[Guidelines of the Italian Society of Nephrology. Peritoneal dialysis Guidelines]. / Linee Guida della Societa' Italiana di Nefrologia. Linee Guida per la dialisi peritoneale (DP).

The adequate dosage of peritoneal dialysis (PD) has been defined (using unrandomized and uncontrolled studies) asKt/V = 2, with a total (peritoneal + renal) creatinine clearance = 60 mL/min. The recent prospective, randomized ADEMEX study, suggests targets of 1.8 and 54 mL/min respectively. Dialysis must also be adequate to control fluid removal, phosphate levels, nutritional status, and hypertension. The targets for automated PD (APD) should be either 10% more than CAPD or similar, depending on the time of blood sample collection either immediately at the end of the automated exchanges or 6 to 8 hours after. A peritoneal equilibration test should be done 1 to 2 months after the start of PD, yearly, and when peritoneal permeability or ultrafiltration changes occurr. Residual renal function must be protected as long as possible by avoiding nephrotoxic drugs and excessive dehydration. Every effort must be taken in the attempt to maintain a good nutritional status and to diagnose as soon as possible any changes toward malnutrition. Hypertension has a high prevalence in PD patients and has negative effects on both cardiovascular status and patient survival. However, anti-hypertensive therapy should avoid hypotension, mainly in older patients, who are more at risk for cerebrovascular accident. Hyperparathiroidism must be controlled by diet, phosphate binders, and calcitriol supplement, but attention must be paid to avoid cardiac and vascular calcifications. Peritonitis and exit-site infection should be prevented by all means available. In the case of infection, empiric antibiotic therapy should be started as soon as possible and then adapted according to the antibiogram.

Direct effect of the correction of acidosis on plasma parathyroid hormone concentrations, calcium and phosphate in hemodialysis patients: a prospective study.

BACKGROUND: Metabolic acidosis contributes to renal osteodystrophy and together with hyperphosphatemia, hypocalcemia and altered vitamin D metabolism may result in increased levels of intact parathyroid hormone (iPTH) and metastatic calcifications. However, the impact of the correction of metabolic acidosis on iPTH levels and calcium-phosphate metabolism is still controversial. STUDY DESIGN: The effects of the correction of metabolic acidosis on serum concentrations of iPTH, calcium (Ca), phosphate (PO(4)) and alkaline phosphatase were prospectively studied. Twelve uremic patients on maintenance hemodialysis (HD) for 49 months (median; range 6-243 months) with serum bicarbonate levels < or =20 mmol/l were studied before and after 3 months of oral sodium bicarbonate supplementation. Predialysis serum bicarbonate, arterial pH, ionized calcium, plasma sodium, plasma potassium, serum creatinine, hemoglobin, K(t)/V, postdialysis body weight, predialysis systolic and diastolic blood pressure were also evaluated before and after correction. RESULTS: Serum bicarbonate levels and arterial pH increased respectively from 19.3 +/- 0.6 to 24.4 +/- 1.2 mmol/l (p < 0.0001) and 7.34 +/- 0.03 to 7.40 +/- 0.02 (p < 0.001). iPTH levels decreased significantly from 399 +/- 475 to 305 +/- 353 pg/ml (p = 0.026). No changes in total serum Ca, plasma PO(4), serum akaline phosphatase, K(t)/V, serum creatinine, hemoglobin, body weight, predialysis systolic and diastolic blood pressures were observed. iCa decreased significantly. CONCLUSIONS: Our study demonstrates that the correction of metabolic acidosis in chronic HD patients reduces iPTH concentrations in HD patients with secondary hyperparathyroidism possibly by a direct effect on iPTH secretion.

Adequacy of dialysis reduces the doses of recombinant erythropoietin independently from the use of biocompatible membranes in haemodialysis patients.

