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Background: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease, characterized by progressive renal function deterioration, nephrotic proteinuria, and risk of chronic renal failure. We present long-term results of 5 patients with primary FSGS and recurrence of nephrotic proteinuria after renal transplantation treated with plasma exchange (PE) and immunoadsorption (IA)., Methods: We retrospectively investigated the relationship between the delay in initiation of the therapy and treatment outcomes, particularly achievement of remission of proteinuria., Results: Remission occurred in all three patients who started PE/IA in interval 3-7 days after diagnosis of recurrence of FSGS. Remission was achieved after 3-4 weeks in two patients with 3 days of delay to the start of PE. The third patient (PE started with 7 days of delay) reached complete remission after 6 months of PE/IA treatment. All these patients had remission sustainable for a long time. The remaining two patients with 14 and 406 days of delay to PE treatment did not achieve remission sustainable for a long time. The two patients who did not achieve remission developed end-stage renal disease with graft loss (1 and 6.7 years after transplantation). Patients who achieved remission of proteinuria during PE/IA treatment have still functioning grafts (2.8, 9.7 and 3.8 years after renal transplantation). All these patients are still treated with PE/IA., Conclusions: The present 5 cases suggest that if recurrence of FSGS occurs, the probability of achieving remission is dependent on the early initiation of PE/IA therapy. Therefore, we suggest that PE/IA treatment might be started as soon as possible after recurrence of FSGS.

Background: Proteinuria is a common manifestation of chronic kidney disease (CKD), and there is a high incidence of CDK and its complications following renal transplantation. However, little data are available on the association between proteinuria and graft/patient survival in the paediatric transplant population. The primary aim of this study was to investigate the associations between posttransplant proteinuria and graft/patient survival in children after renal transplantation., Methods: In this retrospective study, we screened all 91 children receiving renal allografts at a single institution between 1997 and 2007. The inclusion criteria were a functioning graft at 1 year posttransplant, data availability and no recurrence of focal-segmental glomerulosclerosis. The final cohort included 75 patients. Proteinuria was considered to be pathologic if the urinary protein/creatinine ratio was >30 mg/mmol. Donor and recipient characteristics, data on proteinuria, estimated glomerular filtration rate (eGFR) and rejection episodes were analysed. The most recent of the biopsies performed during the follow-up after 1 year posttransplant were analysed separately in the proteinuric group and the non-proteinuric group., Results: Proteinuria at 1-year posttransplant was pathologic in 35 % of patients. The 5-year graft survival rate was significantly lower in the proteinuric group than in the non-proteinuric group (77 vs. 100 %; p < 0.001). Proteinuria at 1 year posttransplant was associated with reduced long-term graft survival independent of other risk factors, including decreased eGFR or episodes of acute corticosensitive and corticoresistant rejection. The most frequent histologic finding in the proteinuric group was chronic rejection. There was no significant difference in the 5-year patient survival rate between the proteinuric group and the non-proteinuric group., Conclusion: This study emphasizes the importance of proteinuria as a prognostic factor of renal allograft survival in children.

Lung transplantation has become a standard therapeutic procedure for patients with end-stage pulmonary diseases in the Czech Republic. There were 246 lung transplantations performed from December 1997 to the end of November 2014 at the 3rd Department of Surgery, 1st Faculty of Medicine, Charles University in Prague and Motol University Hospital. The most common indications for transplantation were chronic obstructive pulmonary disease in 39.4 % of patients, idiopathic pulmonary fibrosis in 28.9 % of patients and cystic fibrosis in 19.1 % of patients. The trans-bronchial biopsy is important for monitoring patients after lung transplantation. The biopsy helps to detect acute cellular rejection, which was found within 63 % of our patients. Patients with the mild and moderate grade of acute cellular rejection got better after the anti-rejection therapy. The severe rejection in three patients led to the shock change in lung and to respiratory failure. Humoral rejection cannot be determined based on biopsy only - the capillaritis and the linear binding of C4d fraction of the complement to the capillaries are inconsistent findings and are not pathognomonic. The classification of chronic rejection, which corresponds to the bronchiolitis obliterans, is limited for the common absence of bronchioli in the biopsy. Therefore, bronchiolitis obliterans in our study group was detected in only 3.7 % of patients.Since the first transplantation, 109 of our patients have survived (44.3 %). After transplantation about 90 % of patients live one year, about 70.9 % of patients live 3 years and 69.1 % live 5 years. An autopsy at our department was performed in 79 cases. The most common causes of death were mycotic infections (aspergillosis, candidiasis), bacterial infections (Klebsiela, Pseudomonas aeruginosa, Burkholderia cepacia) followed by sepsis and viral infection (CMV, varicella zoster). At the autopsy, chronic rejection was found in 13 patients and it led to chronic respiratory failure, which was often complicated by an infection. The tumors as the cause of death were mostly generalized carcinomas.

