Peritoneal catheters and exit-site practices: toward optimum peritoneal access.

The peritoneal catheter is the CAPD patient's lifeline. Advances in catheter knowledge have made it possible to access the peritoneal cavity safely and maintain access over an extended period of time. Infection at the exit site remains a major problem, a solution for which is being extensively researched. The successful outcome of a catheter in an individual depends on meticulous care and adherence to sound principles of catheter insertion and management. The guidelines provided in this publication represent the consensus based on the extensive experience of several major centers worldwide.

Renal scans in pregnant transplant patients.

This study demonstrates the normal technetium-99m diethylenetriaminepentaacetic acid ([99mTc]DTPA) renal scan in pregnant patients with transplanted kidneys. Five pregnant renal transplant patients had seven [99mTc]DTPA renal studies to assess allograft perfusion and function. All scans showed the uteroplacental complex. The bladder was always compressed and distorted. The transplanted kidney was frequently rotated to a more vertical position. In all patients allograft flow and function were maintained. There was calyceal retention on all studies and ureteral retention activity in three of five patients. Using the MIRD formalism, the total radiation absorbed dose to the fetus was calculated to be 271 mrad. This radiation exposure is well within NRCP limits for the fetus of radiation workers and an acceptable low risk in the management of these high risk obstetric patients.

Leukotrienes, thromboxane, and platelet activating factor in organ transplantation.

The antirejection eicosanoids--PGE2, (PGD2), and PGI2--have an attenuating effect on T-cell proliferation by inhibition of IL-1, IL-2, and class II antigen expression on macrophages, and the prorejection eicosanoids--TXA2, LTB4, LTC4, and LTD4--enhance T-cell proliferation. LTB4 stimulates IL-1 and IL-2 formation and expression of IL-2 receptor. The mechanism of enhancement of T-cell proliferation by TXA2 has not been demonstrated. LTC4 and LTD4 promote gamma-interferon release and can replace IL-2 as a stimulator of gamma-interferon. PAF at high concentrations inhibits lymphocyte proliferation. The eicosanoids interfere with the same mechanisms as CsA and corticosteroids on T-cell clonal expansion. In experimental organ transplantation, corticosteroids can be replaced by compounds preventing the formation or expression of the prorejection eicosanoids or analogs of antirejection eicosanoids as well as by PAF antagonists. In addition, these drugs exert synergistic effect with CsA and azathioprine.

Early immunological prediction of renal allograft rejection.

Reliable predictors of impending renal allograft rejection would be valuable for better patient management. To date, no available test has been shown to be consistently predictive and results have often been conflicting. We evaluated an effector of cell-mediated immunity, antibody-dependent cell-mediated cytotoxicity (ADCC) as well as the response of these cells to different biological response modifiers (BRM) in patients following renal allograft transplantation. The in vitro test used assayed monocytes as ADCC effector cells against antibody-sensitized chicken red blood cells. The effects of BRM were studied by preincubating the monocytes with lymphoblastoid IFN, recombinant alpha 2-interferon or gamma-interferon. A follow-up study was performed on 47 patients with end-stage renal disease treated with renal allograft transplantation. ADCC activity and its response to BRM were assayed prior to transplantation, 2, 4, and 9 weeks post transplantation. In the case of rejection, ADCC was then studied prior to initiation of antirejection therapy and for 2 months following treatment of rejection episode. We noted that in patients with stable grafts, the ADCC activity as well as its response to BRM declined gradually during the first 2 weeks post grafting and remained decreased up to 3 months after transplantation. In contrast, in recipients who experienced rejection episodes there was a sustained and significant increase in ADCC response to BRM during the first 3 weeks post grafting. By the time the diagnosis of rejection had been established the baseline ADCC activity had also increased. Following treatment and stabilization of the graft, ADCC activity and its response to BRM was decreased, similar to that in patients with stable grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell-mediated immunity and biological response modifiers in insulin-dependent diabetes mellitus complicated by end-stage renal disease.

Previous studies have shown several immunoregulatory abnormalities in insulin-dependent diabetes mellitus (IDDM). In this report we compared peripheral blood mononuclear cells (PBMC) from patients with IDDM complicated by end-stage renal disease (ESRD) to those from normal subjects and from patients with ESRD of different etiologies for their: natural killer (NK) and antibody-dependent cell-mediated cytotoxic (ADCC) activities; modulation of NK and ADCC activities by biological response modifiers (BRM) including purified human lymphoblastoid interferon, human recombinant alpha-2 interferon, human gamma interferon and human recombinant interleukin 2; proliferative response of T and B lymphocytes to concanavalin A (Con A), phytohemagglutinin and pokeweed mitogen, and ability to produce T-cell growth factor (interleukin 2; IL-2). PBMC of diabetic patients demonstrated significantly lower NK activity than normal and ESRD subjects. Upon treatment with BRM, NK activity was augmented and achieved normal levels. ADCC activity was not different from that of normal controls and exhibited similar increases when stimulated by BRM. The proliferative responses to Con A, phytohemagglutinin and pokeweed mitogen as well as IL-2 production in response to Con A stimulation were significantly lower in the IDDM group. Our results indicated that NK cells from patients with IDDM can respond to IL-2 with enhanced cytotoxicity, and, because activation of resting T cells by mitogenic stimuli depends on the production of IL-2 as well as the appearance of a receptor for IL-2, our finding of low levels of in vitro IL-2 production by PBMC from patients with IDDM may explain the depressed NK activity and the observed poor response to T-cell mitogens.