BACKGROUND: The effect of the adequacy of dialysis on the response to recombinant human erythropoietin (rHuEpo) therapy is still incompletely understood because of many confounding factors such as iron deficiency, biocompatibility of dialysis membranes, and dialysis modality that can interfere. METHODS: We investigated the relationship between Kt/V and the weekly dose of rHuEpo in 68 stable haemodialysis (HD) patients (age 65+/-15 years) treated with bicarbonate HD and unsubstituted cellulose membranes for 6-343 months (median 67 months). Inclusion criteria were HD for at least 6 months, subcutaneous rHuEpo for at least 4 months, transferrin saturation (TSAT) > or = 20%, serum ferritin > or = 100 ng/ml, and haematocrit (Hct) level targeted to 35% for at least 3 months. Exclusion criteria included HBsAg and HIV positivity, need for blood transfusions or evidence of blood loss in the 3 months before the study, and acute or chronic infections. Hct and haemoglobin (Hb) levels were evaluated weekly for 4 weeks; TSAT, serum ferritin, Kt/V, PCRn, serum albumin (sAlb), and weekly dose of rHuEpo were evaluated at the end of observation. No change in dialysis or therapy prescription was made during the study. RESULTS: The results for the whole group of patients were: Hct 35 +/- 1.2%, Hb 12.1 +/- 0.6 g/dl, TSAT 29 +/- 10%, serum ferritin 204 +/- 98 ng/ml, sAlb 4.1 +/- 0.3 g/dl, Kt/V 1.33 +/-0.19, PCRn 1.11+/- 0.28 g/kg/day, weekly dose of rHuEpo 123 +/- 76 U/kg. Hct did not correlate with Kt/V, whereas rHuEpo dose and Kt/V were inversely correlated (r = -0.49; P < 0.0001). Multiple regression analysis with rHuEpo as dependent variable confirmed Kt/V as the only significant variable (P < 0.002). Division of the patients into two groups according to Kt/V (group A, Kt/V < or = 1.2; group B, Kt/V > or = 1.4), showed no differences in Hct levels between the two groups, while weekly rHuEpo dose was significantly lower in group B than in group A (group B, 86 +/- 33 U/kg; group A, 183 +/- 95 U/kg, P < 0.0001). CONCLUSIONS: In iron-replete HD patients treated with rHuEpo in the maintenance phase, Kt/V exerts a significant sparing effect on rHuEpo requirement independent of the use of biocompatible synthetic membranes. By optimizing rHuEpo responsiveness, an adequate dialysis treatment can contribute to the reduction of the costs of rHuEpo therapy.

Clinical aspects of peritoneal sclerosis.

Peritoneal sclerosis (PS) occurs in various clinical situations in Peritoneal Dialysis (PD) patients. Some degree of PS is often present in long-term PD patients, generally without clinical or functional consequences. At the other end of the spectrum of PS there is Sclerosing encapsulating peritonitis (SEP). Though infrequent, it is very severe. SEP is not a complication exclusive to PD; it is a syndrome related to many diseases of abdominal organs, some drugs and abdominal surgery. Remarkably, in many cases, the first symptoms of SEP appear months or years after the change from PD to HD has occurred. Today there is no full agreement about the microscopical findings of SEP or about the name of this syndrome: SEP or Encapsulating Peritoneal Sclerosis (EPS). The main etiopathogenetic factor for PS is the poor biocompatibility of PD solutions. In the etiopathogenesis of SEP, other factors in addition to the PD fluids have been suggested as possible causes (peritonitis, drugs, disinfectants, etc.). This paper reviews all the clinical aspects of PS and SEP: pathogenesis, clinical signs, diagnosis and therapy.

Pneumoperitoneum in peritoneal dialysis patients.

The prevalence and clinical significance of pneumoperitoneum in peritoneal dialysis (PD) patients is not fully defined in current literature and some reports suggest that unlike in non-PD patients, it is rarely caused by gastrointestinal perforation. We reviewed 403 chest X-ray films of the 118 PD patients following our PD program in 1995-96, in order to define the prevalence of pneumoperitoneum. We found pneumoperitoneum in 3.7% of the X-rays (15/403) from five patients (4.2%). Its causes might have been: faulty bag exchange technique in two cases and extension tube exchange in three. One patient suffered from a simultaneous episode of peritonitis. Our data and the literature review suggest that 0-11% of pneumoperitoneum episodes in PD patients are due to gastrointestinal perforation; the main causes generally are abdominal operations and catheter manipulation. The amount of air is not useful in assessing the cause of pneumoperitoneum, which takes some weeks to disappear. Computed tomography is more sensitive than standard X-ray in diagnosis.

Low concentrations of glucose degradation products in peritoneal dialysis fluids and their impact on biocompatibility parameters: prospective cross-over study with a three-compartment bag.

The side effects of glucose degradation products (GDPs) in conventional peritoneal dialysis (PD) fluids are well described. Using the three-compartment bag concept--that is, in situ preparation of concentrated glucose solution into a standard ionic solution--a GDP-free solution can be processed. To investigate the possible impact of this product on biological and clinical parameters, we carried out a prospective cross-over study with 31 patients, comparing the short-term effects of conventional PD and GDP-free PD solutions. Classical peritoneal parameters and ultrafiltration rate did not change during the study. After three months and after six months with the three-compartment bag, cancer antigen 125 (CA125) concentration in overnight fluid increased significantly (p < 0.001) from 24.4 IU/mL to 44.4 IU/mL and 41.1 IU/mL respectively. CA125 decreased significantly (p < 0.01) to 21.7 IU/mL after three months with the conventional solution. No change in hyaluronan concentration was observed. A slight increase of procollagen III N-terminal peptide in overnight effluent with the GDP-free solution was followed by a significant reduction after three months with standard solution. In summary, our data show that the GDP-free PD fluid improves mesothelial cell mass and turnover even after a short-term period of three months. A better quality of PD solution is obtained by using the three-compartment bag.

