Does delayed graft function in the first kidney transplant influence graft outcome in a subsequent transplant?

Background

In kidney transplantation, delayed graft function (DGF) portends adverse graft and patient outcomes. It is unclear whether DGF in the first kidney transplant would adversely impact the outcome of a subsequent transplant.

Methods

Utilizing data from the Organ Procurement and Transplant Network, we identified patients ≥ 18 years of age who underwent at least two deceased donor kidney transplantation (DDKT) between 1987 and 2010. Patients were then divided into two groups based on whether or not they developed DGF in the first transplant (1st TXP DGF group and 1st TXP no-DGF group). Unadjusted and adjusted graft survivals (Cox regression) between the groups were compared.

Results

A total of 10,628 patients were identified who received more than one DDKT (3672 patients in the 1st TXP DGF group and 6956 patients in the 1st TXP no-DGF group). A higher incidence of DGF was observed with the second transplant in patients who had DGF in the first transplant (34% vs 26%, P = .001). Unadjusted graft survival for the second transplant was superior in the 1st TXP no-DGF group (P = .002). After correction for confounding variables, DGF in the first transplant did not have significant adverse impact on the graft survival of the second transplant (hazard ratio 1.2 with 95% confidence interval 0.96–1.09, P = .44).

Conclusions

In patients undergoing more than one DDKT, DGF in the first transplant is associated with higher incidence of DGF in the subsequent transplant but did not have independent adverse influence on the outcome of that graft.     

Living donor kidney transplant in Italy: is the underutilization justified?

Living donor transplants (LDtx) represent an underutilized resource in Italy. It is, however, a therapeutic option that deserves greater consideration not only due to the increasing gap between the number of uremic patients on waiting lists (6956) and the number (1464) of cadaveric transplants (CADtx), as evidenced in 2002, but also due to the advantages of LDtx over CADtx. The superiority of LDtx include better graft survival, independent of the donor/recipient relationship, less need for dialytic treatment with preemptive transplants and reduced immunogenicity of the graft due to the brain death-related "cytokine storm." Moreover, some emerging procedures namely laparoscopic nephrectomy instead of open surgery and spiral CT instead of renal angiography namely, reduce the physical and socioeconomic burden of the donor. In the light of these considerations, LDtx should be reconsidered in the Italian scenario of kidney transplantation.     

Does subclinical rejection contribute to chronic rejection in renal transplant patients?

Renal allograft biopsies have traditionally been performed in the setting of acute graft dysfunction. However, several groups have performed graft biopsies at times of stable graft function, and more recently, after treatment of rejection episodes. Surprisingly, unequivocal histologic criteria for acute rejection have been demonstrated in a high proportion of these protocol biopsies. The Winnipeg Transplant Group has documented the high prevalence of clinically silent inflammatory infiltrates in early protocol biopsies, and demonstrated their inflammatory and cytotoxic potential by immunohistochemical and molecular biological techniques. Furthermore, in a randomized trial, our group has demonstrated that subclinical rejection, if untreated, is associated with the development of early chronic pathology and late graft dysfunction. In this overview, we will summarize the early data on subclinical allograft inflammation, present the experience of the Winnipeg Transplant Group, and discuss the possible implications of subclinical rejection on the development of chronic rejection.     

Does pretransplant obesity affect the outcome in kidney transplant recipients?

