Vassilis Liakopoulos

Improvement in uremic symptoms after increasing daily dialysate volume in patients on chronic peritoneal dialysis with declining renal function.

Objective: Patients on peritoneal dialysis (PD) can develop uremic symptoms as their residual renal function declines. In this retrospective study, we assessed the effect of increasing the dose of dialysis in patients who developed uremic symptoms. Methods: Patients on PD who had an increase in their dialysis dose due to either the appearance of uremic symptoms or to worsening biochemical parameters were included in this study. These patients had to have been on PD for at least 6 months before and after the increase in their dialysis dose. Patients whose dialysis dose was increased after the initial Adequest (done within 2–3 months of starting PD) findings or for reasons other than underdialysis were excluded from this study. The symptoms studied in 104 patients included fatigue, anorexia, insomnia, pruritus and nausea. The presence or absence of theses symptoms was evaluated before and after the increase in the dialysis volume. Several clinical and laboratory data including the adequacy results were compared before and after the increase in dialysis dose. Results: Patients were on PD for 24.6 ± 16 months when dialysis dose was increased. Eighty-five (82%) of them were on continuous ambulatory peritoneal dialysis (CAPD) while the remaining were on continuous cycler peritoneal dialysis (CCPD). Fatigue was the most common symptom that led to an increase in the dialysis dose (64%). The prevalence of all the symptoms studied decreased significantly after the increase in dose of dialysis. The weekly peritoneal creatinine clearance increased from 47.35 ± 0.88 to 57.34 ± 1.40 l (P < 0.0001) and the weekly Kt/V increased from 1.8 ± 0.03 to 2.27 ± 0.05 (P < 0.0001). The daily urine volume and the residual GFR decreased from 318.7 ± 36.4 to 151.9 ± 22.8 ml/day (P < 0.0001) and 2.05 ± 0.2 to 0.82 ± 0.12 ml/min (P < 0.0001) respectively during the study period. Conclusion: The prevalence of all uremic symptoms decreased significantly after the daily dialysate volume was increased. The improvement in symptoms despite the decline in residual function emphasizes the beneficial effect of increased dialysate volume, which produced a significantly higher peritoneal creatinine clearance and Kt/V after the change in the PD prescription.

A Case Report of Recurrent Vascular Access Thrombosis in a Hemodialysis Patient Reveals Combined Acquired and Inherited Thrombophilia

Abstract:  Vascular access thrombosis represents a serious and unfortunately common problem in hemodialysis patients. Usually, but not always, this complication can be attributed to low access blood flow. However, there are some patients who experience thrombosis despite a well functioning vascular access. We describe the case of a 31‐year‐old Caucasian male, who was hemodialyzed via an arteriovenous fistula for two years due to Alports syndrome. During this time period he had two episodes of vascular access thrombosis that destroyed two arteriovenous fistulas. Both fistulas were functioning well and the thrombosis events took place in days between the hemodialysis sessions. Thrombophilia was suspected and the relative investigation revealed high levels of factor VIII procoagulant, which is frequent in hemodialysis patients, and resistance to activated protein C. Polymerase chain reaction detected that the patient was heterozygous for factor V Leiden, which is quite common in general population. Thereafter, a new arteriovenous fistula was formed and the patient started oral anticoagulation therapy with warfarin. Now, three years after the last arteriovenous fistula formation, the patient is hemodialyzed without vascular access problems. In conclusion, evaluation of the coagulation cascade in hemodialysis patients with recurrent vascular access thrombosis is necessary.

Age and underdialysis as predictors of sleep disorders in peritoneal dialysis patients.

