Effects of dietary protein, angiotensin I converting enzyme inhibition and mesangial overload on the progression of adriamycin-induced nephropathy

Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular lesions in rats, resulting in persistent proteinuria and glomerulosclerosis. We studied the effects of dietary protein and of an angiotensin I converting enzyme inhibitor on the progression of this nephropathy and the evolution of the histological lesions, as well as mesangial macromolecule flow. Adriamycin nephropathy was induced by injecting a singl iv dose of adriamycin (3 mg/kg body weight) into the tail vein of male wistar rats (weight, 180-200 g). In Experiment I animals with adriamycin-induced nephropathy were fed diets containing 6 percent (Low-Protein Diet Group = LPDG), 20 percent (Normal-Protein Diet Group = NPDG) and 40 percent (High-Protein Diet Group = HPDG) protein and were observed for 30 weeks. In Experiment II the rats with adriamycin nephropathy were divide into 2 groups: ADR, that received adriamycin alone, and ADR-ENA, that received adriamycin plus enalapril, an angiotensin I converting enzyme inhibitor. The animals were sacrificed after a 24-week observation period. Six hours before sacrifice the animals were injected with 131I-ferritin and the amount of 131I-ferritin in the glomeruli was measured. In Experiment III, renal histology was performed 4, 8 and 16 weeks after adriamycin injection. At the end of Experiment I the tubulointerstitial lesion index was 2 for LPDG, 8 for NPDG, and 7.5 for HPDG (P,0.05); the frequency of glomerulosclerosis was 19 + or - 6.1 percent in LPDG, 42.6 + or - 6 percent in NPDG, and 54 + or - 9 percent in HPDG (P,0.05); and proteinuria was 61.1 + or - 25 mg/24 h in LPDG, 218.7 + or - 27.5 mg/24 h in NPDG, and 324.5 + or - 64.8 mg/24 h in HPDG (P,0.05). In Experiment II, at sacrifice, 24-h proteinuria was 189 + or - 16.1 mg in ADR, and 216 + or - 26.1 mg in ADR-ENA (P.0.05); the tubulointerstitial lesion index was 5 for ADR, and 5 for ADR-ENA (P.0.05); the frequency of glomerulosclerosis was 40 + or - 5.2 percent in ADR and 44 + or - 6 percent in ADR-ENA (P.0.05); the amount of 131I-ferritin in the mesangium was 214.26 + or - 22.71 cpm/mg protein in ADR and 253.77 + or - 69.72 cpm/mg protein in ADR-ENA (P.0.05). In Experiment III, sequential histological analysis revealed an acute tubulointerstitial cellular infiltrate at week 4, whigh was decreased at week 8. Tubular casts and dilatation were first seen at week 8 and increased at week 16 when few glomerular lesions were found. The results suggest that the tubulointerstitial lesions may play a role in the development of glomerulosclerosis in adriamycin-induced nephropathy

Reduction of urine volume ameliorates adriamycin-induced nephropathy

1. Adriamycin, a commonly used antineoplastic antibiotic, induces glomerular lesions in rats, resulting in persistent proteinuria and glomerulosclerosis. 2. The effect of urine volume on the progression of adriamycin-induced nephropathy was studied in 70 male Wistar rats (180-200 g) observed for 30 weeks and separated into 4 groups: healthy control group (HCG, N = 10) inoculated i.v. with 1 ml of saline, and nephrotic groups inoculated iv with a single dose of adriamycin of 3 mg/kg body weight. The nephrotic rats were separated into 3 groups (N = 20): nephrotic control group (NCG) receiving only adriamycin; dehydrated nephrotic group (DNG) water deprived for 36 h within each 48-h period, and furosemide nephrotic group (FNG) treated with 12 mg/dl furosemide, and 0.9 g/dl NaCl in the drinking water. 3. The 30-week survival rates of the DNG (100 per cent ) and HCG (100 per cent ) were significantly higher than those of the NCG (85 per cent ) and FNG (55 per cent ). 4. The proteinuria observed in the HCG (range, 7.38 +/- 0.7 to 13.6 +/- 1.27 mg/24 h) was significantly lower than that observed for all the nephrotic groups throughout the experiment. The DNG presented significantly less proteinuria (range, 42.71 +/- 6.83 to 140.10 +/- 19.22 mg/24 h) than the NCG (range, 35.32 +/- 7.64 to 250.00 +/- 25.91 mg/24 h) from week 10 on. There was no significant difference between the mean 24-h proteinuria of the NCG (range, 35.32 +/- 7.64 to 250.00 +/- 25.91 mg/24 h) and the FNG (range, 35.82 +/- 7.91 to 221.54 +/- 26.74). 5. The mean frequency of damaged glomeruli was 0.3 per cent +/- 0.3 for HCG, 42 per cent +/- 6 per cent for CNG, 40.8 per cent +/- 8 per cent for DNG, and 47 per cent +/- 14 per cent for FNG. The median value of the tubulointerstitial lesion, evaluated by a semiquantitative method, was 0 in HCG, 10 in CNG, 8.5 in DNG and 9.5 in FNG (P < 0.05 for all groups compared to HCG). 6. The data indicate that reduction of urine volume has a protective effect on adriamycin-induced nephropathy

