A plasma creatinine- and urea-based equation to estimate glomerular filtration rate in rats.

Monitoring renal function is a vital part of kidney research involving rats. The laborious measurement of glomerular filtration rate (GFR) with administration of exogenous filtration markers does not easily allow serial measurements. Using an in-house database of inulin clearances, we developed and validated a plasma creatinine- and plasma urea-based equation to estimate GFR in a large cohort of male rats [development cohort n = 325, R2 = 0.816, percentage of predictions that fell within 30% of the true value (P30) = 76%] that had high accuracy in the validation cohort (n = 116 rats, R2 = 0.935, P30 = 79%). The equation was less accurate in rats with nonsteady-state creatinine, in which the equation should therefore not be used. In conclusion, applying this equation facilitates easy and repeatable estimates of GFR in rats.NEW & NOTEWORTHY This is the first equation, that we know of, which estimates glomerular filtration rate in rats based on a single measurement of body weight, plasma creatinine, and plasma urea.

Increased expression of SOCS3 in monocytes and SOCS1 in lymphocytes correlates with progressive loss of renal function and cardiovascular risk factors in chronic kidney disease.

Inflammation, an independent cardiovascular disease risk factor is common in patients with chronic kidney disease. Suppressors of cytokine signaling (SOCS) are induced by cytokines in a variety of cells and modulate inflammatory responses. We hypothesized that in chronic kidney disease, SOCS expression in peripheral blood mononuclear cells is increased, and related to inflammation and renal function. We also tested correlations between SOCS expression and biomarkers and risk factors of cardiovascular disease. Whether monocytes and lymphocytes differentially respond to interleukin-6 (IL-6) was tested ex vivo. Monocytes and lymphocytes were isolated from peripheral blood of chronic kidney disease patients (n=9) and controls (n=11). In three other healthy subjects, whole blood was incubated with IL-6 before cell isolation. SOCS expression was assessed by real-time quantitative PCR. Plasma cytokines were measured as well as pulse wave velocity. SOCS3 expression was increased in monocytes and SOCS1 in lymphocytes along with increased plasma levels of IL-6 and tumor necrosis factor-alpha (TNFalpha) in chronic kidney disease patients. While monocyte SOCS3 correlated with glomerular filtration rate, urea and diastolic blood pressure, lymphocyte SOCS1 correlated with TNFalpha, pulse wave velocity and systolic blood pressure. IL-6 stimulation of whole blood caused expression of different SOCS genes in monocytes and lymphocytes. Increased expression of SOCS3 in monocytes versus SOCS1 in lymphocytes coincided with elevated plasma levels of IL-6 and TNFalpha, suggesting that these cell types process the uremic milieu differently. This could reflect cell-specific responses to inflammation, as supported by our ex vivo study. Moreover, increased SOCS expression in peripheral blood mononuclear cells correlated with decreased renal function. Since chronic kidney disease predisposes to cardiovascular disease, we speculate that increased SOCS expression in peripheral blood mononuclear cells could be a new marker of cardiovascular disease in chronic kidney disease patients.

Effects of gender on hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and LDL receptor in hereditary analbuminemia.

Hypoalbuminemia is accompanied by hypercholesterolemia in both nephrotic syndrome and hereditary analbuminemia. Hypercholesterolemia is more severe in the female than in the male Nagase analbuminemic rats (NAR). The sex difference in plasma cholesterol diminishes after ovariectomy (OVX) and reappears after estrogen replacement in the NAR. The molecular mechanism responsible for the sex difference in severity of hypercholesterolemia in NAR is not known and was investigated here. To this end, hepatic hydroxylmethylglutaryl (HMG)-CoA reductase, cholesterol 7alpha-hydroxylase, and LDL receptor were determined in male, female, and OVX female NAR and Sprague-Dawley (SD) rats. Plasma cholesterol, triglycerides, and hepatic HMG-CoA reductase activities were greater in both female and male NAR than in SD rats. This was coupled with upregulation of cholesterol 7alpha-hydroxylase in both male and female NAR compared with SD controls. LDL receptor in male NAR was similar to that in male SD rats but was significantly reduced in female NAR. OVX partially, but significantly, reduced plasma cholesterol and triglyceride levels in female NAR. This was coupled with a significant rise in hepatic cholesterol 7alpha-hydroxylase and a modest increase in hepatic LDL receptor. In contrast, OVX resulted in a mild elevation of plasma cholesterol and no significant changes in total hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, or LDL receptor in female SD rats. Thus the greater severity of hypercholesterolemia in the female NAR appears to be due, in part, to a combination of the constrained compensatory upregulation of cholesterol 7alpha-hydroxylase and LDL receptor deficiency.