Soft tissue tumors (SSTs) constitute a broad spectrum of neoplasms with diverse biological properties. Rare or unusual types are often difficult to classify. Recent studies show, that a significant subset of SSTs including many types of sarcomas are associated with specific genetic changes such as chromosomal translocations producing chimeric genes, which play a role in the pathogenesis of SSTs. Because SSTs represent a diagnostically challenging group of tumors, molecular-genetic techniques (FISH or PCR) are useful as supplementary and/or confirmatory diagnostic tools. In the present paper we demonstrate the usefulness of a combined diagnostic approach using the tools of classical histopathology and immunohistochemistry together with the molecular diagnostic approach in selected nosologic entites.

Background: The shortage of available kidneys for renal transplantation could be addressed, to some extent, by expanding the criteria for acceptance of marginal donors. The study of these criteria is limited by the selection of grafts actually retrieved and transplanted, therefore reduced to a study of risk factors. We have evaluated the potential of procurement renal biopies as an instrument for acceptance or refusal of donor kidneys for transplantation., Methods: This was a prospective study of a consecutive series of 200 donors. Biopsies were performed by wedge technique at the donor operation and were evaluated for proportion of glomerulosclerosis, vascular and tubular changes, and interstitial fibrosis. The study included 387 renal grafts with a representative biopsy, transplanted, and followed-up for survival and functional evaluation; 24 hr creatinine clearance at 1 and 3 weeks, and 3, 6, 12, 18, and 24 months., Results: Factors associated with initial graft function included cold ischemia time, number of DR mismatches, tubular changes, although donor age showed the strongest correlation with short- and long-term level of graft function. DR mismatches and retransplantation appeared to be the only significant risk factors for graft loss. The proportion of glomerulosclerosis (mean 8%, range 0-48%) correlated with graft function in the simple regression analysis. However, when age was taken into account glomerulosclerosis did not correlate significantly with graft function. Furthermore, glomerulosclerosis as high as 25% or more had an acceptable 3-year graft survival rate of 74.7%., Conclusion: Procurement biopsy provides only limited information for the decision whether or not to accept a kidney donor.

It has been suggested that cyclosporin A (CsA) nephrotoxicity can be reduced by the concomitant administration of omega-3 fatty acids or vitamin E. The present study was designed to establish whether the effect of the above substances can also be demonstrated in rats with hereditary hypertriglyceridemia (HTG) whose sensitivity to the nephrotoxic effect is greater than in control AVN rats. CsA administration at a dose of 10 mg/kg/day to HTG rats resulted in a significant rise (p<0.001) in serum levels of creatinine (from 66.0+/-7.6 to 108.4+/-11.6 micromol/l) and urea (from 8.3+/-0.7 to 22.3+/-18 mmol/l) which was not found in AVN rats. The baseline values of systolic blood pressure (SBP) were significantly higher in HTG rats. However, in both strains CsA administration was associated with a similar SBP increase which was not prevented by omega-3 fatty acids (EPAX) or vitamin E administration. Concomitant administration of CsA with EPAX at a dose of 600 mg/kg b.w./day in HTG rats prevented the rise in the serum levels of creatinine (65.4+/-14.7 micromol/l) and reduced the increase in the serum urea levels (11.9+/-7.6 mmol/l). Concomitant administration of CsA and vitamin E (at a dose of 25 mg/kg/day) also reduced the increase (p<0.05) in the serum levels of creatinine (70.7+/-14.3 micromol/l) and urea (9.8+/-3.4 mmol/l) compared to the effects elicited by the administration of CsA alone (p<0.05). Administration of CsA alone or in combination with EPAX or vitamin E did not have a marked effect on diuresis, proteinuria, urinary osmolality, urinary excretion of urea, creatinine and potassium. Under all experimental conditions, the rate of urinary excretion of sodium in HTG rats was significantly lower (p<0.01) than in AVN rats. The results obtained support the assumption that omega-3 fatty acids and vitamin E at the doses used reduce CsA nephrotoxicity in rats with hereditary hypertriglyceridemia whose sensitivity to the nephrotoxic effect of CsA is significantly higher than in AVN rats.

The objective of the paper is to draw attention to a rare cause of rapidly progressing renal failure which developed in the course of four months as a result of light chain deposition disease. The authors submit two case-histories of the disease assessed by renal biopsy after previous clinical and laboratory suspicion of monoclonal gammapathy. In one patient in the sternal punctate plasmacytoma was diagnosed and in the second case it was not possible to detect any type of monoclonal gammapathy or another possible cause of disease. Renal failure was in both cases irreversible and both patients were enlisted in regular haemodialyzation treatment.

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.

