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Biomedical subjects

Matthew J McIntosh

Publications and source records attributed to Matthew J McIntosh.

3 recordsLinked to original sources

The influence of immunomodulatory diets on transplant success and complications.

BACKGROUND: Animal studies have shown that dietary supplementation with arginine and lipids containing the omega-3 and omega-9 fatty acids prolong allograft survival in animals receiving a short course of low-dose cyclosporine. They also reduce cardiovascular complications and infections in humans. METHODS: Adult renal transplant patients receiving standard immunosuppression were stratified according to gender, diabetic state, donor source (LD or CD), and first versus repeat transplant, and randomized to receive or not receive supplemental arginine and canola oil (containing both omega-3 and omega-9 fatty acids) twice daily. Patients were followed for a minimum of 3 years. RESULTS: Seventy-six patients were randomized to the supplement group (S) and 71 patients to the control group (C). Intent-to-treat analysis revealed that S patients had fewer post-30 day first rejection episodes (5.4%) when compared with the C group (23.7%) (P=0.01) and fewer post-30 day episodes of calcineurin inhibitor (CNI) drug toxicity (9.2% vs. 35.3%, P=0.003). S patients developed new onset diabetes mellitus (NODM) less frequently by 3 years (2.3% vs. 14.5%, P=0.04), had fewer cardiac events (5.0% vs. 17.1%, P=0.05), and fewer episodes of sepsis (6.5% vs. 18.7%, P=0.05). CONCLUSIONS: Dietary supplementation with L-arginine and canola oil is a safe, inexpensive, and unique treatment, which is associated with decreased rejection rates and CNI toxicity after the first month in renal transplant patients. Due to reductions in NODM and cardiac events, long-term benefits for patient survival may be particularly important.

Body Weight↗

Pretransplant recipient cytomegalovirus seropositivity and hemodialysis are associated with decreased renal allograft and patient survival.

BACKGROUND: Pretransplant systemic inflammation has been associated with decreased renal allograft survival, and infectious agents such as cytomegalovirus (CMV) may play a role. We hypothesized that pretransplant CMV seropositivity is a risk factor for decreased patient and allograft survival after cadaveric renal transplantation and that other factors believed to modulate systemic inflammation, such as dialysis modality, might act synergistically with CMV to decrease patient and allograft survival. METHODS: The United Network for Organ Sharing database was reviewed to identify all patients undergoing cadaveric renal transplantation in the United States from 1988 to 1997. Outcomes for CMV seropositive and seronegative recipients of organs from CMV seronegative donors were analyzed. Subgroup analysis was performed to identify any synergistic influence on outcome between CMV serostatus and known determinants of risk, including degree of human leukocyte antigen mismatch, pretransplant dialysis, and cold ischemia time. RESULTS: Of 29,875 patients who underwent transplantation, 12,239 were CMV seronegative and 17,636 were CMV seropositive. Patient survival was decreased by pretransplant seropositivity (relative risk [RR] 1.11, P =0.001). In addition, this group demonstrated worse overall allograft survival (RR 1.05, P =0.029), although this adverse effect disappeared when patients who died with a functioning graft were censored. Decreased allograft survival was most pronounced in patients who were on hemodialysis before transplantation (RR 1.62, P =0.004). CONCLUSIONS: Pretransplant CMV seropositivity is associated with decreased patient survival. Pretransplant CMV seropositivity and hemodialysis have a synergistic adverse effect on graft survival, independent of patient mortality. Additional studies are required to define mechanisms by which pretransplant CMV infection and dialysis modality may contribute to decreased allograft survival.

Acute Disease↗

A comparison between recipients receiving matched kidney and those receiving mismatched kidney from the same cadaver donor.

The optimal allocation of cadaveric kidneys for transplantation with reference to human leukocyte antigen (HLA) match and sharing these organs to a distant center remains controversial. The current analysis was performed using the United Network for Organ Sharing (UNOS) database for cadaveric kidney transplants (Tx) between 1988 and 1997. The graft survivals of zero-mismatch (matched) kidneys with the mate (mismatched) kidneys were compared. There were 2385 donors and 4770 Tx. Significant differences in recipient demographics between matched and mismatched Tx were: fewer African-American race (AA) in the matched group (9.0% vs. 21.9%), higher number of previous Tx (25.5% vs. 14.8%) and elevated mean cold ischemia time (24.0 vs. 22.2 h). Post-Tx dialysis requirements were similar (22.8% vs. 24.1%, p = 0.62) and matched kidneys had to travel more distance (920 vs. 232 miles). Using a Cox model, the matched group had a decreased relative hazard of graft failure of 23.0% (p = 0.0002) or 35% (p < 0.0001) with and without censoring for death. There was significantly better graft survival in the matched recipients in all pairs except AA (matched) and non-AA (mismatched). For older donors (> or = 50 years, n = 1508), the matched grafts survival was marginally significant (p =0.05). Matched kidneys have improved survival compared with the mismatched kidneys despite the longer distance traveled. The benefit of mismatched transplants was predominantly seen in non-AA.

Adolescent↗