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.

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.