[Pregnancy after kidney transplantation]. / Tehotenství po transplantaci ledviny.

In the period 1966-1997 renal allografting was performed in 1746 recipients, 244 of whom were women in fertile age. In 32 of them 45 pregnancies were registered. 29 of them (64%) resulted in abortion, which was spontaneous in 4 and medically advised in 25. There were 16 labours, 4 of them free of any complications; of the latter, hypertension was the most frequent one (8). Of the former, 13 were solved by caesarean section and 3 were vaginal deliveries. Of 15 live babies 7 were immature (one died 1.5 year later of renal failure due to microcystic kidneys). No unfavourable effect of pregnancy on prognosis and on long-term graft function was found.

[Conversion from Consupren sol. to Consupren S capsules in kidney transplant patients]. / Prevod z Consuprenu sol. na Consupren S kapsle u nemocných po transplantaci ledviny.

In a group of patients after transplantation of the kidney with stabilized graft function treated by Consupren sol. combined with prednisone and azathioprin in 20 patients (group A) Consupren sol. was replaced by Consupren S capsules, in 17 patients (group B) Consupren sol. therapy proceeded without any change. To maintain the cyclosporin blood concentration within the therapeutic range it was necessary after the change of drug form in group A to adjust the dosage of the drug in 12 patients of group A while in group B only in one patient (p<0.01). The mean doses and levels of Cy-A however did not change significantly during the three-month investigation period in the two groups and and the bioequivalence of the two preparations was evident. Conversion from Consupren sol. to Consupren S capsules is not associated with the risk of rejection or undesirable effects. It can be implemented at a ratio of 1:1 or 1: the closest dose divisible by 25 (the smallest capsules are 25 mg) and after conversion a check-up or possible modification of the dose is necessary.

[Repeat kidney transplantation]. / Opakované transplantace ledviny.

BACKGROUND: The objective of the study was an analysis of results of repeated kidney transplantations (Tx2, Tx3) implemented during the first 29 years of activities of the Transplantation Centre of the Institute of the Clinical and Experimental Medicine in subjects with a different maintenance immunosuppression. METHODS AND RESULTS: The retrospective study pertains to 134 Tx2 and 17 Tx3 in 134 non-diabetic subjects: 43 of them had during Tx1 and Tx2 (1966-1981 and 1966-1985 resp.) immunosuppression on the basis of azathioprin (Aza, sub-group AA), 42 during Tx1 (1972-85), Aza, while during Tx2 (1984-85) immunosuppression on the basis of cyclosporin (CyA, subgroup AC) and 49 both during Tx1 and Tx2 (1985-93 and 1986-95 resp.) CyA (subgroup CC). Compared was survival of grafts by the actuarial method (with regard to all losses regardless of cause) by the end of the 4th year inside the subgroups (Tx2, vs. Tx1 and Tx3 vs. Tx2 in the same subjects) and between subgroups (Tx1 vs. Tx1 and Tx2 vs. Tx2 in different subjects). Moreover in paired investigations the survival of recipients and grafts after Tx2 was compared after immunosuppression on the basis of CyA with the same parameters after Tx1 in different subjects with the same immunosuppression, operated at approximately the same time (n = 81) and survival of subjects with Tx1 + Tx2 on the CC regime regardless whether the second grafts functioned at the time of the last examination, with survival of subjects after Tx1 where after graft failure Tx2 was not performed (n = 34). Prophylaxis with antilymphocyte globulins was not used. Survival of second and first grafts did not differ in any of the subgroups, third grafts survived at the end of the third year more frequently than second grafts (66 vs. 18%, p < 0.01). Second grafts in CC survived more than in AA (55 vs. 28%, p < 0.01). In the paired study Tx2 vs. Tx1 the survival of grafts and recipients was the same (88 vs. 89%, N.S. and 47 vs. 62% resp.), in the paired study Tx1 + Tx2 vs. Tx1 more subjects with Tx1 + Tx2 survived 10 years after Tx1 than subjects who did not have Tx2 (82 vs. 49%, p < 0.05). CONCLUSIONS: A further transplantation of the kidney after functional loss of the first graft is the method of choice: the mortality is low, the probability of several years' function is considerable and the prognosis as regards quality and length of life better than with regular dialysis treatment.

[Early changes in vascular graft rejection in transplanted kidneys: the past and the present]. / Casné cévní rejekcní zmeny transplantované ledviny: minulost a soucasný stav.

