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The success of organ transplantation depends mostly on immunosuppressive treatments which depress the host vs allograft immune response. The drugs mostly used in the past, Azathioprine and Corticosteroids, act in a non specific way. Heterologous antilymphocyte sera are progressively replaced by monoclonal antibodies specific of lymphocyte subpopulations, such as OKT3 which is a highly potent immunosuppressive agent. Cyclosporin, a new original immunosuppressive agent which acts specifically on T lymphocytes, has considerably improved organ graft survival rates especially for heart and liver. Moreover, it allows reduction of the doses or corticosteroids given after transplantation an thus limits their side-effects, especially on statural growth. However, cyclosporin nephrotoxicity represents the major problem, at least in the long-term.

A study was done of 15 children and adolescents, aged 2.5 to 17.5 years, who were treated by continuous ambulatory peritoneal dialysis (CAPD) for 6 to 24 months. Plasma albumin concentration decreased from 34.4 +/- 4.8 g/liter at the onset of therapy to 31.3 +/- 5.3 g/liter after 19 to 24 months. Children less than 6 years old had lower albumin levels (29.4 +/- 1.7 g/liter) than did the older group (36.3 +/- 4.2 g/liter). The lower plasma albumin was related to peritoneal protein loss but not to protein intake. Plasma free amino acid concentrations were not significantly modified. No changes occurred in the oral glucose tolerance test during the course of CAPD. Plasma cholesterol and triglycerides were abnormally high for age, with a correlation seen between cholesterolemia and peritoneal protein loss.

Cyclomunine, a cyclic peptide extracted from Fusarium equisiti, inhibits responses of human lymphocytes to mitogens, soluble antigens and allogeneic cells and the proliferation of lymphoblastoid cell lines. Cyclomunine has little effect on small lymphocytes but acts rather on lymphoblasts. It has no effect on fibroblasts and myeloid cells. Cyclomunine partially inhibits the generation of suppressor cells induced by Con A and the generation of cytotoxic T cells in a mixed lymphocyte culture and totally inhibits the in vitro synthesis of Ig by PBL. Cyclomunine merits consideration as a new in vitro anti-lymphoblastic agent.

The effects of intravenous Nitrogen Mustard (NM), given with a total cumulative dose of 0.8 mg/kg BW, were studied in 60 children with idiopathic nephrotic syndrome (INS). Thirty patients were frequent relapser with corticosteroid dependence. In this group the actuarial remission rate was 43, 30 and 15% after 1, 2 and 3 years respectively. The relapse rate per year was decreased from 2.76 +/- 1.56 to 0.88 +/- 0.79 after NM. Ten of the 17 patients showing a partial response to steroids went into complete remission after NM but 6 of them relapsed. Of the 13 patients who did not respond to steroids only 3 went into remission for a short time. Vomiting and leukopenia were noted in one third of cases. The data indicate that NM may improve the course of corticosteroid dependent INS, being less effective in partial responders and probably without effect in non responders.

Purified alveolar lymphocytes obtained by bronchial lavage have been studied in 66 subjects: 8 normals, 24 sarcoidosis, 8 tuberculosis, 4 hypersensitivity pneumonitis, 6 collagen diseases and 16 miscellaneous. The following T and B lymphocyte markers have been used: E and EAC Rosettes, Surface membrane immunoglobulins, la antigen and human T lymphocyte antigens. The PHA or ConA responses of some blood and alveolar lymphocyte cultures have also been compared. The results emphasize: -- the tight correlation between the different marker techniques to T and B lymphocytes; -- the larger increases of T lymphocytes in active vs inactive sarcoidosis (p less than 0.001); -- the difference in T lymphocyte number in active vs inactive tuberculosis and in treated vs untreated miliary tuberculosis; -- the absence of alveolar lymphocyte increase in collagen diseases.

