Changes of endogenous erythropoietin level and iron status during a 30-month hemodialysis treatment of a group of patients.

In our earlier paper we found that among 50 hemodialysis patients (HD pts) 48% (24 pts) control anemia with hemoglobin (Hb) concentration >9.5 g/dl and hematocrit (Hct) >30% without recombinant human erythropoietin (rHuEpo) therapy. These HD pts had significantly higher mean endogenous erythropoietin (eEpo) level and lower iron reserves (IR) than HD pts who need rHuEpo therapy. The aim of this study was to judge whether the possibility to control anemia in pts not requiring rHuEpo therapy changes during a 30-month HD treatment. Serum eEpo and ferritin were measured every 6 months. After 30 months of HD treatment 18 pts remained in this group--5 pts died, 1 underwent transplantation. During the study period 4/18 pts permanently had a very low level of eEpo (under detection limit), 7/18 had the level of eEpo within normal range for healthy control, 7/18 pts had a high level of eEpo (up to 3 times higher than the mean for healthy control). Pts who had the highest level of eEpo had the lowest IR. After 30 months IR were significantly lower than at the beginning of observation (292 +/- 87 vs 143 +/- 127 mg). Important negative correlation between eEpo and IR was observed throughout the whole period of study: r = -0.4820, p < 0.02 at the start of the study, and r = -0.6126, p < 0.007 after 30 months of treatment. The study shows that the possibility to control anemia in pts not treated with rHuEpo did not change significantly during 30 months of HD treatment. Endogenous Epo level in HD pts not treated with rHuEpo varied between different pts: it was permanently low in some pts, permanently high in others and stayed normal in remaining pts.

[Renin-angiotensin system genes in chronic glomerulonephritis]. / Geny ukladu renina-angiotensyna w przewleklych klebuszkowych zapaleniach nerek.

Glomerulonephritis is a group of diseases with complex etiology, pathogenesis, morphological features and clinical course. The renin-angiotensin system genes are important group of candidate genes involved in pathogenesis of chronic renal diseases. The purpose of our study was to analyze the association of genetic polymorphisms of these genes with glomerular kidney diseases. The study population consisted of 52 patients with immunological glomerular kidney diseases and 50 hemodialyzed patients with end-stage renal failure with glomerulonephritis as primary disease. The control group consisted of 200 healthy subjects. By means of the polymerase chain reaction (PCR) the following polymorphisms were evaluated: insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin-converting enzyme gene (ACE), M235T polymorphism of the angiotensinogen gene (AGT) and A1166C polymorphism of the angiotensin II type 1 receptor gene (AT1R). No significant association was found between the ACE allele and genotype frequencies and the disease. The allele frequency of the M235T polymorphism was different from that observed in the control group, but differences in the genotype distribution were not statistically significant. The CC genotype of the AT1R gene polymorphism was significantly more frequent in patients than controls. This suggests an increased susceptibility to renal diseases in individuals carrying the CC genotype. This relationship is not associated with hypertension. Our results suggest that in the Polish population the AT1R gene polymorphism might be associated with increased susceptibility to chronic renal diseases.

Plasma erythropoietin level and iron reserves in haemodialysis patients with and without acquired cystic kidney disease.

Concentration of erythropoietin (Epo) and iron reserves (IR) belong to the essential factors determining erythropoiesis in haemodialysis patients. Patients on dialysis with acquired kidney disease (ACKD+) can control anaemia better than patients without acquired kidney disease (ACKD-). Therefore we decided to check if plasma Epo levels and IR differ significantly in both groups of patients. Forty chronically haemodialyzed patients after ultrasound diagnosis were divided into 18 patients (45%) with ACKD+ and 22 (55%) without ACKD-. In both groups of patients we compared their plasma levels of Epo and IR. Plasma erythropoietin and ferritin levels were measured by enzymatic immunoassay. Iron reserves were estimated by the formula: IR = 400 x [ln (ferritin)-ln (50)]. In the ACKD+ group 72% of patients and in the ACKD- group 32% of patients did not require rHu Epo therapy. Plasma levels of erythropoietin and iron reserves did not differ significantly between ACKD+ and ACKD- patients. There must be also other factors than erythropoietin levels and iron reserves regulating erythropoiesis in these patients.

Influence of some immune factors on the IL-6 and soluble IL-2 receptors in haemodialysed patients.

In respect to the immune deficiency state of long-term haemodialysed patients, both cytokines and their receptor disturbances have been taken into consideration. The purpose of our study was to evaluate the effect of uraemic and haemodialysis factors on the interleukin-6 and interleukin-2 soluble receptor levels and the reactivity after influenza vaccination. We have found that IL-6 and IL-2 receptor levels were statistically significantly elevated (98.8 +/- 39 pg/ml and 1557 +/- 544 U/ml, respectively) in serum of haemodialysed patients. The fact that increased immune complexes statistically correlated with soluble IL-2 receptor levels (p < 0.01) was very interesting for us. In order to study the immunological response after vaccination, 10 patients have been investigated after influenza vaccination. Plasma samples were collected before, as well as 1 and 4 weeks after vaccine administration. Antibody titres measured by haemagglutinin inhibition showed decreased antibody levels in haemodialysed patients. We conclude that the interleukin disturbance and the elevated interleukin-2 receptor levels together with the presence of circulating immune complexes can influence in some way the immune response of haemodialysed patients.

