[Proportion of surgical workload related to chronic renal failure in an urology and transplantation operating room]. / Importance de l'activité chirurgicale liée à l'insuffisance renale 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.

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.

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.

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 1 alphaOH-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.

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 1alpha-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 1alpha-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 1alpha-OH vitamin D-based approaches to hyperparathyroidism, are needed.

Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.

Bone mineral density directly correlates with elevated serum leptin in haemodialysis patients.

BACKGROUND: Experimentally, leptin has a positive effect on bone mass when infused intravenously, but a negative one after intracerebroventricular administration. Renal failure increases its serum level above the concentration beyond which its transport to the brain may be saturated. Thus, we tested, in a chronic haemodialysis population, the hypothesis of a positive relationship between serum leptin and bone mineral density (BMD) when serum levels are above this threshold. METHODS: Serum leptin (using a two-site RIA), and BMD at the femoral neck, midshaft, and ultradistal radius, as measured by DEXA, were assessed in 17 female and 16 male chronic dialysis patients, with comparable calcium and phosphate metabolism, age and dialysis duration. RESULTS: Polynomial regression analysis showed a U-shaped correlation between BMD Z-score, with an inflexion point, which may correspond to the concentration threshold at which leptin blood-brain carrier is saturated. Linear regression analysis showed no correlation between BMD and serum leptin levels below these points but a significant positive correlation between BMD at the two radius sites and leptin levels above these points. The correlation remained significant after adjustment for BMI, serum PTH and duration of dialysis. Leptin levels were twice as high in female patients and associated with higher BMD Z-scores close to zero. CONCLUSIONS: This study suggests a bone-sparing effect of serum leptin in haemodialysis patients only when the serum levels of leptin were higher than the presumed threshold of blood-brain transport saturation. Higher leptin levels in post-menopausal female haemodialysis patients than in male patients may account for their slower bone loss with ageing.