The effects of dietary protein and converting enzyme inhibition (CEI) on chronic puromycin aminonucleoside nephropathy (PAN) were studied. PAN was induced with seven SQ injections of puromycin aminonucleoside 20 mg/kg over 10 weeks in male Sprague-Dawley rats. The rats were divided into a 22.5% protein diet group (Gr 1), a 6% protein diet group (Gr 2), and an enalapril-treated group on 22.5% protein diet (Gr 3). Group 4 animals served as age-matched controls. Both diets were isocaloric and had the same phosphorus content. Rats from groups 1, 2, and 4 were sacrificed at 12, 18 and 24 weeks. Five rats of group 3 were sacrificed at 12 weeks, and the others were divided in subgroups 3A (diet changed to 6% protein) and 3B (no changes); half of each subgroup was sacrificed at 18 and 24 weeks, respectively. Group 2 had significantly less proteinuria than group 1 at all times. Group 3 had the same proteinuria as group 1 until 12 weeks and then began to decrease. In group 3A proteinuria decreased to group 2 levels, while in group 3B the decrease was slower but still prominent. Early lesions of focal and segmental glomerular sclerosis/hyalinosis (FSH) were present in groups 1, 2, 3 at 12 weeks (16 +/- 1.2%, 15 +/- 1.3%, 7 +/- 1.3%, respectively, versus 1.3 +/- 0.4% in controls), but by 18 weeks a reversal in FSH was seen in groups 2 and 3A/B (3 +/- 1.6%, 2 +/- 0.4%, and 3 +/- 0.9%, respectively, vs. 14 +/- 1.5% in group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

The ability of heparan sulfate, an endogenous component of the glomerulus, to regulate the growth of cultured rat mesangial cells was investigated. Heparan sulfate caused a dose-dependent inhibition of rat mesangial cell growth, 85% inhibition compared with controls at the highest dose (1,000 micrograms/ml). Chondroitin sulfate produced no inhibition. The low-sulfated fraction of heparan sulfate (9%) produced more inhibition than the high-sulfated fraction (13%), 90 +/- 1 vs. 71 +/- 2% (P = 0.002). The effects of the heparan sulfate were completely reversible. Treatment of heparan sulfate with heparitinase increased the degree of inhibition, 71 +/- 1 vs. 84 +/- 1% (P less than 0.001). Four different oligosaccharides derived from heparan sulfate and heparin were tested for their ability to inhibit growth. One of the oligosaccharides, low-sulfated (10%), caused significant inhibition, 76 +/- 2%. Heparan sulfate was also able to inhibit the growth of Swiss 3T3 fibroblasts (63 +/- 5%). This inhibition was less marked than that seen with mesangial cells. Thus heparan sulfate was able to significantly inhibit rat mesangial cell growth in culture. Alterations in glomerular heparan sulfate may play an important role in alterations in mesangial cell growth.

Sarcoid reactions have been described in association with lymphomas and rarely with other solid tumors. We describe a patient with renal papillary adenocarcinoma and prominent sarcoid-like granulomatous infiltration of the ipsilateral and most likely the contralateral kidney. There was no evidence of extrarenal granulomas. This is the first description of impairment in renal function in a patient with renal carcinoma and with sarcoid reaction to this tumor isolated in the kidney.