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

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

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

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

Results: At the end of the study, as competing events, chronic graft loss and death with functioning graft were seen in 27 (10.2%) and 53 cases (19.9%), respectively, while 186 cases (69.9%) were accounted as censored. The incidence rate of death was approximately two-time of the incidence rate of chronic graft loss (8.6 vs. 4.4 per 100 person-years). In multivariate analysis, significant risk factors associated with cumulative incidence of death included age (P < 0.007, subhazard ratio (SHR) = 1.03), type of cancer (P < 0.0001), and response to treatment (P < 0.0001, SHR = 0.027). The significant risk factors associated with cumulative incidence of chronic graft loss were gender (P = 0.05, SHR = 0.37), treatment modality (P < 0.0001), and response to treatment (P = 0.048, SHR = 0.47). Conclusions: Using these factors, nephrologists may predict the occurrence of graft loss or death. If the probability of graft loss was higher, physicians can decrease the immunosuppressive medications dosage to decrease the incidence of graft loss.

/pdf/chronic-graft-loss-and-death-in-patients-with-post-y6kq09ggfa.pdf

Chronic Graft Loss and Death in Patients With Post-Transplant Malignancy in Living Kidney Transplantation: A Competing Risk Analysis

Renal transplantation between monozygous identical twins provides an opportunity to utilize minimal immunosuppression to maintain stable allograft function, thereby alleviating the toxicities of immunosuppressive therapy. Despite monozygosity, there is a possibility of discordant protein presentation in identical twins that could trigger alloimmune response and lead to graft injury. Therefore, the optimal immunosuppression regimen in this patient population is unknown, and the safety of immunosuppression withdrawal remains controversial. Herein, we describe two patients who underwent successful renal transplantation from monozygotic identical twin donors. Monozygosity was determined using short tandem repeat (STR) analysis. All immunosuppression was successfully discontinued at 2 days and 3 weeks, respectively, after transplantation. Both patients are alive with functioning renal grafts at 1 year and 5 years after transplant, respectively. These two cases suggest that immunosuppression can be withdrawn safely and rapidly in select monozygous identical twin renal transplant recipients.

/pdf/successful-renal-transplantation-between-identical-twins-zbv9w6m25a.pdf

Successful Renal Transplantation between Identical Twins with Very Brief Immunosuppression

Macrophages manifest as various subtypes that play diverse and important roles in immunosurveillance and the maintenance of immunological homeostasis in various tissues. Many in vitro studies divide macrophages into two broad groups: M1 macrophages induced by lipopolysaccharide (LPS), and M2 macrophages induced by interleukin 4 (IL-4). However, considering the complex and diverse microenvironment in vivo, the concept of M1 and M2 is not enough to explain diversity of macrophages. In this study, we analyzed the functions of macrophages induced by simultaneous stimulation with LPS and IL-4 (termed LPS/IL-4-induced macrophages). LPS/IL-4-induced macrophages were a homogeneous population showing a mixture of the characteristics of M1 and M2 macrophages. In LPS/IL-4-induced macrophages, expression of cell-surface M1 markers (I-Ab) was higher than in M1 macrophages, but lower expression of iNOS, and expression of M1-associated genes (Tnfα and Il12p40) were decreased in comparison to expression in M1 macrophages. Conversely, expression of the cell-surface M2 marker CD206 was lower on LPS/IL-4-induced macrophages than on M2 macrophages and expression of M2-associated genes (Arg1, Chi3l3, and Fizz1) varied, with Arg1 being greater than, Fizz1 being lower than, and Chi3l3 being comparable to that in M2 macrophages. Glycolysis-dependent phagocytic activity of LPS/IL-4-induced macrophages was strongly enhanced as was that of M1 macrophages; however, the energy metabolism of LPS/IL-4-induced macrophages, such as activation state of glycolytic and oxidative phosphorylation, was quite different from that of M1 or M2 macrophages. These results indicate that the macrophages induced by LPS and IL-4 had unique properties.

/pdf/induction-of-unique-macrophage-subset-by-simultaneous-303ily2c.pdf

Induction of unique macrophage subset by simultaneous stimulation with LPS and IL-4

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

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Induction of unique macrophage subset by simultaneous stimulation with LPS and IL-4

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