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Donation from alive people has been growing strongly in the recent years, thanks to the advance in the field of organ transplantation and its success as a treatment to procure quality-adjusted life years for many patients with end–stage diseases. The choice of transplantation from a living donor (LD) offers some advantages compared to that for a deceased donor. However, it also carries disadvantages related to donor risks in terms of health and safety, and there are several controversial ethical aspects to be taken into account. There is no specific pronouncement of the European Union in relation to standards to quality and safety for the living donor process, and there is a great heterogeneity among European Countries legislation, ethical concern, and protection systems and donor´s data registries on the topic. The EULID project aims to establish European common standard framework regarding living donor issues to guarantee their health and safety thorough common practices and regulation.

SUMMARY The mixed leukocyte culture (MLC) of peripheral blood lymphocytes (PBLs) from two prospective kidney transplant recipients and their respective donors, produced a primed cell population that functioned as suppressors. The primed cells suppressed the primary and secondary MLC when added as third components, without demonstrable cytotoxic cells. Suppressor cells were derived from the MLCs of related pairs that were genotyped to be: (1) serologically defined (SD) identical and lymphocyte-defined (LD) nonidentical, and (2) HLA (total MHC) identical. Primed cells derived from MLC of unrelated HLA nonidentical subjects also showed similar effects. Two general patterns of inhibition were observed: a marked specific suppression of the autologous responding cells and, to a lesser degree, nonspecific suppression. The T cell fraction derived from the primed suppressor population was suppressive, the cells with B cell characteristics were not suppressive. The suppressive effect of cells generated in MLC was serially monitored after kidney transplantation. The suppressive activity of the primed cells was absent in the early postoperative period (4 weeks), perhaps because of high dose immunosuppression, but later in the course suppression was evident again (2 to 5 months). Manipulation of this T suppressor cell population may prove to be of value in enhancing graft acceptance.

A method of autotransplantation of duct ligated pancreatic segments has been described. In untreated animals autotransplants underwent significant destruction within 2 weeks after transplantation due to inflammation following ligation of the duct. Insulin production by these grafts was significantly decreased. Radiation and Trasylol failed to prevent these inflammatory and fibrotic changes. Steroids had a protective effect on these grafts, preserving both their morphology and function. Insulin production was preserved and continued exocrine function resulted in accumulation of large volumes of peripancreatic fluid. When glucagon was added to the steroid treatment there was virtually total inhibition of the exocrine function and negligible peripancreatic fluid accumulation, but insulin production continued and the grafts appeared normal morphologically. The implications of the use of high dose steroid therapy and glucagon to prevent the acute damage to duct ligated pancreatic autografts are that major obstacles to the use of this method in allografts can now be removed.

A modified collagenase digestion method is described for the isolation of large numbers of islets from the canine pancreas ( 3500 islets/g). The islets isolated by this technique remained viable and released insulin in response to secretagogues after one week of maintenance in tissue culture. Islets isolated from a single donor pancreas were re-implanted into the spleen of the same animal made diabetic by subtotal pancreatectomy and two injections of streptozotocin. Hyperglycemia was corrected in two dogs and decreased in a third dog followed for 30 days. The islet isolation method described, therefore, provides a sufficiently large yield of viable islets from one donor pancreas to correct or improve diabetes in a recipient animal. © 1982. 31 2 184 187

