Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence.
- Klíčová slova
- children, focal-segmental glomerulosclerosis, recurrence, renal transplantation, steroid-resistant nephrotic syndrome,
- MeSH
- dítě MeSH
- fokálně segmentální glomeruloskleróza prevence a kontrola terapie MeSH
- glukokortikoidy terapeutické užití MeSH
- léková rezistence MeSH
- lidé MeSH
- nefrotický syndrom prevence a kontrola terapie MeSH
- pooperační komplikace prevence a kontrola terapie MeSH
- recidiva MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- transplantace ledvin * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
- Názvy látek
- glukokortikoidy MeSH
BACKGROUND: Reactive oxygen species produced during metabolism of adriamycin are purported to play an important role in the pathogenesis of experimental adriamycin nephropathy in rats. ICRF-187 (dexrazoxan, Cardioxan), an iron chelator, has been shown to inhibit adriamycin-induced formation of hydroxyl radical and to decrease adriamycin cardiotoxicity in oncological patients. The aim of our study was to assess the putative protective role of ICRF-187 in adriamycin nephropathy by evaluating the possible participation of free radicals in its pathogenesis. METHODS: We examined five experimental groups. Group A, received a single dose of adriamycin (5 mg/kg bw i.v.), group CA was given a single dose of ICRF-187 (100 mg/kg bw i.v.) before adriamycin administration, group CCA received a single dose of ICRF-187 (100 mg/kg bw i.v.) before adriamycin administration followed by three weekly intraperitoneal injections (100 mg/kg bw) ICRF-187. Group CC received one dose of ICRF-187 (100 mg/kg bw i.v.) followed by three weekly intraperitoneal injections of ICRF-187, and group N served as control receiving saline. Common biochemical parameters, malondialdehyde (MDA) and antioxidant enzymes (glutathione peroxidase--GPx and superoxide dismutase--SOD) in blood and kidney homogenates were measure and histology of the kidney was studied after the rats were sacrificed. RESULTS: Full-blown nephrotic syndrome developed after 3 weeks only in A rats. Nephrotic syndrome was completely prevented in all ICRF-187 treated rats (CA, CCA). Proteinuria was significantly increased in A rats (108.2 + 48.4 mg/l of glomerular filtrate) compared with CA (12.4 + 6.8 mg/l, P < 0.0001) and with N (6.1 + 3.5 mg/l, P < 0.0001). Total MDA in erythrocytes was significantly increased only in A rats (1.7 + 0.3 micromol/l) and was completely normalized by ICRF-187 in CA (1.1 + 0.2 micromol/l, P < 0.001). Total TBARS and MDA in kidney homogenates were significantly elevated in groups with repeated administration of ICRF-187 (CC and CCA rats) compared to N, CA, A groups. Activity of GPx and SOD in kidney homogenate and in erythrocytes was not significantly increased by ICRF-187 in adriamycin treated rats. Histologic changes in A rats resembled minimal change nephropathy with fusion of foot processes and hyaline casts in tubules. There was only minimal mesangial proliferation and perivascular mast cell infiltrates in all groups of ICRF-187-treated rats. CONCLUSIONS: We conclude that ICRF-187, probably by chelation iron, completely protected rats from adriamycin-induced nephrotic syndrome. It supports the role of iron-mediated reactive oxygen species in the development of this type of glomerular injury. However, repeated administration of ICRF-187 alone is able to increase parameters of oxidative stress in the kidney.
