Correction of metabolic acidosis on serum albumin and protein catabolism in hemodialysis patients.

BACKGROUND: The effect of the correction of metabolic acidosis (MA) on serum albumin concentrations (sAlbs) in hemodialysis (HD) patients is controversial. This study evaluated the role of the correction of MA on sAlb concentrations, normalized protein catabolic rate (nPCR), and the effect of the concomitant inflammatory status, in a group of acidotic HD patients. METHODS: The correction of MA by oral supplementation with sodium bicarbonate, and the evaluation of its effect on sAlb, nPCR, and high-sensitivity C-reactive protein (hsCRP), were performed in 29 patients on bicarbonate dialysis for a median of 30 months. Other variables included pre-HD arterial pH, serum bicarbonate, serum creatinine, serum Na, body weight, interdialytic weight gain, pre-HD systolic and diastolic blood pressure, and Kt/V. RESULTS: Serum bicarbonate and pH increased significantly (P < .0001), from 19.1 +/- 0.7 mmol/L to 24.6 +/- 1.1 mmol/L and from 7.33 +/- 0.03 to 7.39 +/- 0.02, respectively (all values with +/- are SD). The nPCR decreased from 1.13 +/- 0.14 g/kg/day to 1.05 +/- 0.14 g/kg/day (P < .0001). The other variables did not change significantly. In 17 patients with high-sensitivity C-reactive protein <10 mg/L, sAlb increased from 3.7 +/- 0.3 g/dL to 4.0 +/- 0.3 g/dL (P < .01), whereas in 12 with high-sensitivity C-reactive protein >or=10 mg/L, sAlb did not change (3.5 +/- 0.17 g/dL vs. 3.4 +/- 0.13 g/dL; P = NS). CONCLUSIONS: Oral sodium bicarbonate supplementation is effective in correcting MA in HD patients and does not affect interdialytic weight gain, plasma Na, and blood pressure. The correction of MA is effective in reducing protein catabolism (nPCR) in both inflamed and less inflamed HD patients, but increases sAlb only in patients without inflammation. In inflamed patients, the correction of MA is not sufficient per se to improve sAlb concentrations.

Efficacy and safety of a very-low-protein diet when postponing dialysis in the elderly: a prospective randomized multicenter controlled study.

BACKGROUND: A supplemented very-low-protein diet (sVLPD) seems to be safe when postponing dialysis therapy. STUDY DESIGN: Prospective multicenter randomized controlled study designed to assess the noninferiority of diet versus dialysis in 1-year mortality assessed by using intention-to-treat and per-protocol analysis. SETTING & PARTICIPANTS: Italian uremic patients without diabetes older than 70 years with glomerular filtration rate of 5 to 7 mL/min (0.08 to 0.12 mL/s). INTERVENTION: Randomization to an sVLPD (diet group) or dialysis. The sVLPD is a vegan diet (35 kcal; proteins, 0.3 g/kg body weight daily) supplemented with keto-analogues, amino acids, and vitamins. Patients following an sVLPD started dialysis therapy in the case of malnutrition, intractable fluid overload, hyperkalemia, or appearance of uremic symptoms. OUTCOMES & MEASUREMENTS: Mortality, hospitalization, and metabolic markers. RESULTS: 56 patients were randomly assigned to each group, median follow-up was 26.5 months (interquartile range, 40), and patients in the diet group spent a median of 10.7 months (interquartile range, 11) following an sVLPD. Forty patients in the diet group started dialysis treatment because of either fluid overload or hyperkalemia. There were 31 deaths (55%) in the dialysis group and 28 deaths (50%) in the diet group. One-year observed survival rates at intention to treat were 83.7% (95% confidence interval [CI], 74.5 to 94.0) in the dialysis group versus 87.3% (95% CI, 78.9 to 96.5) in the diet group (log-rank test for noninferiority, P < 0.001; for superiority, P = 0.6): the difference in survival was -3.6% (95% CI, -17 to +10; P = 0.002). The hazard ratio for hospitalization was 1.50 for the dialysis group (95% CI, 1.11 to 2.01; P < 0.01). LIMITATIONS: The unblinded nature of the study, exclusion of patients with diabetes, and incomplete enrollment. CONCLUSION: An sVLPD was effective and safe when postponing dialysis treatment in elderly patients without diabetes.