Six infants, 4.5 to 19 months old, whose creatinine clearance was less than 6 ml/min/1.73 m2 received, successively, three low-nitrogen diets. Diet A contained 9.3 g of human milk protein; and diet B, 4.2 g of human milk protein plus synthetic essential amino acids. Diet C was the same as B except that five essential amino acids were replaced by alpha-keto and hydroxy analogs. Serum urea decreased as the infants were transferred from diet A to diets B and C, and the serum urea/creatinine ratio decreased from diet A to diet B and from diet B to diet C. Urea appearance was 14.8 +/- 4.5, 9.1 +/- 4.3, and 6.9 +/- 1.7 mmoles/day, with diets A, B, and C, respectively. Weight gain was also lowest with diet C, as was the difference between nitrogen intake and urea nitrogen appearance, an indicator of nitrogen balance. Plasma free amino acids were not modified by diets A and B, but valine, leucine, and the plasma free essential amino acid pool decreased significantly with diet C.

The proliferative response of highly purified human peripheral blood or tonsil lymphocytes in the presence of soluble protein A (SpA) was investigated. SpA was shown to be a potent mitogen for T lymphocytes from peripheral blood or tonsils. Conversely, the non-T lymphocyte population from peripheral blood responded poorly to SpA, and SpA did not stimulate non-T lymphocytes from tonsils. The addition of mitomycin-treated T lymphocytes from peripheral blood enhanced the response of blood non-T lymphocytes to protein A. This effect was not found when non-T lymphocytes isolated from tonsils were cultured with mitomycin-treated T lymphocytes. The proliferative response of unseparated cells or purified lymphocyte populations was enhanced when adherent cells were added to the cultures. It is concluded that the soluble form of protein A activates mainly T lymphocytes and does not induce B lymphocyte proliferation.

During peritoneal dialysis, some blood proteins including bound substances, are lost via the peritoneal membrane. There is considerable interpatient variability in protein loss, but the factors responsible for this variation have not been elucidated. The aim of this study is to examine the factors which may influence the ability of the peritoneal membrane to restrict protein leakage and to evaluate the consequences of these losses.

Recent advances have shown that the pathogenesis of systemic lupus erythematosus involves a number of interacting factors. Renal involvement is frequent and is one of the leading factor in the prognosis. Renal histopathology is most important in the management of patients. Immunologic tests may help in the diagnosis and also in the evaluation of diseases activity. Although survival has improved dramatically with the use of corticosteroids, there is as yet no evidence that immunosuppressive drugs may be beneficial.

We studied the occurrence of diabetes mellitus in 6 children receiving corticosteroid therapy after renal transplantation. The first hyperglycemic episode occurred in all cases before the fortieth day of treatment but other episodes were observed thereafter. All children were glycosuric, without ketonuria. The diabetes has always been transient, and easily managed with insulin treatment and usual diabetic diet. A glucose tolerance test was performed 3 to 6 months after these episodes; glycemic response to glucose was abnormal in 2 of 6 children; in all cases, the insulin response to the glucose load was inadequate. In 2 children, the fasting blood glucose is still abnormal after a follow-up of 3 years. The other patients have recovered despite sustained corticotherapy. No specific background (genetics, HLA groups) or specific circumstances of treatment were identified. Therefore, we recommend to follow closely glycemia in children after renal transplantation, with a daily glycemic determination especially during the first 3 weeks.

Administration of a circulating thymic factor isolated from normal pig blood prevented the development of the exaggerated production of anti-polyvinyl pyrrolidone (PVP) antibody in young NZB mice. However, treatment was ineffective if initiated after the 4th week of life at a time when endogenous serum thymic factor (TF) normally disappears in these mice. These data suggest that circulating TF is necessary for the survival of short-lived suppressor T cells normally implicated in the regulation of the production of antibodies against PVP, a thymus-independent antigen. In older NZB mice, TF treatment increased paradoxically anti-PVP antibody production, which suggests that "amplifier" T cell activity could also be under TF influence.

The successful transplantation of a human malignant histiocytosis into nude mice allowed the examination of its atypical histiocytic cell proliferation. Histiocytic type cells were identified by positive reactions with acid phosphatase and non-specific esterase and with anti human DR or OKI1 antisera. Presence of OKT9 antigen and negative results obtained with most OKT antisera, rosettes, erythrophagocytosis and lysozyme corroborate the histiocytic immature state of the cells and preclude another type of tumor. All positive tests to prove a mature mononuclear phagocytic origin were attributable to the murine host cell reaction.