A controlled trial of two bicarbonate-containing dialysis fluids for CAPD--final report.

BACKGROUND: The combination of a low pH and a high concentration of lactate which is present in most dialysis fluids is found to be cytotoxic in vitro. For these reasons it would seem logical to use a bicarbonate-containing solution and thus automatically provide a solution with a neutral pH. METHODS: A parallel, randomized, open-label, prospective 2-month trial with an optional 4 month extension was undertaken to compare two novel bicarbonate-based solutions; one containing 38 mmol/l of bicarbonate (B), and one containing a mixture of 25 mmol/l bicarbonate and 15 mmol/l of lactate (B/L), with a control solution (C) containing 40 mmol/l lactate. RESULTS: Three groups of 19 (C), 20 (B), and 20 (B/L) patients were recruited and data from approximately 55 patient months were accumulated in each group. The data show that both bicarbonate-based solutions maintain acid-base levels within the normal range, that there were no changes in any of the other blood biochemistry parameters measured in the peritoneal equilibration test or with regard to adequacy of dialysis, and that furthermore, both solutions were well tolerated. CONCLUSIONS: This study showed that either the bicarbonate or bicarbonate/lactate solutions could be utilized efficaciously in patients undergoing CAPD.

Correction of metabolic acidosis increases serum albumin concentrations and decreases kinetically evaluated protein intake in haemodialysis patients: a prospective study.

BACKGROUND: Metabolic acidosis in haemodialysis (HD) patients increases whole body protein degradation while the correction of acidosis reduces it. However, the effects of the correction of acidosis on nutrition have not been clearly demonstrated. STUDY DESIGN: In this study we have evaluated the effects of 3 months of correction of metabolic acidosis by oral sodium bicarbonate supplementation on protein catabolic rate (PCRn) and serum albumin concentrations in 12 uraemic patients on maintenance HD for at least 6 months (median 49 months; range 6-243 months). Pre-dialysis serum bicarbonate, arterial pH, serum albumin, total serum proteins, serum creatinine, plasma sodium, haemoglobin, PCRn, Kt/V, and TACurea, were evaluated before and after correction. RESULTS: Serum bicarbonate levels and arterial pH increased respectively from 19.3 +/- 0.6 mmol/l to 24.4 +/- 1.2 mmol/l (P < 0.0001) and 7.34 +/- 0.03 to 7.40 +/- 0.02 (P < 0.0001). Serum albumin increased from 34.9 +/- 2.1 g/l to 37.9 +/- 2.9 g/l (P < 0.01), while PCRn decreased from 1.11 +/- 0.17 g/kg/day to 1.03 +/- 0.17 g/kg/day (P < 0.001). No changes in Kt/V, total serum proteins, serum creatinine, plasma sodium, haemoglobin, body weight, pre dialysis systolic and diastolic blood pressure, and intradialytic weight loss were observed. CONCLUSIONS: Our data demonstrate that correction of metabolic acidosis improves serum albumin concentrations in HD patients. The correction of acidosis induces a decrease in PCRn values, as evaluated by kinetic criteria, suggesting that in the presence of moderate to severe acidosis this parameter does not reflect the real dietary protein intake of the patients probably as a result of increased catabolism of endogenous proteins. The correction of metabolic acidosis should be considered of paramount importance in HD patients.

Evidence for an independent role of metabolic acidosis on nutritional status in haemodialysis patients.

