Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences.

BACKGROUND: Vascular calcifications (VCs) are frequently observed in chronic kidney disease (CKD) and haemodialysis (HD) patients. They have been associated with numerous factors, particularly hyperphosphataemia, excess calcium load, hypertension and increased mortality rate. The purpose of this study is to measure VCs in long-HD patients with good blood pressure and phosphate control, with the occasional use of sevelamer, using a plain radiological score to identify the associated factors and effects on the 1-year survival rate. METHODS: We studied HD patients from one centre using a semi-quantitative score ranging from 0 to 3 according to the severity and extent of VCs. The following patients' characteristics were compared according to their VC scores: medical history, treatments, blood pressure, standard biological data, fibroblast growth factor (FGF) 23, osteoprotegerin (OPG), whole PTH, beta-crosslaps, bone alkaline phosphatases and bone mineral density scores. One-year survival analyses were also performed. RESULTS: Among the 250 HD patients of the centre, 161 were studied; the mean age was 67.2 +/- 13 years, 45% of the subjects were females, 35% were diabetics, and they had been on dialysis for between 1-486 months (median: 45 months) with a 3 x 5-3 x 8 h dialysis schedule using 1.5 mmol/l dialysate calcium and providing a mean 2.25 +/- 0.5 Kt/V. Only 17% of the patients were free from VCs and 11% had severe VCs. The factors associated with VCs were classified into 'classic' (age, diabetes, male gender, tobacco use, inflammation, more frequent warfarin treatment and peripheral vascular and cardiac diseases) and 'non-traditional' (higher FGF-23 and OPG serum levels, low albumin serum levels and low alfacalcidol and CaCO(3) use). In logistic regression, only age, diabetes and FGF-23 serum levels were associated with VC scores of 2 and 3. The patients with a score of 3 had a higher 1-year mortality rate (RR 2.1; P = 0.01) as compared to patients with a 0 score. CONCLUSION: A plain radiological score showed the high prevalence (83%) of VCs in HD patients in spite of a long and intensive dialysis strategy and adherence to guidelines. The main associated factors were classic factors such as ageing and diabetes. No relationship was found with blood pressure and phosphataemia that remained well controlled in long dialysis; the association with FGF-23 serum levels may aggregate some non-traditional risk factors. The harmful effects of VCs on survival require their systematic assessment and optimization of the potentially modifiable associated factors in CKD and HD patients.

High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients.

BACKGROUND: Fibroblast growth factor (FGF)-23, a novel bone-derived phosphaturic factor involved in mineral metabolism, is increased in chronic kidney disease (CKD); in dialysis patients, it has been linked to increased mortality rates and vascular calcification (VC). The present investigation aimed to study the factors associated with elevated serum FGF-23 levels in patients treated with long haemodialysis (LHD) sessions and to determine whether a relationship exists between serum FGF-23 levels and patient survival. METHODS: All patients treated in one haemodialysis centre from September 2006 were included in the study. Standard laboratory values, medical history, cardiovascular events and risk factors, medication and FGF-23 levels [ELISA (C-Term) Immutopics] were recorded. Patients received haemodialysis three times a week, on a 5- to 8-h schedule. Patient data were analysed according to FGF-23 quartiles. The effect of FGF-23 on the 2-year survival rate was assessed using the Cox proportional hazard model, adjusted for confounding variables and according to the serum phosphate tertiles. RESULTS: The study included 219 patients. Serum FGF-23 levels were high: 7060 +/- 13 500 RU/mL (median, 2740 RU/mL). In logistical regressions, only calcaemia (P = 0.002), phosphataemia (P = 0.008) and warfarin use (P = 0.04) were associated with the highest FGF-23 quartile. In the subgroup of patients with an estimated VC score, the third and fourth quartiles of the FGF-23 levels were associated with more severe VC. In multivariate linear regressions, only phosphataemia remained significantly correlated with FGF-23 (P = 0.04). The 2-year mortality rate was significantly higher for haemodialysis patients with serum FGF-23 levels in the higher quartile [P = 0.007; hazard ratio, 2.5 (1.3-5)] than in the first quartile, whereas within the phosphataemia tertiles, the lowest serum FGF-23 quartile was associated with lowered mortality. CONCLUSION: This study demonstrated a high level of circulating FGF-23 in LHD patients, despite infrequent hyperphosphataemia. However, phosphataemia is still the main factor correlating with serum FGF-23. The association of higher serum FGF-23 levels with mortality and VC, regardless of the serum phosphate levels, has thus been confirmed.

