[Demands on dialysis access from the nephrologists point of view]. / Ansprüche des Nephrologen an den guten Dialysezugang.

Vascular access is the lifeline of hemodialysis patients. The superiority of autogenous arteriovenous fistulas compared to prostethic arteriovenous grafts or a central venous catheter is well established. Fistulas have a far lower risk of failure and a reduced requirement for revision compared to prosthetic grafts. Alternative vascular access can be achieved via a prosthetic graft or permanent central venous catheter but the risk of infection is increased. The most important complications are shunt thrombosis, stenosis, aneurysms or steal syndrome. Signs of these complications should be recognized by the dialysis team and early surgical intervention can avoid major complications. In many cases a complex shunt is necessary if the patient has been on dialysis for a long time. Interaction between the dialysis team, nephrologists, surgeons and interventional radiologists can improve the prognosis of dialysis patient.

Reduction of gastrointestinal complications in renal graft recipients after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium.

Gastrointestinal (GI) complications such as diarrhea or indigestion frequently occur in renal graft recipients treated with mycophenolate mofetil (MMF), requiring dose reductions to reduce side effects, thereby increasing the risk of rejection episodes and graft loss. In a prospective clinical trial, the immunosuppressive therapy of renal graft recipients was converted from MMF to enteric-coated mycophenolate sodium (EC-MPS) to identify a strategy to reduce GI symptoms without dose reduction. At baseline and 6-8 weeks later patients filled in 4 questionnaires related to GI symptoms and general and health-related quality of life. In 15 German study centers, 196 renal graft recipients (mean age 49.5 ± 13.5 years; male/female, 120/76) were included; 51.0% of patients suffered from GI complications at baseline. The Gastrointestinal Symptom Rating Scale score decreased significantly (P < .001) in patients with GI complications from 2.61 ± 0.86 at baseline to 2.14 ± 0.86 at visit 2. Health-related and general quality of life improved significantly. Fifty percent of patients with GI symptoms and 34% of the total per protocol population reported an improvement of their physical condition after converting the medication. In conclusion, conversion from MMF to EC-MPS reduces GI complications in renal graft recipients, reduces the patients' physical discomfort, and maintains their quality of life. (ClinicalTrials.gov number NCT00149968.).

Trough levels of mycophenolic acid and its glucuronidated metabolite in renal transplant recipients.

OBJECTIVE: The prophylactic use of the immunosuppressant prodrug, mycophenolate mofetil (MMF) to prevent graft rejection in renal transplant patients is continuing to increase. We measured trough levels of the active metabolite, mycophenolic acid (MPA) and its inactive glucuronide (MPAG) in renal recipients with the aim of characterizing individual variability and of ascertaining factors influencing trough levels, in particular the effect of differences in renal function and the effect of drugs given concurrently. METHODS: Laboratory and clinical data obtained in 35 renal recipients treated with triple therapy (MMF, cyclosporin A (CsA), steroids) were included in this retrospective study. Trough levels of MPA and MPAG were obtained after transplantation and up to 16 months post transplantation where the mean observation period was 5.7 months. Plasma levels were measured using a validated HPLC assay. RESULTS: A total of 212 plasma concentrations of MPA and 209 of MPAG were measured. There was considerable intra- and interindividual variability in MPA and MPAG trough levels especially in the early post-transplantation phase. At a fixed dose of 2 g/d MMF, the mean MPA level during the first 30 days averaged 1.46 +/- 1.31 microg/ml vs. 1.87 +/- 0.89 microg/ml after 30 days and later (p = 0.130) and the mean MPAG concentration averaged 188.1 = 142.8 [microg/ml vs. 98.09 +/- 52.4 microlg/ml (p 0.003). The MPAG levels were positively correlated with the serum creatinine concentrations (r = 0.815, p < 0.001), and in the case of MPA there was a correlation with the serum protein concentrations (r = 0.258, p = 0.001). Concomitant drug treatment using CsA, steroids and furosemide were without effect of the measured plasma concentrations, but in the case of xipamide (+) and diltiazem (-) an effect on MPA and MPAG levels and a co-effect depending on the serum creatinine could not be excluded. Neither CsA trough levels nor hemoglobin levels were related to MPA and MPAG trough levels. CONCLUSIONS: The data of this study demonstrate that there is substantial individual variability in the trough levels of MPA and MPAG after renal transplantation which may be associated with the functional status of the graft and the serum protein level. Whether comedication with xipamide and diltiazem affects the plasma levels of MPA and MPAG remains to be clarified in further investigations.

