https://www.kidney-international.org/article/S0085-2538(15)46731-6/pdf

Long-term survival in renal transplant recipients with graft function.

An examination of the mechanisms by which four new immunosuppressive drugs--rapamycin, mizoribine, mycophenolate mofetil, and 15-deoxyspergualin--exert their effects reveals three major categories. Rapamycin binds to an intracellular immunophilin. The resulting drug-immunophilin complex inhibits the action of cytokines, thus blocking the activation and proliferation of T cells. Mizoribine and mycophenolate mofetil are antimetabolites that inhibit a key enzyme in the de novo purine biosynthetic pathway. As a result, the proliferation of T cells and B cells is inhibited selectively compared with that of nonlymphoid cells because the salvage pathway is unavailable to lymphocytes. Finally, 15-deoxyspergualin has a unique mechanism of action, which includes suppressive effects on macrophage function, the induction of cytolytic T cells, B-cell reactivity, and antibody responses. The demonstrated synergism among certain immunosuppressants allows reduction in the dose of each agent to minimize the individual toxicities. As more of these new agents become available, it is likely that azathioprine will be replaced, and it may be possible to eliminate the need for long-term maintenance steroid therapy.

New immunosuppressive drugs in organ transplantation.

The survival of transplant recipients is significantly lower than age-matched controls in the general population. The aim of this study was to analyze the trends in mortality of renal allograft recipients at our centre. We retrospectively analyzed data from all patients who were transplanted between October 1988 and June 2010 and were followed at our center. Patients were considered to have death with graft function (DWGF) if death was not preceded by return to dialysis or re-transplantation. The study included 98 renal allograft recipients (male : female - 7.99 : 1). The mean recipient and donor ages were 35.06 ± 11.84 (range: 15-69) and 41.17 ± 10.44 (range: 22-60) years, respectively. Basic kidney diseases were CGN (chronic glomerulonephritis) (60.20%), CIN (chronic interstitial nephritis) (15.31%), DN (diabetic nephropathy) (8.16%), ADPKD (autosomal dominant polycystic kidney disease) (2.04%) and others (14.29%). They were followed up for a mean 79.91 ± 60.05 patient-months. Mortality occurred in 25 (25.51%) patients (male : female - 4 : 1). Causes of death were sepsis/infection (36%), coronary artery disease (28%), CVA (8%), failed graft (4%), and rest unknown (24%). DWGF was 88% of total death and contributed to 78.57% of total graft loss. Overall patient survival at 1, 5, 10, and 15 years were 90.8%, 80.2%, 65.6%, and 59.1%, respectively (Kaplan-Meier analysis). Those who died exhibited significant differences in recipient's age (median 40 years vs 31 years, P=0.007), pretransplantation hypertension (HTN) (100% vs 65.75%, P<0.001), post-transplant infection (76% vs 42.47%, P=0.005), coronary artery disease (28% vs 1.37%, P<0.001), and serum creatinine at last follow up (median 2.3mg/dL vs 1.56mg/dL, P=0.003). Cardiovascular disease, in addition to infection, is an important cause of death during the first 15 years following renal transplantation even in nondiabetic recipients. Death with functioning graft is of concern.

Causes of death in renal transplant recipients with functioning allograft

The purpose of this research was to study the occurrence of gingival overgrowth (GO) in children after kidney transplantation and to investigate the relationship of GO to medical and dental parameters. Forty-nine kidney transplant patients taking the immunosuppressive drug cyclosporine A (CsA) were evaluated for plaque (PI), calculus (CI), gingival inflammation (GI), probing depth (PD), width of keratinized gingiva (GW), and gingival overgrowth (GO). Blood trough levels and oral dosages of CsA were obtained from medical charts on the day of examination. Most (77.5%) subjects exhibited GO, suggesting that GO is a frequent problem in children and adolescents ingesting CsA. GI, PD, and GW were found to be statistically significantly greater in subjects with GO than in those without GO. CsA dose/day was not significantly different between subjects with GO and those without GO. CsA dose/kg body weight and blood trough levels of CsA were significantly higher in subjects without GO, but the average length of time subjects without GO had been ingesting CsA was only 1.3 months, compared with an average 3.5 years for subjects with GO. The results indicate that in young subjects, duration of CsA ingestion may be the most critical factor related to eventual GO development.

Factors affecting cyclosporine-induced gingival overgrowth in pediatric renal transplant recipients.

Background and objects: We explored the relationship between hospital/surgeon volume and postoperative severe sepsis/graft-failure (including death). Methods: The Taiwan National Health Insurance Research Database claims data for all patients with end-stage renal disease patients who underwent kidney transplantation between January 1, 1999, and December 31, 2007, were reviewed. Surgeons and hospitals were categorized into two groups based on their patient volume. The two primary outcomes were severe sepsis and graft failure (including death). The logistical regressions were done to compute the Odds ratios (OR) of outcomes after adjusting for possible confounding factors. Kaplan-Meier analysis was used to calculate the cumulative survival rates of graft failure after kidney transplantation during follow-up (1999-2008). Results: The risk of developing severe sepsis in a hospital in which surgeons do little renal transplantation was significant (odds ratio [OR]; p = 0.0115): 1.65 times (95% CI: 1.12-2.42) higher than for a hospital in which surgeons do many. The same trend was true for hospitals with a low volume of renal transplantations (OR = 2.39; 95% CI: 1.62-3.52; p < 0.0001). The likelihood of a graft failure (including death) within one year for the low-volume surgeon group was 3.1 times higher than for the high-volume surgeon group (p < 0.0001); the trend was similar for hospital volume. Female patients had a lower risk than did male patients, and patients ≥ 55 years old and those with a higher Charlson comorbidity index score, had a higher risk of severe sepsis. Conclusions: We conclude that the risk of severe sepsis and graft failure (including death) is higher for patients treated in hospitals and by surgeons with a low volume of renal transplantations. Therefore, the health authorities should consider exporting best practices through educational outreach and regulation and then providing transparent information for public best interest.

/pdf/renal-transplantation-relationship-between-hospital-surgeon-4wpfovarnq.pdf

Renal Transplantation: Relationship between Hospital/ Surgeon Volume and Postoperative Severe Sepsis/Graft- Failure. A Nationwide Population-Based Study

Causes of death after renal transplantation: a long-term follow-up study.

Studies of immunosuppression with quadruple regimen treatment (cyclosporine, mizoribine, prednisolone, and antilymphocyte globulin) in cadaveric and living-related donor renal allotransplantation.

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Causes of death after renal transplantation: a long-term follow-up study.

Studies of immunosuppression with quadruple regimen treatment (cyclosporine, mizoribine, prednisolone, and antilymphocyte globulin) in cadaveric and living-related donor renal allotransplantation.