Protocol biopsy of a transplanted kidney as a tool for monitoring adequacy of immunosuppressive therapy: 10 years of experience from a single transplant center.

BACKGROUND: The aims of this prospective study were to determine the prevalence of clinically silent rejection changes and of nephrotoxicity of calcineurin inhibitors among repeated protocol biopsies of transplanted kidneys and to assess their impacts on chronic graft function and damage at the end of 1 year. METHODS: We performed 424 protocol biopsies among 158 patients over the first year after transplantation. We monitored parameters of graft function and progression of chronic changes among subjects with clinically silent rejection or toxicity for comparison with a control cohort showing normal histological findings. The results of statistical tests were considered to be significant at a level of P < .05. RESULTS: At 3 weeks, 3 months, and 12 months, there were normal histological findings among 30 (19%), 21 (14.8%), and 14 (11.3%) patients, respectively; subclinical rejection changes occurred in 49 (31%), 36 (25.4%), and 20 (16.2%) grafts, respectively. At the third week, histological signs of toxicity occurred in 33 (20.9%) patients with significant persistence despite reductions in calcineurin inhibitor doses. At the end of 1 year of follow-up, both subclinical and toxic changes produced similar increases in chronic changes as quantified by the Banff score and were significantly different from the control group (P < .05). Serum creatinine concentrations and glomerular filtration rates did not accurately reflect the degree of graft damage in the early posttransplantation period. CONCLUSIONS: Subclinical rejection and toxic changes among a significant proportion of grafts are associated with progression of chronic changes already over the first year following transplantation. Hence they represent independent risk factors for the development of irreversible graft damage. Protocol biopsy seems to be an important method to monitor immunosuppressive therapy.

Significance of HLA nondependent risk factors of chronic transplant nephropathy for the development of endothelial dysfunction after kidney transplantation.

More than 40% of renal allografts show chronic transplant nephropathy (CTN) early after renal transplantation. Cardiovascular disease is the leading cause of death in this population. Thus endothelial dysfunction represents an early angiopathy causing CTN and atherosclerosis. We sought to evaluate changes in endothelial dysfunction and vascular wall thickness during the first year posttransplantation as well as their association with HLA nondependent risk factors for CTN. At 3 and 52 weeks after grafting, we studied 25 patients without overt atherosclerotic disease and acute posttransplant complications for von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), big endothelin-1 (ET-1), flow-mediated dilatation (FMD), intimal media thickness (IMT), serum total cholesterol (TC), and triglycerides (TAG). FMD and IMT at 52 weeks showed significant correlations (P < .05) with recipient age, and the FMD ratios at 3 and 52 weeks correlated with the time on hemodialysis. Recipient age was significantly correlated with TC and PAI-1 with TAG. vWF was the only parameter that significantly correlated with donor age. There were no significant correlations with creatinine clearance. Decreased TAG approached statistical significance (P = .07) and TC decreased nonsignificantly. The worsening of FMD and ET-1 was not significant. A nonsignificant improvement in IMT was not associated with any analyzed parameters. Our results implied that the time on hemodialysis, the presence of hyperlipoproteinemia, and the recipient age significantly contributed to endothelial dysfunction during the first year after transplantation.

[Fibrillary glomerulonephritis--a rare cause of nephrotic syndrome]. / Fibrilární glomerulonefritida--vzácná prícina nefrotického syndromu.

Fibrillary glomerulonephritis (FGN) is a rarely diagnosed disease with clinical manifestations such as proteinuria, microscopic hematuria, nephrotic syndrome or decreased kidney function. Around one half of patients develop chronic renal failure in the course of several years. The diagnosis of fibrillary glomerulonephritis is to be established only basing on the results of renal biopsy. Pathognomonic is the electron-microscopic examination, evidencing fibrillar deposits in mesangium and in basal membranes of glomeruli. Fibrils are similar to those seen at amyloidosis, however, with larger diameter, non-linear deposition and do not stain with Congo red or thioflavin T. Immunofluorescency test usually shows the presence of IgG, namely the subclasses IgG4, C3 and kappa and lambda of light immunoglobulin chains. The presented case report describes clinical and laboratory findings at a patient suffering from nephrotic syndrome. Results of renal biopsy and detailed histological examinations concluded the diagnosis as fibrillary glomerulonephritis. The patient was treated with a combination of prednisone (1 mg/kg/24 hrs) with cyclophosphamide (2 mg/kg/24 hrs) for six months. This led to a decrease of proteinuria from the initial value of 5.38 g/24 hours to 1.88 g/24 hours, as well as to a partial remission of nephritic syndrome. Glomerular filtration, evaluated using endogenous creatinine clearance, remained within limits of normal values throughout the follow-up, with the value of 2.6 ml/s after the treatment.

[Histologic findings in protocol biopsies of transplanted kidneys]. / Histologické nálezy v protokolárních biopsiích transplantovaných ledvin.

Fourty eight patients with cadaveric kidney allografts treated by cyclosporin A (CSA) or tacrolimus (FK506) underwent protocol graft biopsies at 1, 3 and 12 months after transplantation, and 110 biopsy specimens were obtained. Histologic diagnosis was made according to the Banff scheme. The main cause of the graft instability at 1 and 3 months was acute clinical rejection, these biopsies showed all known histological patterns of tubulointersticial and vascular rejection. Acute tubular nephropathy was found in 13% and borderline changes or nephrotoxicity in 8.7% of instable grafts. Specifically, we focused on the occurRence of subclinical rejection and toxic reactions in stable renal allografts. Of these, 36.1% showed histological patterns of acute tubulointersticial and vascular rejection. The Banff score of subclinical rejection was significantly lower than in clinically apparent rejection. CSA and tacrolimus nephrotoxicity were seen in 14.2%, 19.5% and 27.2% of specimens at 1, 3 and 12 months, respectively. In over one half of the identified cases of nephrotoxicity neither increased level of immunosuppression nor features of allograft dysfunction were found. At 12 months, 45.5% of specimens showed mild chronic transplant nephropathy and 18.1% moderate chronic transplant nephropathy. Normal morphology was found in 36.4% of biopsies. We found a high prevalence of subclinical rejection and nephrotoxicity in the studied cohort. We conclude that protocol biopsy is a reliable method in the diagnosis of clinically silent, as well as clinically apparent, disorders of the transplanted kidney.

