Effects of dietary fish oil on renal insufficiency in rats with subtotal nephrectomy

Abstract

We studied the effects of fish oil on the progression of renal insufficiency in rats with subtotal nephrectomy. Five weeks after a 1-2/3 nephrectomy, sixteen rats were fed two different diets which differed only in fat composition. Lipid in the control diet was primarily beef tallow; that of the experimental diet, menhaden oil. Fish oil-fed rats had significant increases in plasma creatinines, decreases in urinary PGE2 and accelerated death rates. An additional twelve rats underwent 1-1/3 nephrectomies, and the same dietary manipulations, followed by renal clearance, histologic and biochemical studies after 12 weeks on the diets. Fish oil-fed rats again did worse, with decreased glomerular filtration rates and filtration fractions, more proteinuria and more glomerular sclerosis. Glomeruli and slices of cortex, medulla and papillae from rats fed fish oil produced much less PGE2 and TXB2 than dietary controls. Fish oil-induced suppression of renal PGE2 may be deleterious in this model and may outweigh the beneficial effect derived from TXA2 suppression. In contrast to fish oil's potentially therapeutic role in cardiovascular and immune-mediated renal disease, this diet is detrimental in rat renoprival nephropathy. This illustrates the importance of examining the effects of fatty acid manipulation individually for each disease entity.

Short– and Long–Term Effects of Fish Oil on Proteinuria, Morphology and Renal Hemodynamics in the Milan Normotensive Rat Model of Spontaneous Glomerulosclerosis

“…In the MN rat model, however, Kliem et al [7] found no beneficial effect of low-dose captopril treatment on glomerulosclerosis and proteinuria after 8 months of treatment. One must also note that the nephroprotective effect Schmitz et al [16] found after 9 weeks is in contrast to the observations of Scharschmidt et al [17] who found an increase in proteinuria and glomerulosclerosis after 12 weeks of 21% fish oil diet in the renal ablation model. Also Melhardo et al [18] observed no protective effect of fish oil on glomerulosclerosis and proteinuria.…”

“…The results of fish oil feeding in rat models of renal injury vary substantially with the model used: whereas in five-sixths nephrectomized rats after 60 days [18] and 12 weeks [17], in heminephrectomized rats after 4 weeks [20], and in obese Zucker rats after 34 weeks [24] no beneficial effects of an EPA-rich diet on the glomerular filtration rate and the progression of renal disease were seen, short-term trials of EPA in models of immunologically induced glomerulosclerosis showed favorable results: the glomerular filtration rate was higher in nephrotoxic serum nephritis with EPA supplementation after 8 weeks [25] and after 12 weeks [23], and proteinuria was lower in Adriamycin-induced glomerular sclerosis after 7 weeks [26]. The trials are, however, difficult to compare not only because of the different rat models used, but also for the varying amounts of polyunsaturated Ω3 fatty acids and tocopherol administered.…”

Relationship between Hyperlipidemia, Lipid Mediators, and Progressive Glomerulosclerosis in the Nephrotic Syndrome

“…In adriamycin-induced nephrotic syndrome in rats, a small beneficial effect of fish oil supplementation has also been described [47], It should be noted, however, that in other models of kidney disease, the results of the use of fish oils have been less clear. In the model of subtotal renal abla tion, Scharschmidt et al [48] found that rats supple mented with menhaden oil had a greater decline in renal function, and a greater degree of glomerulosclerosis than did animals fed beef tallow. Other authors, however, have noted beneficial effects of fish oils in the remnant kidney model [49], It has been suggested that the differences in results could be seconday to the toxicity of oxidized fish oil in the former study [50], as an antioxidant used by Barcelli was not used in the Scharschmidt study.…”

Omega-3 Polyunsaturated Fatty Acids in Chronic Renal Insufficiency

“…The reaction could neither be predicted from either the underlying cause of the CRI, nor from the initial severity of renal function loss. Thus fish oil will not be a panacea for renal function preservation in all pa tients with CRI, as Scharschmidt et al [85] already stressed in their animal studies. Longer-term studies directed towards the possible preservation of renal function with fish oil have been reported in patients with IgA nephropathy [86][87][88].…”