Randomized equivalence study evaluating the possibility of switching hemodialysis patients receiving subcutaneous human erythropoietin directly to intravenous darbepoetin alfa.

BACKGROUND: Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) used either intravenously or subcutaneously with no dose penalty; however, the direct switch from subcutaneous recombinant human erythropoietin (rHuEPO) to intravenous darbepoetin has barely been studied. OBJECTIVE: To establish the equivalence of a direct switch from subcutaneous rHuEPO to intravenous darbepoetin versus an indirect switch from subcutaneous rHuEPO to intravenous darbepoetin after 2 months of subcutaneous darbepoetin in patients undergoing hemodialysis. METHODS: In this open, randomized, 6-month, prospective study, patients with end-stage kidney disease who were on hemodialysis were randomized into 2 groups: direct switch from subcutaneous rHuEPO to intravenous darbepoetin (group 1) and indirect switch from subcutaneous rHuEPO to intravenous darbepoetin after 2 months of subcutaneous darbepoetin (group 2). A third, nonrandomized group (control), consisting of patients treated with intravenous rHuEPO who were switched to intravenous darbepoetin, was also studied to reflect possible variations of hemoglobin (Hb) levels due to change from one type of ESA to the other. The primary outcome was the proportion of patients with stable Hb levels at month 6. Secondary endpoints included Hb stability at month 3, dosage requirements for darbepoetin, and safety of the administration route. RESULTS: Among 154 randomized patients, the percentages with stable Hb levels were equivalent in groups 1 and 2, respectively, at month 3 (86.0% vs 91.3%) and month 6 (82.1% vs 81.6%; difference -0.5 [90% CI -12.8 to 11.8]). Mean Hb levels between baseline and month 6 remained stable in both groups, with no variation in mean darbepoetin dose. Mean ferritin levels remained above 100 microg/L in the 3 groups during the whole study, and darbepoetin was well tolerated. CONCLUSIONS: This study has shown equivalent efficacy on Hb stability without the need for dosage increase in patients switched directly from subcutaneous rHuEPO to intravenous darbepoetin.

The plasma level of brain natriuretic peptide is increased in malnourished hemodialysis patients.

BACKGROUND: In hemodialysis (HD) patients, the plasma brain natriuretic peptide (BNP) level is associated with left ventricular dysfunction and patients' survival. Malnutrition is common in HD patients, it is associated with inflammation and contributes to the high incidence of cardiovascular (CV) disease in this setting (malnutrition-inflammation-atherosclerosis syndrome). In a cross-sectional study, we assessed the relationship between predialysis plasma BNP level and nutritional markers in chronic HD patients. METHODS: Of 210 patients receiving HD treatment in our unit, 51 patients who were treated with three times weekly long-hour HD (5-8 h/session) for at least 6 months (mean age 65.8 +/- 15.0 years; F/M ratio 23/28; vintage 71.3 +/- 71.9 months; BMI 24.9 +/- 5.9; session time 6.9 +/- 1.3 h; percentage of diabetic patients 31%) were studied before a mid-week HD session for nutritional markers (plasma albumin 35.3 +/- 3.7 g/l; prealbumin 0.36 +/- 0.09 g/l; CRP 15.3 +/- 14.7 mg/l; nPNA 1.29 +/- 0.29 g/kg/day) and plasma BNP (246.9 +/- 252.2 ng/l, normal <100 ng/l, Bayer(R) kit). The interdialytic weight gain was 2.1 +/- 1.0 kg. In the last 3 months prior to the commencement of the study, the patients' dry weight varied by +0.17 +/- 1.9 kg. RESULTS: Predialysis plasma BNP levels did not differ according to gender and the presence of diabetes. It was not correlated with age and vintage but was found to be negatively associated with the session time (r = -0.34, p = 0.018). Several nutritional markers were negatively correlated with BNP levels: prealbumin (r = -0.46, p = 0.001), BMI (r = -0.33, p = 0.018), nPNA (r = -0.46, p = 0.002). The plasma albumin relationship with the BNP level was close to significance (p = -0.26, p = 0.070). The 3-month dry weight variation was also negatively correlated with BNP levels (r = -0.34, p = 0.018). With multiple stepwise regression analysis, prealbumin and session time remained significant (respectively p = 0.004 and 0.01). BNP levels were higher in a subgroup of malnourished patients (n = 12) (400 +/- 405 vs. 202 +/- 166 ng/l, p = 0.03) than in patients who did not meet the malnutrition criteria (34 patients). They were not correlated with CRP levels, interdialytic weight gain, or predialysis MAP. CONCLUSIONS: Hence, the plasma BNP level was found to be associated with malnutrition but not with inflammation. This underlines the relationship between nutrition and the CV system in HD patients. The body weight variations associated with malnutrition and the difficulties in assessing and adjusting dry weight may lead to fluid overload, which could explain, in part, these correlations.