Improved attainment of NKF classified lipid target levels after conversion from cyclosporine to tacrolimus in renal graft recipients.

In an open, prospective, multicenter study, stable renal graft recipients were converted to tacrolimus because of cyclosporine-related side effects. Seventy-five patients were switched primarily because of hyperlipidemia. After the switch to tacrolimus, mean total cholesterol was reduced by 15% at month 6. One hundred seventy-seven additional patients were switched primarily for other indications: hypertrichosis, gingival hyperplasia, and arterial hypertension, and these symptoms also improved after the switch. In this analysis, serum lipid levels were categorized according to a modified standard classification of lipid parameters for renal transplant patients (published by the NKF Work Group). The aim was to estimate the proportion of patients reaching normal lipid levels after the conversion to tacrolimus therapy. In patients with primary indication hyperlipidemia, the proportion with normal cholesterol levels increased significantly from 5.6% at baseline to 37.5% at month 6 (P < .05). For LDL cholesterol, the increase was from 54.1% at baseline to 64.9% at month 6, and for triglycerides the improvement was from 25.4% to 33.8%. HDL cholesterol levels remained stable. Similar changes of lipid parameters were also observed in the subgroups of patients converted to tacrolimus primarily because of other indications. After conversion from cyclosporine to tacrolimus, a significantly higher proportion of stable renal graft recipients reached normal total cholesterol levels. For LDL cholesterol and triglycerides, a trend for normalization was observed. Thus, the improvement of serum lipid levels resulted for many patients in a change to a better level class and improved or normalized their cardiovascular risk parameters.

Differential expression of beta-chemokines MCP-1 and RANTES and their receptors CCR1, CCR2, CCR5 in acute rejection and chronic allograft nephropathy of human renal allografts.

BACKGROUND: The beta-chemokines MCP-1 (CCL2) and RANTES (CCL5) have been shown to play important roles in acute renal transplant rejection (AR) and chronic allograft nephropathy (CAN). The potential relationship of expression of these chemokines, their chemokine receptors CCR1, CCR2, CCR5, and the cell populations of inflammatory infiltrate, histological and clinical diagnoses were investigated in biopsies at the time of AR and compared with biopsies of CAN. METHODS: In 24 renal transplant biopsies with AR (n = 15) and CAN (n = 9), the expression of MCP-1 and RANTES, their receptors CCR1, CCR2, and CCR5 and the infiltration with monocytes/macrophages and T cells were studied. RESULTS: As previously described, chemokine and chemokine receptor expression was found mainly in mononuclear cells infiltrating the interstitium and glomeruli. In the tubulointerstitial area and glomeruli the expression of MCP-1, RANTES, and their receptors correlated with an infiltration by monocytes/macrophages. Biopsies with CAN revealed a lower expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in tubulointerstitial cells, and a significantly lower infiltration with MRP14-positive monocytes/macrophages than biopsies with AR. In AR, MCP-1 and CCR1 showed a lower expression compared to RANTES, CCR2, and CCR5. CONCLUSIONS: The positive correlation between chemokines and chemokine receptors and infiltrating leukocytes during acute rejection, the lower but detectable expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in CAN, and the differences in the quantity of expression between the different chemokines and chemokine receptors point to a complex regulation of chemokine expression in renal allografts. Since chemokines are not only involved in inflammation but also in tissue regeneration, this could have impact on the development of CAN.

Determination of erythrocyte antioxidant capacity in haemodialysis patients using electron paramagnetic resonance.