[Arteriovenous fistula as a complication of renal biopsy]. / Arteriovenózní pístel jako komplikace biopsie ledvin.

Renal biopsy is nowadays considered a relatively safe and routine examination method in nephrology. Its development was made possible by extension of sonography and introduction of modern automatic bioptic sets. Relatively frequent complications of biopsy include macrohaematuria, perirenal haematomas and AV fistulae. The majority of complications is unimportant from the clinical aspect. Some 30% fistulae do not recede spontaneously and gradual remodelling of the circulation near the fistula may lead to the development of complications. In the submitted paper the authors inform on the case of a 55-year-old woman where 24 hours after biopsy of a renal graft a sonographically revealed arteriovenous fistula closed spontaneously within one month; the case of a 40-year-old woman where 5 days after biopsy progression of a subcapsular haematoma and manifestation of a fistula occurred, and a 35-year-old man who developed 6 years after biopsy gradually an arteriovenous fistula with uncontrollable hypertension, hypercirculation syndrome and functional deterioration of the transplanted kidney. Superselective embolization led to improvement of the circulatory sequelae of the vascular shunt but did not have a favourable impact on renal function. Analysis of hitherto assembled experience indicates that direct ultrasound control of biopsy is effective. Because the manifestation of possible complications of biopsy need not follow immediately after the operation ultrasound follow up of native and transplanted kidneys after biopsy is justified even after a longer time interval after the operation.

[Personal experience with lovastatin, a HMG-CoA reductase inhibitor (Mevacor, MSD) in the treatment of hypercholesterolemia]. / Nase zkusenosti s inhibitorem HMG-CoA reduktázy lovastatinem (Mevacor, MSD) v lecbe hypercholesterolémie.

The authors administered lovastatin (Mevacor, MSD) to 18 patients with primary hyperlipoproteinaemia (familial and non-familial) with a lipoprotein pattern type IIa and IIb. During treatment a marked reduction of atherogenic indicators of the lipid metabolism occurred, i.e. a decline of total cholesterol (-28.6%), LDL-cholesterol -39%), apolipoprotein B (-18.6%), the index of total cholesterol/HDL-cholesterol (-44.6%) and the index LDL-cholesterol/HDL-cholesterol (-48.2%). At the same time a favourable effect on indicators of the lipid metabolism to which a protective action is ascribed was recorded: a rise of HDL-cholesterol (+13.6%) and apolipoprotein AI (+13%) and AII (+13%). An excellent effect was observed also in four heterozygotes with familial hypercholesterolaemia which is usually rather resistant to other types of hypolipidaemic treatment. The drug was very well tolerated and subjective side-effects of treatment were minimal. Despite the fact that a number of laboratory indicators was followed up, the authors did not observe any undesirable side-effects, only a transient and marginal rise of ALT in one patient. Lovastatin is, due to its potent hypolipidaemic effect, a new hope in the treatment of hypercholesterolaemia. Its usefulness in the prevention of ischaemic heart disease, as well as its safety during prolonged administration are tested at present in long-term investigations.

Injury to gastric mucosa due to cortisonoid therapy.

Drawing on their own experience and reports in literature the present authors analyze the problem of the incidence and origin of alterations on the gastric mucosa (steroid ulcer) in the course of cortisonoid therapy. Over the period of 5 years, 576 patients were studied, 29 (5.03%) of which were found to have developed a lesion of the gastric mucosa. Patients with rheumatoid arthritis and collagenoses were the most frequent of these. This is followed by an analysis of the mechanism of origin and the peculiarities of this lesion as compared with the picture of the classical ulcer. Apart from medicamentous therapeutic procedures in the treatment of steroid ulcers, local application of a HeNe laser radiation has come to be used recently in the healing of a chronic gastroduodenal ulcer. Despite all the vast experience and more accurate knowledge of the drawbacks cortisonoid therapy brings along, the steroid ulcer still represents a feared and not quite rare complication of glucocorticoid therapy.

[Development of a moral consciousness in medical schools]. / Formirovanie nravstvennogo soznaniia v usloviiakh meditsinskogo fakul'teta.

In the conditions of developed socialism, changes in social consciousness are also reflected in one of its forms - the morals. The problems of moral education as an inseparable part of communist education is coming to the foreground. It plays its role in all the stages of the education system, having its unsubstitutable place also in the conditions of universities and technical colleges, the faculties of medicine not excluding. It is its task to form the personality of the student and graduate, to make them, among others, acquire the moral codex of a builder of communism (habits of moral behaviour in professional activities - medical ethics). Such crucial situations must be found that are of cardinal importance for the formation of the medical student's moral profile (transition from the secondary school to university, entering the clinic, meeting the patient, running health institutions, positive and negative influences in the health service). The student must live the moral situation, obtain the experience from moral acting on his own self and be an active participant in the events creating his moral qualities, primarily in collective conditions. We stress the necessity of engagement - mobilisation of students to all-round social activities, connection of the theoretical findings of marxist ethics with their particular problems and actual activities. A special accent is laid on the method of personal example, the moral example of the university teacher himself, in the first place his authority based on all the progressive components of his personality.(ABSTRACT TRUNCATED AT 250 WORDS)