The authors present the description of a family comprising father (his mother had died middle-aged from renal failure) and his two children aged 15 and 17 years who developed is young age (already in the second decade) gouty arthritis and primary interstitial nephritis. Based on the laboratory finding of hyperuricaemia with disproportionately low urate excretion and excretion of excessive uric acid formation, an enzyme defect and other renal disease the authors diagnosed familial gouty juvenile nephropathy. This diagnosis was confirmed also by histological examination of renal biopsy in the youngest member of the family. It is a disease which belongs into the group of hereditary types of nephritis. In the literature worldwide some nine families were described, in the Czech Republic it is the first description of this condition.

Cyclosporin A is a basic immunosuppresive drug after organ transplantation. Morphological and functional features of Cyclosporin A nephrotoxicity caused by Sandimmune (Sandoz) and Consupren (of the Czech origin) were investigated in male Wistar rats. Rats were subjected to a right side nephrectomy followed by 45-minute- ischemia of remaining left kidney. Sandimmune was administered to one group of animals, Consupren to another group, both in the amount of 10 mg/kg/day. The second part of the experiment was performed in animals with right side nephrectomy only (without ischemia of the left side kidney) followed by the same administration of drugs. Changes were checked the 3rd and 21st day after nephrectomy. Ischemic arterial insudation lasted in the 3rd day set of animals with nephrectomy and left kidney ischemia treated by Consupren and was lacking after Sandimmune. Microvascularization of tubular epithelial cells was observed in significant frequency in the 21st day set of animals with unilateral nephrectomy without ischemia after Consupren and not after Sandimmune. The finding correlated with significantly higher blood level of Consupren and higher creatinine concentrations in serum than those of Sandimmune in rats with unilateral nephrectomy only.

The authors investigated in rats after unilateral nephrectomy morphological changes in the remaining kidney where the blood flow was arrested for 20, 30, 45 or 60 min. The investigation period was 24 hours, 3, 7, 14, 21 and 28 days after ischaemization. After short-term ischaemia monocellular necroses of the cortex epithelium in the canals occurs and rapid regeneration. In the initial stages after 20 min. ischaemia and in all periods after 30 min. ischaemia the authors observed slight hyperplasia of the juxtaglomerular apparatus manifested by fine granulations. After ischaemia persisting for 45 min. in addition to necroses of the tubules regressive arterial changes are observed with subsequent regeneration from the deep cortex to the surface. After discontinuation of the blood flow for 60 min. the animals die after 7 days with diffuse damage of the cortical parenchyma and regression of smooth muscle cells of the arterial walls with subsequent insudates of the media.

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.

Background: In conjunction with organ transplantation and subsequent treatment there is a number of influences which potentiate the development and possibly the growth of tumours. This applies naturally also to transplantations of the kidneys. The objective of the present study was to assess the frequency and type of tumours in patients after renal transplantation and compare these results with data of the at present most extensive worldwide register in Cincinnati (CTTR)., Methods and Results: The authors analyzed a group of 879 patients where within the period between March 21, 1966 and Sept. 29, 1992 a total of 989 renal transplantations were performed from dead relations-934 or from living relations (55); in 38 patients combined transplantations of kidney and pancreas were performed. The group comprised 59% men and 41% women. In the course of years the pattern of prophylactic immunosuppression changed: up to 1984 the basic drug was azathioprin combined with prednisone, during the same year cyclosporin A was introduced as a rule in a triple combination with azathioprin and prednisone; less frequent was the combination of cyclosporin A and prednisone. For antirejection treatment corticoids were used, later supplemented with polyclonal or monoclonal antibodies. During the period 1966-1992 tumourous diseases were diagnosed in 32 patients (3.64%); in two of these patients; combined transplantation of the kidney and pancreas was performed (5.3%). There was no difference in the frequency of tumours in patients with immunosuppressive medication (azathioprin with prednisone-3.80%) and cyclosporin A (3.51%). The mean age of the patients at the time of diagnosis of the tumour was 50.2 years, the interval after transplantation was 42.2 months (in patients treated with azathioprin 57 months, in the group treated with cyclosporin A 29.2 months). As far as the location of tumours is concerned, tumours of the skin predominated 25% (as compared with CTTR where it was 30%), tumours of the patient's own kidneys 21.9% and of the urinary pathways 15.6%, tumours of the gastrointestinal tract 12.5%, lymphomas in 9% (as compared with 15-20% in CTTR), tumours of the lungs 6.25% and other localizations also 6.25%. Some tumours frequently encountered in the population (lung cancer, cancer of the prostate, breast, colorectal carcinoma) are less frequent in patients after transplantation (CTTR); however, this fact was not confirmed by the authors. In renal tumours and tumours of the efferent urinary pathways data on analgetic nephropathy were encountered very frequently., Conclusions: The prevalence of tumours of various organs in patients after transplantations of the kidneys are not a frequent but a very serious complication. Its causes are multifactorial. The group after renal transplantations in the Czech Repubic has some deviations as compared with CTTR as regards affection of organs.

