Parameters associated with therapeutic response using peritoneal dialysis for therapy refractory heart failure and congestive right ventricular dysfunction.

BACKGROUND: In patients with refractory heart failure (HF) peritoneal dialysis (PD) is associated with improved functional status and decrease in hospitalization. However, previous studies did not focus on right ventricular dysfunction as an important pathophysiologic component of cardiorenal syndrome. METHODS: In a prospective cohort study PD was started in 40 patients with refractory right HF (with/without left HF). Refractoriness to conservative therapy was defined as persistent right heart congestion/ascites with intensified diuretic treatment and/or ≥2 hospitalizations within 6 months because of cardiac decompensation despite optimal medical treatment, and/or acute renal failure during intensified conservative treatment of cardiac decompensations. RESULTS: Patient survival was 55.0% at 1 year, 35.0% at 2 years and 27.5% at 3 years. The number of hospitalization days declined after initiation of PD for both cardiac [13 (IQR 1-53) days before vs. 1 (IQR 0-12) days after start of PD, p<0.001] and unplanned reasons [12 (IQR 3-44) days before vs. 1 (IQR 0-33) days after start of PD, p = 0.007]. Using a combined endpoint including survival time of ≥1 year and either improvement in quality of life or decline in hospitalizations we found that patients with extended ascites, higher systolic pulmonary artery pressure, more marked impairment of right ventricular function and tricuspid valve insufficiency, higher residual renal function as well as those who could perform PD without assistance have benefited most from this therapy. CONCLUSIONS: Patients with more pronounced backward failure, less marked residual renal functional impairment and those not depending on assistance for therapy are likely to profit most from PD.

[Peritoneal dialysis--an ideal initial dialysis mode]. / Peritonealdialyse--ein ideales initiales Dialyseverfahren.

Peritoneal dialysis (PD) has become an established dialysis modality besides hemodialysis (HD). Although PD is an equal form of dialysis compared to HD, patients numbers on PD remain low worldwide. There are several reasons for this fact. The medical staff in some centers is not used to PD, so there is not enough information about the different dialysis methods available for the patients and the staff doesn't get the training that would be necessary to get familiar with PD. There are some concerns about offering PD to certain groups of patients despite excellent results as to quality of dialysis, good preservation of residual renal function, low costs compared to HD and better quality of life than on HD. However, PD should be offered to all patients requiring dialysis with very few exeptions as an ideal initial dialysis method. This includes patients with diabetes, patients with kidney transplant failure, patients with congestive heart failure and older patients.

Effects of comorbid and demographic factors on dialysis modality choice and related patient survival in Europe.

BACKGROUND: The mean age of patients starting dialysis increased over the years, as has the proportion of patients with diabetes mellitus, ischaemic heart disease, peripheral vascular disease (PVD), cerebrovascular disease (CD) and malignancy. We assessed dialysis modality choice within subgroups of patients with these comorbidities and in different age categories and subsequently evaluated the association between modality choice and patient survival in these subgroups. METHODS: Seven European renal registries participating in the ERA-EDTA Registry provided data from 15,828 incident peritoneal dialysis (PD) and haemodialysis (HD) patients (1998-2006) with available comorbidity data. The likelihood to receive PD rather than HD was assessed with logistic regression and 3-year survival on PD versus HD was evaluated using Cox regression. RESULTS: Besides large international variations in the likelihood to receive PD, we found that elderly patients and patients with PVD, CD, malignancy and multiple comorbidities were significantly less likely to receive PD than HD. Overall patients starting on PD had survival benefits [adjusted hazard ratio (HR(adj)) 0.82 (0.75-0.90)], especially patients without comorbidity [HR(adj) 0.65 (0.53-0.80)] or those with malignancy [HR(adj) 0.73 (0.56-0.94)]. In males, survival benefits of PD were independent of diabetic status. Conversely, diabetic females tended to have increased mortality risk on PD [HR(adj) 1.16 (0.93-1.44)], especially if they were >70 years [HR(adj) 1.55 (1.15-2.08)]. CONCLUSIONS: In general, modality choice was consistent with expected survival. However, elderly patients, non-diabetic patients and those with malignancy were less likely to receive PD, even though they had decreased mortality risk on PD. Also, although a survival benefit of PD was found for male patients without comorbidity, HD was just as likely to be the chosen dialysis modality as was PD for these patients.