A high calcium-phosphate product is associated with high C-reactive protein concentrations in hemodialysis patients.

BACKGROUND: An elevated CaxPO4 product and C-reactive protein (CRP) have been associated with coronary artery calcification and increased cardiovascular mortality in hemodialysis (HD) patients. However, it has not been defined, so far, whether and how both parameters are related to each other. For this reason we have evaluated in a cross-sectional and in an interventional study the possible correlation between CaxPO4 and CRP and the effect of the correction of a high CaxPO4 on CRP levels. METHODS: 47 uremic patients (age 65 +/- 16 years) on regular chronic HD were selected from a total population of 125 prevalent patients treated at our Institution. Patients had no clinical evidence of either acute infectious or inflammatory diseases for at least 4 weeks before the study. They were on regular bicarbonate HD for 6-329 months (median 42). CRP, hemoglobin (Hb), serum albumin (sAlb), protein catabolic rate (PCRn), serum calcium (Ca), serum phosphorus (PO4), CaxPO4, intact PTH, Kt/V, presence of ischemic heart disease (IHD) and/or peripheral vascular disease (PVD) were recorded. CRP was Ln-transformed in all statistical analyses because of positive skewness. RESULTS: The main findings were: LnCRP 2.17 +/- 0.77 mg/l, Ca 10.1 +/- 0.4 mg/dl, PO4 5.8 +/- 0.6 mg/dl, CaxPO4 59 +/- 6 mg2/dl2, andPTHint 218 +/- 195 ng/ml. 18/47 had IHD, 18/47 PVD. A significant hyperbolic correlation between CaxPO4 and CRP was observed. A piecewise linear regression model analysis identified a break-point for CaxPO4 at 55 mg2/dl2. Comparison of CRP levels after the division of the patients into two groups according to CaxPO4 break-point (group A, CaxPO4 < or = 55 mg2/dl2, n = 16 patients; group B, CaxPO4 >55 mg2/dl2, n = 31 patients) showed that CRP levels were significantly lower in patients in group A (LnCRP 1.43 +/- 0.22 mg/l) than in group B (LnCRP 2.55 +/- 0.67 mg/l, p < 0.0001). Multiple regression analysis bearing LnCRP as dependent variable confirmed CaxPO4 as the most significant variable among the other variables examined. In 22 patients with CaxPO4 > or = 60 mg2/dl2, we performed intensive lowering of the CaxPO4 product in order to reach and maintain a CaxPO4 , or =55 mg2/dl2 for 3 months. At the end of observation, a significant reduction in CaxPO4 and LnCRP was observed (CaxPO4 pre 62.8 +/- 1.9 vs. post 46.3 +/- 6.2 mg2/dl2: p < 0.0001; LnCRP pre 2.32 +/-0.36 vs. post 1.83 +/- 0.14 mg/l: p < 0.0001). No significant variation in the other biochemical parameters was observed. CONCLUSIONS: Our data show that in chronic HD patients in steady clinical conditions with no clinical evidence of either infectious or inflammatory diseases, a high CaxPO4 is associated with high CRP concentrations. Intensive lowering of CaxPO4 reduces CRP

Predialysis versus postdialysis hematocrit evaluation during erythropoietin therapy.