BACKGROUND: Malnutrition in haemodialysis (HD) patients has been referred to underdialysis with low protein intake, and to acidosis. However, the separate effects of underdialysis and acidosis on nutrition have not been clearly demonstrated. To evaluate the role of the dialysis dose and of metabolic acidosis on nutrition, we measured the predialysis serum HCO3, pH, serum albumin, PCRn, Kt/V, and BMI in 81 uraemic patients on maintenance bicarbonate HD for 93+/-80 months. Patients with chronic liver diseases, malignancies, and cachexia were excluded. RESULTS: Mean age was 59+/-17 years, Kt/V was 1.29+/-0.21, PCRn 1.06+/-0.22 g/kg/day, serum albumin 4.07+/-0.28 g/dl, BMI 23+/-4 kg/m2, HCO3 21.1+/-1.9 mmol/l, pH 7.36+/-0.04. Serum albumin showed a significant direct correlation with: PCRn (P=0.001), HCO3 (P=0.001), pH (P=0.002), but no correlation with Kt/V and BMI. Serum HCO3 correlated inversely with PCRn (P=0.027). Multiple regression analysis confirmed the significant role of serum bicarbonate and age, but not of Kt/V, on serum albumin concentrations. The role of PCRn appeared to be marginal compared to serum bicarbonate in determining serum albumin levels. Dividing patients into two groups, serum albumin was 3.96+/-0.22 g/dl with HCO3 < or = 20 mmol/l and 4.18+/-0.31 g/dl in those with serum HCO3 > or = 23 mmol/l (P=0.002). PCRn in the same groups was respectively 1.14+/-0.24 g/kg/day and 1.01+/-0.23 g/kg/day (P=0.03). Most importantly, serum albumin levels did not appear to be affected by the dialysis dose, with Kt/V ranging from 0.90 to 1.88. CONCLUSIONS: In HD patients with adequate Kt/V, metabolic acidosis exerts a detrimental effect on serum albumin concentrations partially independently of the protein intake, as evaluated by PCRn. In the presence of moderate to severe metabolic acidosis, PCRn does not reflect the real dietary protein intake of the patients, probably as a result of increased catabolism of endogenous proteins. For this reason PCRn should be considered with caution as an estimate of the dietary protein intake in HD patients in the presence of metabolic acidosis.

Clinical evaluation of a peritoneal dialysis solution with 33 mmol/L bicarbonate.

OBJECTIVE: To evaluate the efficacy and safety of a new peritoneal dialysis solution with 33 mmol/L bicarbonate. DESIGN: In an acute, prospective, randomized cross-over study, 8 patients were randomized in two groups of 4. On the first study day, the first group performed two consecutive 4-hour exchanges with a dialysis solution containing 35 mmol/L lactate: the first exchange with 13.6 g/L and the second with 38.6 g/L dextrose. On the second study day, the same type of exchanges were performed with bicarbonate. The second group underwent the same treatment, but used bicarbonate solutions on the first day and control solutions on the second study day. Thirty-three patients participated in a 2-month prospective and randomized study. After a 4-week baseline period using solutions containing 40 mmol/L lactate, the patients were dialyzed with either 33 mmol/L bicarbonate solutions or 40 mmol/L lactate solutions. SETTING: Peritoneal dialysis units at the University Hospital of Brescia and the Niguarda Hospital of Milan, Italy. RESULTS: Acute study: Control and bicarbonate solutions had similar effects on blood chemistries and peritoneal transport. Chronic study: Mean venous bicarbonate concentrations remained unchanged in the control group (26.6-27.2 mmol/L), but decreased significantly in the bicarbonate group from 28.8 mmol/L at the start of the study to 23.0 mmol/L after 2 months of bicarbonate administration. Other biochemical parameters remained unchanged. CONCLUSION: A peritoneal dialysis solution with a bicarbonate level of 33 mmol/L does not adequately correct uremic acidosis.

A randomized controlled trial of a bicarbonate- and a bicarbonate/lactate-containing dialysis solution in CAPD.

OBJECTIVE: To evaluate the safety and efficacy of bicarbonate- and bicarbonate/lactate-based PD fluids. DESIGN: A randomly allocated prospective controlled trial lasting eight weeks. SETTING: Five renal units in Europe. PATIENTS: Individuals who have been treated by CAPD for at least three months and who have had at least one month's therapy with 40 mmol/L lactate PD fluid. Those with recent infection, diabetes or other serious illness are excluded. Forty-seven individuals have entered the study so far. INTERVENTIONS: Patients are randomly allocated to three groups. Group 1 receive 40 mmol/L lactate dialysate, Group 2 are given 38 mmol/L bicarbonate fluid and Group 3 are tested with a 25 mmol/L bicarbonate and 15 mmol/L lactate dialysate. OUTCOME MEASURES: The primary outcome measure is the plasma bicarbonate level. Adverse events and ease of use of the two-chambered bags used by Groups 2 and 3 are also being assessed. RESULTS: To date, plasma bicarbonate levels have been the same in all treatment groups up to the end of the trial period. There are no differences in serum lactate levels. No side effects are attributable to the test fluids. The patients have managed the two-chambered bags successfully. CONCLUSION: This trial is still ongoing, but to date, neutral bicarbonate based fluids have been as effective as lactate dialysate in treating uremic acidosis.

