Hemodialysis-associated hemosiderosis in the era of erythropoiesis-stimulating agents: a MRI study.

BACKGROUND: Most dialysis patients receiving erythropoesis-stimulating agents (ESA) also receive parenteral iron supplementation. There are few data on the risk of hemosiderosis in this setting. METHODS: We prospectively measured liver iron concentration by means of T1 and T2* contrast magnetic resonance imaging (MRI) without gadolinium, in a cohort of 119 fit hemodialysis patients receiving both parenteral iron and ESA, in keeping with current guidelines. RESULTS: Mild to severe hepatic iron overload was observed in 100 patients (84%; confidence interval, [CI] 76%-90%), of whom 36% (CI, 27%-46%) had severe hepatic iron overload (liver iron concentration >201 µmol/g of dry weight). In the cross-sectional study, infused iron, hepcidin, and C-reactive protein values correlated with hepatic iron stores in both univariate analysis (P<.05, Spearman test) and binary logistic regression (P <.05). In 11 patients who were monitored closely during parenteral iron therapy, the iron dose infused per month correlated strongly with both the overall increase and the monthly increase in liver iron concentration (respectively, rho=0.66, P=.0306 and rho=0.85, P=0.0015, Spearman test). In the 33 patients with iron overload, iron stores fell significantly after iron withdrawal or after a major reduction in the iron dose (first MRI: 220 µmol/g (range: 60-340); last MRI: 50 µmol/g (range: 5-210); P <.0001, Wilcoxon's paired test). CONCLUSIONS: Most hemodialysis patients receiving ESA and intravenous iron supplementation have hepatic iron overload on MRI. These findings call for a revision of guidelines on iron therapy in this setting, especially regarding the amount of iron infused and noninvasive methods for monitoring iron stores.

Modulation of oxidative stress and microinflammatory status by colloids in refractory dialytic hypotension.

BACKGROUND: Intradialytic hypotension may adversely affect the outcome of chronic hemodialysis. Therapeutic albumin has powerful anti-oxidant and anti-inflammatory properties. We have recently shown that systematic colloid infusion during hemodialysis sessions improves hemodynamic parameters in most dialysis hypotension-prone patients unresponsive to usual of preventive measures.We postulated that frequent hypotensive episodes may lead to a noxious inflammatory response mediated by oxidative stress induced by ischemia-reperfusion. The aim of this study was therefore to analyze the effect of 20% albumin and 4% gelatin infusions on oxidative stress and microinflammatory status in hypotension-prone patients unresponsive to usual preventive measures. METHODS: Prospective cross-over study (lasting 20 weeks) of routine infusion of 200 ml of 20% albumin versus 200 ml of 4% gelatin in 10 patients with refractory intradialytic hypotension. We analyzed the effect of 20% albumin and 4% gelatin on microinflammatory status, oxidative stress, serum nitrite and nitrate levels by analysis of variance. RESULTS: A significant decrease in serum ceruloplasmin and serum C3 was observed during the albumin period (p < 0.05, repeated measure ANOVA). A significant decrease in serum hydrogen peroxide was seen during albumin and gelatin administration (p < 0.01, repeated measure ANOVA) and a very large decrease in serum lipid peroxides was observed during the albumin period only (p < 0.01, Friedman test). Serum lactoferrin, serum proinflammatory cytokines and serum nitrite and nitrate levels remained stable during the different periods of this pilot trial. CONCLUSIONS: We conclude that the improvement in microinflammatory status observed during colloid infusion in hypotension-prone dialysis patients may be related to a decrease in ischemia-reperfusion of noble organs, together with a specific reduction in oxidative stress by albumin. TRIAL REGISTRATION: ISRCTN 20957055.

A pilot study of routine colloid infusion in hypotension-prone dialysis patients unresponsive to preventive measures.