Immunological monitoring and early prediction of rejection in renal allograft recipients.

Graft rejection remains the major problem complicating renal allograft transplantation. A reliable posttransplant predictor of impending rejection will be valuable to help maintain better graft function. We monitored 47 patients with end-stage renal disease treated by renal allograft starting 1 day pretransplantation and continuing for up to 90 days postgrafting. Peripheral blood mononuclear cells (PBMC) from both patients and 71 healthy subjects were compared for: (1) DNA synthesis in T and B lymphocytes in response to mitogens; (2) interleukin-2 (IL-2) production; (3) natural killer (NK) and antibody-dependent cell-mediated cytotoxic (ADCC) activities; (4) induced augmentation of NK and ADCC activities by the biological response modifiers (BRM), lymphoblastoid interferon, recombinant alpha-2-interferon, gamma-interferon and recombinant IL-2. During the 2 weeks preceding rejection we found lower than normal levels of IL-2 production (p less than 0.0005) and DNA synthesis (p less than 0.01) in concanavalin A-stimulated PBMC. IL-2 yield reached its lowest level on the day of rejection and increased sharply the following week after antirejection therapy was started. Mitogen-stimulated DNA synthesis rose in parallel with increasing levels of IL-2 production. Both NK and ADCC activities increased during rejection (p less than 0.05). The ADCC response to BRM activation measured during the first 2 weeks postgrafting was found to correlate with the stability of the graft. Recipients whose graft function remained stable had a minimal ADCC response to BRM.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary artery thrombosis and elevated urine immunoreactive thromboxane B2.

Immunoreactive thromboxane B2 (i-TXB2) was measured by radio-immunoassay (RIA) in urines collected over eight hours on the day of admission in 25 patients who were admitted with the diagnosis of myocardial infarction. In 16 of the patients myocardial infarction was confirmed by ECG and plasma enzymes. Another patient presented with pulmonary embolism and the remaining eight patients had angina pectoris. A further eight hour urine collection was obtained 24 hours later from eleven of the sixteen patients with myocardial infarction. In these eleven patients myocardial infarction was associated with five fold higher urine i-TXB2 (2.72 +/- 0.48 ng/ml) at the day of admission when compared to patients admitted under the same diagnosis but found to have angina only (0.51 +/- 0.08 ng/ml, p less than 0.001). In patients with myocardial infarction the urine i-TXB2 values were reduced 24 hours later (1.58 +/- 0.27 ng/ml, p less than 0.01). One patient was followed with urine i-TXB2 from three days prior to diagnosis of myocardial infarction and to one day prior to a second infarction. In this patient i-TXB2 was highest three days prior to infarction. We conclude that this early elevation of urine i-TXB2 three days prior to diagnosis of infarction and the increased i-TXB2 in patients with myocardial infarction when compared to patients with angina suggest thromboxane is probably released from activated platelets prior to infarction. We suggest that urine i-TXB2 may be of value in the differential diagnosis between myocardial infarction and angina.

Eicosanoids, gamma-interferon and inflammatory cells in kidney transplant patients.

Urinary i-TXB2 of renal transplant patients was found to be unaffected by CsA administration. Thus CsA treatment is unlikely to contribute to false positive values in this diagnostic indicator of rejection. It is possible that CsA treatment may suppress the peak i-TXB2 attending rejection but this does not seem to be the case. Studies on rats with cardiac allografts show CsA not to attenuate the rejection i-TXB2 peak (8). The causal role of thromboxane in transplant rejection was further amplified by experimental studies in rats where the cardiac allograft was protected by thromboxane synthase inhibitors and receptor antagonists. The inflammatory cell infiltrate of clinical renal allografts correlated with urine i-TXB2. These data strengthens the diagnostic value of urine i-TXB2 as a non invasive indicator of transplant rejection. Serum gamma-interferon was studied in nine patients and detected for 14 and 10 consecutive days, respectively in 2 patients. Three of the remaining patients had mild rejection episodes. Of the two patients one rejected the kidney and the other had CMV infection. No correlation was found between gamma-interferon and urine-TXB2. Thus elevated serum gamma-interferon does not interfere with urine i-TXB2.

Single-donor cold storage versus machine perfusion in cadaver kidney preservation.

Preservation of thirty-eight consecutive renal allograft donors was studied in a prospective, randomized protocol. Procurement was in-situ cooled, en-bloc nephrectomy accomplished by a single program. Nine pairs were deleted because of nonutilization of one kidney or change in mode of preservation. The remaining twenty nine pairs were implanted by twenty two institutions through usual organ sharing policies. Results showed that posttransplantation dialysis was required in 17% of machine-perfused and 63% of cold-stored allografts, which reached statistical significance (P less than 0.01). This increased number of dialyses in patients receiving the cold-stored kidneys offsets cost savings achieved through transporting cold stored allografts. This study shows machine-perfused renal allografts to be superior to paired, cold-stored allografts when analyzed with respect to early graft function.