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.

Background: Cyclosporine A is in transplantology an irreplaceable immunosuppressive agent. Its only manufacturer preparation Sandimmune--was the Swiss firm Sandoz. In 1990 the Czech firm Galena introduced cyclosporine A with the name Consupren on the market. The objective of the present investigation was to assess whether the nephrotoxic effect of the two preparations is comparable, or whether it differs., Methods and Results: In a group of 65 rats after unilateral nephrectomy and 45-minute ischaemia of the remaining kidney the nephrotoxic action of cyclosporine preparations Sandimmune (Sandoz) and Consupren (Galena, CZ) administered in doses of 10 mg/kg body weight/24 hours throughout the experiment was investigated. The functional and morphological examination was made 3 or 21 days following nephrectomy. After three days the serum levels of creatinine, urea, sodium, osmolality and their urinary excretion as well as the intensity of proteinuria and morphological findings using light and electron microscopy did not differ in the two groups. The same was found during follow-up after 21 days; the small difference in the serum creatinine level only (Sandimmune 96.0 +/- 9.7 mumol/l, Consupren 111.4 +/- 11.2 mumol/l; p < 0.005) may be associated with the significantly higher cyclosporin levels following Consupren administration., Conclusions: The findings of the investigation support the idea that even after ischaemic kidney damage the nephrotoxicity of Consupren is not higher than that of Sandimmune.

Rats with 5/6 nephrectomy were used to compare the nephrotoxic effects of Consupren (cyclosporine A by Galena, Czech Republic) and Sandimmun (Sandoz, Switzerland). Twenty-one days after the administration of the same dosage, 10 mg/kg 24 hr, the blood levels of cyclosporine A were statistically significantly higher (P < 0.025) in rats given Consupren than in rats receiving Sandimmun. The serum concentrations of creatinine, urea, electrolytes, and osmolality did not differ after Consupren and Sandimmun. No significant difference between the two drugs was found in urinary excretion or proteinuria. The increase in the weight of residual renal parenchyma at 21 days after 5/6 nephrectomy did not differ significantly between rats administered Consupren or Sandimmun. Histology revealed gross hypergranularities in the juxtaglomerular apparatus equally present in both studied groups. Results show no significant differences in any of the evaluated parameters of the functional capacity of residual renal parenchyma or in the nephrotoxic effect as demonstrated in the histologic picture.

The authors, presenting a group of 23 cardiac myxomas over the past 20 years, provide a review of the most common clinical symptoms, such as mitral valve stenosis, dyspnoea, tachycardia, and/or myxoma mass embolizing the systemic circulation as well as the diagnostic modalities available, echocardiography and angiography in particular. Based on the histologic picture and the ultrastructure. They assume that, histogenetically, cardiac myxomas are true neoplasms from undifferentiated mesenchymal cells. Echocardiographic confirmation of cardiac myxomas warrants immediate surgical removal of the neoplasm.

The authors demonstrate on the example of two patients after transplantation of the kidney with pneumocystis pneumonia their experience with this disease. Predisposing factors include prolonged immunosuppression, protein and energy malnutrition, chronic inflammations and large doses of methylprednisolone. In the clinical picture dominated acute dyspnoea with hypoxaemia and non-productive cough. In one patient the X-ray picture was quite atypical. The prognosis of the disease is poor, both patients died.

Membranoproliferative glomerulonephritis (CN) of types I and III was diagnosed in 154 patients (15.5% out of primary CN). Out of this number 60% were men. During biopsy, one third of the patients were normotensive, 40% were slightly hypertensive and one third suffered from severe hypertension. Mean proteinuria was 6.5 +/- 5.5 g/24 h. In two thirds of the patients erythrocyturia was higher than 35 mil. in Addis' sediment and the findings in the urine were characterised by the proportion between proteinuria and erythrocyturia (p less than 0.001). During biopsy in one half of the patients, the serum creatinine level was already elevated. The presence of creatininemia was found to be directly linked to blood pressure, proteinuria, the degrees of extracapillary proliferation, tubulointerstitial regression and vascular arteriolosclerosis. The cumulative duration of the kidney function within the period of 10-20 years was 41 or 28%, the cumulative cure amounted to 14% 10 years after biopsy.

A total of 7017 women were examined during a year in a specialized dispensary for prevention of cervical cancer and in a department of obstetrics. Diagnosis of PAP III or higher was established in 227 smears, i.e. 3,3% of cases. A correlation of positive cytology with following biopsy was performed. The influence of cervical inflammation and virus lesion on possible modification of suspect cytology was discussed.

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.