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Low molecular weight heparin in the treatment of puromycin-induced nephrosis
Ana Maria Ribeiro Dos Santos1, Albanita Viana de Olveira, Carla Cavalheiro da Silva Lemos
1Nephrology Division, University of State of Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract:
Heparin may have a beneficial effect in proteinuric renal diseases, where negative charges of the glomerular capillary membrane are compromised. We evaluated the role of low molecular weight heparin (LMWH - 3000 Da) in puromycin aminonucleoside (PAN)-induced focal and segmental glomerulosclerosis in male Wistar rats: Controls (C) n=7, LMWH-treated group, n=9, subcutaneously (SC), 6 mg/kg every day. The PAN group (n=7) received 7 doses on weeks 0, 1, 2, 4, 6, 8, 10 (SC - 2mg/100g), and a group PAN+LMWH (n=6). After 12 weeks, cholesterol and triglycerides were higher in nephrotic groups, as well as proteinuria and urinary IgG. Kidney weight, glomerular volume, and glomerular sclerosis index were higher in the PAN-treated groups. Glomerular capillary length density (L(Vcap)) and glomerular capillary surface density (S(Vcap)) were lower in the PAN group, and mesangial fractional volume was higher. Fibronectin immunostaining was more intense in the PAN group, and collagens I and III were absent in the studied glomeruli. Thus, LMWH prevented mesangial expansion and capillaries changes, showing antiproliferative properties, despite worsening glomerular permeability changes in the PAN model. In conclusion, LMWH interferes in the complications of PAN model, but not through inhibition of the proteinuria.
Insights
Low molecular weight heparin (LMWH) showed antiproliferative effects in a rat model of focal and segmental glomerulosclerosis, preventing mesangial expansion and capillary changes. However, LMWH did not inhibit proteinuria in this study.
Area of Science:
- Nephrology
- Pharmacology
- Pathology
Background:
- Proteinuric renal diseases involve compromised glomerular capillary membrane charges.
- Heparin's potential benefits in such conditions are under investigation.
Purpose of the Study:
- To evaluate the role of low molecular weight heparin (LMWH) in puromycin aminonucleoside (PAN)-induced focal and segmental glomerulosclerosis in rats.
- To assess LMWH's effects on renal pathology, proteinuria, and lipid profiles.
Main Methods:
- Male Wistar rats were induced with PAN to model glomerulosclerosis.
- Groups included controls, LMWH-treated, PAN-treated, and PAN+LMWH-treated rats.
- Evaluations included kidney weight, glomerular volume, sclerosis index, capillary density, mesangial volume, fibronectin, and collagen expression after 12 weeks.
Main Results:
- PAN-induced nephrotic rats exhibited higher cholesterol, triglycerides, proteinuria, urinary IgG, kidney weight, glomerular volume, and sclerosis index.
- Glomerular capillary density decreased, while mesangial volume and fibronectin increased in PAN-treated rats.
- LMWH treatment prevented mesangial expansion and capillary changes, indicating antiproliferative properties, but did not reduce proteinuria.
Conclusions:
- LMWH demonstrates antiproliferative effects and interferes with complications in the PAN-induced glomerulosclerosis model.
- LMWH's mechanism does not involve the inhibition of proteinuria in this specific model.
- Further research is needed to elucidate LMWH's role in proteinuric renal diseases.
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