Mario Salomone

Long-Term Outcome in Continuous Ambulatory Peritoneal Dialysis: A 10-Year Survey by the Italian Cooperative Peritoneal Dialysis Study Group

Over a 10-year period, 1,990 end-stage renal disease patients in 30 centers were treated with continuous ambulatory peritoneal dialysis by the Italian Cooperative Peritoneal Dialysis Study Group. At the start of treatment, patients had an average age of 58.4 years, with a 66% prevalence of one or more clinical risk factors for premature death. Patient survival was 51% and 33% at 4 and 8 years on continuous ambulatory peritoneal dialysis, respectively, and technique survival was 62% and 48%, respectively. Occurrences of peritonitis progressively reduced until they reached an incidence of 0.50 episodes/yr in the last 5 years (1985 to 1989). Hernias and catheter-related problems did not influence the dropout rates. These Italian Cooperative Peritoneal Dialysis Study Group results demonstrate that continuous ambulatory peritoneal dialysis is a viable dialysis technique for long-term treatment of chronic renal failure and that it is an effective alternative to hemodialysis, especially for older and high-risk patients.

Level of renal function in patients starting dialysis: an ERA-EDTA Registry study

BACKGROUND The aims of this European study were (i) to compare the level of renal function at the start of dialysis between age groups, gender, primary renal disease, comorbid conditions, treatment modality, time periods and countries, and (ii) to determine which baseline characteristics are associated with the level of renal function at the start of dialysis. METHODS Renal registries participating in the European Renal Association-European Dialysis and Transplant Association Registry provided data on serum creatinine 0-4 weeks before the start of dialysis in incident dialysis patients in 1999 and 2003. Data were available in 11 472 patients from nine renal registries. Glomerular filtration rate (GFR) was estimated by the four-variable Modification of Diet in Renal Disease equation. RESULTS The unadjusted median eGFR at the start of dialysis was 7.0 mL/min/1.73 m(2) in the 1999 data (median serum creatinine 7.5 mg/dL) and 7.7 mL/min/1.73 m(2) in the 2003 data (serum creatinine 7.0 mg/dL). Using linear regression with adjustment for the other covariates, older patients, males, patients with diabetes mellitus, hypertension/renal vascular disease (HT/RVD) as primary renal disease (vs glomerulonephritis), ischaemic heart disease or peripheral vascular disease and patients starting on peritoneal dialysis (PD) initiated dialysis at higher levels of eGFR (range Δ eGFR: 0.1-1.2 mL/min/1.73 m(2)). Using the same analyses, eGFR differed between countries (range: 6.5-8.6 mL/min/1.73 m(2)). CONCLUSIONS During 2003, patients started dialysis at somewhat higher eGFR levels than those starting during 1999. There were also international differences in eGFR. Such differences may, at least in part, be explained by differences in creatinine measurement methods between countries and time periods. Finally, older patients, males, patients with HT/RVD or comorbidity and those starting on PD had slightly higher eGFR levels than younger patients, females, those with glomerulonephritis, without comorbidity and those starting on haemodialysis. Further research is needed into other, more clinically related factors affecting the decision to start dialysis.

Urokinase Treatment for Arteriovenous Fistulae Declotting in Dialyzed Patients

Urokinase treatment, previously employed with success in the declotting of deep venous thrombosis and arteriovenous shunts in patients undergoing regular dialytic treatment (RDT), was used in 23 cases of arteriovenous fistula thrombotic occlusion in 18 RDT patients. The treatment was successful in 65.2% of the cases without any negative side effects, except 1 case which may have developed a pulmonary embolism. Patients with severe hypofibrinolysis may need larger doses or may have a recurrence of the thrombotic episode. All therapeutic failures correlated with the presence of fibrosis or sclerosis.

