Subclinical toxicity of calcineurin inhibitors in repeated protocol biopsies: an independent risk factor for chronic kidney allograft damage.

The purpose of the prospective study was to determine the prevalence of subclinical toxicity of calcineurin inhibitors (CI) in repeated protocol renal allograft biopsies and to assess its impact on the development of chronic graft changes. A total of 424 biopsies were conducted in a cohort of 158 patients; of these biopsies, 158 were in the third week, 142 were in the third month and 124 were in the first year after transplantation. Histological signs of toxicity occurred in the third week in 33 (20.1%) patients, with persistence after CI dose reduction in the third month in 27 (19.0%) and in the first year in 23 (18.5%) patients. Of the toxic changes, 52% were clinically silent. At the end of the one-year follow-up, both subclinical and clinically manifest toxicity resulted in a similar progression of chronic changes quantified by Banff chronicity score and they significantly differed from the control group (P < 0.05). Subclinical toxicity affects a significant percentage of grafts; it occurs independently of dosage, blood level and type of applied CI. It is associated with the progression of chronic changes as early as in the first year after transplantation and represents an independent risk factor for chronic allograft damage. We report here our clinical approach to toxicity.

Sonographic findings in borderline changes and subclinical acute renal allograft rejection.

PURPOSE: A clinically manifested acute rejection is associated with graft dysfunction and with some ultrasound findings. The aim of our study was to determine the potential of ultrasound evaluation in the detection of subclinical acute rejective changes diagnosed in stable grafts by protocol biopsy. METHODS: Gray-scale evaluation, color Doppler imaging (CDI) and power Doppler imaging (PDI) was performed before each of 184 protocol graft biopsies in 77 patients in the third week, third month and first year after transplantation. The group was divided into four subgroups-normal histological finding, borderline changes, subclinical acute rejection of IA grade, and a clinically manifested acute rejection of IA grade. The sonographic findings were compared with individual groups. RESULTS: Detection of parenchymal edema using gray-scale imaging significantly differentiated borderline changes and subclinical acute rejection of IA grade from normal histological findings in the third week and in the third month (P=0.013, P=0.002 and P=0.024, P<0.001), respectively. A similar finding could be recorded in the latter group in the first year after transplantation (P=0.024). The presence of edema and reduced peripheral parenchymal perfusion in PDI significantly more often indicated a clinically manifested acute IA rejection (P=0.019, P=0.004, P=0.044). Parenchymal CDI hyperperfusion had a high specificity (89.5%) but a low sensitivity (60%) in the detection of the subclinical form of acute IA rejection. CONCLUSION: A composite gray-scale, PDI and CDI evaluation provide a significant differentiation of groups with borderline changes and subclinical acute rejection and groups with normal histological finding and clinically manifested acute rejection.

Protocol biopsy of donor kidney in renal transplantation.

This review article defines the term marginal (suboptimal) donor of organs and there is a summary of current opinions on the importance of protocol biopsies of kidneys performed in these donors during graft collection. Bioptic examination of kidneys in marginal donors provides information that cannot be obtained in any other way. Most authors engaged in this problem hold the view that evaluation of the extent of involution changes and the decision about the appropriateness of the organ for transplantation cannot be based only on the age criteria and there should always be a biopsy performed in suboptimal donors. Histological examination enables an objective evaluation of a pre-existing morphological lesion; especially the extent of glomerulosclerosis, interstitial fibrosis and vascular damage that may limit the functional level and vitality of the graft. As marginal are usually considered kidneys with more than 20% of glomerulosclerosis, kidneys with interstitial fibrosis affecting more than 25% of cortex or kidneys with a finding of arteriosclerotic changes causing more than 25% obliteration of the vascular lumen. It has to be considered, during a transplantation of a marginal kidney, that a long-term survival of the graft will be significantly decreased. But because the number of patients waiting for transplantation is increasing faster than the number of transplants performed, there are possibilities mentioned briefly in this article advising how to optimally use these marginal kidneys as well.

Selected indicators of bone metabolism in patients after kidney transplant.

Bone metabolism defects and skeleton diseases, so called renal osteopathy (RO), represent very serious clinical problems in the care of patients with kidney dysfunction. Renal osteopathy is a complicated skeletal disorder with a very complicated pathogenesis and we can encounter its individual forms in kidney transplant patients.

Protocol biopsy and subclinical rejection in patients after kidney transplantation treated by tacrolimus (Prograf).

The article deals with the contribution of tacrolimus (Prograf) to improvement in kidney transplant results. Tacrolimus, in comparison with cyclosporine significantly reduces the incidence of acute rejection and improves survival of grafts as well as patients. Based on the literature, the primary immunological differences between tacrolimus and cyclosporine effects are pointed out. These differences explain the better immunosuppressive effectiveness of tacrolimus. Based on analysis of the results, subclinical rejection problems and significance of protocol biopsy for present-day transplantology are discussed. There is also a critical analysis of the questions, which priority, in relationship to the expanding availability of immunosuppressive substances currently has high interest for nephrologists researching subclinical rejection.

Effect of various protective solutions on function after kidney transplantation.

UNLABELLED: From 1995 to 2002 we monitored a group of 127 patients who had undergone kidney transplantations in the Olomouc transplantation centre. The aim of our study was to assess the function of the kidneys after the transplantation, which were rinsed during the removal from cadaverous donors and afterwards were treated by different preservative dilutions. We divided the patients into three groups of approximate similar size, according to the used dilution - EC (Eurocollins), HTK (Custodiol) and UW (Viaspan). In the first three weeks we assessed in each group, the immediate function of the kidneys as primary, belated and afunction. The EC group showed the primary function in 51.2 % of cases, belated in 46.8 % of cases and afunction in 2.1 % of cases. In the HTK group, primary function was found in 73.7 %, belated 23.6 % and afunction 2.7 %. The results of the UW group came to primary function 71.5 %, belated 26.2 % and afunction 2.3 %. The criteria of the immediate but also the long-term function (five year investigation) was a serum creatinine figure. The lowest decline of creatinine in three weeks after the transplantation was noticed in the EC group (the average figure = 429 micro mol/l). In contrast the HTK group (the average figure 279 micro mol/l) and the UW group (the average figure 288 micro mol/l) had comparable figures and there was no significant difference between them from the statistical point of view. It means later in the first, the third and the fifth year after the transplantation the figures levelled out: EC 154 micro m/l, HTK 182 micro m/l, and UW 133 micro m/l. There was statistically a minimum significant difference between the HTK group and the UW group. Another criteria was to determine the amount of functional grafts in alive donees. The Assessment was carried out always in each year after the transplantation, altogether five years. The amount of the functional renal grafts in EC and HTK group was 100 %, in the UW group 76.9 %. CONCLUSION: HTK and UW gave better immediate functionality results, but there were no differences found among EC, HTK and the UW group from the long-term point of view.