BACKGROUND: The increased oxidative stress of uraemia is caused both by an increased generation of oxygen-free radicals and a decrease of antioxidative forces. There are, however, conflicting data concerning disturbances of the radical-scavenging power of red blood cells (RBCs) in uraemic patients. METHODS: The antioxidant capacities of the RBCs of 10 haemodialysis (HD) patients and 10 controls were examined after treatment with 0.324 mM tert-butylhydroperoxide (t-BOOH) in phosphate-buffered saline at 37 degrees C using electron paramagnetic resonance (EPR) with 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap and glutathione (GSH) regeneration as an indicator of hexose monophosphate shunt (HMPS) activity. EPR investigations were also done after pre-incubation with N-ethylmaleimide (NEM) to inhibit the GSH system. Furthermore, we determined the RBC redox state in 15 HD patients and 15 controls. RESULTS: There was no difference between HD patients and controls in the elimination of t-BOOH-generated free radicals in the RBCs. A more than 20-fold increase in radical concentration was observed after GSH trapping with NEM. In this case, we found a delayed decrease of the relative radical concentration in HD patients compared with controls with a significant difference after 7 min (2.2+/-0.26 vs 1.60+/-0.21; P=0.005) and after 10 min (1.82+/-0.41 vs 0.83+/-0.44; P=0.001). GSH regeneration via HMPS did not differ between the RBCs of HD patients (99.5+/-13.5 nmol/min x ml RBC) and those of the controls (94.2+/-16.9 nmol/min x ml RBC). There were no differences in the RBC concentrations of GSH, GSSG, NADP, NADPH, and in the GSH/GSSG and NADP/NADPH ratios between HD patients and controls. CONCLUSIONS: These data suggest a strong antioxidant potential in the GSH system of erythrocytes without any evidence of a disturbance in HD patients. The HMPS pathway also appears not to be impaired in the RBCs of HD patients. However, the slower radical elimination in the RBCs of HD patients after inhibition of GSH-depending radical scavengers as compared with controls indicates a defect in the antioxidant forces outside the GSH system, and could be one reason for the reduced lifespan of RBCs in HD patients.

Influence of dialysis modalities on serum AGE levels in end-stage renal disease patients.

BACKGROUND: The accumulation of advanced glycation end-products (AGEs) in end-stage renal disease (ESRD) influenced by dialysis modalities is of current interest. Highly permeable membranes in haemodialysis or haemofiltration should be able to eliminate circulating AGEs as well as their AGE precursors more efficiently. METHODS: In our study, 10 non-diabetic and 10 diabetic ESRD patients were on haemodialysis with low-flux membranes (LF) followed by a cross-over haemodialysis with high-flux or super-flux polysulfone membranes (HF, SF) for 6 months each. We measured the protein-bound pentosidine and free pentosidine serum levels by high-performance liquid chromatography (HPLC) as well as the serum AGE peptide, AGE-beta(2)-microglobulin and beta(2)-microglobulin concentrations, using ELISA assays. RESULTS: All parameters investigated were significantly higher in dialysis patients than in healthy subjects. The reduction rates during a single dialysis session were found to be higher using the SF than those obtained with the HF (free pentosidine 82.4+/-7.3 vs 76.6+/- 8.7%; AGE peptides 79.7+/-7.7 vs 62.3+/-14.7%; AGE-beta(2)-microglobulin 64.0+/-16.5 vs 45.4+/-17.7%; beta(2)-microglobulin 70.5+/-5.6 vs 58.2+/-6.0%). The protein-bound pentosidine levels remained constant over the respective dialysis sessions. In the 6-month treatment period with the SF, decreased pre-dialysis serum levels of protein-bound pentosidine, free pentosidine and AGE peptides were observed in non-diabetics and diabetics as compared with values obtained with the LF. The respective pre-dialysis AGE-beta(2)-microglobulin concentrations decreased insignificantly, whereas those of beta(2)-microglobulin were significantly lower. Using the HF dialyser, only moderate changes of the parameters measured were noted. CONCLUSION: Treatment with the biocompatible polysulfone SF dialyser seems to be better suited to lower serum AGE levels and to eliminate their precursors.

Homocysteine, its metabolites, and B-group vitamins in renal transplant patients.