recently published in your journal. The authors studied the quality of sleep among patients on maintenance hemodialysis as well as among predialysis chronic kidney patients. They assessed quality of sleep using the Kidney Disease Quality of Life (KDQOL) sleep scale, where higher scores represent a better self-assessed quality of sleep. The most important findings of the study can be summarized as follows: sleep disorders were prevalent in 34% of hemodialysis patients and ranged from 14% to 27% in pre-dialysis patients with moderate or advanced renal impairment respectively. KDQOL results directly correlated with age and the difference between sleep disorders among dialysis and pre-dialysis patients was prominent among younger subjects and attenuated among older subjects. In a retrospective analysis published by our team in 2004 in your journal [2] we found a prevalence of some degree of insomnia in 36% of 104 peritoneal dialysis (PD) patients who had some evidence (clinical or laboratory indices) of underdialysis. After increasing dialysis dose (peritoneal Kt/V rose from 1.8–0.1 to 2.27–0.1) the prevalence of insomnia decreased significantly from 36% to 18% (P=0.0002, Mc Nemar’s test). In a reanalysis of our data we found that there was no difference in the age of patients with or without insomnia before the increase in dialysis dose (P=ns, unpaired t-test). On the contrary, 6 months after dialysis dose was increased, the patients with insomnia had a higher mean age than those without sleep problems (61.7–9 vs. 52.2–15, P=0.01). In a logistic regression model which included age, duration on dialysis therapy, serum creatinine and phosphorous (parameters that Kurella et al. [1] reported to correlate with sleep quality) as independent variables, only age was a significant predictor of poor quality of sleep and only after the increase in dialysis dose (P=0.01). Therefore, it can be speculated (with all the drawbacks of retrospective studies and self assessment of quality of sleep) that a sufficient increase in the dose of dialysis could compensate for a degree of renal failure and decrease the prevalence of sleep disorders, at least in PD patients. After the increase in dialysis dose the pattern of sleep disorders seems to resemble that of the general population where older people complain of poorer quality of sleep [3]. Other studies in peritoneal dialysis patients found no correlation of Kt/V and quality of sleep and were not able to detect an effect of age either [4–6]. V. Liakopoulos Æ C. G. Musso Æ D. G. Oreopoulos Division of Nephrology and the Peritoneal Dialysis Program, University Health Network and University of Toronto, Canada

Coronary Artery Calcification, Coronary Artery Stenosis and Hyperphosphatemia in Hemodialysis Patients

Dear Editor, We write in response to a report by Yokoyama et al. which was published in your journal (1). The article was about a study of the relationship between coronary artery calcification (CAC) and coronary artery stenosis (CAS), assessed by CT angiography, as well as the relationships between serum Ca, P, intact-PTH and CAC. With regard to the first topic, Yokoyama et al. reported that they failed to detect a relationship between CAC and CAS. We have also examined the same issue in 40 hemodialysis patients, using both exercise electrocardiography and Thallium dipyridamole scintigraphy for assessing CAS. We also found no relation between CAC and CAS (2). Regarding the second topic Yokoyama et al. reported that they found that CAC was related to serum Ca, but not to P and intact-PTH. We examined the same issue in 40 hemodialysis patients using a more reliable methodology. More precisely, we did not correlate CAC score value, which took years to ensue, with a single Ca, P or intact-PTH value. Instead, we repeated the CT after 1 year and we examined the relationship between the differences in CAC score, calculated according to Agatston’s method, and the mean values of monthly measured serum Ca, P, CaxP and bimonthly measured intactPTH during the 1-year interval. The results are presented here for the first time. At the beginning of the study CAC score was 267.8 ± 847.81 (min = 0, max = 5280). After 1 year, the CAC score was 544.48 ± 1330.05 (min = 0, max = 8010). There was a statistically significant difference in CAC score between the two measurements (P < 0.0001, Wilcoxon’s test). The mean increase in CAC score in patients who increased it (N = 25, 62.5%) was 442.6 ± 610.3 (min = 24, max = 2730). CAC progression was correlated with serum P (r = 0.482, P = 0.007, Pearson correlation test), Ca (r = 0.319, P = 0.05, Pearson correlation test), CaxP (r = 0.471, P = 0.009, Pearson correlation test) and intact-PTH (r = 0.479, P = 0.009, Pearson correlation test). In conclusion, we agree with Yokoyama et al. on the absence of relation between CAC and CAS. Similar were the results reported by Sharples et al. who used conventional coronary angiography for detection of CAS, but in symptomatic hemodialysis patients (3). In contrast, we detected that CAC progression is influenced by the serum level of Ca, P and intact-PTH. Thus, we cannot agree with the opinion of Yokoyama et al. that re-evaluation of the K/DOQI Clinical Practice Guidelines regarding hyperphosphatemia management in hemodialysis patients is necessary. Despite the absence of a relationship between CAC and CAS, medial wall arterial calcification decreasing vascular compliance, increases cardiovascular mortality per se (4).

No effect of serum parathyroid hormone level on antigen presenting cell-dependent T-cell reactivity in hemodialysis patients.

