masses. This net gain was in average 63% of apparent gain in HD and 74% in HDF. Conclusions: Uremic acidosis was well corrected without risk of alkalosis. An unexpected result was the continuous decay of bicarbonate dialysance both in HD and HDF during runs.

Importance de l'activité chirurgicale liée à l'insuffisance rénale chronique dans un bloc opératoire d'urologie et de transplantation

OBJECTIVE To evaluate the proportion of surgical workload, in terms of time and number of procedures, devoted to chronic renal failure surgery in an urology and transplantation operating room. MATERIAL AND METHODS Analysis of the operative activity of the urology and transplantation operating room of Amiens Hospital over a period of one year (2003), by evaluating the number of procedures and the operating room occupation time (time between entry and exit from the operating room) recorded on ecology forms completed for each operation. Procedures performed in this operating room comprise conventional adult urological surgery and chronic renal failure procedures (from creation of venous access sites for haemodialysis to treatment of complications of renal transplantation). RESULTS Surgical management of chronic renal failure in the operating room represents 22.6% of all procedures and 30.1% of the operating room occupation time. 69% of the renal transplantation operating time and 95% of kidney harvesting operating time are performed on an oncall basis. CONCLUSION Operative activity related to chronic renal failure represents almost one third of the total surgical workload of a department managing this disease. These data justify the allocation of additional surgical resources adapted to this activity that is growing in parallel to the number of patients with chronic renal failure.Resume Objectif Evaluer en temps et en nombre d’actes, la part de l’activite consacree a la chirurgie de l’insuffisance renale chronique dans un bloc operatoire d’urologie et de transplantation. Materiel et methodes Analyse de l’activite operatoire du bloc d’urologie et de transplantation du CHU d’Amiens au cours d’une annee (2003), en evaluant le nombre d’actes et le temps d’occupation du bloc (temps entre l’entree et la sortie du bloc) recueillis partir des fiches d’ecologies remplies pour chaque intervention. Ces actes regroupent d’une part ceux de la chirurgie urologique classique de l’adulte et d’autre part l’ensemble des actes de I’insuffisance renale chronique (depuis la creation des voies d’abord de l’epuration extra renale jusqu’aux complications de la transplantation renale). Resultats La prise en charge de l’insuffisance renale chronique au bloc operatoire represente 22,6% des actes et 30,1% du temps d’occupation du bloc operatoire. Soixante neuf pour cent du temps operatoire des transplantations renales et 95% de celui des prelevements d’organes sont effectues sur l’astreinte. Conclusion L’activite operatoire liee a l’insuffisance renale chronique represente pres d’un tiers de l’activite operatoire globale d’un Service qui prend en charge cette pathologie. Ces donnees justifient l’attribution de moyens chirurgicaux supplementaires adaptes a cette activite dont l’importance croit parallelement au nombre de patients insuffisants renaux chroniques.