BACKGROUND AND AIMS: Intradialytic hypotension may adversely affect the outcome of chronic hemodialysis. The aim of this study was to assess the effects of routine infusion of 20% albumin and 4% gelatin in dialysis hypotension-prone patients unresponsive to prevention measures. METHODS: This was a prospective crossover study (lasting 20 weeks) of routine infusion of 200 mL of these colloids in 10 patients. We analyzed the effect of these colloids by n-of-1 trial methodology (Wilcoxon test) and analysis of variance. RESULTS: Twenty percent albumin increased systolic blood pressure (SBP) in 6 patients (p<0.05), whereas 4% gelatin improved SBP in only 2 patients (p<0.05). Albumin infusions increased diastolic blood pressure (DBP) in 4 patients (p<0.05), whereas gelatin improved DBP in only 1 patient (p<0.05). Weight gain between dialysis sessions was generally similar during the periods in most patients. An increase in the ultrafiltration rate was observed in 4 of the 6 patients whose blood pressure was improved by colloids (p<0.005). Kt/V and the fall in relative blood volume remained stable during the study, whereas ionic dialysance at the end of the dialysis sessions was improved only by albumin infusion (p<0.05, repeated measures ANOVA). CONCLUSIONS: Systematic colloids infusion during hemodialysis sessions improves hemodynamic parameters in most dialysis hypotension-prone patients unresponsive to usual measures of prevention. Prospective controlled trials are warranted to confirm these preliminary results.

Left-ventricular diastolic dysfunction as a risk factor for dialytic hypotension.

OBJECTIVES: Intradialytic hypotension may adversely affect the outcome of chronic hemodialysis and thus reduce the patients' life expectancy. The aim of this study was to assess the link between left-ventricular diastolic dysfunction and dialytic hypotension. METHODS: We performed a prospective cross-sectional study of 72 hemodialysis patients with a low dialysis vintage, 36 of whom had dialysis hypotension, based on echocardiography and brain natriuretic peptide (BNP) assay. RESULTS: There was no difference between normotensive patients and those with dialysis-associated chronic hypotension as regards BNP level, cardiac index, left-ventricular ejection fraction, or myocardial fractional shortening. Both hypotension-prone patients requiring dialysate sodium profiling and chronic refractory hypotensive patients requiring macromolecule infusion had cardiac diastolic dysfunction as shown by a similarly abnormal E/A ratio <1 in 89-91% of cases, associated with a significant decrease in color M-mode diastolic flow propagation velocity (V(p), p < 0.05 nonparametric ANOVA). The area under the ROC curve for V(p) was 0.69. A V(p) cutoff of 39.5 cm/s was optimal for predicting dialysis-associated hypotension. CONCLUSIONS: We conclude that diastolic dysfunction is associated with dialytic hypotension and that a low V(p)--a preload-independent index--is predictive of dialysis-associated hypotension.

Improving the efficiency of short-term single-needle hemodialysis.

