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Immunohistochemical studies of the peritoneal membrane and infiltrating cells in normal subjects and in patients on CAPD. We performed immunohistochemical studies on biopsies of the parietal peritoneal membrane of 33 subjects to investigate whether other cell populations, in addition to mononuclear cells free have in the dialysate, might participate in the defense of the peritoneum against microbial invasion during CAPD. Leukocytes were found to concentrate in two areas: a submesothelial layer composed of elongated macrophages displaying activation and maturation markers, and perivascular, less mature macrophages closely associated with T cells and HLA-DR, ICAM-1 and VCAM-1 expressing endothelial cells. Normal mesothelial cells were found to express constitutively the transferrin receptor and the adhesion molecules ICAM-1 and VCAM-1 but not ELAM-1. There were no major differences between normal and uremic subjects, while peritoneal dialysis patients exhibited minor derangements of the submesothelial layer and slight up-regulation of the expression of HLA-DR on endothelial cells. Peritonitis was associated with increased submesothelial cellularity and, particularly, perivascular leukocyte infiltration accompanied by increased expression of HLA-DR and adhesion molecules. Besides mononuclear cells free in the dialysate, this study demonstrates the existence of two additional peritoneal membrane leukocyte populations: submesothelial macrophages, and perivascular macrophages and T cells. It also suggests the existence of a fourth population of intracavitary leukocytes adherent to mesothelial cells. Studies are now necessary to evaluate their exact role in the host defence against peritonitis during CAPD.

Of 104 patients with idiopathic mesangiocapillary glomerulonephritis studied for at least two years, 69 patients had type I disease and 35 had type II. Forty-five patients were children, and 59 were adults. Type II mesangiocapillary glomerulonephritis was more common in children than in adults, but no other clinical feature distinguished the two types at onset. Complement studies revealed that patients with type II had lower serum C3 concentrations and more frequently showed C3-splitting activity (C3 nephritic factor) in the serum. Children had hypertension or a lowered glomerular filtration rate less frequently at onset than did adults, but children had a higher incidence of a hematuric onset; C3 nephritic factor was also more frequent in the children. During a follow-up period of two to 21 years (mean eight years), only seven patients (five with type I and two with type II) showed clinical remission, whereas 38 percent of patients with type I and 49 percent of patients with type II died or required dialysis; a further 23 percent of patients with type I and 16 percent of patients with type II had continuing disease and reduced glomerular filtration rate. Only the presence and persistence of a nephrotic syndrome in type I predicted renal failure. In both types, the presence of sclerosis or crescents in the initial renal biopsy specimen was associated with a poorer prognosis, but no other feature was of major prognostic value.

Activation of immunocompetent cells in the peritoneum of patients treated with CAPD. Chemiluminescence and flow cytometry, employing a number of monoclonal antibodies, was used to investigate activation of immunocompetent cells in the blood and peritoneum of patients treated with CAPD. Increased expression of HLA-DR and RFD7, both markers of macrophage maturation, was observed on peritoneal macrophages, 78% and 33.5% cells positive, when compared to blood monocytes, which were 46% and 5.3%, respectively (P < 0.001). Macrophage chemiluminescent response to opsonized zymosan was greater than that of circulating blood monocytes in CAPD patients, whereas the inverse was true for normal controls. Enhanced expression of IL-2 receptor and surface IgG by peritoneal macrophages were 24.9% and 65.3% cells positive compared with monocytes, 5.7% and 12.3% (P < 0.01), and also suggests their activation. There was a marked increase in the HLA-DR expression by peritoneal lymphocytes from CAPD patients (32% cells positive) compared with those from CAPD blood (13.8%), normal blood (11.3%) and normal peritoneal fluid (14.5%), P < 0.001. This was partially accounted for by increased numbers of B cells (18%) and activated T cells bearing HLA-DR. TFR and IL-2 receptor expression by CAPD peritoneal lymphocytes was similar to that of blood lymphocytes, implying the lack of an organized immune response within the peritoneum. Taken together, these results suggest that peritoneal macrophages from CAPD treated patients have features of maturation and activation, while changes in the lymphocyte populations are compatable with the actions of IL-1, indicating activity of the cellular immune system within the peritoneum.

