Effects of dietary fish oil on renal growth and function in uninephrectomized rats

Abstract

The basic mechanisms of renal growth remain poorly understood. The work hypertrophy theory holds that after an acute reduction in renal mass, the growth of the kidney occurs as a consequence of increased renal function. Pharmacological inhibition of renal prostaglandin synthesis impairs the acute adaptive increases in both renal function and mass following partial nephrectomy. The present study examines the effects of four weeks of dietary fish oil on renal growth, function and arachidonic acid metabolites in intact and uninephrectomized male Sprague-Dawley rats. Dietary fish oil interferes with dienoic prostaglandin and thromboxane production in favor of synthesis of trienoic analogues. Control animals were pair-fed an identical diet with the exception that the fat was replaced by beef tallow. Renal cortical concentrations of arachidonic acid metabolites were reduced in animals fed fish oil, and urinary excretion of prostaglandin E2 was impaired. Fish oil feeding resulted in increased kidney weight without concomitant increases in renal function in intact animals. Glomerular filtration rate and renal plasma flow were greater in uninephrectomized rats fed fish oil compared to uninephrectomized controls pair-fed beef tallow. Augmentation of the compensatory increases in renal function observed with fish oil feeding was not associated with any additional renal hypertrophy. These data indicate that dietary fish oil has a profound impact on renal growth and function, which may be the consequence of altered renal and/or extrarenal arachidonic acid metabolism. Furthermore, the direction of the alterations in renal mass oppose that of renal function, providing clear and unique evidence against the work hypertrophy theory of renal growth.

Advanced lipoxidation end‐products mediate lipid‐induced glomerular injury: role of receptor‐mediated mechanisms

“…Likewise, increased renal lipid synthesis in the absence of hyperlipidaemia resulted in renal disease 6, thus pointing to the importance of cellular lipid metabolism 7. In addition, lipid abnormalities occurring in several animal models of kidney disease were shown to contribute significantly to renal injury 8–13. In humans, evidence is still sparse.…”

Effect of Prostaglandins on Renal Function in Uninephrectomized Humans

“…It remains unclear whether this adaptive response is dependent on established hypertrophy or hormonal-humoral mediators. A recent ani mal study showed that augmentation of the compensatory increases in renal function observed with fish oil feeding was not associated with any additional renal hypertrophy [6]. Thus, hyperfunctioning after unilateral nephrectomy seems to be independent of renal growth.…”

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

“…Whereas the pronounced glomerular sclerosis and reduced renal plasma flows indicate renal microvascular damage, the increased relative kidney weights in the fish oil group after 32 weeks without concomitant glomerular hypertrophy point to an increased interstitial cell proliferation and/or increased matrix synthesis, although the latter have not been directly assessed in this study. Another explanation for the increased kidney weight could be a direct effect of the altered PG metabolism on kidney growth, as proposed by Logan et al [20].…”

“…Also an induction of extra-or intrarenal growth factors is possible which could account for an increased kidney weight and accelerated renal fibroblast proliferation. The results of Logan et al [20] show that, already after 4 weeks of fish oil diet, in healthy Sprague-Dawley rats the clearance in relation to the kidney weight was reduced, and the increased kidney weight, therefore, could not be explained by the work hypertrophy concept [21]. Moreover, fish oil has been shown to possess immunomodulating properties, and on the one hand the inhibition of proinflammatory cytokine and leukotriene [22] as well as superoxide production [see ref .…”

“…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.…”