It is widely believed that single-needle (SN) hemodialysis is inferior to conventional double-needle (DN) hemodialysis. The purpose of this study was to compare two SN dialysis regimens using different blood flow rates with conventional DN hemodialysis. The primary outcome measure was ionic dialysance. We studied eight patients (two women, six men) undergoing chronic intermittent DN bicarbonate hemodialysis three times per week on a Cimino-Brescia fistula for at least three months. The study had a prospective four-period design and lasted four weeks. During weeks 1 and 3, the participants had standard DN hemodialysis sessions, with Wallace needles at a blood flow rate of 250-300 mL/min. During week 2, they had single-needle dialysis sessions with a short 15-gauge stainless-steel needle, an effective blood flow rate of 180 mL/min (360 mL/min for each of the two pumps), and venous pressure below 200 mmHg. During week 4, they had SN dialysis sessions with a short 15-gauge stainless-steel needle, an effective blood flow rate of 250 mL/min (500 mL/min for each of the two pumps), and a venous pressure below 200 mmHg. Ionic dialysance recorded 45 minutes after the beginning of the dialysis session and 30 minutes before the end of the session were used for statistical analysis. The effective blood flow target of 250 mL/min was achieved in six of the eight patients. Ionic dialysance 45 minutes after the beginning of the session differed among the four periods (p < 0.001, Friedman test). Ionic dialysance was better during each DN dialysis period than during the 180 mL/min SN period (p < 0.01, Dunn's multiple comparison tests), but there was no difference with the 250 mL/min SN period. Ionic dialysance 30 minutes before the end of the dialysis session differed among the four periods (p < 0.001, Friedman test). Ionic dialysance was far better during each DN period than during the 180 mL/min SN period (p < 0.001, Dunn's multiple comparison test) and slightly better than during the 250 mL/min SN period (p < 0.05, Dunn's multiple comparison test). The single-pool Kt/V ratio differed among the four periods (p < 0.0001, Friedman test). The Kt/V ratios were far better during each DN period than during the 180 mL/min SN period (p < 0.001, Dunn's multiple comparison test) and slightly better than during the 250 mL/min SN period (p < 0.01, Dunn's multiple comparison test). The Kt/v provided by the dialysis monitor gave identical results to single pool Kt/v. We conclude that single-needle dialysis with an effective blood flow rate of 180 mL/min delivers an inadequate dialysis dose, which may be harmful. In contrast, an effective blood flow rate of 250 mL/min appears acceptable for brief periods of single-needle dialysis lasting one or two weeks. Otherwise, an increase in the length of the dialysis session and/or the use of a larger membrane surface area and even higher blood flow is required to obtain the same quality of dialysis as with conventional double-needle hemodialysis. Careful monitoring of the dialysis dose delivered is mandatory during single-needle dialysis.

Candesartan cilexetil on regular hemodialysis: inability to reduce excessive thirst, but good tolerance and efficacy in hypertensive patients.

It has been postulated that hypertension and interdialytic weight gain in hemodialysis patients are related to the activation of the renin-angiotensin system. Angiotensin II type 1 (ATI) receptor antagonists are new anti-hypertensive agents and are currently the most specific means of blocking the renin-angiotensin enzymatic cascade. Recent studies show that candesartan cilexetil regulates thirst and hypertension in rodents, via cerebral AT1 receptor blockade. We therefore conducted a prospective open study of candesartan cilexetil in 21 hypertensive patients on long-term hemodialysis during 6 weeks, focusing on thirst regulation. We also performed a prospective follow-up study of tolerance of candesartan and its anti-hypertensive efficacy after this 6-week study, while the patients remained on this therapy. Weight gain between hemodialysis sessions did not differ between the periods before and during candesartan cilexetil therapy. Median absolute interdialytic weight gain was 2.35 kg (range: 0.55-5) before therapy, compared to 2.25 kg (range: 0.35-4.65) during therapy (p > 0.05, Wilcoxon test). The median interdialytic weight gain/dry weight index was 3.7% (range: 1.15-7) before therapy and 3.6% (range: 0.7-6.6) during candesartan therapy (p > 0.05, Wilcoxon test). The median dose of candesartan cilexetil was 12 mg/day (range: 4-24). The median total duration of therapy with candesartan (including the 6 weeks of the thirst study) was 12 months (range: 2-25). During candesartan cilexetil therapy, the number of concomitant anti-hypertensive drugs per patient fell significantly (median number of anti-hypertensive drugs before candesartan =2 (range: 1-6); during candesartan =1 (range: 1-5) (p < 0.02, Wilcoxon test). No anaphylactoid reactions occurred. A total of 161 episodes of hypotension (5%) occurred during 3074 hemodialysis sessions (including the 6 weeks of the thirst study) We conclude that, like angiotensin converting enzyme inhibitors and the other angiotensin receptor antagonists, candesartan cilexetil is unable to reduce interdialytic weight gain in hemodialysis patients. This study also shows that the irreversible angiotensin II receptor antagonist candesartan cilexetil is a safe and effective therapeutic option for hypertensive hemodialysis patients.