BACKGROUND: With maintenance azathioprine+prednisone and in biopsies performed exceptionally earlier than in the 4th week (1966-1984, 476 cadaveric kidney transplantations), prevalence of obliterative arteriopathy (OA, transmural arteritis, 4/III/v3 Banff classif.) was 22.1%, with graft loss by rejection within 6 mos. in 89.4%. The aim of this analysis was to study prevalence and prognostic importance of the former and of further early vascular lesions in subjects with maintenance cyclosporin A using biopsies performed as early as in the 1st week. METHODS AND RESULTS: In a retrospective study on 449 transplantation (1987-92, cyclosporin A+prednisone+azathioprine, 64.7% grafts histologically--mostly repeatedly--examined), prevalence and prognostic classification (A-good, B-uncertain, C-poor prognosis) in recipients with OA, with cellular arteriopathy (CA, intimal arteritis, 4/II-III/v2-v3 Banff classif.) and with minimal arterial lesions (MZ) were assessed. Prevalence of OA was found to be 7.1% transplantations, with graft loss by rejection within 6 mos. in 71.9%, and with A:C proportion 25.0%: 62.5%. CA was found in 5.1% and showed A:C proportion 34.7%: 34.7%; in 6/13 cases with repeated histology, OA was later encountered, which is a strong point against its humoral pathogenesis. Prevalence of MZ was 10.9%, with A:C proportion 40.8: 4.1%. CONCLUSIONS: Both OA and CA are related to rejection, while the etiology of MZ remains to be clarified. With cyclosporine, prevalence of OA markedly decreased and its prognosis somewhat improved; secondary prevention is possible when an early diagnosis (early and repeated biopsies) is done and immediate treatment (antilymphocyte globulins) started.

[Etiopathogenesis of insudative vasculopathy in transplanted kidneys]. / Príspevek k etiopatogenezi insudativní vaskulopatie transplantované ledviny.

In 99 renal allograft recipients with insudative vasculopathy of graft, mean serum cholesterol levels, prevalence of subjects with hypercholesterolaemia, mean cumulative doses of methylprednisolone, prevalence of subjects with methylprednisolone doses > or = 6,000 mg and prevalence of patients with hypertension, all in the period between transplantation and the first diagnostic biopsy, were compared between 51 those with conventional and 48 with cyclosporine maintenance immunosuppression. In subjects treated with cyclosporine the lesion was found in biopsies performed sooner and was present more frequently, prevalence of hypercholesterolaemia and of hypertension was similar and that of subjects with both hypercholesterolaemia and hypertension lower than in subjects treated with azathioprine. A positive correlation was present between high doses of methylprednisolone and prevalence of hypertension, regardless of the type of immunosuppression and of severity of vasculopathy. In etiopathogenesis of insudative vasculopathy atherogenic factors are most probably involved, more markedly when azathioprine is used for maintenance immunosuppression. With cyclosporine, changes of graft haemodynamics and possibly also toxic damage to the vessels involved seem to be more important.

[Therapy in kidney transplant rejection using murine monoclonal IgG2a A1CD3 (Cedetrin)]. / Lécba rejekce transplantované ledviny mysím monoklonálním IgG2a A1CD3 (Cedetrin).

BACKGROUND: One of the substances used in recent years to suppress immune reactions after organ and tissue transplantations is mouse IgG2a globulin which acts selectively on CD3 lymphocytes; it is known under the name of Orthoclone (Ortho Co.) An analogous preparation was developed in the Institute of Molecular Genetics, Academy of Sciences, Czech Republic, although the idiotype is different. The authors submit a report on the experience with treatment of rejection of transplanted kidneys. METHODS RESULTS: Monoclonal mouse globulin IgG2a (Cedetrin) was administered to 20 patients after renal transplantation on account of a rejection episode or progressing rejection; the mean interval after transplantation was 16.1 (range 0.25-96) months; the rejection episode or progressing rejection responded little in the majority of patients to 6-alpha-methyl prednisolone (Urbason, Hoechst, Solu-Medrol, Upjohn). For prophylactic immunosuppression the following combinations were used: cyclosporin + azathioprine + prednisone (17x) or azathioprine + prednisone (3x). Cedetrin was administered by the i.v. route in two to 11 doses a 3 mg substance. Of 20 patients in 6 Cedetrin administration had to be discontinued (allergy, infection, leucopenia, hyperhydration). In 14 the tolerance was satisfactory, the type and frequency of side-effects was similar as after Orthoclone; the antibody formation was less frequent. The specificity of Cedetrin as regards its action on T lymphocytes was confirmed. The effect was good to very good in 6 of 8 patients where the rejection filtrate was histologically active. In 9 patients treated during the first year after renal transplantation the cumulative survival of the graft at the end of the 12th, 24th and 36th month following transplantation was 89%, 67% and 56% resp. Because the therapeutic effect depended on histologically proved rejection activity, the authors consider biopsy of the graft before Cedetrin treatment essential. CONCLUSIONS: The therapeutic administration of monoclonal mouse globulin IgG2a A1CD3 (Cedetrin), developed in the Institute of Molecular Genetics, Academy of Sciences, Czech Republic, produced by Exbio Co., CR) has a favourable effect on rejection episodes or progressing rejection of transplanted kidneys. Treatment is indicated in confirmed histologically active rejection.