Sir, Both clinical and experimental evidence, like impaired response to vaccination with T-celldependent antigens [1] or T-cell proliferation after stimulation with staphylococcal enterotoxin B (SEB) [2], suggest a defective T-cell immune response in hemodialysis patients. The contribution of parathyroid hormone (PTH) levels in this situation is not fully clarified. Some investigators showed that in patients with high serum intact PTH (iPTH), T-cell proliferation after stimulation with the T-cell receptor (TCR) dependent phytohemagglutinin (PHA) is increased in comparison with T-cells derived from patients with low iPTH levels [3]. Others proposed that chronic T-cell exposure to PTH could be responsible for altered T-cell proliferation after stimulation with mitogens [4] due to interference with cellular calcium kinetics. In order to evaluate the role of serum PTH level on T-cell reactivity in hemodialysis patients we used SEB as stimulator, since it provokes Tcell stimulation not only in a TCR-dependent, but also in an antigen presenting cell-dependent manner by cross-linking the major histocompatibility complex class II (MHCII) molecules with the TCR [5]. Consequently, SEB imitates conventional peptide antigens better than PHA and other mitogens. Moreover, in contrast with conventional peptide antigens, SEB stimulates a large proportion of T-cells [6, 7], a crucial feature for obtaining reliable results from the usual cell cultures. A total of 25 hemodialysis patients were enrolled into the study. Besides end-stage renal disease, none of them suffered by conditions like active infection, cancer, autoimmune disease or diabetes mellitus, or received medications like corticosteroids, non-steroid antinflammatory drugs, cytotoxic drugs, statins, vitamin D or calcium channel blockers that are known to alter the immune response. In total, 20 age and sex matched healthy individuals served as a control group. An informed consent was obtained from all subjects enrolled into the study. In hemodialysis patients, blood samples were drawn just before the onset of the second dialysis T. Eleftheriadis (&) AE V. Liakopoulos AE G. Antoniadi AE A. Poultsidi AE I. Stefanidis Department of Nephrology, University Hospital of Larissa, Papakiriazi 22, PC 41222 Larissa, Greece e-mail: elefthe@otenet.gr

Can we expect something from prohepcidin measurement in hemodialysis patients

HD patients, or its accumulation due to renal failure, logically inhibits the iron release by macrophages, limiting its availability for erythropoiesis [4] . In accordance with the negative correlation between prohepcidin and hematocrit are the findings of Dallalio et al. [5] , who in a recent in vitro study detected that hepcidin can contribute to anemia not only through an effect on iron metabolism, but also through inhibition of erythroid progenitor proliferation and survival. What then is the explanation for the discrepancy among the three studies regarding the correlation of prohepcidin with hematocrit? Why was no relation detected between prohepcidin and markers of iron metabolism? The same kit was used for accessing prohepcidin levels in HD patients and its mean value was similar in all three studies (200–250 ng/ml). Is prohepcidin measurement useless for understanding better the anemia in HD and consequently as a marker of erythropoietin resistance in the future? In our opinion, at the present time we are not able to answer the above question due to the complex interrelations among the various factors involved in the regulation of hepcidin expression. For example, serum iron and transferrin saturation are markers of iron metabolism but are also influenced by inflammation, which decreases their levels. Ferritin is a marker of iron stores and an acute phase reactant. Inflammation increases CRP as well as hepSir, We read the article by Hsu et al. [1] that was recently published in your journal. The authors evaluated the effect of plasma prohepcidin on iron metabolism and erythropoiesis – in relation to inflammation as well – in hemodialysis (HD) patients. Their results were unexpected, since they detected a positive correlation between prohepcidin and hematocrit, no correlation with iron metabolism markers and CRP, and a negative correlation with IL-6. These results are very disappointing regarding the role of hepcidin in anemia of chronic disease and the resistance in recombinant erythropoietin therapy in HD patients. Our team performed a similar study, which is going to be published in a future issue of Acta Haematologica [2] . It has already been presented in abstrcat from in the XLIII ERA–EDTA Congress. We also failed to detect a correlation of serum prohepcidin with various serum iron metabolism markers and CRP. However, multiple linear regression analysis considering age, inflammation, iron adequacy, erythropoietin dose and prohepcidin levels revealed that prohepcidin was the major determinant of hematocrit, but in a negative way. Malyszco et al. [3] also showed, in a univariate analysis, that prohepcidin correlated negatively with hematocrit. The negative correlation of prohepcidin with hematocrit seems reasonable, since the prohepcidin hyperproduction due to microinflammation usually encountered in Published online: November 16, 2006