The mechanisms of clearance of circulating plasma DNA are not fully understood, and so we aimed to examine it in patients with impaired renal function compared with healthy individuals. We also assessed the effect of peritoneal dialysis and hemodialysis on circulating plasma cell‐free DNA (cfDNA) in our treated patients. Overall, 20 healthy volunteers, 20 patients with chronic kidney disease (CKD), 18 patients undergoing peritoneal dialysis (PD), and 17 patients on hemodialysis (HD; high‐flux polysulfone membrane) were examined. Cell‐free DNA levels were determined using real‐time GADPH gene sequence amplification. The levels of cfDNA in all groups of our patients did not differ significantly from those of healthy volunteers. In HD patients, cfDNA levels were significantly increased compared with those of CKD patients ( P < 0.05) and PD‐treated patients ( P < 0.01). In PD‐treated patients, cfDNA was detectable in overnight effluent, with its levels correlating inversely with the duration of PD treatment ( r =−0.619, Spearman's coefficient, P = 0.008). Factors contributing to these differences may include changes in the quality and quantity of the cell population of the peritoneum, highlighting the need for additional studies clarifying the dynamics of cfDNA during PD. The plasma levels of cfDNA do not seem to be dramatically altered even in CKD patients or those on PD or HD (as long as they are measured prior to the procedure in the latter two). Our data suggest renal elimination is not the main mechanism of circulating cfDNA clearance.
Free radicals (FR), highly reactive substances with an unpaired electron in the outer orbital attack lipids, proteins and nucleic acids and alter the structure and function of these macromolecules. Against the negative effects of FR during evolution various defense mechanisms developed described comprehensively as antioxidant defense. Under physiological conditions in the organism equilibrium is established between free radical production and antioxidant defense factors. Extracorporeal renal replacement mechanisms can interfere in a negative way with this equilibrium. They provoke the formation of FR and at the same time they weaken the antioxidant defense e.g. by elimination of substances with antioxidant properties. Impairement of the equilibrium between FR production and antioxidant mechanisms to the disadvantage of antioxidant defense in patients with chronic renal failure was proved and is described as oxidative stress. Oxidative stress threatens dialyzed patients with serious clinical complications e.g. accelerated atherosclerosis, amyloidosis, haemolysis and the development of a state of chronic inflammation. Reduction of oxidative stress can be achieved by reducing FR production by using biocompatible dialyzation membranes, proper correction of acid-base disorders, by preventing an iron overload of the organism. The second approach is to foster the antioxidant defense by supplementation with antioxidants. Final recommendations as regards selection of the optimal dialyzation membrane, type of extracorporeal renal replacement and the amount and composition of antioxidant supplements have not yet been established and the problem is the subject of intense research.
Acetate-free biofiltration (AFB) is a modern haemodiafiltration method used at present as a variant in treatment of chronic renal failure. In AFB and standard bicarbonate haemodialysis (BHD), performed under equal conditions in 20 patients with chronic renal failure the authors investigated the degree of lipid peroxidation and the antioxidant defence system. As a marker of lipid peroxidation they used malondialdehyde (MDA); as to antioxidant factors they investigated the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSHP) in red blood cells and the selenium (Se) concentration in blood. The MDA values were elevated in both dialyzation methods, as compared with 30 healthy controls (p < 0.001). The SOD value before AFB did not differ from controls, before BHD it was higher than in controls (p < 0.01). In the course of AFB or BHD the SOD values did not change. The GSHPx activity at the end of AFB rose significantly as compared with the initial value (p < 0.05) and the value during the 30th minute of AFB (p < 0.02). In BHD the GSHPx activity was lower than in controls and did not change during the procedure (p < 0.01). The selenium blood levels were before both AFB and comparative BHD lower than in controls (p < 0.001). The authors found a positive correlation between the GSHPx activity and the Se level. The rise of GSHPx activity at the end of AFB may imply improved antioxidant defence during AFB and contribute to reduced tissue damage by free radicals.
The objective of the investigation was to assess whether therapeutic membrane plasmapheresis accelerates protein synthesis. To this end pseudouridine (PSI), a modified nucleoside was investigated which provides information on the tRNA turnover and thus indirectly also on protein synthesis. The authors made 10 plasmapheresis on a A 2008 PF monitor with Plasmaflux P2 filters which they use to exchange 1 plasma volume of the patients. Laboratory indicators were investigated one day before plasmapheresis, on the day of plasmapheresis and during its course, and on the 1st, 2nd and possibly 3rd day after plasmapheresis. They revealed that the clearance of the plasma filter for PSI (0.41 +/- 0.04 ml/s, arithmetical mean +/- SEM) did not differ significantly from the filtration rate (0.49 +/- 0.01 ml/s, p = 0.15). As compared with the initial examination (0.49 +/- 0.06 ml/s) on the first day after plasmapheresis as a result of reduced glomerular filtration rate the renal clearance of PSI was reduced (0.33 +/- 0.05, p less than 0.01). PSI serum concentrations were therefore expressed as the serum PSI/serum creatinine ratio. This ratio was, as compared with the initial examination (80.4 +/- 4.8 nmol/mumol), raised midway during the procedure (100.8 +/- 8.6, p much less than 0.05) and after its termination (132.3 +/- 6.1, p much less than 0.01). The increase was not due to disintegration of cells or dietary factors. The rise of the serum PSI/serum creatinine ratio was due to a more rapid tRNA turnover and thus provided evidence that therapeutic membrane plasmapheresis accelerates protein synthesis.