BACKGROUND: Increased plasma total homocysteine (tHcy) levels are an independent risk factor for cardiovascular morbidity in patients with normal and impaired renal function, including stable renal transplant recipients (RTRs). Plasma concentrations of the metabolites of Hcy, such as cystathionine (Cys), methylmalonic acid (MMA), 2-methylcitric acid (MC), and its diastereomers MCI and MCII have been reported in only a few articles. We therefore looked for the serum concentration of these metabolites and their relationship to renal function, cardiovascular diseases, the immunosuppressive treatment, and serum concentrations of cobalamin and folate. METHODS: Fifty RTRs (mean age 50.4 +/- 11.8 years, 35.9 +/- 44.4 months after kidney transplantation) and 35 controls (NP; mean age 43.5 +/- 14.4 years) were studied. Total Hcy and its metabolites were measured by gas chromatography-mass spectrometry (GC-MS). RESULTS: Total Hcy, MMA, Cys, and MC were elevated twofold to sixfold as compared with NP, with a significant interrelationship between these compounds. With the exception of Cys, they were significantly correlated with serum creatinine. Serum folate levels were inversely correlated with tHcy, Cys and cobalamin with MMA and the ratio of MCI/MCII. There was no correlation between tHcy concentration and its metabolites with immunosuppressive treatment (CsA vs. FK506), clinical history, or current findings of cardiovascular complications and blood pressure profile. CONCLUSION: Prospective studies are needed to find out whether the lowering or normalization of serum concentrations of tHcy and its metabolites due to treatment with B vitamins should be achieved to reduce the cardiovascular risk and improve the long-term outcome of allografts and of patients.

[Strategy for informed consent before a planned live kidney donation]. / Aufklärungsstrategie vor geplanter Nierenlebendspende.

It has been observed an increasing discrepancy between the supply and demand of cadaveric organs for transplantation for a few years, particularly in renal transplantation. For this living organ donation will occupy an lasting place also in Germany. The new regulation organ donation and transplantation in Germany provides a legal protection and prohibits all forms of organ trading. First of all the transplant team have to take into consideration medical and psychological aspects of donor and recipient but a detailed enlightenment of the pair concerning risks, complications and long term outcome is important as well. In this paper is introduced the enlightenment procedure and the common declaration of donor and recipient of the transplant center Jena. The authors conclude, that living organ donation is not a problem after intensive preparation and enlightenment of donor and recipient with the new Transplant Law in the background.

[The effect of erythropoietin (rh-EPO) om in vitro proliferation of granulocyte/monocyte-determined stem cells in bone marrow and peripheral blood]. / Der Einfluss einer rh-EPO-Therapie auf die In-vitro-Proliferation granulozytär-monozytär determinierter Stammzellen aus Knochenmark und peripherem Blut.

AIM: The aim of the investigation was to determine the effect of recombinant human erythropoietin (rh-EPO) therapy on in-vitro proliferation of granulocyte/monocyte(gm)-determined stem cells in bone marrow and peripheral blood. PATIENTS AND METHODS: The study comprised 28 dialysis patients (15 female, 13 male, aged between 22 and 78 years, dialysis sessions 3 times weekly 4 to 5 hours, mean duration time of dialysis treatment 4 to 99 months). Stem cell parameters were estimated before and after reaching the target hematocrit and the absolute number of leukocytes in peripheral blood was measured. RESULTS: No alteration in total leukocyte number (PMN, monocytes, lymphocytes) of peripheral blood was found. Dialysis patients had a diminished proliferation capacity of colony forming unit-granulocyte/monocyte (CFU-GM) in bone marrow and an increased one in peripheral blood. The CFU-GM proliferation capacity in bone marrow improved during rh-EPO (34.3 +/- 5.8 x 10(5)/ml vs 120.5 +/- 37.8 x 10(5)/ml), whereas no changes in peripheral blood could be observed (46.7 +/- 7.15 x 10(5)/ml vs 37.6 +/- 12.05 x 10(5)/ml).

[Urologic complications after kidney transplantation (II)]. / Urologische Komplikationen nach Nierentransplantation (Teil II).

Urological complications after renal transplantation are often responsible for postoperative morbidity and mortality in spite of a decrease in incidence and severity of such complications in the last decades. It is of particular interest to detect this complications early and to treat them in an adequate manner especially in regard to the increasing lack of human organs for transplantation. The number of transplanted patients in the population is still increasing and they are treated not only in transplant centers but also by general practitioners, nephrologists and urologists in private consultings. This necessitates a survey about the most important complications including diagnostics and therapeutic options. Measures of prevention and early detection are taken into account. Questions concerning impotence and incontinence are discussed in detail. Attention must be paid to the fact of immunosuppression and its peculiarities in transplanted patients. In this way the outcome of patients and transplants can be prolonged.