Effect of radio contrast media on residual renal function in peritoneal dialysis patients--a prospective study.

BACKGROUND: Residual renal function is an independent predictor of survival in peritoneal dialysis patients. Systemic administration of radio contrast media (CM) may increase the risk of acute renal failure in patients with impaired renal function not on dialysis. There are few data on the influence of CM administration in dialysis patients. METHODS: We investigated residual renal function in 10 continuous ambulatory peritoneal dialysis (CAPD) patients who underwent elective diagnostic intravenous or intra-arterial administration of CM (study group). Iopromide (a iodinated, non-ionic hypo-osmolar CM) was used for all interventions. The median dose of CM given was 107.5 ml/patient. Residual renal function (calculated as the average of renal creatinine and renal urea clearance) was measured on the day before the intervention (baseline), on days 1-7, day 10 and day 30 after intervention. Eight CAPD patients without exposure to CM acted as the control group. RESULTS: There was no significant difference between the two groups in age, gender, diabetes, duration of dialysis and renal clearance at baseline. In the study group, we observed a temporary decline of residual renal clearance after administration of CM (P<0.05; Friedman test). On day 30, clearances were not significantly different from baseline. In the control group, there was no significant change of residual clearance during the observation period. Repeated measures ANOVA revealed no significant difference in the course of residual renal function between study and control groups. The decline of residual renal clearance between baseline and a routine visit after 4 months was comparable between groups. CONCLUSION: Administration of iopromide did not lead to a persistent decline of residual renal function in CAPD patients. Nevertheless, non-ionic hypo-osmolar CM should be given to these patients with the lowest possible dose and only if there is a real clinical indication.

Intravenous iron increases labile serum iron but does not impair forearm blood flow reactivity in dialysis patients.

BACKGROUND: There are concerns about adverse vascular effects of intravenous iron by inducing oxidative stress. We therefore examined the effect of a single high dose of intravenous iron on endothelial function and biochemical markers of iron homeostasis. METHODS: In a randomized, placebo-controlled, double-blind, parallel-group study, forearm blood flow (FBF) was assessed by strain-gauge plethysmography in 38 peritoneal dialysis patients before and after a single intravenous infusion of 300 mg iron sucrose. RESULTS: Iron infusion increased total (Delta 601 microg/100 mL, CI 507, 696) and non-transferrin-bound iron (Delta 237.2 micromol/L, CI 173.6, 300.8) approximately 10-fold, as well as redox-active iron nearly five-fold (Delta 0.76 micromol/L, CI 0.54, 0.98). After iron infusion basal FBF was 59% higher than after placebo. FBF response to acetylcholine before and after iron infusion was 263 +/- 32% and 310 +/- 33%, corresponding to 304 +/- 43% and 373 +/- 29% in the placebo group, respectively. Before and after iron or placebo infusion, glyceryl-trinitrate increased resting FBF to 232 +/- 22% and 258 +/- 21% in the iron group, and to 234 +/- 18% and 270 +/- 30% in the placebo group. L-N-monomethyl-arginine decreased FBF to 70 +/- 4% and 72 +/- 3% before and after iron, and to 74 +/- 4% and 73 +/- 4% before and after placebo infusions, respectively. Despite higher basal FBF after iron infusion, absolute and relative FBF changes in response to vasoactive substances were not significantly different between iron and placebo groups. CONCLUSION: Our data suggest that 300 mg intravenous iron sucrose has a vasodilatory effect, but does not impair vascular reactivity in dialysis patients, despite a significant increase in non-transferrin-bound and redox-active iron.