American guidelines for the management of renal anemia by recombinant human erythropoietin (rHuEPO) recommend collecting a predialysis blood sample to evaluate hemoglobin (Hb) and hematocrit (Hct) levels in hemodialysis patients. Although a predialysis blood sample is appropriate for evaluating when to start rHuEPO treatment, the same sample would not be appropriate for evaluating the target Hb/Hct to be maintained, particularly when normal or near-normal values are pursued. We measured the degree of intradialytic and extradialytic variation of Hb, Hct, and body weight in 68 stable hemodialysis patients on maintenance subcutaneous rHuEPO treatment. Hb and Hct concentrations were determined before and after dialysis. In 16 patients, Hb and Hct concentrations also were assessed 24 hours after the end of dialysis. Predialysis versus postdialysis Hb and Hct concentrations for all patients were 10.5 +/- 1.3 g/dL versus 11.5 +/- 1.3 g/dL (P < 0.0001) and 32 +/- 4% versus 35 +/- 4% (P < 0.0001). The intradialytic percent variation (%Delta) of Hct and body weight were 10 +/- 6% and -6.3 +/- 3.5%. There was a close inverse correlation between %Delta of Hct and Hb and %Delta of body weight (P < 0.0001). In patients with body weight losses 2.5 kg or more per session, the mean %Delta of Hct was 12 +/- 7%. In the 16 patients studied 24 hours after the end of the dialysis session, Hct and Hb values remained significantly higher compared with the predialysis levels (P < 0.001), suggesting a slow reequilibration of the intravascular volume in the first 24 hours after hemodialysis. For these reasons, predialysis samples for monitoring the target Hb and Hct levels in patients treated by rHuEPO should be considered with caution.

Long-term outcome in PD morbidity and mortality.

Two main dialysis modalities exist to treat chronic uremic patients: hemodialysis (HD) and peritoneal dialysis (PD); the latter is used less extensively than the former, but its penetration greatly differs among countries and among different regions of the same country. The comparison of the outcome in PD and HD is not easy, since many factors (mainly criteria for patient selection) oppose an adequate balance of the many factors influencing the patient's outcome. After the very different results in favor of HD in the early '80s, the difference in patient survival between PD and HD is progressively reduced and, in the '90s, many studies have shown comparable results. As far as the cardiovascular system is concerned, PD has some advantages versus HD due to stability in blood volume and electrolyte concentration, and lack of hyperkinetic circulation due to artero-venous fistula. However, this does not positively affect cardiovascular mortality whose prevalence is similar between the two modalities. Factors suggested to explain this unexpected result, namely: some degree of thrombophilia in PD, greater lipid metabolism derangement, and chronic fluid overload. Probably for these reasons, the de novo appearance of cardiovascular disease is similar in both modalities. Technique success is definitely worse in PD in nearly all the papers published. Many improvements in peritoneal solution biocompatibility have been made during the late '90s, but their effects on long-term outcome have to be defined.

Recovery of renal function after right nephrectomy, cavectomy and left renal vein ligation.

Right nephrectomy and ligation of the left renal vein often lead to acute renal failure, but not obligatorily to renal infarction and chronic uremia, thanks to the peculiar venous supply of the left kidney. A man underwent right nephrectomy, inferior cavectomy and ligation of the left renal vein and became anuric. Hemodialysis was necessary for some days, but he partially recovered his renal function. Proteinuria occurred a few days after the operation and decreased but had not disappeared after ten months. Eventually the patient died of brain metastases. There are a few reports of similar operations, some successful, others not, but very few papers report an adequate follow-up of subsequent changes in renal function. Nephrologists could be involved in the postoperative care of these cases. They should be aware of the possible recovery of renal function and should try all possible strategies to help the left kidney recover its function.

Epoetin requirement does not depend on dialysis dose when Kt/N > 1.33 in patients on regular dialysis treatment with cellulosic membranes and adequate iron stores.