Because successful allotransplantation of islets of Langerhans isolated by collagenase digestion has been difficult in many animal species, we asked whether isolated islet preparations might have tissue specific determinants conferring amplified immunogenicity in vitro. Lymphocyte proliferative responses ([(3)H]thymidine uptake) were studied in beagle dogs in mixed culture combinations of lymphocyte vs. lymphocyte (MLC) and lymphocyte vs. islet (MLIC). In five MLC responder and five nonresponder pairs, peripheral blood lymphocytes of dogs A and B were used as responding cells, and dog B x-irradiated lymphocytes (Bx), x-irradiated (or nonirradiated) islets (BI), or hepatic cells (BH) were used as stimulating cells in primary and secondary reactions. For the secondary reactions, A + Bx, A + BI, or B + BI were incubated for 9 d (A'B, A'BI, B'BI, respectively) before addition of new stimulating cells. The results showed that islets were autostimulatory, eliciting a tissue-specific lymphoproliferative response in a primary MLIC. Thus, B + BI reactivity was evident at 3,5, and 7 d in primary culture, whereas collagenase-digested liver cells, or lymphocytes obtained from collagenase-digested lymph nodes did not stimulate autologous lymphocytes. A separate reactivity was observed in the allogeneic A + BI combination in MLC responder pairs, and the peak response of A + BI at 9 d was markedly greater than that of B + BI, suggesting the presence of major histocompatibility complex lymphocyte-defined locus determinants in the islet preparations, in addition to islet-specific determinants. A secondary reaction was observed if lymphocytes were primed with islets and challenged with islets (A'BI + BI or B'BI + BI), but not if they were challenged with lymphocytes (A'BI + Bx, B'BI + Bx) or hepatic cells (A'BI + BH, B'BI + AH). Furthermore, priming of lymphocytes with autologous islets (B'BI) led to exclusion of any reactivity against allogeneic lymphocytes, i.e., B'BI suppressed A + Bx, and B'BI also markedly suppressed phytohemagglutinin-stimulated lymphoproliferative responses. Experiments were performed that excluded the possibility that the insulin levels present in the MLIC, the presence of passenger lymphocytes in the islets, or the maintenance of islets in tissue culture for 1-7 d affected the observations. These results provide evidence for the existence of alloantigens as well as tissue-specific antigens on collagenase-isolated islets of Langerhans.

The mixed lymphocyte kidney culture (MLKC) in humans has been studied in normal and abnormal clinical conditions. Human renal cortical cells were extracted by collagenase treatment from the kidneys of "normal" heart-beating cadaver organ donors (n = 13), patients with end-stage renal disease (ESRD) at pretransplant bilateral nephrectomy and splenectomy (n = 13), and from irreversibly rejected renal allografts at the time of graft nephrectomy (n = 5). Proliferation of peripheral blood T lymphocytes of 2-DR-mismatched volunteers occurred in response to kidney cortical cells extracted from each of the 3 donor categories in a reaction termed the allogeneic mixed lymphocyte kidney culture. Additionally, splenic T cells from cadavers and patients with ESRD were seen to react to their autologous kidney cells. The renal cortical cells extracted from ESRD kidneys were more stimulatory in the allogeneic and autologous MLKC responses than those extracted from "normal" cadaver kidneys even when the ESRD kidneys were 99% depleted of passenger T and B lymphocytes by treatment with monoclonal antibodies T11 and B1. In order to help define the antigens operative in the MLKC, we pretreated stimulating lymphocytes and renal cortical cells with anti-class II monoclonal antibodies. The allogeneic mixed lymphocyte reaction and MLKC were inhibited ca. 80% and 30%, respectively. The autologous MLKC was unaffected by this treatment. To further support that tissue-specific immune mechanisms were operative in the reaction, experiments were performed with infiltrating lymphocytes isolated from the ESRD kidneys, which were seen to generate a proliferative response when stimulated with autologous cortical cells. However, the response of these same infiltrating lymphocytes when stimulated with allogeneic lymphocytes (MLR), was markedly weaker than the response of the patients' autologous spleen cells. In addition, two kidneys were obtained at rejection from recipients that had received grafts from HLA-MLR-identical sibling donors. A lymphoproliferative reaction of recipient peripheral blood T lymphocytes occurred in response to (donor) renal cortical cells, but not to donor peripheral blood lymphocytes. In contrast, infiltrating (recipient) kidney lymphocytes responded to the kidney cortical cells and to donor peripheral blood lymphocytes. Moreover, peripheral blood T lymphocytes of the HLA-identical donor responded to his own kidney cortical cells, which were isolated from the rejected recipient kidney, and did not respond to recipient peripheral blood lymphocytes. Finally, a "normal" cadaveric kidney was fortuitously available at the same time that a rejected transplant (cadaver)

