[Treatment of secondary hyperparathyroidism resistant to conventional therapy and tertiary hyperparathyroidism with Cinacalcet: an efficiency strategy]. / Traitement de l'hyperparathyroïdie secondaire, résistante aux thérapeutiques conventionnelles, et de l'hyperparathyroïdie tertiaire par le cinacalcet: une stratégie efficace.

INTRODUCTION: The treatment of secondary hyperparathyroidism (SHPT) in dialysis patients has changed with the introduction of cinacalcet (CC), which represents a medical alternative to surgical parathyroidectomy (PTX). The aim of our study is to prospectively assess the tolerance and efficacy of CC in patients, treated in one centre using long haemodialysis, with SHPT who do not respond to conventional therapy. PATIENTS AND METHODS: We prospectively observed all patients treated with CC between September 2004 and 2009. The characteristics of the patients were compared with that recorded for the patients non treated with CC. Biological factors and the efficacy of the treatment in the patients were compared before (T-0) and after (T-End) CC therapy. The haemodialysis (HD) schedule was 3 x 5 to 3 x 8 h per week. The biological criteria for CC prescription were a serum PTH level greater than 300 pg/ml, calcium level greater than 2.45 mmol/l and bone alkaline phosphatase level greater than 20 microg/l or, in cases of tertiary hyperparathyroidism (THPT), a calcium level greater than 2.55 mmol/l. RESULTS: Eighty-one (14.7%) among the 550 HD patients were treated with CC. As compared to the untreated population, these patients were younger and had higher body mass index (BMI) and higher protein-catabolic rate (nPCR). The treatment failed in 6.1% of the treated patients; 12.3% had severe gastrointestinal side effects and 10% underwent PTX. The treatment was successful in 81.4% patients who were prescribed a mean final CC dosage of 51+/-30 mg/day. Between T-0 and T-End (18+/-15) months), the serum PTH levels decreased by 77%, calcaemia levels decreased by 10% and phosphataemia levels decreased by 14%. Therefore, the percentage of patients with normal biological parameters increased significantly : serum PTH (150-300 pg/ml: 0 to 50%), calcaemia (2.1-2.37 mmol/l: 6 to 77%) and phosphataemia (1.15-1.78 mol/l: 58 to 84%). After 12 months, eight patients (10%) successfully weaned from CC therapy. No episodes of hypocalcaemia (<2.0 mmol/l) occurred. Treatments with alfacalcidol (68 to 40%) and sevelamer (72 to 50%) decreased, treatments with CaCO(3) remained stable (20%), those with native vitamin D increased (55 to 95%). CONCLUSION: The treatment of HD patients having SHPT and THPT with CC and vitamin D derivatives was efficacious and well tolerated in a majority of cases after the failure of conventional therapies. These treatments improved mineral metabolism significantly.

Intensive dialysis and blood pressure control: a review.

The prevalence of hypertension in hemodialysis (HD) patients has increased over the years. In the early days of maintenance HD blood pressure (BP) control was achieved in most patients. As sessions were shortened, the prevalence of hypertension increased. Yet, in principle, dialysis is able to control hypertension. Today, in programs using long HD, most patients are normotensive without antihypertensive medication. The same is true for patients on daily dialysis, but not for those on short thrice-weekly HD. In all studies reporting BP normalization, dry weight is regularly achieved. Why the poor control of hypertension now? At first sight the shortened session duration is the culprit. This is suggested by several epidemiologic observations and strongly supported by a prospective experience of changing the HD schedule (short to long HD or conversely) in the same group of patients. Recent studies, however, using strict volume control show that BP normalization can be obtained in conventional 3 x 4 hr/week dialysis with relatively low delivered Kt/V(urea). Therefore, prolonging the dialysis time and/or increasing the dialysis dose are not required to achieve BP control. Intensive dialysis most probably normalizes BP by getting the extracellular volume and the amount of sodium in the body back to normal. It acts in conjunction with a moderate dietary sodium restriction and the use of reasonably low dialysate sodium. With this approach improved BP control can be achieved in the vast majority of HD patients.

Long 3 x 8 hr dialysis: a three-decade summary.

A long hemodialysis (HD), 3 x 8 hours/week, has been used without significant modification in Tassin for 35 years with excellent morbidity and mortality results. It can be performed during the day or overnight. The relatively good survival is mainly due to a lower cardiovascular mortality than usually reported in dialysis patients. This in turn is mainly due to the good control of blood pressure (BP) including drug-free hypertension control and low incidence of intradialytic hypotension. This control of BP is probably the result of the tight extracellular volume normalization (dry weight), although one cannot exclude the effect of other factors such as serum phosphorus control well achieved using long dialysis. The high dose of small and even more of middle molecules is another essential virtue of long dialysis, leading to good nutrition, correction of anemia, control of serum phosphate and potassium with low doses of medications and providing a very cost-effective treatment. In 2002 one must aim at optimal rather than just adequate dialysis. Optimal dialysis needs to correct as perfectly as possible each and every abnormality due to renal failure. It can be achieved using longer (or more frequent) sessions. Overnight dialysis is the most logical way of implementing long HD with the lowest possible hindrance on patient's life. Due to the change in case mix a decreasing number of patients are able or willing to go on overnight dialysis, education to be autonomous is more difficult, but the benefit is still there.

Clinical Determination of Dry Body Weight.

While nephrologists wait for the ideal, non invasive, inexpensive, precise, and reproducible tool to evaluate extracellular volume (ECV), they need to exert their clinical acumen in the quest of that holy grail, dry weight (DW). Estimation of DW using a clinical approach based on blood pressure (BP) and ECV is feasible and reliable as shown by successful experiences in various dialysis modes over more than three decades. But a need still exists to resolve difficulties associated with accurate assessment of BP (methods and circumstances of measurement, and the confounding effects of antihypertensive drugs) and ECV (evaluation of weight changes unrelated to ECV, lack of specificity and sensitivity of clinical symptoms, lag time, confusion in terminology). An essential point in clinical assessment of DW is that a normal BP is at the same time the target and the crucial index of DW achievement. For this reason, a trialand-error "probe" process has to be used at intervals to make sure that the dry weight target point is correctly estimated. The various "non clinical" methods proposed for dry weight assessment increase the complexity and the cost of hemodialysis. They are, in the present state of things, more clinical research than practice tools. They do not replace clinical judgment.