Influence of Pretransplant Dialysis Vintage on Repeated Kidney Transplantation Outcomes.

Dialysis has a dose-dependent effect on first kidney transplantation outcomes, and a shorter waiting time on dialysis is associated with superior graft function. There are not enough data to support this statement in the case of a repeated transplantation. As such, we aimed to evaluate the influence of the dialysis vintage before the last transplantation on graft function as well as patient and graft survival in repeated transplantation situations. Patients who underwent repeated kidney transplantations were included in the retrospective study. Specifically, 79 patients were included who were divided into 4 groups according to the dialysis vintage before the last transplantation. We assessed graft function and patient and graft survival rates after 1- and 3-year follow-up. One-year graft function was worse for patients with a dialysis vintage of more than 31 months (P = .005), but there was no difference after 3 years. One- and 3-year graft survival was better for patients with a dialysis vintage of less than 12 months (P = .017). We concluded that a longer waiting time on dialysis was associated with worse graft function and diminished long-term graft survival after repeated kidney transplantation.

Effect of Sandimmun Neoral on the level of bivalent cations in erythrocytes of kidney transplant recipients.

In a 4 month study, a group of 16 patients with stable renal graft function receiving triple immunosuppressive therapy including cyclosporin A (Cy A) were investigated for the levels of calcium, magnesium and zinc in erythrocytes. The patients were randomized to be converted to the new microemulsion formulation (Sandimmun Neoral) in a 1:1 fashion (n = 8) or to continue with the classical formulation (Sandimmun) (n = 8). The concentrations of creatinine, phosphate, alkaline phosphatase activity, calcium, magnesium and zinc were measured twice a month in blood plasma. The concentration of calcium, magnesium and zinc in erythrocytes was also measured. The concentration of magnesium in blood plasma and erythrocytes during the study showed no deviation from normal values. The level of zinc in erythrocytes was almost twice as high as in normal healthy controls and was not dependent on Cy A formulation. Calcium content in erythrocytes of patients receiving Sandimmun was 27.6% higher than in healthy persons. Conversion of the patients to Sandimmun Neoral normalized the calcium concentration in erythrocytes and caused a transient increase of calcium levels in blood plasma.

Disorders of calcium metabolism at various times after renal transplantation.

OBJECTIVES: Increased parathyroid hormone (PTH) production and related defects of calcium-phosphorus metabolism could persist even after successful kidney transplantation. Much more serious long term consequences after the transplantation are bone defects caused by immunosuppressive drugs. Many authors consider steroid therapy as one of the factors that maintain this process. Our study aimed to investigate calcium-phosphorus and bone pathological features during the various post transplantation periods, using non-invasive bone research methods (bone ultrasound structurally-densitometric analysis), and also to analyse the risk of hyperparathyroidism and steroid therapy in the development of post transplantation osteopathy. METHODS: 52 patients after successful kidney transplantation were investigated. All patients were divided in three groups according to the time after transplantation. 1st group-patients in the earlier post transplantation period, up to 1 year (n = 12); 2nd group-patients in the period from 1 to 5 years after transplantation (n = 25); 3rd group-patients in later post transplantation period (more than 5 years after the transplantation, n = 15). RESULTS: 8 patients from the 1st group (66.7%), 18 patients from the 2nd group (72%) and 8 patients from the 3rd group (53.3%) had an increased level of serum creatinine. The level of corrected serum Ca was increased (p < 0,05) in the first year after the transplantation. Hypercalcaemia was noted in 5 patients (41.7%) from the 1st group, in 3 patients (12%) from the 2nd group and in 2 patients (13.3%) from the 3rd group. Urine Ca level was lower (p < 0.05) in patients with post transplantation period over 5 years. Serum iPTH level as well as the level of osteocalcin was higher in all groups. The highest iPTH and osteocalcin level (p < 0.05) were observed during the first post transplantation year, but in the later post transplantation period they had a tendency to decrease, but never reached the norm for healthy subjects even in later post transplantation period. The decreased speed of ultrasound in the trabecular bones and osteopenia were noted in 6 patients from the 1st group (50%), osteoporosis -- in 1 patient from the 1st group(8.3%). In the 2nd group 8 patients had osteopenia (32%) and 1 patient had osteoporosis (4%), and in the 3rd group 7 patients had osteopenia (46.7%) and 4 patients -- osteoporosis (26.7%). A negative correlation was noted between patient age and speed of sound in all patient populations (r = -0.39, p<0,01), both in the early post transplantation period (r = -0.67, p<0.01), and during the period 1-5 years after transplantation (r = -0.5, p <0.01). The whole patient population showed negative correlation (r = -0.28, p<0.05) between Z-score and time after the transplantation. Z-score negatively correlates with a cumulative steroid dose in all investigated patients groups(r = -0.35, p<0.02). CONCLUSIONS: Disorders of calcium metabolism and immunosuppression related bone disease are the most common complications after transplantation, especially in patients with an impaired graft function. The mild hyperparathyroidism is usually noted in these patients at various times after transplantation. We also can note hypocalciuria in the later post transplantation period in these patients, which is based on the parathyroid glands hyperfunction and on the negative effects of the steroid therapy. The cumulative steroid dose and patient age are the determining factors for the development of osteopenia in transplantation patients at the stage of 5 or more years after transplantation.