[An efficient strategy to decrease the central venous catheter-related adverse events rate in haemodialysis patients]. / Une stratégie efficace pour diminuer l'utilisation et les complications des cathéters veineux centraux tunnelisés en hémodialyse.

INTRODUCTION: Catheter-related adverse events (CAE) remain a major cause of mortality and morbidity. AIM: We aimed to compare the CAE prevalence and adverse events rate at 10 years interval in one centre using different devices, dressing procedures. METHODS: We compared two periods, from 1994 to 1997 (period 1) and from 2004 to 2007 (period 2). We recorded all prevalent tunnelled CAE and their related adverse event rate: catheter-related bacteraemia (CRB), catheter local infection (CLI), catheter dysfunction leading to CAE exchange, thrombolytic use and spontaneous pulling up. RESULTS: In period 1, PermCath catheter (Quinton, N=63) and TwinCath catheter (MedComp, N=76) were used in 95 HD. BioFlex catheter (N=52) and ASPC split catheter (MedComp, N=52) were used in 72 HD in period 2. In period 1, we performed catheter dressing using povidone iodine versus alcoholic chlorexidine in period 2. Between period 1 and period 2, the CAE prevalence decreased from 15-18% to 9-6%, CRB from 1.1 to 0.23/1000 day-catheter (p<0.001), CLI from 1.1 to 0.28/1000 day-catheter (p<0.001), definitive dysfunction from 12 to 1.2% (p<0.001) and CAE pulling up from 4 to 0%. The annual urokinase consumption decreased from three to one unit per CAE. CONCLUSION: This study shows the dramatic decrease in CAE prevalence (-50%) and related-adverse events (approximately -200%) since 10 years. Switching povidone iodine to chlorexidine and using more recent catheter devices appear very efficient in decreasing catheter-related adverse events.

Daily oral 25-hydroxycholecalciferol supplementation for vitamin D deficiency in haemodialysis patients: effects on mineral metabolism and bone markers.

BACKGROUND: Vitamin D deficiency is frequently observed in end-stage renal disease (ESRD) patients; however, the effects of vitamin D supplementation have rarely been reported. We aimed to assess the effects of daily 25(OH)D(3) supplementation on mineral metabolism, bone markers and Kidney Disease Outcomes Quality Initiative (KDOQI) targets in haemodialysis (HD) patients for a period of 6 months. METHODS: HD patients were included in this study if their serum 25(OH)D level was <75 mmol/L. Oral 25(OH)D(3) was administered daily at 10-30 microg/day based on the severity of the deficiency. Characteristics of the patients were compared from the baseline to 6 months on the basis of their response to 25(OH)D(3) administration and the patients were divided into three groups. Patients who showed partial response [serum 25(OH)D <75 nmol/L] were placed in group 1, those who showed normal response [serum 25(OH)D ranging from 75 to 150 nmol/L] were placed in group 2 and those who showed excessive response [serum 25(OH)D >150 nmol/L] were placed in group 3. RESULTS: Of the 253 HD patients, 225 (89%) showed vitamin D insufficiency or deficiency, 172 were included in the study and 149 patients completed the study. After 6 months of treatment [mean daily 25(OH)D(3): 16 +/- 5 microg/day], the serum 25(OH)D level increased (30 +/- 19 to 126 +/- 46 nmol/ L, P < 0.001), with 13% of patients in group 1, 57% in group 2 and 30% in group 3. The serum intact parathyroid hormone (iPTH) level decreased (235 +/- 186 to 189 +/- 137 pg/mL, P = 0.05), except in group 1. Bone alkaline phosphatase (BALP) showed a tendency to normalize (23 +/- 16 to 18.3 +/- 11 microg/L, P < 0.05), leading to a decrease in alfacalcidol administration from 66% to 43% (P < 0.05), except in group 1. The KDOQI targets achieved increased significantly for serum calcium (76% to 85%) and phosphate levels (66% to 77%) in all patients. The serum albumin level increased in all groups (34.6 +/- 4 to 36.8 +/- 4 g/L, P < 0.05), without any significant improvement in normalized protein catabolic rate (nPCR) or C-reactive proteins (CRP). CONCLUSION: With a daily dose ranging from 10 to 30 microg, daily oral 25(OH)D(3) supplementation corrects most vitamin D deficiencies or insufficiencies in HD patients, without any evident toxicity. The main effects observed included correction of excessive bone turnover, despite less alfacalcidol administration, increase in serum albumin level and increase in the percentage of patients with serum calcium and phosphorus levels within the recommendation of the KDOQI guidelines.

