Malik Touam

Octogenarians Reaching End-Stage Renal Disease: Cohort Study of Decision-Making and Clinical Outcomes

The fate of octogenarians reaching end-stage renal disease (ESRD) is poorly defined, and implicit dialysis rationing may be practiced in this age group. The main objectives of this study were to analyze the characteristics of pre-ESRD octogenarians offered dialysis or not and to identify factors influencing mortality while on dialysis, to improve prognosis assessment and decision-making. In this single-center cohort, 146 consecutive pre-ESRD octogenarians were referred to a nephrology unit over a 12-yr period (1989 to 2000). Main outcome measures were baseline characteristics of patients offered dialysis and conservative therapy and overall and 1-yr survival according to effective treatment. A therapeutic decision was made for 144 patients. Octogenarians who were not proposed dialysis (n = 37) differed from those who were proposed dialysis (n = 107) mainly in terms of social isolation (43.3% versus 14.7%; P = 0.03), late nephrologic referral (51.4% versus 28.9%; P = 0.01), Karnofsky score (55 +/- 18 versus 63 +/- 20; P = 0.03), and diabetic status (22.2% versus 6.5%, P = 0.008). Six patients refused the dialysis proposal. During the 12-yr observation period, 99 patients died (68.7%). Median survival was 28.9 mo (95% CI, 24 to 38) in patients undergoing dialysis, compared with 8.9 mo (95% CI, 4 to 10) in patients treated conservatively (P < 0.0001). In multivariable piecewise Cox analysis, independent predictors of death within 1 yr on dialysis were poor nutritional status, late referral, and functional dependence. Included in a survivor function, these covariates predict groups with low and high 1-yr mortality risk. Beyond 1 yr on dialysis, the only independent predictor of death was the presence of peripheral vascular disease. It is concluded that beside a patients individual refusal, late referral, social isolation, low functional capacity, and diabetes may have oriented medical decision toward withholding dialysis in a significant proportion of pre-ESRD octogenarians. Although most patients on dialysis experienced a substantial prolongation of life, identification of mortality predictors in this age group should improve the process of decision-making regarding the expected benefit of renal replacement therapy.

Calcium balance in haemodialysis—do not lower the dialysate calcium concentration too much (con part)

The debate on the most adequate dialysate calcium concentration for intermittent haemodialysis therapy is ongoing. There is probably no one optimal concentration. In general, one would like to maintain a neutral calcium balance in adult haemodialysis patients. However, a slightly negative balance may be preferable to avoid soft-tissue calcium accumulation in face of net calcium loss from the bone with ageing. The problem with measurements of calcium balance is that they are generally imprecise, as are estimations of total body calcium and its distribution in various compartments, unless done with labour-intensive methods and great care. The choice of the dialysate calcium will depend on several factors, including parathyroid and vitamin D status, type and severity of concomitant bone disease, presence or absence of arterial calcification, dietary habits, drug treatment and dialysis modality. Ideally the dialysate calcium would be adapted to each patients needs. This is not feasible, however, in most dialysis settings and neither is it cost-effective. From a practical point of view, a relatively high dialysate calcium concentration in the range of of 1.50-1.75 mmol/L (3.0-3.5 mEq/L) should probably be preferred in haemodialysis patients with high serum PTH levels who are not prescribed calcium-based phosphate binders or high doses of active vitamin D sterols, and in those who are receiving a calcimimetic. In those who are treated with high doses of calcium-based binders and/or active vitamin D derivatives or who have a very low serum PTH level, the optimal dialysate calcium concentration is probably lower, in the range of 1.25-1.50 mmol/L (2.50-3.0 mEq/L). In the present pro/con debate about the optimal dialysate calcium concentration used for the haemodialysis session, we have accepted to defend the viewpoint that a low calcium concentration may do more harm than benefit in many patients. This viewpoint is opposite to that taken by Gotch. He argues that since calcitriol and other active vitamin D derivatives have become available virtually all haemodialysis patients are in positive calcium balance. We would like to take issue with this statement and warn against the indiscriminate use of a low calcium dialysate in all patients receiving haemodialysis therapy.