[Comparison of the ability to control anemia in patients on hemodialysis and peritoneal dialysis considering iron reserves and plasma erythropoietin]. / Porównanie mozliwosci wyrównania niedokrwistosci przez chorych hemodializowanych i dializowanych otrzewnowo w aspekcie oceny zasobów zelaza i stezenia endogennej erytropoetyny.

It is known, that patients undergoing CAPD have less severe anaemia than those receiving hemodialysis (HD). In addition they require smaller doses of rHuEpo to control anaemia than HD pts. We have decided to compare plasma erythropoietin (pEpo) and iron reserves (IR) in these both groups of pts. 17 pts on CAPD and 50 pts on HD were diagnosed. 35% pts on CAPD and 52% pts on HD required permanent rHuEpo treatment to maintain hemoglobin (Hb) concentration above 9.5g/dl and Ht above 30%. Plasma EPO and ferritin levels were measured by enzymatic immunoassay. IR were estimated by formula: IR = 400x [ln (ferritin) - ln(50)]. Compared to CAPD, HD pts had higher IR (405 +/- 76 vs. 358 +/- 120 mg) but differences are not statistically significant. Plasma Epo level (geom. mean) was statistically significant higher p = 0.025 in HD pts compared to CAPD pts (8.68, range 2-53 vs. 5.21 range 2-15 mV/ml) Hb concentrations did not differ significantly between pts on CAPD and HD. CAPD pts controlled anaemia better than HD pts despite lower concentration of endogenous erythropoietin.

Comparison of plasma erythropoietin concentrations and iron status in hemodialyzed patients not requiring and requiring rHuEpo therapy.

Fifty patients treated with chronic hemodialysis (HD) were observed for 1 year. 24 of them (48%) did not require treatment with recombinant human erythropoietin (rHuEpo) (group I) because the permanent hemoglobin (Hb) concentration was > 5.9 mmol/l (9.5 g/dl), hematocrit > 30%. The remaining 26 patients (group II) permanently or periodically required rHuEpo treatment. After 6 months of initial observation and after 6 months of clinical study we made a comparison of endogenous erythropoietin (Epo) and iron status in two groups of patients. Patients not requiring treatment with rHuEpo had statistically significant higher Epo concentration and lower iron reserves than patients on rHuEpo treatment. We did not find significant differences in Hb, albumin and creatinine between patients in both groups. Hb concentration did not correlate with the level of Epo, serum creatinine, transferrin saturation, ferritin, iron reserves and time of dialysis therapy in both groups. In both groups we found a significant negative correlation between the concentration of Epo and iron stores. Our results indicate that in patients on HD treatment, plasma Epo level appears to depend either directly or indirectly on iron status.

The effect of recombinant human erythropoietin (r-Hu EPO) administration on the blood chemistries and composition in uremic rats.

Recombinant human erythropoietin (r-Hu EPO) therapy improves the anaemia of patients on chronic hemodialysis, on peritoneal dialysis and those with chronic renal failure who have not yet started any form of renal replacement therapy. In the last category there is concern that r-Hu EPO therapy may be associated with deterioration of the reserve renal function. But new data showed that even during more prolonged treatment the correction of anaemia does not have a major detrimental effect on renal function. The study was undertaken to examine the influence of r-Hu EPO therapy on renal function and rheological erythrocytes finding in uremic rats.

[Effectiveness of peritoneal dialysis using dialysis fluid of modernized composition]. / Wydajnosc dializy otrzewnowej prowadzonej plynem dializacyjnym o zmodernizowanym skladzie.

In six patients with terminal renal failure the effectiveness was assessed of intermittent peritoneal dialyses (IPD) using the dialysing fluid of modernised composition. On the basis of the obtained results the values were calculated of the total sodium (TMTNa) and potassium (TMTK) elimination glomerular filtration rate, and the sodium elimination index. The values were calculated of the dialysing clearance of urea, creatinine, potassium, and inorganic phosphorus. The correlations were analysed between the dialysing clearance of studied substances and the body area of patients, the duration of dialysis, and glomerular filtration rate. The results were compared with the effectiveness of peritoneal dialysis carried out with the dialysing fluids of formerly used electrolyte composition.

High and low sodium acetate haemodialysis and ultrafiltration. I. Comparison of haemodynamic effects.

This study was undertaken to evaluate the effect of increasing the dialysate sodium concentration on haemodynamic effects, arterial blood gases and chemistries during haemodialysis and ultrafiltration. Significant changes in mean blood pressure (MBP) and heart rate (HR) were not noted; but significant differences in sodium, potassium, total protein concentration, haematocrit and plasma osmolality during dialysis and ultrafiltration were found with both dialysates. Significant differences were also noted in pCO2 during dialysis and ultrafiltration with both dialysates and increase of pH during dialysis with low sodium dialysate. Significant changes in kind and frequency of unpleasant symptoms were found with both dialysates.

High and low sodium acetate haemodialysis and ultrafiltration. II. Comparison of plasma renin activity (PRA), catecholamine levels (CA) and plasma aldosterone concentration (PAC).

CA levels, PRA, PAC responses to low and high sodium dialysates in haemodialysed patients were investigated. Increased levels of dopamine (DA), adrenaline (A) and noradrenaline (NA) were found during dialysis and ultrafiltration with high sodium dialysate (148 mEq/l), and significantly higher PRA with low sodium dialysate (131 mEq/l). PAC slightly but significantly decreased during dialysis with low sodium dialysate and significantly increased during ultrafiltration. The present results suggest that sodium dialysate concentration has a significant influence on the function of the autonomic system, PRA and PAC in haemodialysed patients.