Primary Oxalosis Mimicking Hyperparathyroidism Diagnosed after Long-Term Hemodialysis

Primary oxalosis is a rare inborn error of oxalate metabolism. Most cases are discovered in children, but occasionally symptoms begin later in life. Since early deaths in the past were from renal failure, prolonged survival obtained with chronic dialysis allows oxalosis to develop. This paper presents a 38-year-old man with an atypical history of type-I primary hyperoxaluria, not diagnosed until after 5 years of dialysis. Bone biopsy was performed because the biochemical and radiologic features did not seem consistent with a putative diagnosis of secondary hyperparathyroidism. This case emphasizes the clinical heterogeneity of this disorder, and the need for its considerations in the spectrum of dialysis-related bone diseases. It also stresses that bone oxalosis may mimic hyperparathyroidism, especially radiologically. Differential diagnosis is therefore mandatory.

The production of platelet-activating factor during hemodialysis.

Regenerated cellulosic membranes (CU) induced the aggregation of plasma-free human neutrophils when recirculated in a dynamic model of dialysis without the patient on the circuit. Neutrophil aggregation was linked to the production of PAF by these cells. In the absence of detectable PAF production, no neutrophil aggregation occurred, as observed during recirculation with polymethylmethacrylate (PMMA) membranes. With polycarbonate (PC), PAF production and aggregation of neutrophils were both almost half the values with CU. PAF production was studied in ten hemodialysis (HD) patients tested twice with CU and once with PC and PMMA membranes. PAF was extracted in the venous blood during filling of the dialyser for 9/20 of patients with CU (3.1 ± 2.9 ng/ml, mean ± 1 S.D.) a membrane that induced marked leukopenia (> 50% of basal values at 15 min), C3a des Arg generation (> 500% at 5 min), and plasma levels of the elastase-alpha1-proteinase inhibitor complex (> 500% at the end of HD). Membranes such as PC and PMMA showing intermediate or low potential to induce leukopenia and C3a des Arg generation, respectively, did not trigger the production and release of PAF in detectable amounts at any interval. However, with PMMA, plasma neutrophil elastase was significantly higher than baseline at the end of dialysis. These levels were not significantly different (p < 0.05) from those observed with CU and PC membranes

Hypervitaminosis B12 in Maintenance Hemodialysis Patients Receiving Massive Supplementation of Vitamin B12

We have administered routinely a multivitamin preparation containing a megadose of B12 to 106 hemodialysis patients after dialysis treatments. We found that these patients had very high levels of serum vitamin B12 which returned to original values only after a period of three years after stopping the vitamin. Discontinuing therapy had no effect on hemoglobin, mean erythrocyte corpuscular volume, or motor nerve conduction velocity. It is not known whether maintaining a prolonged high level of vitamin B12 is harmful. However, animal and epidemiologic studies have suggested that both cobalamin and cobalt may be potentially toxic. In view of the absence of demonstrable benefit and the possible risk of toxicity, we believe that the use of such megadose vitamin compounds in dialysis patients should be re-evaluated.

Concomitant Iron and Aluminum Mass Transfer Following Deferoxamine Infusion During Hemofiltration

Variable tissue overloading can alter the removal rate of iron and aluminum from uremics. Owing to its higher affinity to deferoxamine (DFO) and higher plasma concentrations, Fe could impair Al removal in cases of simultaneous body burden. Fe and Al plasma kinetics and mass transfer were therefore studied in 12 uremic patients with different Fe and Al status: six with normal ferritin levels (less than 400 micrograms/L [ng/mL]), and Al 1.4 to 4.7 mumol/L (40 to 131 micrograms/L) (group A); six with increased ferritin (greater than 2,000 micrograms/L), and Al 1.7 to 17 mumol/L (47 to 476 micrograms/L) (group B). DFO (40 and 80 mg/kg in a random sequence) was administered once a week during the first hour of the first hemofiltration (HF). The results show that in both groups and with both DFO doses, maximum Fe and Al mass transfer was achieved in the first and second HF, respectively. The 80-mg/kg dose of DFO significantly raised Al mass transfer in both groups, whereas Fe mass transfer was only slightly affected. Even though plasma Fe levels were almost always higher than Al, Al mass transfer eventually exceeded that of Fe, in both Fe-normal and Fe-overload patients. The bias towards Al in mass transfer was enhanced in both groups in the second HF, and at the higher DFO doses. Thus, DFO once a week reduced Fe loss to less than 30 mumol/wk in patients with normal ferritin levels. In both Fe and Al overloaded patients, Al can be removed, and Al mass transfer may often exceed Fe mass transfer, depending on the degree of tissue burden, the time from DFO infusion, and the DFO dose.