History of cardiovascular disease is associated with endothelial progenitor cells in peritoneal dialysis patients.

BACKGROUND: It is unknown whether traditional cardiovascular disease risk factors influence the number of endothelial progenitor cells (EPCs) and whether numbers of EPCs correlate with endothelial function in patients with end-stage renal disease. METHODS: In a cross-sectional study of 38 peritoneal dialysis patients, we examined numbers of circulating CD34+/KDR+/CD133+ cells, CD34+ hematopoietic stem cells, and EPCs cultured from peripheral blood. We also assessed conventional cardiovascular disease risk factors, such as history of vascular disease, diabetes, hypercholesterolemia, hypertension, and smoking. We determined endothelial function by measurement of endothelium-dependent and endothelium-independent reactivity of forearm resistance arteries by using strain-gauge plethysmography. RESULTS: Numbers of EPCs cultured from peripheral blood and forearm blood flow reactivity did not differ between erythropoietin-treated peritoneal dialysis patients and healthy individuals. A history of vascular disease was associated with number of cultured EPCs, but other cardiovascular disease risk factors showed no association. Furthermore, there was no association of endothelial-dependent and endothelial-independent forearm blood flow reactivity with EPCs in peritoneal dialysis patients. CONCLUSION: In this first study of EPCs in peritoneal dialysis patients, we found an association between history of vascular disease and EPCs, but no association of EPCs with endothelial function or other cardiovascular disease risk factors.

[Peritoneal dialysis in patients with chronic kidney-graft failure]. / Peritonealdialyse bei Patienten mit chronischer Transplantatinsuffizienz.

Patients with chronic kidney-graft failure who are starting peritoneal dialysis (PD) treatment need special consideration. The question of whether mortality is higher in these patients than in those who have not received a transplant is controversial. However, some studies suggest that differences in mortality between these groups are mainly explained by variations in age, duration of dialysis and comorbidity. One study showed similar survival between patients with chronic graft failure treated with hemodialysis (HD) and those on PD, but there is some evidence that residual renal function in PD patients with chronic graft failure declines faster than in PD-patients without transplants. Until now there have been no data on whether PD has a positive influence on the course of residual renal clearances compared with the influence of HD. The fact that PD patients with transplants show significantly higher peritoneal transport rates than patients without transplants may have an influence on technique survival. In patients with chronic graft failure, the type and dose of immunosuppressive therapy, as well as its influence on the incidence of acute rejections, residual renal function and infection rates, are also controversial. Immunosuppressive therapy may preserve residual graft function, but these patients have a higher risk of Gram-negative peritonitis, a shorter interval between start of dialysis and first episode of peritonitis, and a higher risk of catheter infections with Staphylococcus aureus than PD patients without transplants. In conclusion, PD is an acceptable treatment option for patients with chronic kidney-graft failure provided that the above clinical aspects are considered (e.g., intensified monitoring of infections and residual renal function).

Ferrous sulfate does not affect mycophenolic acid pharmacokinetics in kidney transplant patients.

BACKGROUND: Oral administration of ferrous-sulfate was reported to decrease intestinal absorption of mycophenolate mofetil (MMF) in healthy Japanese individuals by 90%. METHODS: We examined the effect of a single oral dose of ferrous sulfate on steady-state mycophenolic acid pharmacokinetics in 10 iron-deficient (hypochromic red blood cells >2.5%), Caucasian, long-term kidney graft recipients using a randomized, open-label, crossover design. On days A and B, MMF (1,000 mg) was given orally at 8:00 am. On day C, MMF and ferrous sulfate (105 mg) were coadministered at 8:00 am. On day D, MMF was given at 8:00 am and ferrous sulfate was given orally 4 hours later. RESULTS: The interindividual variability of the 12-hour area under the plasma mycophenolic acid concentration versus time curves (AUC(0-12)) under control conditions was small (89.5 +/- 27.8 and 87.6 +/- 39.1 mg x h/L, respectively). Concomitant or subsequent administration of MMF and ferrous sulfate did not affect the bioavailabilty of MMF (AUC(0-12), 91.9 +/- 30.4 mg x h/L and 96.0 +/- 31.7 mg x h/L). CONCLUSION: Oral therapy of iron deficiency using ferrous sulfate in long-term kidney graft recipients does not impede intestinal absorption of MMF; hence, exposure to this immunosuppressive agent is not reduced.