Insulin action and insulin binding following pancreas transplantation.

Insulin action and insulin specific binding to erythrocytes were examined in ten recipients of a pancreatic segment and renal graft (Group 1), in nine non-diabetic kidney recipients (Group 2) and in ten age- and weight-matched healthy control subjects (Group 3). All transplant recipients were normoglycaemic without need of insulin, received the same immunosuppression and had good renal graft function at 11-18 months post-transplantation, when the investigation was performed. Using the insulin clamp technique, insulin action was expressed as the metabolic clearance rate of glucose at insulin infusion rates of 1.0 (MCRsubmax) and 10.0 (MCRmax) mU.kg-1.min-1. In comparison with the healthy control subjects, fasting free insulin and C-peptide levels were significantly higher in Groups 1 and 2, but no differences between Groups 1 and 2 were found (p greater than 0.05). Mean values +/- SEM of MCRsubmax in Groups 1, 2 and 3 were 6.30 +/- 0.55, 6.09 +/- 0.69 and 10.52 +/- 1.10 ml.kg-1.min-1 respectively, and of MCRmax 12.65 +/- 0.78, 13.14 +/- 0.92 and 19.28 +/- 1.42 ml.kg-1.min-1 respectively. Insulin action was significantly decreased in Groups 1 and 2 at the low as well as the high insulin infusion rates but there was no difference between the two groups of recipients (p greater than 0.05). No differences in binding data (specific binding, number of binding sites per cell) were found. It is concluded that insulin resistance is common to all immunosuppressed organ recipient and is not related to the pancreas graft. The decrease maximal response to insulin and normal insulin binding to erythrocytes tend to suggest a post-receptor defect in insulin action.

Arteriolosclerosis of the human renal allograft: morphology, origin, life history and relationship to cyclosporine therapy.

In the decade 1979-1988, 658 biopsies were collected from 568 cadaveric renal allografts. In 118 grafts a non-proliferative insudative vasculopathy (IVA) was found in afferent vessels. Immunosuppression was based on azathioprine (AZA) or on cyclosporin A (CsA), from 1983. The prevalence and extent of IVA has increased significantly since 1984. Light microscopy showed fibrinoid and hyaline masses of varying extent; transmural insudative "knobs", intimal oedema with metachromasia, and microthrombosis were also seen with CsA. The ultrastructure of the insudates was unremarkable but CsA grafts displayed early oedema and hypergranulation of endothelial cells with a disarray of smooth muscle cell (SMC) microfibrils, and pronounced degenerative changes of SMC. Rebiopsy showed stationary IVA in AZA grafts and progression in one-half of CsA-treated patients. Nephrectomy specimens revealed, however, a marked predominance of late rejection endarteritis; in only 3 cases was IVA and/or microthrombosis the possible cause of nephrectomy. The mean donor age was higher in severe IVA in CsA grafts and the mean post-transplantation interval at the time of diagnosis of IVA was significantly shorter in CsA-treated patients. No important differences in cumulative graft survival were seen between grafts with absent, moderate or severe IVA. Unused cadaveric donors' kidneys of comparable age exhibited normal arterioles or a slight focal insudative or hyaline lesion.

[Miliary tuberculosis after kidney transplantation]. / Miliární tuberkulóza po transplantaci ledviny.

The authors describe a case of tuberculosis after kidney transplantation. They discuss diagnostic and therapeutical problems arising from the specific course of this disease which appears in patients with chronic renal insufficiency treated with immunosuppressives after kidney transplantation.

Kinetics of mixed lymphocyte reaction after blood transfusions.

The kinetics of mixed lymphocyte reaction (MLR) was studied in an unrelated pair of potential kidney graft donor and recipient. The recipient immunological reactivity to donor cells was specifically modulated by donor blood transfusions. Prior to transfusions, recipient MLR to donor lymphocytes expressed as per cent of the relative response (% RR) was 85.73. It dropped to 43.75 on the 21st posttransfusion day, and was as low as 19.16 on the 151st day (5th month). Next, a gradual increase in MLR occurred. The % RR increased to 46.15 in the 9th month and returned close to the pretransfusion level, to 78.30, in the 12th month. Transplantation of the kidney from the potential donor was not performed.

