A longitudinal study on the acceptance and effects of a therapeutic renal food in pet dogs with IRIS-Stage 1 chronic kidney disease

Dietary patterns have been linked to such chronic diseases as cardiovascular disease, but sparse data currently are available for associations between dietary patterns and microalbuminuria or kidney function decline. Subgroup analysis from a prospective observational cohort study. Female participants in the Nurses' Health Study who had dietary pattern data from food frequency questionnaires returned in 1984, 1986, 1990, 1994, and 1998 and urinary albumin-creatinine ratios from 2000 (n = 3,121); estimated glomerular filtration rate (eGFR) change between 1989 and 2000 was available for 3,071. Prudent (higher intake of fruits, vegetables, legumes, fish, poultry, and whole grains), Western (higher intake of red and processed meats, saturated fats, and sweets), and Dietary Approach to Stop Hypertension (DASH)-style dietary patterns (also greater intake of vegetables, fruits, and whole grains). Microalbuminuria (albumin-creatinine ratio, 25-354 μg/mg) in 2000 and change in kidney function using eGFR between 1989 and 2000. After multivariable adjustment, the highest quartile of Western pattern score compared with the lowest quartile was associated directly with microalbuminuria (OR, 2.17; 95% CI, 1.18-3.66; P for trend = 0.01) and rapid eGFR decline ≥3 mL/min/1.73 m(2)/y (OR, 1.77; 95% CI, 1.03-3.03). Women in the top quartile of the DASH score had decreased risk of rapid eGFR decline (OR, 0.55; 95% CI, 0.38-0.80), but no association with microalbuminuria. These associations did not vary by diabetes status. The prudent dietary pattern was not associated with microalbuminuria or eGFR decline. Study cohort included primarily older white women and generalizability of results would benefit from validation in nonwhites and men. A Western dietary pattern is associated with a significantly increased odds of microalbuminuria and rapid kidney function decrease, whereas a DASH-style dietary pattern may be protective against rapid eGFR decline. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Symmetrical dimethylarginine (SDMA) is the structural isomer of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine. Whereas the major route of asymmetric dimethylarginine elimination is the hydrolytic degradation by dimethylarginine dimethylaminohydrolase, SDMA is eliminated by renal excretion. SDMA does not directly inhibit NOS but is a competitor of arginine transport. This study showed for the first time that measurement of SDMA can be a marker of estimated GFR and extent of coronary artery disease (CAD). In 97 patients with CAD, SDMA was a marker of estimated GFR. On multiple regression analysis of the CAD parameter stenosis score, SDMA was the only parameter retained. In addition, endothelial cells from the third passage were cultured in medium that contained 70 micromol/L arginine and was incubated for 24 h in the presence of various concentration of SDMA (0, 2, 5, 10, and 100 micromol/L). The levels of nitrate and nitrite in conditioned media, the protein expression of NOS, and the content of reactive oxygen species in endothelial cells were determined. SDMA inhibited dose dependently the NO synthesis in intact endothelial cells, whereas it had no effect on protein expression of NOS. This effect was associated with an increase in reactive oxygen species. Co-incubation with L-arginine but not D-arginine reversed the effect of SDMA on NOS pathway. Our data suggest that SDMA reduced the endothelial NO synthesis, probably by limiting L-arginine supply to NOS. It is concluded that SDMA might be a useful parameter for detecting patients in very early stages of chronic kidney disease and for determining their risk for developing cardiovascular disease.

Background Symmetric dimethylarginine (SDMA) is a small molecule formed by methylation of arginine, and released into blood during protein degradation. SDMA is primarily eliminated by renal excretion and is a promising endogenous marker of glomerular filtration rate (GFR). Objectives To validate an assay for SDMA measurement, determine stability of SDMA in blood, and compare SDMA with serum creatinine concentration (sCr) and GFR for early detection of decreasing kidney function in dogs with chronic kidney disease (CKD). Animals Eight male dogs affected with X‐linked hereditary nephropathy and 4 unaffected male littermates. Methods Prospective study validating SDMA measurement using liquid chromatography‐mass spectrometry, assessing stability of SDMA in serum and plasma, and serially determining sCr, SDMA, and GFR (using iohexol clearance) in dogs during progression from preclinical disease to end‐stage renal failure. Correlations were determined using linear regression. Timepoints at which sCr, SDMA, and GFR identified decreased renal function were compared using defined cutoffs, trending in an individual dog, and comparison with unaffected littermates. Results Symmetric dimethylarginine was highly stable in serum and plasma, and the assay demonstrated excellent analytical performance. In unaffected dogs, SDMA remained unchanged whereas in affected dogs, SDMA increased during disease progression, correlating strongly with an increase in sCr (r = 0.95) and decrease in GFR (r = −0.95). Although trending improved sCr's sensitivity, SDMA identified, on average, <20% decrease in GFR, which was earlier than sCr using any comparison method. Conclusions and Clinical Importance Symmetric dimethylarginine is useful for both early identification and monitoring of decreased renal function in dogs with CKD.