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Conjugated linoleic acid (CLA) slows the progression of disease in models of chronic kidney disease. Because obesity is associated with nephropathy and increased renal cyclooxygenase (COX) levels, the effects of dietary CLA on kidney function, morphology, and COX protein levels in the kidneys of young obese (fa/fa) Zucker rats, a model of metabolic syndrome, were examined. In study 1,6-wk-old fa/fa and lean Zucker rats were given a mixture of CLA isomers (1.5% CLA, wt:wt) or the control diet (CTL) with no CLA for 8 wk. To examine specific isomer effects, study 2 used the same model with the following diets: 0.4% (g/g) cis-9, trans-11 (c9,t11) CLA; 0.4% trans-10, cis-12 (t10,c12) CLA; a combination of these 2 isomers (0.4% each); or CTL diets with no CLA. In study 1, fa/fa rats given the CLA mixture had 11% smaller kidney weights and 28% smaller glomeruli, and feed intake and body weight did not differ from the CTL rats. In study 2, diet also did not affect body weights, but fa/fa rats given a diet containing t10, c12 CLA had 7% lower kidney weights, 20% smaller glomeruli, and 39% lower COX-2 protein levels than CTL rats. In conclusion, dietary t10,c12 CLA reduces the enlargement of glomeruli in young obesity-associated nephropathy and is associated with lower protein levels of renal COX-2. Long-term studies with CLA supplementation are required to determine whether these changes would lead to reduction in development of renal disease associated with obesity.

Selective cyclooxygenase-2 (COX-2) inhibitors appear to have beneficial renoprotective effects in most, but not all, renal disease conditions. The objective of our study was to examine the effects of COX-2 inhibition in a rat model of polycystic kidney disease. Four-week-old Han:SPRD-cy rats were given a standard rodent diet containing NS-398 (3 mg.kg body [wt.sup-1].[day.sup.-1]) or a control diet without NS-398 for 7 wk. In diseased rats, selective COX-2 inhibition resulted in 18% and 67% reduction in cystic expansion and interstitial fibrosis, respectively, but no change in renal function. NS-398 also ameliorated disease-associated pathologies, such as renal inflammation, cell proliferation, and oxidant injury (by 33, 38, and 59%, respectively). Kidney disease was associated with elevated renal COX-1 and COX-2 enzyme activities, and NS-398 blunted the increase in COX-2 enzyme activity (as indicated by 21 and 28% lower renal thromboxane B2 and [PGE.sub.2] levels, respectively). NS-398 reduced urinary excretion of prostanoid metabolites in diseased rats. In summary, COX-2 inhibition attenuated renal injury, reduced the elevated renal COX-2 activity, and ameliorated disease-related alterations in prostanoid production in this rat model of chronic renal disease. NS-398; histology; cyclooxygenase activity

Compared with casein, dietary soy protein slows disease progression in animal models of chronic renal injury. To determine whether dietary soy protein feeding can alter early disease progression, male Han:SPRD-cy rats (n = 87) in a very early stage of chronic kidney disease were fed soy protein compared with casein-based diets for 1 or 3 wk. Kidneys were assessed for fibrosis, cyst growth, fatty acid composition and prostaglandin [E.sub.2] (PG[E.sub.2]) production. Soy protein feeding significantly reduced renal fibrosis by 22% (P = 0.0347) and 38% (P = 0.0102) after 1 and 3 wk of diet, and cyst growth was 34% lower after 3 wk (P < 0.0001). Kidney 18:2(n-6) levels were reduced in normal and diseased rats after as little as 1 wk of consuming the soy protein diet. Dietary soy protein also partially ameliorated the suppression of PG[E.sub.2] production observed in diseased kidneys. Compared with diseased kidneys from casein-fed rats, ex vivo PG[E.sub.2] release was 31-32% higher after 1 (P = 0.0281) and 3 (P = 0.0189) wk of dietary soy protein consumption. Hence, the first signs of a beneficial soy protein effect were observed after 1 wk of feeding, with further improvements evident after 3 wk. These data demonstrate that dietary soy protein compared with casein delays disease progression in an early stage of chronic kidney disease. J. Nutr. 134: 1504-1507, 2004. KEY WORDS: * dietary soy protein * chronic kidney disease * early intervention

Dietary fish oils containing (n-3) fatty acids can modulate renal inflammatory injury. We previously demonstrated that a high fat (HF) diet worsens early renal disease progression in the Han:SPRD-cy rat model of polycystic kidney disease (PKD). Therefore, using HF (20 g/100 g diet) and low fat (LF; 5 g/100 g diet) diets, we compared the effects of menhaden oil (MO), soybean oil (SO) and cottonseed oil (CO) on renal function and histology in male Han:SPRD-cy rats fed the diets for 6 wk in the early stages of renal disease. Overall, rats fed HF compared with those fed LF diets had larger kidneys, more renal fibrosis and lower creatinine clearance (main effects of fat level). Rats fed MO rather than CO and SO diets had significantly lower kidney weights, kidney water content, cyst volumes and serum cholesterol and triglyceride concentrations (main effects of fat type). Rats fed MO diets also had less renal fibrosis than those fed CO diets, but the least fibrosis was in rats fed SO diets. Analysis of simple effects (due to interactions between fat level and type) revealed that HF diets increased renal inflammation in rats fed CO diets, but reduced inflammation was present in those fed SO and MO diets; HF diets also increased compared with LF diets serum urea nitrogen concentrations in rats fed the MO and CO diets, but not the SO diet. These results confirm that high dietary fat worsens early disease progression in this model of renal disease, and further demonstrate that diets with oils containing (n-3) fatty acids ameliorate some of the detrimental effects of a high fat diet. KEY WORDS: * dietary fat level * fish oil * early renal disease * rats

Research shows that rats fed on soy protein develop far less polycystic kidney disease that those fed on casein. Experiments designed to assess the physiological impact of a soy protein diet on ameliorate renal injury in Han:SPRD-cy rats are described. Proton nuclear magnetic resonance techniques were used to analyse urine composition. Animals fed on casein retain more tissue betaine than those fed on soy.