CAPD viability: a long-term comparison with hemodialysis.

OBJECTIVE: To compare the long-term viability of continuous ambulatory peritoneal dialysis (CAPD) to that of hemodialysis (HD). DESIGN: Retrospective study of patients of our institution starting dialysis between January 1, 1981, and December 31, 1993, and surviving for at least 2 months. PATIENTS: Five hundred and seventy-eight new patients (51.3% on CAPD and 48.6% on HD). MAIN OUTCOMES STUDIED: Cox-adjusted assessment of patient and technique survival, and of technique success. Differences in results for two successive periods of time. RESULTS: Patient survival did not differ between CAPD and HD after adjusting for age and comorbidity, and significantly improved in the second part of the follow-up (1987-1993). Technique failure was significantly higher on CAPD, in which it was inversely related to age. The probability of a patient continuing on the first method of dialysis ("technique success") was significantly lower on CAPD than on HD, but the difference decreased progressively with age and disappeared in patients > or = 75 years. CONCLUSION: CAPD is as effective as HD in preserving life in uremic patients in the long-term, and gives better results in the older elderly. In adults, the lower technique success rate may not be a problem for patients with access to a good transplantation program; for others, this drawback must be weighed against the advantages of home treatment.

Differing dialysis treatment strategies and outcome.

The choice of a dialysis treatment depends on many factors, both medical and non-medical. A full and rational treatment requires easy access to a transplantation programme and to all dialysis modalities, extracorporeal or peritoneal. Presently, haemodialysis (HD) is used almost exclusively for in-centre or limited care treatment, peritoneal dialysis (PD) being preferred for home treatment. On HD, bicarbonate buffer is used in preference to acetate. Mixed convective-diffusive HD techniques have a very limited utilization world-wide because of their cost. Use of PD and automated PD continues to grow, although slowly. In our single-centre experience on a large number of patients, 10-year patient survival is not different on CAPD and HD, and there is initial lower risk of death on CAPD for patients > or = 75 years of age. Drop-out from CAPD has increased in recent years, mainly due to the patient/partner 'burn-out'. Drop-out is less for the elderly, and the difference in modality change between CAPD and HD decreases with increasing patient age, suggesting a clear indication for CAPD in the elderly, or in adults waiting for a transplant. The clinical background, e.g. the presence of diabetes mellitus, cardiovascular disease, dyslipidaemia or obesity, is also important in the choice of method.

Comparison of long-term survival between hemodialysis and peritoneal dialysis.

We have reviewed the literature and our own center's results for patients on long-term continuous ambulatory peritoneal dialysis (CAPD) in comparison to results for patients on hemodialysis (HD). Contrary to recent American data showing one-year survivals to be worse on CAPD, the Canadian Registry and other studies show no significant difference in survivals on the two methods. Results are also conflicting for diabetics. Insufficient adjustments for age and case-mix variations are probably the most important causes for differences. For the general population, personal Cox-adjusted data show no difference between CAPD and HD up to ten-year follow-up, with very close curves for the adults and non-significant differences for the elderly. Old elderly (> 75 years) have better survival on CAPD in the first years of treatment. Dropout, which is higher on CAPD, decreases with age, and the patient retention on CAPD is worse than on HD for all patients, except the old elderly, for whom it is similar. These data were obtained in patients receiving a standard treatment, modified in order to give a more adequate dialysis dose only in recent years. The results of a prospective three-year study on the effect of nutritional [serum albumin and transferrin, normalized protein catabolic rate (PCRN), and subjective global assessment of malnutrition] and adequacy indices [Kt/V, creatinine clearance (Ccr), residual renal function] on patient survival on CAPD and HD are reported. Survival was not different for the two methods. Using the Cox analysis, nutritional indices did not affect survival whereas adequacy indices did. The effect of low serum albumin on survival was referable to the predialysis nutritional state. The similar survivals obtained on CAPD and HD, with Kt/V more or less than 1.0/treatment for HD and 1.7/week for CAPD, support the "peak concentration hypothesis" of Keshaviah et al. Survival in different groups of patients with different Kt/V and Ccr shows that the adequate dose on CAPD is Kt/V between 1.96 and 2.03 and Ccr > or = 70 L/week. A group of 26 patients who remained on CAPD treatment for more than eight years was also studied. Patient age and predialysis comorbidity were the most important factors affecting survival. Patients surviving longest had > 3 g/dL of serum albumin, > 0.8 g/kg/day of PCRN, a Kt/V > 1.6, and a weekly Ccr > 54L/week.