[Rejection nephropathy before and after therapeutic administration of cyclosporin A]. / Die Rejektionsnephropathie vor und nach Einführung von Cyclosporin A in die Therapie.

During 1983 to 1986 41 patients were treated with Cyclosporin A (CyA) following kidney allotransplantation (TPL). 31 received the first (29 extra- and 2 intrafamilial) graft; in 10 there was second TPL, in 9 cases under high-risk conditions, where the first graft had been destroyed by (hyper)acute rejection or by rapidly progressive rejection with early vascular lesion. 21 needle biopsies and 5 excised grafts which had been collected 5 days to 18 months after TPL were examined by light microscopy and in addition 6 of the former also underwent electron and immunofluorescence microscopic study. The glomeruli showed discrete, inconstant segmental lesions but the ultrastructure also revealed severe general endothelial swelling. The tubular system had nonspecific degenerative changes of varying extent. In 11 patients focal cytoplasmic microvacuoles appeared in proximal tubular epithelia; there were also inconstant hyaline droplets, microcalcifications, and intratubular crystals. Electron microscopy revealed multiple round dense intramitochondrial inclusions in proximal tubules. The ultrastructure of the microvacuoles resembled that of "osmotic nephropathy". The rejection infiltrate and interstitial fibrosis of various degree did not essentially differ from those of conventionally treated grafts. In 7 patients cortical arterioles and small arteries exhibited a stenosing lesion (toxic?). In 3 cases metachromatic "mucoid" thickening of intima was prominent. Ultrastructure studies showed swollen endothelial cells with numerous globular dense bodies and a severe defect in the leiomyofibrils of muscle cells of the media. Hyperplasia of juxtaglomerular apparatus was apparent in 7 patients. Immunofluorescent microscopy of two biopsies from subsequently excised grafts visualized IgM, C3, and fibrinogen in small arteries and some glomerular capillary loops. Three early nephrectomies were caused by infarct-like necrosis. The discussion deals with differences between CyA- and conventionally treated grafts, diagnostic features, interpretation of findings, and measures following biopsy. In our patients with continual CyA-treatment no case of clinically and morphologically typical obliterative arterio-arteriolopathy (OA) and rapidly progressive irreversible rejection has as yet been noted.

Rejection nephropathy: course and prognosis.

A clinical-morphological study in 134 recipients of first renal allografts (15 related and 119 non-related) was performed with the aim to establish prognosis of different types of rejection nephropathy. Following order of prognosis (from the worst to the best) was found: necrotic lesion, early vascular lesion, late vascular lesion, late interstitial lesion. Several factors of importance were discussed.

The effect of perioperative hydration in allogenic renal graft recipients.

The authors evaluated the effect of perioperative hydration by 20% human albumin, packed red blood cells (RBC) and saline in allogenic renal graft recipients. In the group of recipients selectively hydrated, the incidence of postoperative oligoanuria decreased from the initial 62 to 25.7% compared with 50% in the group of nonhydrated patients. However, in the former group graft ruptures occurred in 10% as against 1.6% only in the latter. Potential causal relation between the higher incidence of ruptures and perioperative hydration has not been demonstrated and will be subject to further study. With respect to the lower risk imposed on the patients with rupture than on those with postoperative oligoanuria (higher survival rate of grafts and lower mortality of patients) the authors recommend routine introduction of body fluid expansion during operation in allogenic renal graft recipients from cadaver donors.

Chromosomal aberrations and sister-chromatid exchanges (SCEs) in patients undergoing long-term Imuran therapy.

13 patients treated daily for an extended time with Imuran and prednisone and 4 patients treated in the same way with Imuran only were cytogenetically analysed for the induction of structural chromosomal aberrations and SCEs. There was an increase in the number of aberrations and SCEs in nearly all patients analysed. However, we did not find any dose-dependent cumulative effect on chromosomal damage, with the exception of 1 patient tested in a small group of 4 patients involved in a prospective cytogenetic study, who showed a significant time-dependent increase in the number of aberrations.

Renal allograft function and cytomegaly.

A retrospective study in 20 seronegative and 61 seropositive (complement fixation) first cadaver donor graft recipients brought evidence that in cytomegaly, not the infection alone, but curtailment of azathioprine shortly after transplantation (or summation of both) may result in rejection and impaired graft survival. Preliminary data (accumulation of 125I-labelled fibrinogen in two and morphology of the graft in two other patients) showed that depression of graft function in cytomegaly is not necessarily due to rejection.