Idiopathic nephrotic syndrome, which is the most frequent glomerular disease in children, is defined by the combination of nephrotic syndrome and minimal change glomerular disease, with foot process fusion on electron microscopy. No immunoglobulin or complement fraction deposits are seen on immunofluorescent examination. However, in some cases, diffuse mesangial proliferation or focal and segmental glomerulosclerosis may be seen on light microscopy. In addition, immunofluorescent examination sometimes reveals mesangial immunoglobulin deposits found either in isolation or in association with C1q and/or C3 deposits. The most frequently found immunoglobulin is IgM, leading some authors to consider IgM nephropathy as a disease entity (1). IgA deposits have also been found in some patients (2, 3) as well as granular C3 deposits.

A prospective serologic study was conducted to determine the incidence of primary Cytomegalovirus (CMV) infection after a renal transplant and to evaluate the consequences on the graft. Serologic tests using the indirect hemagglutination technique with CMV-sensitized erythrocytes were performed serially over 6 years in 370 children initially awaiting renal transplantation. 211 children received a graft during the study period. Transplantation was followed by primary CMV infection in 48 (35.3%) of the 136 children with negative serologic tests at the time of the procedure. The percentage of graft failures is identical in the 75 children with positive tests before transplantation and in the 88 children with negative tests before and after transplantation (24 and 23% respectively). Conversely, only 6 (12.5%) graft failures were recorded among the 48 children who experienced primary CMV infection after transplantation. It can be speculated that these results are due to the immunosuppressive effect of CMV infection.

Eleven children (7 girls and 4 boys) 2 1/2 to 17 years and 8 months of age were treated with CAPD for periods ranging from 6 to 31 months. All children were treated with commercially available dialysate solutions containing lactate. Peritoneal ultrafiltration capacity (PUFC) decreased progressively in all children without accompanying decrease in peritoneal urea and creatinine clearances. Five children developed membrane failure with negative ultrafiltration. One episode of peritonitis occurred in one of these 5 children and in 4 of them only 1.5% glucose solutions had been used. After an initial period (ranging from 14 to 31 months) of CAPD, 2 children were treated with Intermittent Ambulatory Peritoneal Dialysis (IAPD) and two others with Intermittent Cycling Peritoneal Dialysis (ICPD). In these 4 children, PUFC increased within one month from -3.75 ml/kg/day to + 5 ml/kg/day. By providing a shorter dwell time, IAPD and ICPD may allow a reduction in net inward transport of glucose, the maintenance of osmolar gradient and preservation of ultrafiltration capacity. Furthermore, periods of rest may allow some recovery from the progressive deterioration of the peritoneum resulting from long-term irrigation of the peritoneal cavity. These results indicate that IAPD and CPD may be superior to CAPD to maintain the ultrafiltration capacity of the peritoneum.

This article represents an update of our experience with deliberate donor specific blood transfusions (D.S.T.) prior to living-related renal transplantation in children. Eighteen recipients with a negative cross- match to donor T and B cells entered the D.S.T. protocol without regard to the results of the mixed lymphocyte cultures and third party transfusion. The D.S.T. procedure involves the administration of fresh packed cells on 2 or 3 separate occasions at 4 weeks intervals. The potential recipient's sensitization is closely monitored against donor's isolated T and B lymphocytes and against a random panel. This immunological monitoring is done 10 to 20 days after each D.S.T. and just prior to grafting. A negative T and B cross-match at 37 degrees C is a pre-requisite for transplantation. Sixteen patients have been transplanted. All kidneys are functioning with follow-ups ranging from 6 to 48 months; 10 patients have normal renal function, 2 of them experienced reversible acute rejection and 6 have chronic rejection. The benefits derived from pretransplant D.S.T. in parental renal transplantation appear to be substantial, although the nature of the various immunological mechanisms remains unclear.