BACKGROUND: An inverse correlation between Kt/V and epoetin requirement has recently been demonstrated in stable hemodialysis (HD) patients with adequate iron stores, dialyzed with cellulosic membranes. However, there is no evidence as to whether or not this effect continues for Kt/V even in the adequate or higher range. METHODS: We investigated the relationship between Kt/V and the weekly epoetin dose in 85 stable HD patients (age 63 +/- 16 years) treated with bicarbonate HD and unsubstituted cellulose membranes for 6-338 months (median: 70 months). INCLUSION CRITERIA: HD for at least 6 months, subcutaneous rHuEPO for at least 4 months, transferrin saturation (TSAT) > or = 20%, serum ferritin > or = 100 ng/mL, hemoglobin (Hb) level targeted to approximately equal to 12 g/dL for at least 3 months. EXCLUSION CRITERIA: HBsAg and HIV positivity; need for blood transfusions or evidence of blood loss in the 3 months before the study, acute and chronic infections. To evaluate the effect of dialysis adequacy on the epoetin requirement, we also performed the same analysis after dividing of the patients according to Kt/V. Hematocrit (Hct) and Hb levels were evaluated weekly for 3 weeks; TSAT, serum ferritin, Kt/V, PCRn, serum albumin (sAlb), and weekly epoetin dose were evaluated at the end of observation. No change in dialysis or therapy prescription was made during the study. RESULTS: The results for all the patients were: Hct 36 +/- 2 %, Hb 12 +/- 0.7 g/dL, TSAT 28 +/- 7%, serum ferritin 234 +/- 171 ng/mL, sAlb 4.2 +/- 0.4 g/dL, Kt/V 1.33 +/- 0.17, PCRn 1.15 +/- 0.28 g/Kg/day, weekly epoetin dose 117 +/- 74 U/Kg. There was no correlation between Hb and Kt/V, whereas there was an inverse correlation between the reciprocal of the weekly epoetin dose and Kt/V (r = -0.448, p = 0.0001). Further regression line analysis showed a break-point for Kt/V at the level of 1.33. In the 52 patients with Kt/V < 1.33, the correlation was confirmed between epoetin and Kt/V (r = - 0.563, p = 0.0001), while in the 33 patients with Kt/V > or = 1.33, there was no correlation between epoetin dose and Kt/V (r = 0.021, p = NS). In these patients, multiple regression analysis, with the weekly epoetin dose as a dependent variable, confirmed Kt/V as a non-significant factor. CONCLUSIONS: In iron-replete HD patients on cellulosic membranes and stabilized epoetin therapy, inadequate dialysis was associated with higher epoetin requirement, but for Kt/V values > or = 1.33, there was no further effect on epoetin responsiveness.

Effects of a vitamin E-bonded membrane and of glutathione on anemia and erythropoietin requirements in hemodialysis patients.

BACKGROUND: The oxidative damage of RBC membranes in hemodialysis (HD) patients increases red blood cell (RBC) susceptibility to hemolysis and impairs cell survival. Reduction of the oxidative stress might lead to better control of anemia and reduction of the erythropoietin (rhEPO) dose. METHODS: We studied 38 stable HD patients, given a mean dose of rhEPO of 104+/-65 U/kg BW/week, at baseline and during antioxidant treatment with either a full or a 50% dose of EPO. Antioxidant treatment involved the combined use of glutathione, GSH (1200 mg i.v. at the end of each dialysis session) and a vitamin E-bonded HD membrane, CL-E. RBC and reticulocyte counts were done monthly. RBC survival (51Cr T/2) was assayed in 18 patients before and after the end of the study. Oxidative status was determined in 10 patients by measuring plasma concentrations of malondyhaldeide-4-hydroxynonenal (MDA-4HNE), reactive oxygen molecular species (ROMs), and oxydized-LDL (oxLDL) as indices of oxidative stress, alpha-tocopherol and total thiols as single antioxidants, and TAS as a marker of total antioxidant plasma activity. RESULTS: Antioxidant treatment significantly reduced the high basal plasma concentrations of MDA4HNE and oxLDL, and significantly increased those of alpha-tocopherol, whereas TAS and thiols were unmodified. These changes lasted after the reduction of EPO. Anemia significantly improved with treatment, due to a significant increase in RBC survival. A close direct linear relationship was detected between plasma levels of vitamin E and hemoglobin. CONCLUSIONS: Adequate control of oxidative stress achieves better control of anemia in HD patients. Since several antioxidant systems are impaired in uremia, the combined use of the CL-E membrane and GSH seems to be the best antioxidant therapy so far, with significant saving of the rhEPO dose.

Transplantation outcome in patients on PD and HD.

In the past, peritoneal dialysis (PD) has been considered a second choice dialysis modality for many aspects and that negative attitude has been extended also to possible negative effects on renal transplantation. In the last years, many papers have faced the question whether PD could attain similar results in renal transplantation as hemodialysis and there is sufficient evidence to answer that question. On the short time after transplantation, patients coming PD have lower prevalence of delayed graft function than hemodialysis patients, but higher prevalence of renal vascular thrombosis, above all in children. Incidence of acute graft rejection is not different between the two dialysis modalities. The long-term outcome of renal transplantation is similar in patients coming from either PD or hemodialysis.