Regression of hypertensive nephropathy during three years of optimal blood pressure control.

Hypertensive nephropathy is among the leading causes of end-stage renal disease. Once renal function is severely impaired, the effects of strict control of blood pressure on the recovery of renal function remain elusive. Published case series suggest that optimal control of blood pressure results in regression of renal failure to some extent. In the present case of biopsy-proven hypertensive nephropathy we show that renal function can substantially improve over time if blood pressure is optimally controlled. Glomerula filtration rate continuously improved in our patient from 20 ml/min at presentation to 80 ml/min over a period of three years using a fivefold antihypertensive regimen. Hypertensive retinopathy regressed from stage III to stage I, and left ventricular hypertrophy decreased from an initial septum thickness of 19 mm to 12 mm within that period of time. This case clearly illustrates that optimal control of blood pressure is mandatory in patients with pre-terminal renal failure due to hypertensive nephropathy. Such intervention can lead to a regression of hypertension-associated end-organ injury.

Effect of TCN2 776C>G on vitamin B12 cellular availability in end-stage renal disease patients.

BACKGROUND: Transcobalamin II is a serum protein that transports vitamin B12 from the intestine to the tissues. This complex, holo-transcobalamin II, may reflect vitamin B12 availability in the body. Conflicting data exist with regard to the effect of a polymorphism in the gene coding for transcobalamin II, TCN2 776C>G, on transcobalamin II levels in the general population, which in turn may affect holo-transcobalamin II, vitamin B12, as well as total homocysteine (tHcy) plasma levels. The effect of TCN2 776C>G on vitamin B12 cellular availability in dialysis patients is unknown. METHODS: We examined the effect of TCN2 776C>G on holo-transcobalamin II, vitamin B12, and tHcy plasma concentrations in 120 dialysis patients. RESULTS: Holo-transcobalamin II levels were normal or supranormal in all patients and showed a linear association with albumin (r = 0.205, P = 0.025) and with vitamin B12 (r = 0.778, P = 0.001), but not with age, creatinine, body mass index, tHcy, ln-tHcy, vitamin B6, plasma folate, and red blood cell folate concentration. TCN2 776C>G showed no effect on holo-transcobalamin II, vitamin B12, and tHcy concentration [one-way analysis of variance (ANOVA), post-hoc Scheffe test]. Multiple linear regression analyses showed that albumin and B12 are independently associated with holo-transcobalamin II, whereas TCN2 776C>G and MTHFR 677C>T had no effect. Independent predictors of ln-tHcy included creatinine, red blood cell folate, and the MTHFR 677TT genotype. There was also an effect of the TCN2 776CC genotype on ln-tHcy levels in this multivariate analysis, however, that deserves cautious interpretation because there was no effect of TCN2 genotypes by ANOVA and Scheffe test [median ln-tHcy concentrations according to TCN2 genotypes (micromol/L): CC, 3.22; CG, 3.30; GG, 3.23]. CONCLUSION: TCN2 776C>G does not influence holo-transcobalamin II or vitamin B12 levels, and has no major effect on tHcy concentrations of end-stage renal disease patients.

Effect of glutamate carboxypeptidase II and reduced folate carrier polymorphisms on folate and total homocysteine concentrations in dialysis patients.