Oral Aluminum Administration to Uremic, Hyperparathyroid, or Vitamin D-Supplemented Rats

In the present study, the role of factors was investigated that could possibly lead to changes in plasma and tissue aluminum (A1) concentrations following oral A1 exposure. In chronically uremic rats that received an oral A1 supplementation of 150 mumol/g diet during 4 weeks, a significant increase in mean (+/- SEM) liver A1 content was observed when compared to sham-operated, pair-fed control rats (9.9 +/- 2.0 versus 4.8 +/- 0.65 nmol/g wet weight, p less than 0.02). No such difference was found in non-A1-supplemented rats. Plasma A1 and the A1 content of other organs studied except muscle were not increased in uremic as compared to control animals. In rats with hyperparathyroidism secondary to a calcium-poor diet, mean liver and bone A1 content was significantly decreased when not A1-exposed (2.5 +/- 0.13 and 62 +/- 5.5 nmol/g, respectively) and normal when A1-supplemented (4.7 +/- 0.59 and 120 +/- 23 nmol/g, respectively) as compared to normal control rats without A1 supplementation (5.1 +/- 1.5 and 170 +/- 17 nmol/g, respectively). However, in the hyperparathyroid rats, mean plasma A1 concentration was higher than in control, euparathyroid rats. In rats with exogenous hyperparathyroidism (parathyroid extract) a significant increase in liver A1 content was observed when compared to control rats (8.1 +/- 0.95 versus 5.3 +/- 0.53 nmol/g, p less than 0.05). In A1-supplemented normal rats treated with 1,25(OH)2 vitamin D3 during 4 weeks, liver A1 content was significantly lower than in control rats receiving vehicle solution only (2.9 +/- 0.76 versus 5.7 +/- 0.59 nmol/g, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Dialysis-Associated Amyloidosis

Dialysis-related arthropathy represents a major complication of uremic patients treated by hemodialysis or other renal replacement therapies. Nearly 10 years ago, this syndrome was shown to be associated with a new type of amyloid, mainly composed of beta-2 microglobulin (beta 2-M). Retention of the beta 2-M protein due to chronic renal failure, although unquestionably a prerequisite for the occurrence of beta 2-M amyloidosis, appears not to be the unique pathogenetic factor involved in this complication. A role has also been attributed to an enhanced local or systemic generation of inflammatory mediators, an increased production of beta 2-M, and an altered metabolism of the molecule including partial proteolysis and glycation. It is possible that factors related to renal replacement therapy such as dialysis membrane biocompatibility also play a role. However, the clarification of the precise underlying mechanism(s) awaits further study. Because dialysis technology has progressed considerably during the last decade, a significant beta 2-M removal can be achieved at present using high-flux dialyzers. Moreover, a marked reduction in bioincompatibility during the dialysis procedure as manifested by activation of complement and stimulation of mononuclear blood cells can now be attained. Future studies will tell whether technical progress in dialysis technique results in a decrease in the incidence of symptomatic dialysis-associated amyloidosis.

Hemodialysis without Systemic Anticoagulation: A Prospective Randomized Trial to Evaluate 3 Strategies in Patients at Risk of Bleeding

Objective In this clinical trial, we aimed to compare three means of performing chronic hemodialysis in patients with contra-indication to systemic heparinization. Methods This open-label monocentric randomized « n-of-one » trial, conducted in a single tertiary care center, recruited chronic hemodialysis patients with a contra-indication to systemic heparinization for at least 3 consecutive sessions. All patients underwent hemodialysis with an AN69ST dialyzer, and were administered three alternative dialysis procedures in a random sequence: intermittent saline flushes, constant saline infusion, or pre-dialysis heparin coating of the membrane. The primary outcome was the need to interrupt the dialysis session because of clotting events due to either (i) a complete coagulation of the circuit; (ii) a partial coagulation of the circuit; (iii) a>50% rise over baseline in the venous pressure. Results At the end of the inclusion period (May, 2007 to December, 2008), the number of patients to include (n = 75) was not reached: only 46 patients were included and underwent randomization. The study was terminated, and statistical analysis took into account 224 hemodialysis sessions performed in 44 patients with analyzable data. Heparin adsorption was associated with a significant reduction of the need to interrupt the dialysis session because of clotting events: odds ratio 0.3 (CI 95% 0.2 to 0.6; p<0.001, versus intermittent saline flushes). Heparin adsorption was also associated with higher odds for performing >3 h dialysis sessions and for having complete blood restitution. There were no significant effects of the dialysis procedure on weight loss, online ionic dialysance, and adverse events. Conclusion Heparin-coated AN69ST dialysis membrane is a safe and effective method to avoid or delay per-dialytic clotting events in patients with contra-indication to systemic anticoagulation. However, results are not generalizable safely to patients with active bleeding, since weak heparinemia, not assessed in this study, may occur. Trial Registration ClinicalTrials.gov NCT00473109.