Three-year follow-up after withdrawal of iron therapy in uremic patients on regular dialytic treatment

SummaryIron supplementation is commonly recommended in uremic patients undergoing regular dialytic treatment in order to correct a presumed iron deficiency due to impaired absorption and dialytic losses. Serum ferritin levels show an iron overload in 83% of 136 patients on 1.25 g/year i.v. iron therapy. After the withdrawal of iron therapy, directly correlated ferritin levels and percentage transferrin saturation decreased slowly, except in carriers of HLA-A3 antigens and in polytransfused patients. In these latter patients, desferrioxamine reduced but did not normalize the iron balance. The 16 patients who never received iron therapy showed a normal iron balance over a 3-year follow-up. Despite iron-ferritin therapy, 11 patients with baseline ferritin values at the lower normal limits showed a tendency toward further depletion. Orally administered bivalent iron seems to be more promising in normalizing iron-deficient patients without potentially harmful overloading.

Drug-induced erythropoiesis and outcome: should we give up the haemoglobin target approach and return to the ratio between erythropoiesis-stimulating agents and haemoglobin?

Sir, In a recent paper, the authors expressed concern that further evidence has bolstered the link between erythropoiesisstimulating agents (ESA) and the risk of stroke, death due to cancer in patients with history of malignancies and thrombosis in patients with chronic kidney diseases randomized to complete anaemia correction. Therefore, we ask if ‘the authors should give up the haemoglobin (Hb) target approach’ [1]. In fact, recent evidence not only demands the lowering of Hb target levels but also underscores that there is also a price to be paid in terms of the ESA dose to reach this target—that is, a poor haematopoietic response and the associated increased risk of death or cardiovascular events. Therefore, the degree of haematopoietic responsiveness—or lack of responsiveness—to treatment, and not Hb values alone, should be taken into account in ESA therapy [2–5]. But how can we measure this ‘lack of responsiveness’ to ESA? Different arbitrary cut-off definitions of responsive quartiles have been used, thus rendering comparisons impossible. ‘Lack of responsiveness’, ‘ESA response coefficient at the individual level’, ‘poor response to ESA dosage’ and ‘ESA dose requirement’ [4, 5] are terms suggested to identify these new criteria for evaluating ESA efficacy/safety with different arbitrary cut-off definitions: the lowest responsive quartile of change in haemoglobin level is <2 or <3%, but which one should be used? We suggest returning to the common and simple reproducible parameter which is the weekly ESA dose/kg divided by Hb as ESA/Hb ratio (Figure 1). ESA/Hb ratio is a simple, numerical and comparable parameter that can be used for statistical evaluation. In our Regional Audit on Anaemia, weekly ESA dose/kg divided by Hb was used in 3053 uraemic patients (Figure 1). The mean value was 9.0 6 3.5, and logistic regression analyses allowed the identification of the strongest predictors for ESA resistance, such as transferrin saturation <30% [odds ratio (OR) 2.87, 95% confidence interval (CI) 1.34–6.31] and C-reactive protein >12 mg/dL (OR 2.70, 95% CI 1.01–7.14). The adoption of this ratio could allow for comparable criteria beyond those predicted by Hb alone and could replace the use of Hb values exclusively as a target for ESA treatment.

Dialytic Treatment of Diabetic Patients with End-Stage Renal Failure: 17 Years of Experience

The experience of our Center in the treatment of uremic diabetic was analysed. Results show an increased total number of patients on treatment. Despite an increased age at start and higher risk, the adoption of high tolerance modes allow to obtain similar results, in the range of other non diabetic high risk population.