Ogborn, Malcolm R., Evan Nitschmann, Neda Bankovic-Calic, Richard Buist, and James Peeling. Dietary betaine modifies hepatic metabolism but not renal injury in rat polycystic kidney disease. Am J Physiol Gastrointest Liver Physiol 279: G1162-G1168, 2000.--We undertook a morphometric and proton nuclear magnetic resonance ([sup.1]H-NMR) study to test the hypothesis that 1% dietary betaine supplementation would ameliorate renal disease in the heterozygous Han:SPRD-cy rat, a model of polycystic kidney disease (PKD) and progressive chronic renal failure. After 8 wk of pair feeding, betaine had no effect on renal cystic change, renal interstitial fibrosis, serum creatinine, serum cholesterol, or serum triglycerides. [sup.1]H-NMR spectroscopy of renal tissue revealed no change in renal osmolytes, including betaine, or renal content of other organic anions in response to diet. [sup.1]H-NMR spectroscopy of hepatic tissue performed to explore the metabolic fate of ingested betaine revealed that heterozygous animals fed the control diet had elevated hepatic levels of gluconeogenic amino acids, increased [Beta]-hydroxybutyrate, and increased levels of some citric acid cycle metabolites compared with animals without renal disease. Betaine supplementation eliminated these changes. Chronic renal failure in the Han:SPRD-cy rat is associated with disturbances of hepatic metabolism that can be corrected with betaine therapy, suggesting the presence of a reversible methylation defect in this form of chronic renal failure. liver; nuclear magnetic resonance; uremia; methylation

Selective cyclooxygenase-2 (COX-2) inhibitors appear to have beneficial renoprotective effects in most, but not all, renal disease conditions. The objective of our study was to examine the effects of COX-2 inhibition in a rat model of polycystic kidney disease. Four-week-old Han:SPRD-cy rats were given a standard rodent diet containing NS-398 (3 mg·kg body wt-1·day-1) or a control diet without NS-398 for 7 wk. In diseased rats, selective COX-2 inhibition resulted in 18% and 67% reduction in cystic expansion and interstitial fibrosis, respectively, but no change in renal function. NS-398 also ameliorated disease-associated pathologies, such as renal inflammation, cell proliferation, and oxidant injury (by 33, 38, and 59%, respectively). Kidney disease was associated with elevated renal COX-1 and COX-2 enzyme activities, and NS-398 blunted the increase in COX-2 enzyme activity (as indicated by 21 and 28% lower renal thromboxane B2 and PGE2 levels, respectively). NS-398 reduced urinary excretion of prostanoid metabolites in diseased rats. In summary, COX-2 inhibition attenuated renal injury, reduced the elevated renal COX-2 activity, and ameliorated disease-related alterations in prostanoid production in this rat model of chronic renal disease. [ABSTRACT FROM AUTHOR]

Reports that detrimental effects of a high fat diet in early renal injury are ameliorates by fish oil in Han:SPRD-cy rats. Fatty acid composition of renal tissues; Fat level effects; Fat type effects.

Dietary conjugated linoleic acid reduces PGE[sub 2] release and interstitial injury in rat polycystic kidney disease. Background. Conjugated linoleic acid (CLA) describes positional isomers of linoleic acid (LA). Experimental health benefits of CLA include amelioration of malignancy and inflammatory disease and reduction of adiposity. The Han:SPRD-cy rat model of polycystic kidney disease (PKD) features prominent renal interstitial inflammation and fibrosis that is amenable to dietary modification. We studied CLA supplementation in the modification of inflammatory outcomes in the Han:SPRD-cy rat. Methods. Male offspring of Han:SPRD-cy heterozygotes were fed diets, using corn oil or corn oil with a CLA enriched oil (1% of diet by weight as CLA). After 8 weeks, measurements included renal function and morphometry, ex vivo release of renal prostaglandin E[sub 2] (PGE[sub 2] ), and renal and hepatic tissue fatty acid profiles. Results. Urine creatinine was significantly higher in PKD animals fed CLA (P = 0.004), but differences in serum creatinine and creatinine clearance did not quite reach significance in PKD animals. CLA feeding reduced interstitial inflammation (P < 0.001), fibrosis (P = 0.03), and renal PGE[sub 2] release (P = 0.02). Cystic change and oxidized low-density lipoprotein (LDL) staining did not change significantly. CLA feeding produced increased renal and hepatic CLA isomers. Hepatic, but not renal, LA proportion was reduced on the CLA diet. The renal proportion of the PGE[sub 2] precursor, arachidonic acid (AA), was not changed by diet, but hepatic AA proportion increased significantly with CLA feeding (P = 0.009). Conclusion. CLA reduces renal production of PGE[sub 2] , without reduced availability of the precursor fatty acid, AA. Short-term feeding of CLA to Han:SPRD-cy rats also has significant renal anti-inflammatory and antifibrotic effects. As inflammation and fibrosis are important components of the progression of chronic renal injury, CLA may be a useful agent in dietary amelioration of renal disease. [ABSTRACT FROM AUTHOR]