- MeSH
- chelátory farmakologie MeSH
- doxorubicin * MeSH
- erytrocyty metabolismus MeSH
- krysa rodu Rattus MeSH
- látky reagující s kyselinou thiobarbiturovou metabolismus MeSH
- ledviny metabolismus patologie MeSH
- malondialdehyd krev MeSH
- nefrotický syndrom krev chemicky indukované patologie prevence a kontrola MeSH
- potkani Wistar MeSH
- razoxan farmakologie MeSH
- superoxiddismutasa krev MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chelátory MeSH
- doxorubicin * MeSH
- látky reagující s kyselinou thiobarbiturovou MeSH
- malondialdehyd MeSH
- razoxan MeSH
- superoxiddismutasa MeSH
BACKGROUNDS: Hyperlipidemia is not only a prominent complication of nephrotic syndrome, but it may also contribute to the further non-immunologic damage of glomeruli. Analogy between atherosclerosis and glomerular sclerosis was suggested. Treatment of hyperlipidemia may decrease proteinuria in nephrotic animals and subjects and possibly prevent the progression of glomerulosclerosis and renal failure. We decided to study the influence of therapy with the inhibitor of cholesterol synthesis, lovastatin, on the development of the experimental nephrotic syndrome induced by the administration of adriamycine in rats. METHODS AND RESULTS: Nephrotic syndrome was induced in rats by the intravenous administration of adriamycine. One group of animals was treated from the time of adriamycine adminstration with lovastatin. Lovastatin was also given to one group of control animals. Proteinuria increased significantly during 4 weeks in untreated adriamycine rats (from 0.93 + 0.57 to 12.76 + 11.95 g/mmol of urinary creatinine, p < 0.01), but it did not change significantly in adriamycine rats treated with lovastatin (from 0.98 + 0.69 to 1.90 + 4.25 g/mmol of creatinine, p = n.s.) and it was significantly lower than in untreated animals (p < 0.01). Plasma albumin decreased 12 weeks after adriamycine administration in untreated rats (from 21.16 + 1.45 to 10.58 + 3.83 g/l, p < 0.001) significantly more (p < 0.05) than in rats treated with lovastatin (from 20.01 + 2.18 to 15.34 + 2.66 g/l, p < 0.01). Lovastatin also ameliorated the increase of plasma cholesterol and eliminated the increase of plasma triglycerides in adriamycine rats. Metabolic changes were in all groups characterized by the increase of free fatty acids, possibly due to exaggerated lipolysis, but without significant change of glycaemia and plasma urea. Proteinuria was decreasing at the end of the observed period. Histologically there were only minimal changes in glomeruli, without significant glomerulosclerosis. CONCLUSIONS: Administration of lovastatin prevented the development of nephrotic syndrome in experimental adriamycine nephropathy in rats. This finding suggests the possible role of hyperlipidemia in the pathogenesis of glomerular damage and suggests the posibility to prevent glomerulosclerosis and renalisufficiency in some form on nephrotic syndrome by the effective hypolipidemic therapy.
- MeSH
- anticholesteremika farmakologie MeSH
- doxorubicin MeSH
- hyperlipidemie etiologie MeSH
- krysa rodu Rattus MeSH
- lipidy krev MeSH
- lovastatin farmakologie MeSH
- nefrotický syndrom krev komplikace prevence a kontrola MeSH
- potkani Wistar MeSH
- protinádorová antibiotika MeSH
- sérový albumin metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- anticholesteremika MeSH
- doxorubicin MeSH
- lipidy MeSH
- lovastatin MeSH
- protinádorová antibiotika MeSH
- sérový albumin MeSH
BACKGROUND: Alcoholic liver disease may be in humans frequently complicated by mesangial proliferation and sclerosis. The influence of chronic ethanol administration on experimental nephrotic syndrome has not been, however, studied yet. METHODS AND RESULTS: Experimental nephrotic syndrome was induced in rats by the i.v. administration of adriamycin in ethanol fed rats and in rats given common laboratory chow. Chronic administration of ethanol was in nephrotic rats accompanied by the exaggerated lipolysis (free fatty acids were in control nephrotic rats lower than in nephrotic ethylic rats 6 weeks after adriamycin administration: 914.8 + 96.8 mumol/l vs. 1186.3 + 178.7 mumol/l, p < 0.01) and increased proteocatabolism; the development of nephrotic syndrome was ameliorated, or at least delayed, however, in ethylic rats (control nephrotic rats had higher proteinuria than nephrotic ethylic rats 3 weeks after adriamycin administration: 5.79 + 3.15 vs. 0.55 + 0.34 g protein/mmol creatinine, p < 0.01). In autopsy, diffuse global glomerulosclerosis was found in control nephrotic rats with only mild focal and segmental changes in nephrotic ethylic rats. CONCLUSIONS: Chronic ethanol administration ameliorated and/or delays the development of nephrotic syndrome in adriamycin nephropathy in rats. Mechanism of this effect of chronic ethanol feeding remains to be elucidated. Metabolic, immunosuppressive and renal haemodynamic effects of ethanol should be taken into consideration.
- MeSH
- doxorubicin toxicita MeSH
- ethanol farmakologie MeSH
- krysa rodu Rattus MeSH
- nefrotický syndrom chemicky indukované patologie prevence a kontrola MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- doxorubicin MeSH
- ethanol MeSH