Transplantation in mesangiocapillary glomerulonephritis with intramembranous dense "deposits": Recurrence of disease. Six patients with mesangiocapillary glomerulonephritis and intramembranous dense "deposits" developed terminal renal failure and were transplanted, three from living and three from cadaver donors. Eight renal biopsy specimens were obtained from five of the grafts, from 1 to 26 months following transplantation. All six biopsy specimens taken later than seven months following the graft showed recurrence of dense intramembranous "deposits" in the basement membranes of glomeruli, and of Bowman's capsule and tubular basement membrane in five. Recurrence of "deposits" was associated with deposition of C3 on immunofluorescent study in all but one specimen; in addition, lgM was found in two specimens, but lgG and early complement components were absent. Only two patients, however, showed glomerular proliferation associated with profuse proteinuria. In the other subjects the recurrence of the "deposit" was not associated with clinical findings. Graft loss, which occurred in two patients, was predominantly from rejection. Transplantation dans la glomerulopathie a depots denses intra-membraneux: Recidive de la maladie. Six malades atteints de glomerulopathie a depots denses intra-membraneux ont atteint le stade d'insuffisance renale terminale et ont ete transplantes. Trois d'entre eux ont recu un rein de donneur vivant et les trois autres un rein de cadavre. Huit biopsies renales ont ete realisees sur cinq de ces transplants un a trente-six mois apres la transplantation. Les six biopsies prelevees apres le septieme mois de la transplantation montrent toutes la recidive des depots denses intra-membraneux dans les glomerules et cinq d'entre elles montrent aussi ces depots dans la capsule de Bowman et la membrane basale tubulaire. La recidive des depots est associee a la presence de C3, revelee par l'etude en immunofluorescence, dans toutes les biopsies sauf une. De plus, de l'IgM a ete trouvee dans deux biopsies mais l'IgG et les facteurs precoces du complement sont absents. Deux malades seulement ont une proliferation glomerulaire associee a une proteinurie importante. Chez les autres, la recidive des depots n'est pas contemporaine de manifestations cliniques. La destruction du greffon, qui est survenue chez deux malades, a ete essentiellement le fait du rejet.

Plasma amino acids in children and adolescents on hemodialysis. Fasting plasma amino acid concentrations were measured in 16 children on regular hemodialysis for renal failure. Reductions compared to normal were found in valine, leucine, isoleucine, lysine, histidine, tyrosine, and serine; and increases were found in glycine, citrulline, proline, and 1- and 3-methylhistidine. Acute reductions in amino acid concentrations occurred in response to i.v. glucose, similar to those reported in normal adults, but plasma alanine, which was raised only in those with poor glucose tolerance, fell to normal and did not vary in those with normal glucose tolerance. No correlations were found with growth, but the plasma glycine concentration was highest in those patients with poorest energy intakes. Plasma alanine concentrations correlated with raised triglyceride concentrations. It is suggested that many of the abnormalities are due to the excessive utilization of protein for energy because of impaired availability of conventional energy sources in uremia. Acides amines du plasma chez les enfants et adolescents en hemodialyse. Les concentrations des acides amines du plasma ont ete mesurees a jeun chez 16 enfants en hemodialyse iterative pour insuffisance renale. Par comparaison avec des sujets normaux, des diminutions ont ete constatees pour valine, leucine, isoleucine, lysine, histidine, tyrosine et serine et des augmentations pour glycine, citrulline, proline et 1- et 3–methylhistidine. Des dimunutions aigues des concentrations d'acides amines ont ete observees en response a l'administration intraveineuse de glucose, semblable a celles rapportees chez les adultes normaux, a l'exception de l'alanine dont la concentration n' a pas ete modifiee chez les sujets ayant une tolerance au glucose normale et a ete abaissee a des valeurs normales, a partir d'une valeur elevee, chez les sujets ayant une tolerance au glucose diminuee. Aucune correlation n' a ete observee avec la croissance mais la concentration plasmatique de glycine est la plus elevee chez les malades dont l'apport energetique est le plus faible. Les concentrations plas matiques d' alanine sont correlees avec l'augmentation de la concentration des triglycerides. II est suggere que beaucoup de ces anomalies sont liees a l'utilisation excessive des proteines comme source d'energie en raison de la diminution des sources d'energie conventionnelles an cours de l'uremie.

15 patients with severe hypercatabolic renal failure underwent peritoneal dialysis. Illustrative data from 2 patients are presented in detail in support of the conclusion that uraemia in such patients can be controlled by means of peritoneal dialysis and that haemodialysis need only be resorted to when conditions in the abdomen do not permit peritoneal dialysis. Notwithstanding good control of uraemia, 75% in this group died. This was due to the precipitating cause and not to the renal failure; in three-quarters of the patients the renal failure arose after cardiovascular surgery or severe burns.

Six patients with glomerulonephritis associated with systemic lupus erythematosus were treated with cyclophosphamide for an average of 9 months to date. Four of the patients showed some resistance to treatment with corticosteroids; all were cushingoid, and three had severe hypertension. Renal biopsies were done in all six and showed lupus glomerulonephritis in all, active in three. Three patients showed considerable improvement, proteinuria disappearing in two and becoming trivial in the third. The nephrotic syndrome present in all three remitted, and two showed an increase in glomerular filtration-rate. The condition of another two patients remained unchanged, although reduction of corticosteroids and disappearance of toxic signs was achieved in both with continuing control of the disease. One patient, anuric when treatment was started with haemodialysis, heparin, prednisolone, and cyclophosphamide, had an active necrotising renal lesion which was uncontrolled and resulted in death. It is concluded that if a controlled trial of cytostatic agents is set up to evaluate their usefulness in patients with the nephritis of systemic lupus, then cyclophosphamide should be one of the drugs considered for examination.

In five previously healthy women haemolytic uraemic syndrome with acute renal failure developed after taking oral contraceptives or other drugs containing œstrogens. These cases comprised five of the nine females admitted to two medical renal units with this uncommon condition over a 3-year period. There was a striking, virtually isolated depletion of platelets associated with the development of the thrombotic microangiopathy in two patients. It is suggested that this platelet abnormality may predispose women taking oral contraceptives to thrombosis in the microvasculature.