Three cases of pulmonary aspergillosis in a “high risk” population of renal transplant recipients are presented. The source of infection was traced to the forced air exhaust system of the Transplantation Unit. Early definitive diagnosis of the infection was very important for effective management. Immunologic monitoring was demonstrated to be instrumental in indicating the early presence of infection, and as a guideline to reduced immunosuppression during therapy. Bronchoscopy with brushings and endobronchial cavitary biopsy were valuable methods for obtaining the infected tissue. Amphotericin B was effective when therapy was started early. Adequate levels of the drug were obtained by varying the dose and frequency of administration according to serum inhibitory titers. Control of infection was aided by immunologic monitoring at regular intervals.

The functional and morphologic characteristics of free-draining, pancreatic segmental autografts (FDPS) were studied in 8 beagle dogs that had survived longer than 4 yr. After pancreatectomy, animals received FDPS autografts of the left pancreatic limb, representing approximately one-third of the total pancreas with iliac vessel anastamoses. The grafted recipients were given pancreatic enzyme supplements (Viokase). After transplantation (tx), all 8 animals sustained fasting euglycemia with no evidence of microvascular complications. After 4 yr, IVGTT revealed K-values (%/min) that were not significantly different from age-matched controls (2.9 +/- 0.5 versus 3.7 +/- 0.6, P greater than 0.05). Mean fasting serum insulin levels were significantly greater in the tx animals (49 +/- 5 microU/ml versus 12.2 microU/ml, P less than 0.001), although the incremental response to i.v. glucose (0.5 g/kg) was less than in controls (P less than 0.05). Mean fasting plasma C-peptide levels (0.09 +/- 0.01 pmol/ml versus 0.21 +/- 0.5 pmol/ml) and peak C-peptide responses to i.v. glucose were both significantly less than in controls. Sequential pancreatic biopsies up to 2.5 yr post-tx showed atrophy of the exocrine pancreas with coalescence of islets and mild fibrosis that did not progress with time. Immunoperoxidase stains confirmed the presence of insulin, glucagon, and somatostatin within nests of islet cells. Four years after transplantation of FDPS autografts in pancreatectomized dogs, excellent function is retained. The consequences of peripheral hyperinsulinemia remain to be determined.

The Einstein Group in the 1960’s had an abstract showing that the rate of increase of GFR in infants after birth was influenced by the level of protein intake. What the study did not do was look at the parallel effect of increases of sodium and other nutrients that go along with the protein. In the human studies, have people controlled sodium intake, mineral content intake, and so on?

Prolonged survival of the vascularized free-draining intraperitoneal pancreatic segmental allografts (FDPS) has been observed previously in immunosuppressed beagle littermates matched for low mixed lymphocyte culture (MLC) reactivity. When rejection (hyperglycemia) did occur, it was abrupt, unpredictable, and irreversible. This contrasts with renal allograft rejection in which elevations of serum creatinine are reversible with increased immunosuppression. In the present experiments, low MLC-reactive littermate pairs underwent simultaneous transplantation of kidney and FDPS allografts from the same donor. Increases in serum creatinine from 0.5 mg/dl to 1.5 mg/dl (renal rejection) occurred 4 to 5 days after transplantation (mean = 20.5 ± 4.1) and preceded the onset of hyperglycemia by 6 to 22 days (mean = 10.6 ± 4.6) in nonimmunosuppressed animals. At the onset of kidney rejection but before hyperglycemia developed, renal allograft biopsies revealed generalized mononuclear infiltration, while FDPS biopsies showed diffuse interstitial infiltration, but islets of Langerhans appeared to be spared. Treatment intervention with azathioprine and corticosteroids at the time of creatinine elevation prevented the onset of hyperglycemia from 46 to >260 days in four of nine animals. Biopsies after 2 weeks of therapy showed resolution of the lymphoid infiltrates in the kidney and limitation of infiltrates to perivascular areas in the FDPS allografts. Immunological monitoring of peripheral blood lymphocyte function demonstrated the development of positive in vitro cell-mediated lymphocytoxicity shortly before the onset of hyperglycemia but only after creatinine elevation was well established and biopsies revealed evidence of rejection in both the renal and FDPS allografts. © 1982 by The Williams and Wilkins Co. 33 6 606 612