Does intravenous erythropoietin lead to an immediate, transient increase in arterial blood pressure in dialysis patients?

120 no H o 90 so 6 80 S 70 60 50 12 3 4 5 min PLACEBO Dear Sir, The development of hypertension in 20-30% of hemodialysis patients receiving recombinant human erythropoietin (rHuEPO) remains an important side effect often requiring antihypertensive treatment [1-5]. The factors involved in the occurrence or aggravation of high blood pressure with rHuEPO are still matter of controversy. A first explanation is provided by the constant increase in total peripheral resistance secondary to both the rise in hematocrit (and hence blood viscosity) and to the correction of tissue hypoxia. However, our recent findings in rats show that rHuEPO-generated blood pressure elevation cannot be attributed solely to increases in blood viscosity and hemoglobin concentration [6]. It has also been suggested that the pressor effect of rHuEPO may be explained by action of the hormone on vascular smooth muscle, either directly [7] or via an activation of the tissue renin-angiotensin system [8]. Finally, rHuEPO could also induce hypertension by acting on the vascular endo-thelium [9-12]. Because, in a recent preliminary report, a direct blood pressure-raising effect of rHuEPO has been claimed [11], we decided to reexamine this question in 10 chronic hemodialysis patients in our dialysis facility (4 females, 6 males; mean age 47 years, range 20-81 years). The duration of their intermittent hemodialysis treatment was 28.2 months (range 3-120 months). Patients had the usual distribution of nephropathies, with 1 patient having non-insulin-dependent diabetes. Six of the ten patients received antihypertensive therapy (ACE inhibitors in 3 patients, calcium channel-blocking agents in 4, and ß-

Course of chronic kidney disease in French patients

Background In 1998, a French survey showed that the referral of patients with chronic kidney disease to a nephrologist was delayed, resulting in many emergency initiations of dialysis. In 2009, the ORACLE study aimed to describe the renal course of dialysis patients from their first nephrology visit to their first dialysis session. Methods The ORACLE study was a multicentre retrospective study of all patients who started chronic dialysis. Data were collected at the first nephrology visit and at the first dialysis session. Results In total, 720 patients were included (69 centres). At the first nephrology visit, the mean Cockcroft–Gault (CG) indicator was 31.8 mL/min (22.7 in 1998) and 52.4% of patients (73% in 1998) had a CG <30. The mean time between the first nephrology visit and the first dialysis session was 48 months (35 months in 1998). Conclusion In 2009, most patients were referred a long time before dialysis initiation, which likely allowed them to benefit from the impact of nephrology care on early outcomes when on dialysis. However, 34.2% of the dialysis sessions were still initiated under emergency conditions.

Atovaquone for the Treatment of a Severe Pneumocystis carinii Pneumonia in a Non-HIV Hemodialyzed Patient

Pneumocystis carinii (PC) is a leading cause of pneumonia in immunocompromised patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the standard treatment for PC. However, allergic skin reactions are frequent with TMP-SMX, often leading to discontinued use. The authors report the first successful use of Atovaquone in the treatment of severe PC pneumonia in a non-HIV hemodialyzed patient. Atovaquone is a safe and efficacious alternative to TMP-SMX in hemodialyzed patients.