<i>Background:</i> The immune response to vaccination in hemodialysis (HD) patients can be influenced by disorders of iron metabolism, iron overload or chronic inflammatory state. Elevated levels of hepcidin are considered a new marker of iron metabolism impairment and anemia of inflammation in HD patients. <i>Methods:</i> We studied the effects of hepcidin, other markers of iron status and intravenous iron (Fe<sub>iv</sub>) on the response to an influenza vaccine (Influvac® subunit 2008/2009) in 40 HD patients. The immune response of HD patients was compared with that of 46 controls without renal disease according to serum antihemagglutinin antibody titer (anti-HA). <i>Results:</i> A total of 31 HD patients (responders) attained seroconversion (at least a 4-fold increase in anti-HA) to at least 1 of 3 vaccine strains; 9 patients (nonresponders) did not respond to any strain. Responders did not differ from nonresponders in hepcidin [99 µg/l (36–200) vs. 97 µg/l (23–216), p = 0.97]. Responders had lower ferritin (571 ± 291 vs. 821 ± 309 µg/l, p = 0.031) and were administered higher doses of Fe<sub>iv</sub> within the last 12 weeks prior to vaccination [625 mg (312–625) vs. 312 mg (0–625), p = 0.029]. The seroconversion to A(H1N1), A(H3N2) and B strains was noted in 20, 52 and 40% of HD and in 11, 39 and 48% of controls, respectively (HD vs. controls, p = nonsignificant). The rates of seroprotection (anti-HA ≧40) to vaccine strains in HD (27, 85 and 95%) and controls (24, 96 and 98%) were also comparable. <i>Conclusion:</i> Antibody production following influenza vaccination in HD patients may be suppressed by very high ferritin levels. Hepcidin does not correlate with immune response and high levels of hepcidin may reflect its retention in HD patients. Fe<sub>iv</sub> administration was not associated with a poorer immune response. The immunogenicity of the A(H1N1) strain was inadequate in HD patients and controls alike.
Acetate-free biofiltration (AFB) is a haemodiafiltration method which is used nowadays in the treatment of chronic renal failure. In AFB a dialyzation solution without a buffer is used, in the haemofilter some 2 1/hour are filtred. Simultaneously a sodium bicarbonate infusion in a postdilution mode is administered. The AFB investigation was conceived with the aim to introduce the method into clinical practice and to record the effect of AFB on the patient.Using the apparatus Monitral SC 30 of Hospal Co. the author made 120 AFB in 23 patients on long-term bicarbonate haemodialysis. In the investigation capillary haemofilters with an AN 69 membrane (Filtral 10 and 12) were used. The blood flow rate was 260 +/- 23 ml/min, the infusion rate of the substitution solution (NaHCO3 with a concentration of 167 mmol/l) was 1.7 +/- 0.1 l/h, the AFB period of 3.64 +/- 0.25 h. Before and after AFB values of the acid-base balance were investigated as well as the ion concentration, nitrogen catabolites, beta-2-microglobulin and cardiovascular stability of the patients. Optimal adjustment of metabolic acidosis was proved, the pH value before vs. after AFB was 7.359 +/- 0.053 vs. 7.444 +/- 0.048, p < 0.001, standard HCO3 20.2 +/- 2.6 vs. 26.0 +/- 2.1 l mmol/l, p < 0.001, adjustment of the ion balance, nitrogen catabolites were effectively eliminated, the Kt/V value was 1.03 +/- 0.22, beta-2-microglobulin declined after AFB from 36.3 +/- 10.0 to 23.8 +/- 8.2 mg/l, p < 0.001. Cardiovascular stability of patients in the course of AFB was very good, symptomatic hypotension was recorded in one patient (0.83%).AFB is considered by the authors, based on the results of their study and according to data in the literature, an effective and perspective form of substitution of renal function. AFB is particularly suitable for patients with circulatory instability and for those with a limited perspective of renal transplantation who are thus threatened by complications of long-term dialyzation treatment.
Coronavirus disease 2019 (COVID-19) has exposed haemodialysis (HD) patients and kidney transplant (KT) recipients to an unprecedented life-threatening infectious disease, raising concerns about kidney replacement therapy (KRT) strategy during the pandemic. This study investigated the association of the type of KRT with COVID-19 severity, adjusting for differences in individual characteristics.