Ten young subjects (mean age 32.3 yr) and 14 elderly subjects (mean age 71.0 yr) were studied before and after acute hypocalcemia induced by an infusion of neutral phosphate. No difference was observed in the ability of the 2 groups to restore to normal serum calcium at 24 hr after the infusion. Elderly patients responded to the infusion with an increase in fractional urinary excretion of phosphate (Cp/Ccr×100) from 11.6 ± 1.61 before the infusion to 20.4±3.50 (mean ±sem) after the infusion. The corresponding values in the young subjects were 8.4 ±1.23 before the infusion and 10.9 ±1.87 (mean ±sem) after the infusion. The difference between the means of the phosphaturic response in the elderly and that in the younger subjects was statistically significant (p less than 0.05). The cause of the exaggerated phosphaturic response to hypocalcemia in the elderly has not been elucidated. These findings suggest that the age of the test subject should be considered in the evaluation of parathyroid function...

Renal scintigraphy with [99mTc]diethylenetriaminepentaacetic acid (DTPA) and/or sodium-iodine-131-o-iodohippurate (HIP) was performed before and after an oral dose of captopril (50 mg) in 18 patients with renovascular hypertension (RVH) due to renal artery stenosis (RAS) and 18 controls. In every patient with RVH, captopril induced, enhanced or sustained abnormal findings on HIP scintigraphy depending on the degree of RAS. With DTPA scintigraphy, renal function decreased after captopril in ten kidneys with RVH-related RAS and adequate baseline renal function, but this phenomenon was not evident in 11 kidneys with RVH and poor renal function. Captopril did not influence HIP or DTPA studies of kidneys with patent renal arteries (patients after successful renal angioplasty, patients with essential hypertension, contralateral kidneys of patients with unilateral RVH) or ipsilateral kidneys with mild and subcritical (less than 60%) RAS in patients without hypertension and/or normal renal vein renin activity. When HIP and DTPA scintigraphy were compared in the same patients, HIP demonstrated greater sensitivity and specificity than DTPA, particularly in patients with poor renal function. HIP scintigraphy before and after a single dose of captopril may provide a rapid sensitive and minimally invasive test for screening patients with hypertension.

Three cases of bowel obstruction due to internal hernia caused by entrapment of bowel or omentum through a defect in the peritoneum covering the transplanted kidney are described. All three patients survived due to early surgical intervention and reduction of the hernia and/or resection of necrotic bowel or omentum. In view of the high mortality of peritonitis in transplant patients, early surgical treatment is indicated in all cases of intestinal obstruction to avoid the sequelae of bowel infarction. This “paratransplant” hernia represents the newest type of internal hernia described.

Hyperlipidemia (HL) with increase in triglycerides (TG) is frequently seen in uremic patients before TX. In order to assess the lipid abnormalities following renal TX, 22 patient (15 females) x age 17 years (range 5-21), with a functioning renal allograft (serum creatinine x 1.13 mg/dl, range 0.7-2.6) were studied at x 26 months (range 2-55) after renal TX. Serum total cholesterol (TC), TG, and lipoproteins VLDL, LDL and HDL were determined and compared to normal age and sex matched controls. Results (x mg/dl ± SD) are shown in table (†p 95 percentile in 68% and 32% of the patients respectively. A significant correlation between HL and daily Prednisolone dose was found (r=0.55; p