Growth impairment of primary chondrocyte cells by serum of rats with chronic renal failure

Insulin-like growth factor (IGF)/IGF binding protein (IGFBP) abnormalities may be important in the pathogenesis of growth failure in chronic renal failure (CRF). We induced experimental CRF by 5/6 nephrectomy in Sprague Dawley rats (100 g) and observed for 2 weeks comparing with sham-operated pair-fed control rats (Sham- C). CRF rats gained 30% less height than Sham- C rats (P10 kDa, containing IGFBPs) and low (<10 kDa, containing free IGF) molecular weight fractions using a gel filtration column. Both fractions obtained from CRF sera decreased the growth of control chondrocytes up to 40% compared with those from control sera. We suggest that the pathogenesis of growth failure in CRF may be involved in the increase of circulating IGFBP4 as well as the unidentified small molecular weight uremic serum factors which block the growth of chondrocytes in growth plate.

Gene expression in uremic left ventricular hypertrophy: effects of hypertension andanemia

Hypertension and anemia may be causes of left ventricular hypertrophy (LVH) in uremia but the molecular mechanism is not known. Uremia was induced in male Spraugue Dawley rats by 5/6 nephrectomy. The following groups of rats were studied for 6 weeks; uremic rats (U) fed ad. lib., control rats (C) pair-fed with U, U rats given hydralazine (100 mg/kg/day) (UH), U rats given erythropoietin (48U/kg/week, i.p.) (UE). Both diastolic and mean arterial pressures are higher (P<0.01) in U and UE compared with C whereas both pressures in UH were normalized. Hemoglobin in U was lower than in C, and was normalized in UE. U, UH and UE had higher heart weight/body weight ratios (HW/BW) as well as left ventricular weight/body weight ratios (LV/BW) compared with C (P<0.01). Compared with U, UH has lower HW/BW and LV/BW (P <0.05) and UE has normal HW/BW but lower LV/BW than U (P<0.05). To see if the gene expression in uremic LVH is similar to that described in pressure overload LVH in which mRNA levels of angiotensin converting enzyme (ACE), transforming growth factor-beta1 (TGF-beta1), atrial natriuretic factors (ANF) and skeletal alpha-actin were increased, we measured these mRNA levels by Northern analysis. TGF-beta, ACE and alpha-actin mRNA levels were not changed in all 4 groups. ANF mRNA in U and UE was increased 3 fold over C, and normalized in UH. Treatment of anemia with erythropoietin improved uremic LVH but did not change ANF mRNA; whereas treatment of hypertension with hydralazine normalized ANF mRNA but did not completely correct uremic LVH. Thus, gene expression in uremic LVH is distinct from that in pressure- overload LVH, suggesting that other unidentified factor(s) might be involved in uremic LVH.