Effect of castration on renal glycosaminoglycans and their urinary excretion in male and female rats with chronic renal failure

Glycosaminoglycans (GAGs) participate in a variety of processes in the kidney, and evidence suggests that gender-related hormones participate in renal function. The aim of this study was to analyze the relationship of GAGs, gender, and proteinuria in male and female rats with chronic renal failure (CRF). GAGs were analyzed in total kidney tissue and 24-h urine of castrated (c), male (M), and female (F) Wistar control (C) rats (CM, CMc, CF, CFc) and after 30 days of CRF induced by 5/6 nephrectomy (CRFM, CRFMc, CRFF, CRFFc). Total GAG quantification and composition were determined using agarose and polyacrylamide gel electrophoresis, respectively. Renal GAGs were higher in CF compared to CM. CRFM presented an increase in renal GAGs, heparan sulfate (HS), and proteinuria, while castration reduced these parameters. However, CRFF and CRFFc groups showed a decrease in renal GAGs concomitant with an increase in proteinuria. Our results suggest that, in CRFM, sex hormones quantitatively alter GAGs, mainly HS, and possibly the glomerular filtration barrier, leading to proteinuria. The lack of this response in CRFMc, where HS did not increase, corroborates this theory. This pattern was not observed in females. Further studies of CRF are needed to clarify gender-dependent differences in HS synthesis.

Effect of dietary linoleic acid on the progression of chronic renal failure in rats

The role of linoleic acid in chronic renal failure (CRF) is controversial. In the present study 21 male Wistar rats submitted to 5/6 renal mass reduction (R) and 16 normal controls (C) were fed a supplement (S) or normal (N) linoleic acid diet for 60 days starting 10 days after CRF. As expected, serum creatinine, cholesterol and triglycerides (mean SEM) were higher in the CRF groups compared to the C groups (P<0.05). The RS group presented lower cholesterol (84 4 vs 126 13 mg percent) and triglyceride (88 9 vs 132 19 mg percent) levels compared to the RN group. Proteinuria and kidney weight did not differ between CRF groups. Glomerular area increased 78 percent in RS and 100 percent in RN compared to control rats. Glomerular sclerosis index tended to be lower in RS (27 percent) compared to RN (38 percent), tubulointerstitial damage was similar between CRF groups (RS = 1.91 0.2 and RN = 2.14 0.3), and mesangial fractional volume increased to the same extent in both CRF groups. The data suggest that a linoleic acid-enriched diet did not protect against the progression of CRF after 60 days

Effect of time on remnant glomerular function

1. Although hypertrophy and hyperfiltration have been identified in remnant nephrons, the time of their appearance and the relationship between them have not been established. In order to evaluate remnant glomerular hemodynamics over different periods of time, we studied Munich-Wistar rats 7, 30 and 60 days after 5/6 renal mass ablation. 2. Kidney weight increased after 7 days, continued to increase after 30 days and decreased after 60 days. Glomerular filtration rate (GFR) and renal plasma flow decreased by 67 per cent and 7 days, were 35 per cent lower than normal after 30 days, and after 60 days presented the same values as after 7 days. Single-nephron GFR and glomerular plasma flow increased slightly after 7 days, were 118 per cent higher than control after 30 days, and decreased after 60 days. Hydraulic glomerular capillary pressure tended to increase after 30 days (6 per cent ), reaching statistical significance after 60 days (45 vs 62 mmHg). The glomerular ultrafiltration coefficient increased significantly after 30 days (82 per cent ) and decreased to values similar to the control group after 60 days. 3. These data suggest that kidney hypertrophy occurs early after reduction of renal mass, before the hemodynamic adaptations are complete. Glomerular hypertension was observed after 60 days, when single-nephron GFR and the glomerular ultrafiltration coefficient were decreased compared to rats studied after 30 days. 4. These data may indicate that, once glomerular hypertension starts, structural abnormalities are followed by a decline in glomerular function

Effect of cicletanine on the progression of chronic renal failure in rats

1. The effects of chronically administered cicletanine (CICL), an antihypertensive and prostacyclin stimulating agent, on glomerular hemodynamics were evaluated after 30 (CRF-30) or 60 (CRF-60) days of chronic renal failure (CRF) induced by 5/6 nephrectomy in Munich-Wistar rats. 2. CICL administration (3 mg kg-1 day-1, N = 5) for 60 days did not modify glomerular hemodynamics of normal rats (control group). The CRF-60 group (N = 6) presented a significant increase in mean arterial pressure (MAP) compared with control (122 +/- 7 vs 98 +/- 2 mmHg, P < 0.05), which was attenuated by CICL (113 +/- 7 vs 122 +/- 7 mmHg). 3. Hyperfiltration and hyperperfusion were observed in both CRF groups after 30 (N = 5) but not after 60 days of CRF, 73.9 +/- 6.3 and 48.2 +/- 3.2 vs 36.8 +/- 2.6 nl/min for SNGFR and 200 +/- 17 and 147 +/- 8 vs 112 +/- 8 nl/min for QA in CRF-30, CRF-60 vs control group, respectively. However, glomerular hypertension was demonstrable for both CRF groups only after 60 days. CICL treatment starting 7 days prior to nephrectomy reduced the transcapillary hydraulic pressure difference (delta P) in both groups, 36 +/- 3 vs 30 +/- 2 mmHg (30 days) and 41 +/- 4 vs 34 +/- 2 (60 days), but did not significantly modify arteriolar resistances or glomerular hemodynamics, suggesting that the reduction in MAP in response to CICL may have been responsible for the decrease in delta P. CICL administration did not prevent the proteinuria or glomerular sclerosis associated with CRF. 4. The results suggest that the administration of CICL for 30 (N = 4) to 60 days (N = 7) was sufficient to prevent systemic hypertension associated with CRF but not to reduce the additional glomerular hemodynamic factors that participate in the progression of CRF

Alguns fatores na progressäo da doença renal / Some factors in evolution of chronic renal failure

Adaptaçöes estruturais e funcionais foram demonstradas em néfrons remanescentes após lesäo renal. O grau destas adaptaçöes correlaciona-se diretamente com a quantidade de parênquima renal perdido. No entanto, várias observaçöes sugerem que a evoluçäo para insuficiência renal crônica (IRC), após esta perda de massa renal funcionante, é progressiva. Porém, os fatores responsáveis por esta evoluçäo ainda näo estäo estabelecidos. A hipertensäo e o hiperfluxo glomerulares que ocorrem nos néfrons remanescentes, especialmente em pacientes ou animais alimentados com dieta hiperprotéica, foram identificados como fatores que aceleram esta evoluçäo. Sabe-se também que as prostaglandinas (PGs) vasodilatadoras encontram-se elevadas na urina de humanos e animais de experimentaçäo com IRC, e que participam da manutençäo da filtraçäo glomerular. Alguns estudos recentes têm sugerido que estas PGs exercem um papel fundamental na manutençäo da vasodilataçäo renal que ocorre nos néfrons remanescentes. Sugere-se que as PGs teriam um papel fundamental na evoluçäo da IRC paralelamente com a dieta hiperprotéica. Finalmente, mecanismos hemodinâmicos da progressäo da IRC säo sugeridos e possivelmente novos enfoques terapêuticos conservadores (näo dialíticos) deveräo ser indicados