This study was designed to examine the effect of two single nucleotide polymorphisms in the reduced folate carrier 1 (RFC1 80G>A) and the glutamate carboxypeptidase 2 (GCP2 1561C>T) gene on total homocysteine (tHcy) plasma level and folate status in 120 chronic dialysis patients. Red blood cell folate concentration was higher in patients with the GCP2 CT or TT genotype (ANOVA, P = 0.04). Among patient groups with different RFC1 genotypes, red blood cell folate level was not significantly different. A multivariate analysis confirmed that the GCP2 1561C>T genotype (P = 0.011) had a significant influence on the red blood cell folate concentration. Overall, serum folate, creatinine, and the GCP2 polymorphism explained nearly 50% of the variance of red blood cell folate. A linear multivariate regression analysis showed that red blood cell folate (P < 0.001), creatinine (P < 0.001), and the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677T allele (P = 0.013) are independent predictors of tHcy plasma level explaining 49% of the variance of tHcy plasma concentration. GCP2 1561C>T and RFC1 80G>A showed no effect on tHcy and folate plasma level. In conclusion, GCP2 1561C>T, but not RFC1 80G>A, is a predictor of red blood cell folate level in chronic dialysis patients. Both polymorphisms have no major effect on tHcy plasma concentration in end-stage renal disease patients.

Hepatitis B and C in peritoneal dialysis patients.

In most countries the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in peritoneal dialysis (PD) patients is lower than in hemodialysis (HD) patients. Besides a history of blood transfusions, previous HD is an important risk factor for developing HCV infection in PD patients. Many HCV-positive patients already are anti-HCV-positive before initiation of PD. Seroconversion to HCV during PD treatment is, therefore, a rare event. HCV RNA in serum is positive in 53% to 84% of anti-HCV-positive patients. Routine screening for HBV and HCV by using a second- or third-generation enzyme-linked immunosorbent assay (ELISA) should be performed in PD patients every 6 months. Asymptomatic HBV and HCV infection may be detected by elevation of transaminases, but lower cut-off levels should be preferred in PD patients. Prophylactic strategies include hygienic measures and HBV vaccination. The staff should be aware of the infectiousity of the PD effluent, especially in hepatitis B surface antigen (HBsAg)-positive patients. Because of the smaller number of required blood transfusions and the increased use of home therapy, which reduces the risk for environmental contamination, PD is considered to be an important strategy for prevention of hepatitis in end-stage renal disease patients.

Riboflavin is a determinant of total homocysteine plasma concentrations in end-stage renal disease patients.

The effect of thiamine (vitamin B(1)) or riboflavin (vitamin B(2)) availability on fasting total homocysteine (tHcy) plasma levels in end-stage renal disease patients is unknown. A cross-sectional study was performed in a population of non-vitamin supplemented patients maintained on continuous ambulatory peritoneal dialysis. Red blood cell availability of thiamine (alpha-ETK) and of riboflavin (alpha-EGR), along with other predictors of tHcy plasma levels, was considered in the analysis. There was a linear association of alpha-EGR with tHcy plasma concentrations (P = 0.009), which was not observed for alpha-ETK. Among red blood cell vitamins, alpha-EGR was the only predictor of tHcy levels (P = 0.035), whereas alpha-ETK, red blood cell pyridoxal-5-phosphate supply (alpha-EGOT) and red blood cell folate levels had no effect. The risk for having a high tHcy plasma levels within the fourth quartile (plasma tHcy >38.3 micromol/L) was increased by an alpha-EGR > median (odds ratio, 4.706; 95% confidence interval, 1.124 to 19.704; P = 0.026). By way of contrast, alpha-ETK had no effect in these analyses. Independent predictors of tHcy plasma levels were serum albumin, alpha-EGR, red blood cell folate, and certain MTHFR genotypes. A logistic regression analysis showed that the MTHFR genotype is a predictor for having a tHcy plasma concentration within the fourth quartile. In summary, riboflavin availability, as measured by alpha-EGR, is a determinant of fasting tHcy plasma levels in peritoneal dialysis patients. This finding may have implications for tHcy lowering therapy in individuals with end-stage renal disease.