We studied the ability of human peritoneal mesothelial cells (HPMC) to produce the major pro-inflammatory cytokines interleukin-1 alpha (IL-1 alpha) and -beta when stimulated by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) or IL-1 alpha, or combinations of these three factors. Biological activity of IL-1 was measured by bioassay, and levels of IL-1 alpha and beta were determined using specific radioimmunoassays. We found that HPMC are capable of secreting IL-1 alpha and -beta in response to stimulation by these substances, but stimulation with a combination of LPS + TNF alpha, LPS + IL-1 alpha, or TNF alpha + IL-1 alpha, had a marked synergistic effect on cytokine production. A combination of all three substances together had a significantly enhanced synergistic effect. Using reverse transcription PCR, we found a peak in IL-1 alpha and beta mRNA levels three hours after stimulation. We found that LPS, TNF alpha and IL-1 alpha alone, or in combination, caused an increase in IL-1 alpha and -beta mRNA levels. Cycloheximide and actinomycin D blocked the production of IL-1 alpha and -beta protein, showing that de novo production of IL-1 or synthesis of mRNA stabilizing proteins are needed after stimulation. We thus conclude that HPMC play an important role in the amplification of the initial peritoneal inflammatory response which originates in the peritoneal macrophages, and these findings are of importance in understanding the peritoneal response to infection in continuous ambulatory peritoneal dialysis (CAPD) patients.

We determined serum high-density lipoprotein cholesterol content and analyzed the approtein structure of the various lipoprotein fractions in 21 patients on chronic hemodialysis. High-density lipoprotein cholesterol was significantly reduced in all patients as compared with 11 normal persons (mean +/-1 standard deviation: 26 +/- 13 vs. 52 +/- 9 mg per 100 ml; P less than 0.001) whether or not triglyceride levels were raised. In seven of those with Type IV hyperlipoproteinemia, protein content of high-density lipoprotein and its subfractions 1, 2 and 3 were also reduced (P less than 0.001) in parallel with reductions in cholesterol in these fractions. Apoprotein electrophoresis showed an increase in "arginine-rich" peptide in very-low-density lipoprotein and high-density lipoprotein fraction 1, and a reduction in apoprotein Cll in very-low-density and high-density lipoprotein. In addition to their reduced high-density lipoprotein cholesterol levels, a major factor in the atherosclerosis of these patients may be their abnormal high-density lipoprotein composition. Their raised triglyceride levels could be due to defective lipoprotein lipase activation by the reduced very-low-density lipoprotein apoprotein.

Heart failure (HF) refractory to conventional therapy is a major and increasing public health and financial problem. Refractory HF is associated with hypervolaemia due to sodium and fluid retention, and azotaemia due to renal hypoperfusion. There is extreme renal salt and water retention and marked secondary hyperaldosteronism. In this state, the kidneys are relatively resistant to diuretic therapy, and the use of very high doses of oral or parenteral diuretics only worsens the renal hypoperfusion, making the patient more azotaemic. A logical treatment for this 'cardiorenal syndrome' is the use of dialysis, which is efficient in treating both the hypervolaemia and azotaemia of refractory HF. Peritoneal dialysis (PD), haemodialysis or continuous veno-venous haemofiltration can and have been used, but the simplest long-term treatment is PD. We present several case reports of the successful use of PD in refractory heart failure. In our opinion, chronic PD is a highly effective mode of treatment for refractory HF, and should be more widely used in this condition.

We measured peritoneal losses of the active vitamin D metabolites 1,25(OH)₂D₃ and 24,25(OH)₂D₃ in patients receiving continuous ambulatory peritoneal dialysis (CAPD). The serum concentration of 24,25(OH)₂D₃ was considerably lower than in hemodialysis patients. The serum concentration of 1,25(OH)₂D₃ was undetectable and rose to levels similar to those in hemodialysis patients only after loading with much higher oral doses of 1-α-vitamin D₃ than those received by hemodialysis patients. Losses of both metabolites in peritoneal fluid were considerable, averaging approximately 6–8% of the plasma pool per day. These losses lead to low serum levels of these active vitamin D metabolites in CAPD patients, which may be an important factor in exacerbating renal osteodystrophy. Our results indicate the need for increased replacement doses of vitamin D metabolites in CAPD patients.