Recurrence of nephrotic proteinuria in children with focal segmental glomerulosclerosis after renal transplantation treated with plasmapheresis and immunoadsorption: case reports.

Idiopathic focal segmental glomerulosclerosis (FSGS) is believed to be caused by a circulating permeability factor. FSGS recurrence is common after transplantation. The treatment is still a matter of debate; plasmapheresis (PE) and immunoadsorption (IA) are often used. We report on PE and IA in the treatment of two children with recurrent nephrotic proteinuria. Patient 1 was a 16-year-old girl who had recurrence of nephrotic proteinuria on the first day after transplantation (proteinuria-19 g/d). Primary immunosuppressive therapy was changed to high-dose cyclosporine and cyclophosphamide; plasmapheresis was started on day 4. Altogether we performed 53 PE and 38 IA procedures. During the first month, PE procedures were performed with no more than a 2-day interval between sessions, and the girl achieved partial remission (proteinuria 3 g/d). PE was then stopped. After 2 months, a relapse of heavy proteinuria occurred. This relapse was successfully treated again with intensified PE treatment. After achieving remission, a chronic PE regimen was started (PE once a week), similar to the previous series. The child remained in partial remission. Seven months after renal transplantation, she was switched from PE to IA, because of severe hypoproteinemia. Graft biopsy performed at 4 months showed effacement of the foot processes. At the present time she has a good graft function and 3 g/d proteinuria. Patient 2 was a 13-year-old girl with FSGS since 9 years. On the second day after renal transplantation she developed nephrotic proteinuria (proteinuria-14 g/d), which was treated with 39 PE and 16 IA treatments. She went into complete remission on the intensified PE regimen, had one relapse, and was switched to chronic IA. Graft biopsy performed at 2 weeks after transplantation showed effacement of the foot processes. At the present time she has good graft function and low proteinuria (0.3 g/d). In conclusion, intensified PE or IA treatments induced remission of recurrent nephrotic range proteinuria. Chronic PE or IA can maintain patients with frequent relapses in long-term remission.

Adverse effect of donor arteriolosclerosis on graft outcome after renal transplantation.

INTRODUCTION: In recent years less strict criteria for renal graft donors have been applied. Our study was designed to investigate whether the histological picture, with special reference to vascular changes of the donor kidney, has an effect on the development and level of graft function, and on 48-month graft survival. METHODS: Three morphologically distinct groups were formed from 150 consecutive cadaveric kidneys donors transplanted into 290 recipients. A control group (C) consisted of kidneys with a completely normal histological picture. Group M1 included kidneys with mild arteriolosclerosis and group M2 (n=122) was comprised of kidneys showing significant arteriolosclerosis. The onset of graft function was assessed by the need for dialysis treatment post-transplantation and the levels of serum creatinine and creatinine clearance at 6, 12, 24 and 36 months post transplant. RESULTS: The proportion of sclerotic glomeruli (P<0.001) and the incidence and severity of interstitial fibrosis was greater in groups M1 and M2 than in the control group (M1, P<0.01; M2, P<0.001). The incidence of vascular fibrinoid necrosis in M2 was greater than in controls (P<0.001). The onset of graft function did not differ significantly between the groups. Group M2 showed a significantly lower level of graft function (P<0.001). The 4-year graft survival rate of group M2 was 74.2%, significantly lower than in the combined group C+M1 (P=0.03). CONCLUSION: Significant vascular lesions in the donor kidney should be taken into account when predicting graft function and survival.

Proportion of glomerulosclerosis in procurement wedge renal biopsy cannot alone discriminate for acceptance of marginal donors.

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.

Nephrotoxicity of cyclosporin A in hereditary hypertriglyceridemic rats.

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.

[Light chain deposition disease as a cause of renal failure]. / Nemoc z ukládání lehkých retezcu jako prícina renálního selhání.

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.

[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.

Changes in cyclosporine A kinetics after experimental reduction of renal parenchyma.

Experimental chronic renal insufficiency (produced by 5/6 ablation of renal parenchyma) is associated with changes in the kinetics of oral (intragastric) cyclosporine A (CyA). Compared with animals with intact renal parenchyma, significantly lower levels of CyA are reached under these conditions. The factors responsible for reduced CyA availability under these conditions have not yet been identified.

[Familial juvenile gouty nephropathy]. / Familiární dnavá juvenilní nefropatie.

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.

[Nephrotoxicity of Sandimmune and Consupren in an experiment]. / Nefrotoxicita Sandimmunu a Consuprenu v experimentu.

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.

[Comparison of experimental models of renal ischemia. Morphologic study]. / Srovnání modelu ischémie ledvin v experimentu. Morfologická studie.

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.

[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.

[Kidney transplantation and tumors]. / Transplantace ledviny a nádorová onemocnení.

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.