Stability of nutritional parameters during a 5-year follow-up in patients treated with sequential long-hour hemodialysis.

Progressive nutritional impairment has been recently reported during conventional hemodialysis (HD) treatment. We studied the nutritional parameters during a 5-year follow-up in HD patients. Thirty-three patients (15F/18M; 65 years old at the study start) filled out a 3-day food questionnaire once a year between 1995 and 1999 (study group). Twenty patients, who did not fill out the food records during this period served as a control group (control group). The food record was run by the renal dietician using a dedicated software, providing daily energy and protein intakes (DEI and DPI). Serum albumin, normalized protein equivalent of nitrogen appearance (nPNA), and postdialysis body weight (BW) at the time of food record were collected in the study group and from the patient chart in the control group. The energy intake in the study group and the protein intake in both groups were close to the recommended intakes in ESRD patients. Protein intake assessed from food questionnaire or from urea kinetics were not statistically different. Using ANOVA for repeated measures, no difference along the 5 years was found for daily energy intake, daily protein intake, nPNA, and BW in the study group. The BW and nPNA remained stable in the control group. Hence, this study does not confirm the progressive nutritional impairment reported in the HEMO study, whereas the patients' age and vintage are largely higher in the present study. The role of a large dialysis dose in maintaining nutritional status in HD patients is discussed.

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.

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.

[Calciphylaxis in dialysis patients: To recognize and treat it as soon as possible]. / La calciphylaxie chez le patient dialysé : la reconnaître pour la traiter aussitôt que possible.

Calciphylaxis (CPX) or calcific uraemic arteriolopathy is a rare life-threatening complication, affecting mainly dialysis patients. The condition is characterized by calcifications and thrombosis of the small cutaneous vessels and small vessels in the fat tissue, resulting in the development of necrotizing and non-healing ulcers. The development of these lesions leads to poor outcomes owing to infectious complications and some frequently associated unfavourable medical conditions: obesity, diabetes, and peripheral vascular disease. We report the case of six patients with different clinical forms of CPX in the past 10 years with favourable outcomes observed in five of the six patients. The diagnosis was based on clinical presentation: bilateral and hyperalgesic necrotic lesions along with a history of mineral metabolism disorder or warfarin use. The therapeutic strategy included the following: daily dialysis, hyperbaric oxygen therapy, treatment of limb artery stenosis, maintenance of the optimal haemodynamic stability, delivery of cutaneous care, administration of analgesics and antibiotics, warfarin and calcium cessation, and additional therapy with cinacalcet or parathyroidectomy and therapy with bisphosphonates or sodium thiosulphate. Healing was observed in five out of six CPX patients by using this strategy that should be rapidly employed in order to decrease the necrotizing areas that result in poor outcomes. Prevention includes identification of at-risk patients in order to optimize the treatment of the identified risk factors for CPX.

[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.

Treating mineral metabolism disorders in patients undergoing long hemodialysis: a search for an optimal strategy.