Does the switch from sandimmun to Sandimmun neoral reduce patient need for Phenihydine?

In patients receiving cyclosporine A (CyA)-based immunosuppressive therapy, Ca2+ channel blockers (CCBs) prevent the development of CyA-related nephrotoxicity in which increased Ca2+ content plays an important role. We evaluated the dynamics of the intracellular (erythrocytes) and extracellular (plasma) Ca2+ levels and the influence of the CCB, Phenihydine, on this process during the conversion from Sandimmun (S) to Sandimmun Neoral (SN). Forty-two patients were enrolled. The conversion from S to SN normalized the elevated CA2+ level of erythrocytes in groups with Phenihydine (n = 20) and without Phenyhidine (n = 12) 4 weeks after the switch (P < 0.05); this level remained stable until the end of study. Therefore we suggest that the switch from S to SN is effective in reducing elevated intracellular Ca2+ levels. The decrease of Ca2+ content in erythrocytes was similar in all groups switched to SN (with or without Phenihydine). The last effect should be an important argument to focus the further long-term investigations on the ability of CCBs to act as cytoprotective and neophroprotective agents during immunosuppressive protocols with the new microemulsion formulation of CyA.

Co-infection of two beta-herpesviruses (CMV and HHV-7) as an increased risk factor for 'CMV disease' in patients undergoing renal transplantation.

The ubiquity of human cytomegalovirus (CMV) and human herpesvirus-7 (HHV-7), as well as activation of these viruses during immunosuppression, allows the suggestion that both viruses could participate in the development of 'CMV disease' in patients after renal transplantation (RT). The aim of our research was to study the prevalence of latent CMV and HHV-7 infections in patients before RT, to determine interaction between these viruses in dual infection and possible association of their reactivation with the progression of 'CMV disease' after RT. Peripheral blood samples were collected from 49 patients before and up to 10-12 wk after RT. The methods used for diagnostics of viral infections were: serology, nested polymerase chain reaction (nPCR) analysis of peripheral blood leukocytes (PBL) and plasma, and virus isolation in cell cultures (morphological changes, nPCR analysis of cellular and cell-free samples, indirect immunofluorescence analysis). Before RT, CMV and HHV-7 DNAs were detected in PBL but not in the plasma samples, which indicates the presence of latent viral infection in patients. Latent dual (CMV + HHV-7) infection was prevalent (51.0%) in 49 patients, while CMV and HHV-7 infections alone were detected in 26.5 and 12.2% of patients, respectively. Risk of viral disease after RT, for recipients with latent dual infection before RT, was 12- and 2.2-fold higher in comparison with CMV and HHV-7 infections alone, respectively. Frequency of dual infection in 18 recipients with 'viral syndrome' or 'CMV disease' after RT was reliably higher (13/18, 81.3%) than CMV (1/18, 6.2%) (p < 0.025) and HHV-7 (2/18, 12.5%) (p < 0.025) infections alone. HHV-7 reactivation preceded CMV reactivation in 77.0% of the cases of dual infection in the recipients with viral disease and reactivation of both viruses preceded the development of viral disease. Severe 'CMV disease' developed in 2 out of 2 recipients with CMV primary infection and 'viral syndrome' in 1 recipient with CMV reinfection. The reactivation of CMV was detected in all recipients prior to onset of the disease. Correlation was shown between reactivation of latent HHV-7 infection and development of febrile syndrome in 2 out of 2 recipients with HHV-7 infection alone. Taking into account that dual infection is an increased risk factor for 'viral syndrome' and 'CMV disease' development, screening diagnostic should include testing for both viral infections in transplant donors as well as in recipients before and after RT.