Reticulin antibodies: relationship with endocardium-vessel-interstitium antibodies and heterophilic antibodies

Indirect immunofluorescence was used to compare reticulin antibodies, endocardium-vessel-interstitium (EVI) antibodies and heterophilic antibodies in serum samples from patients with degenerative and inflammatory diseases, Chagas' disease, or paracoccidioidomycosis and from healthy blood donors. The antigen substrates used were rat, mouse and human liver for reticulin antibodies, mouse and human heart and skeletal muscle for EVI factor, and rat heart and rat, mouse and human kidney and stomach for heterophilic antibodies. The three antibodies produced extremely similar fluorescent patterns and were present simultaneously in a large proportion of reticulin-positive serum samples. The three antibodies were significantly absorbed by heterophilic antigens such as sheep and rat red blood cells and guinea pig kidney, by Trypanosoma cruzi (an antigen associated with EVI factor) and by Paracoccidioides brasiliensis. However, they did not react with several human tissues. These results suggest that reticulin and EVI antibodies can be considered to be heterophilic antibodies

Estudo do quadro clinico de 121 pacientes portadores de glomerulopatias. 1). Estudo geral. / Clinical characteristics of 121 patients with glomerulopathy. 1). General study

Estudou-se retrospectivamente o quadro clinico de 121 pacientes portadores de glomerulopatias. Destes, 42 apresentaram sindrome nefritica (hematuria, edema, hipertensao diastolica), 33 sindrome nefrotica com proteinuria superior a 3,0g nas 24 horas e 46 constituiram o grupo "nao nefrotico" por apresentarem sintomas e sinais isolados ou associados sem, no entanto, satisfazerem os criterios de inclusao nas duas sindromes anteriores. Observou-se que: a idade media dos pacientes do grupo "sindrome nefrotica" foi superior a dos outros grupos; a funcao renal, avaliada pela creatinina plasmatica, esteve mais comprometida no grupo "nao nefritico nao nefrotico", nos pacientes hipertensos e nos mais idosos; os sinais mais frequentes de glomerulopatia foram edema (85,9%) e hipertensao (78,5%). O seguimento durante 36 meses do grupo "nao nefritico nao nefrotico mostrou que os pacientes com creatinina plasmatica inicial alterada tiveram pior prognostico

Correlacao anatomo-clinica em glomerulopatias. Estudo retrospectivo de 65 casos em adultos. / Anatomo-clinical correlation in glomerulopathies. Retrospective study of 65 cases in adults

O presente trabalho compreende estudo anatomo-clinico retrospectivo de 65 casos de glomerulopatias em adultos. Os casos foram classificados em tres sindromes clinicas: nefritica, nefrotica, nao nefritica - nao nefrotica. A intensidade das lesoes histologicas renais foi avaliada no material de biopsia e/ou autopsia atraves de metodo semiquantitativo (0 a 4 +) obtendo-se indices de lesao glomerular, tubular, intersticio-vascular e renal total. Para cada paciente, foram estabelecidas correlacoes entre estes indices com a apresentacao clinica, niveis pressoricos, funcao renal (creatinina serica) e evolucao. No conjunto, observou-se que lesoes historicas mais graves associam-se a agravamento da funcao renal e piora da evolucao dos pacientes.A analise estatistica de regressao linear simples demonstrou correlacao significante entre os diferentes indice de lesao com os niveis de creatinina serica, porem o indice de lesao intersticio-vascular foi o que melhor se correlacionou com a funcao renal (r2 = 0,53)