In hemodialysis (HD) patients, mineral metabolism (MM) disorders have been associated with an increased mortality rate. We report the evolution of MM parameters in a stable HD population undergoing long hemodialysis by performing an annual cross-sectional analysis for every year from 1994 to 2008. The therapeutic strategy has changed: the dialysate calcium concentration has decreased from a mean of 1.7 +/- 0.1 to 1.5 +/- 0.07 mmol/L and has been adapted to parathyroid hormone serum levels (from 1 to 1.75 mmol/L). The use of calcium-based and aluminum-based phosphate binders has decreased and they have been replaced by sevelamer; alfacalcidol has partly been replaced by native vitamin D. The percentage of patients with a parathyroid hormone serum level between 150 and 300 pg/mL has increased from 9% to 67% (P<0.001); the percentage of patients with phosphataemia between 1.15 and 1.78 mmol/L has increased from 39% to 84% (P<0.001). The percentage of those with albumin-corrected calcemia between 2.1 and 2.37 mmol/L has increased from 29% to 61% (P<0.001), and that of patients with a calcium-phosphorous product (Ca x P) level >4.4 mmol/L decreased from 8.8% to 2% (P=0.02). Although patients undergo long and intensive HD treatment, MM disorders are common. However, an appropriate strategy, mostly consisting of native vitamin D supplementation, progressive replacement of calcium-based phosphate binders with non-calcium-based ones, and individualization of dialysis session duration and dialysate calcium concentration, would result in a drastic improvement.

Length of Dialysis Session Is More Important Than Large Kt/V in Hemodialysis.

Long, slow hemodialysis (3 × 8 hours/week) has been used without significant modification in Tassin, France, for 30 years with excellent morbidity and mortality rates. A long dialysis session easily provides high Kt/Vurea and allows for good control of nutrition and correction of anemia with a limited need for erythropoietin (EPO). Control of serum phosphate and potassium is usually achieved with low-dose medication. The good survival achieved by long hemodialysis sessions is essentially due to lower cardiovascular morbidity and mortality than in short dialysis sessions. This, in turn, is mainly explained by good blood pressure (BP) control without the need for antihypertensive medication. Normotension in this setting is due to the gentle but powerful ultrafiltration provided by the long sessions, associated with a low salt diet and moderate interdialytic weight gains. These allow for adequate control of extracellular volume (dry weight) in most patients without important intradialytic morbidity. Therefore, increasing the length of the dialysis session seems to be the best way of achieving satisfactory long-term clinical results.

Does Blood Pressure Control by Gentle Ultrafiltration Improve Survival in Hemodialysis Patients?

Agentle ultrafiltration can be achieved using a long and slow hemodialysis. It is easier to achieve gentle ultrafiltration if the interdialytic weight intake is moderate ( i.e., if the patient maintains a low sodium diet) and if diffusion allows for a negative or nil sodium balance during the session ( i.e., dialysate sodium < 140 mmol/L). A gentle ultrafiltration allows control of blood pressure by reducing the extracellular volume to its ideal level, the "dry weight," at the end of the session. Controlling blood pressure reduces cardiovascular mortality, which is by far the foremost cause of death in hemodialysis. Controlling blood pressure means reducing the occurrence of both hypertension and hypotension. Hypotension has been reported to correlate with mortality in hemodialysis as much as or more than hypertension itself. This "U-curve" phenomenon is not paradoxical. It displays two distinct facts on the same figure: an increased early mortality in hypotensive patients (hypotension is a marker of frailty or congestive heart failure, both of which cause increased mortality) and, on the other hand, the well-established, long-term increased mortality in hypertensive patients. Hypotension is not a mandate to undertreat hypertension.

Volume Control in Hemodialysis Patients.

Cardiovascular disease is the main cause of the high mortality of dialysis patients and is largely due to poor control of blood pressure. Establishing and maintaining normal extracellular volume (ECV) is required to achieve normotension. The dry weight concept links ECV and blood pressure by a simple clinical relationship. Dry weight is the ideal postdialysis weight that allows a constantly normal blood pressure to be maintained without using antihypertensive medications. Maintenance of normal ECV requires control of salt intake to reduce interdialytic weight gain ( i.e., saline overload) combined with the diffusive and convective removal of salt and water from the body during dialysis sessions. Several problems are to be faced when using the dry weight method. Clinical evaluation must take into account the following confounding factors: weight varies with nutrition, clinical symptoms are unspecific and sometimes discordant, and there is a lag time between ECV and blood pressure changes. On the other hand, achievement of dry weight is hampered by dialysis times that are too short (and weight gains that are too high), by antihypertensive medications, and by poor heart conditions. A longer session time allows for a slower, easier, and more comfortable ultrafiltration.

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.