The kind of vascular access influences the baseline inflammatory status and epoetin response in chronic hemodialysis patients.

BACKGROUND: Arteriovenous grafts (AVG) and tunneled permanent catheters (TPC) are increasingly being used in hemodialysis (HD) patients. However, their role in baseline inflammatory status has not been fully evaluated. Aim of the study was to evaluate the influence of the current kind of vascular access on the baseline inflammatory status, marked by serum C-reactive protein (CRP), and the response to epoetin therapy in a group of iron-replete HD patients, under steady clinical conditions, without evidence of acute infections and/or inflammatory diseases. METHODS: We studied 79 patients who had been on bicarbonate HD for 8-410 months and were receiving epoetin therapy. They all had adequate iron stores and stable hemoglobin (Hb) levels. Exclusion criteria were fever, signs of infection, white blood cell count (WBC) > 10 x 1,000/microl, for at least 4 weeks before study. 48 patients (group A) had arteriovenous fistula (AVF), 18 patients (group B) AVG, 13 patients (group C) TPC. CRP, Hb, transferrin saturation, serum ferritin, WBC, serum albumin, protein catabolic rate, Kt/V, and epoetin dose (U/kg body weight/week) were measured. CRP values were log-transformed to normalize the distribution. RESULTS: Log-transformed CRP values among the 3 groups were significantly different: group A 1.81 +/- 0.48; group B 2.12 +/- 0.50, and group C 3.00 +/- 0.25 (group A vs. B p < 0.003; group B vs. C p < 0.001; group A vs. C p < 0.0001). CRP and the epoetin dose were directly correlated (r = 0.519; p < 0.0001). The epoetin doses among the 3 groups were significantly different. Multiple regression analysis confirmed AVG and TPC as factors independently influencing CRP levels. CONCLUSIONS: AVG and TPC have a higher degree of chronic inflammation than AVF. The epoetin requirement is increased in TPC and AVG compared with AVF.

Inter-dialytic variations in blood volume and total body water in uraemic patients treated by dialysis.

BACKGROUND: An optimal balance of sodium and water is one of the most important goals of haemodialysis (HD) therapy. However, while inter-dialytic variations in blood volume (BV) have been well described, very little is known about the dynamics of fluid accumulation and distribution in body compartments during the inter-dialysis period. METHODS: We studied inter-dialysis variations in BV, measured as percent variation of plasma haemoglobin (Hb) concentrations (% triangle up BV) and percent variation of total body water (% triangle up TBW), in 24 uraemic patients treated by standard bicarbonate dialysis. These parameters were determined at the end of the last weekly dialysis (T0), after 24 h (T1), 48 h (T2), and at the beginning of the following dialysis session (T3). At each time point we measured Hb, haematocrit (Hct), serum albumin (sAlb), plasma sodium (Na), plasma potassium (K), blood urea nitrogen (BUN), plasma osmolality (Osm), body weight (BW), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). All patients were clinically stable and had no evidence of acute blood loss in the 3 weeks before the study. RESULTS: During the inter-dialysis period, there were increases in BUN, K and Osm, but Na did not change. SBP and DBP also did not change. HR tended to decrease, and showed a significant reduction between T0 and T3. TBW increased in a linear fashion whereas BV increased exponentially, showing a slow rise during the first 24 h followed by a greater increase in the following time intervals. This was confirmed by concomitant but opposite percent variations in Hct and sAlb concentrations. CONCLUSIONS: Despite the limitations of the current methodology, our data show that the increase in TBW is redistributed during the long inter-dialysis period and this may prevent the effects of a too premature expansion of the intra-vascular compartment. This is especially evident during the first 24 h after HD, during which % triangle up BV is lowest, indicating a preferential distribution of the fluid load towards the extra-vascular space. During the following time intervals, the extra-vascular compartment refills in conjunction with an exponential expansion of BV that reaches its maximum in the last 24 h before HD.