Frease Baker

Dietary Protein Manipulation in Experimental Nephrotic Syndrome

Evidence that glomerulosclerosis may be accelerated by high-protein diet and ameliorated by low-protein diet has led to debate concerning appropriate dietary recommendations in nephrotic syndrome. In this study, dietary protein was manipulated in a chronic, non-uraemic experimental model of nephrotic syndrome. Groups of 12 AS rats received 12, 24 or 48% protein diet after nephrotic syndrome was induced by adriamycin. Animals were sacrificed 8 weeks after change of diet when all were normotensive and none were uraemic. Animals on 24 and 48% maintained initial body weight and had persistent nephrosis. There was renal hypertrophy and histology showed tubular casts, focal tubulo-interstitial injury and glomerulosclerosis. Animals on 48% diet had more renal hypertrophy and worse histological damage but no differences in other parameters compared to 24% diet. On a 12% protein diet animals lost 15 +/- 3% of initial body weight (from 221 +/- 6 to 188 +/- 6 g; p less than 0.001). There was less proteinuria (p less than 0.0001), and lower serum cholesterol (p less than 0.0001) and triglyceride (p less than 0.01). Serum albumin was not different but total protein was lower than on 24 and 48% diet (p less than 0.01). Renal histological damage, although less severe than on 48% diet, did not differ from 24% diet. There was fatty infiltration of the liver. In view of the effects of low-protein diet in this model of nephrotic syndrome, dietary protein restriction should be applied with caution in human nephrotic syndrome.

Visceral glomerular epithelial cell DNA synthesis in experimental and human membranous disease.

Background: Membranous nephropathy (MN) is a ‘non-proliferative’ glomerulonephritis. However, visceral glomerular epithelial cell (vGEC) proliferating cell nuclear antigen staining and increased glomerular histone mRNA in passive Heymann nephritis (PHN), suggest that vGECs may enter the cell cycle and undergo DNA synthesis. We used in situ hybridisation for histone mRNA, an S-phase specific marker, to investigate this possibility and identify the cellular origin of histone mRNA in PHN and MN. Methods: PHN was induced in 16 Sprague-Dawley rats. There were 8 saline/serum controls. 12 animals were sacrificed on days 5 and 10. Renal biopsies from 10 proteinuric cases with MN and matched controls were studied. Results: Day-5 Heymann animals demonstrated more S-phase cells/glomerulus than controls (0.53 ± 0.09 vs. 0.195 ± 0.045; p < 0.01). Glomerular S-phase cells were also increased in patients compared to controls (0.24 ± 0.07 vs. 0.04 ± 0.018; p < 0.03). In both experimental and human MN, the peripheral location and morphology of glomerular histone mRNA-positive cells was typical of vGECs. Conclusion: The results in PHN indicate that vGECs recently injured with antibody and complement enter into the cell cycle and undergo DNA synthesis. The S-phase vGECs in MN may indicate the persistence of immune injury. Whether or not this process leads to cell replication is open to question.

Peritonitis rate: Traditional versus low calcium dialysate

The results of nonrandomized retrospective studies have suggested that low calcium dialysate (LCD; ionized calcium concentration 1.25 mmol/L) is associated with a higher peritonitis rate than traditional dialysate (TD; ionized calcium concentration 1.75 mmol/L). For this reason, 86 consecutive new continuous ambulatory peritoneal dialysis patients were randomized, in a single-blind fashion, to TD or LCD for 1 year. The results were analyzed on an intention-to-treat basis, no matter what fluid or what modality of treatment was being used at the end of the year. The two groups were well matched at baseline. At 1 year, 28 of 43 TD patients were still on continuous ambulatory peritoneal dialysis (one had a catheter changed due to peritonitis), four had a working transplant, one had recovered renal function, nine had died, and one had been transferred to hemodialysis because of peritonitis. Twenty-seven of 43 LCD patients were on continuous ambulatory peritoneal dialysis (one catheter change), nine had a working transplant, six had died, and one was on hemodialysis. There were 17 proven (33 possible) peritonitis episodes in 417 patient-months in the TD group. In the LCD group, there were 17 (35 possible) episodes in 432 patient-months. The proven peritonitis rate was 0.49 episodes/patient/yr in the TD group versus 0.48 episodes/patient/yr in the LCD group (P = NS). In conclusion, there is no controlled evidence that LCD is associated with a higher incidence of peritonitis than TD.