The effect of obesity on renal transplant outcome remains unclear due to conflicting published studies. The purpose of this study was to assess whether obesity affects the outcome in renal transplant patients. METHODS: We retrospectively analyzed 33 obese (BMI >30; mean = 34.1 +/- 3.68; group I) and 35 nonobese (BMI < or = 30; mean = 23.6 +/- 3.18; group II) renal transplants performed at our center between March 1999 to December 2002. These two groups were well matched with respect to age, sex, donor source, hypertension, diabetes, ischemic heart disease, hyperlipidemia, native kidney disease (PCKD, 6 vs 4; diabetic, 5 vs 4; glomerulonephritis, 6 vs 7; FSGS, 2 vs 2 and IgA, 2 vs 7), HLA mismatch and immunosuppressants medications (Neoral, 21 vs 25; tacrolimus, 11 vs 10; Cellcept, 28 vs 31; Prednisone, 33 vs 35; ATG, 7 vs 8; Basiliximab, 14 vs 13 and Rapamycin, 5 vs 2, groups I and II, respectively). Follow-up was from 7 months to 4.4 years. RESULTS: Significant differences were noted in operating time, wound infection, perinephric hematoma, lymphocele, and number of hospital days. There were no significant differences between the two groups in the incidence of wound dehiscence, deep vein thrombosis, pulmonary embolism, atelectasis, urine leak, delayed graft function, acute rejection rate, and the following posttransplant variables: diabetes mellitus, myocardial infarction, hyperlipidemia, hypertension, and incisional hernia. We conclude that obesity significantly increases operating time, wound complications, and hospitalizations.     

Does cytomegalovirus status influence acute and chronic rejection in heart transplantation during the ganciclovir prophylaxis era?

BACKGROUND: The effect of cytomegalovirus (CMV) status on acute rejection in heart transplantation is not well understood. Furthermore, there is some evidence to suggest that CMV antibody positivity is associated with cardiac allograft vasculopathy (CAV). METHODS: This study compared the effect of CMV antibody status in heart transplant donors (D) and recipients (R) on acute and chronic rejection episodes during the ganciclovir prophylaxis era. RESULTS: All heart transplant recipients at Papworth Hospital during the ganciclovir prophylaxis era were included (n = 374). They were grouped according to recipients and their respective donor CMV serology: R(-)/D(-) (n = 82); R(+)/D(-) (n = 114); R(-)/D(+) (n = 73); and R(+)/D(+) (n = 105). Ganciclovir prophylaxis was administered to the R(-)/D(+) group. The mean (SD) recipient and donor ages were 46 (11), 51 (9), 47 (11) and 52 (8) years (p < 0.001), and 32 (11), 33 (14), 36 (12) and 38 (14) years (p = 0.01), respectively, for the CMV groups. The mean number of acute rejection episodes (as confirmed by cardiac biopsy) per 100 patient-days was 0.13 (0.36), 0.11 (0.34), 0.12 (0.34) and 0.12 (0.34), respectively (p > 0.05) There was no statistical difference in the development of CAV as assessed by angiography (p = 0.92). At 2 years, the "freedom from CAV" rates were 96%, 97%, 97% and 98%, respectively. The 5-year post-operative survival rates were 83%, 79%, 67% and 73% (p = 0.08 overall). CONCLUSIONS: CMV status of heart transplant recipients and their respective donors does not influence acute or chronic rejection in terms of cardiac allograft vasculopathy.     

Does immunosuppressive regimen influence the lipid disturbances in kidney recipients?

Though it is said that some immunosuppressive agents are implicated in the development of hyperlipidemia in kidney recipients, this subject is still controversial. Main plasma lipid parameters, as well as apolipoproteins A1 and B were measured periodically in 39 kidney first cadaveric, nondiabetic recipients during 24 months of clinic follow-up after transplantation. Standard triple immunosuppressive therapy: prednisone + cyclosporine + azathioprine was administrated from the beginning. After the second year of kidney transplantation, a significant reduction refers to values of TC, LDL, apo A1 and apo B. In the group with antirejection - methylprednisolone therapy, and without it only TG in the 24th month and apo B in the 1st month were statistically lower in the latter group (both p < 0.05). In the multiple regression test, a linear coincidence was observed between apo A1, apo B and prednisone cumulative dosage after the 1st month, TG and cyclosporine in the 6th month and LDL and cyclosporine in the 12th month after transplantation. It appears that steroids had an impact on lipids directly after transplantation, while cyclosporine did so thereafter.     

Does donor kidney to recipient body weight ratio influence long-term outcomes of living-donor kidney transplantation?

This study evaluated the effect of the donor kidney to recipient body weight (Kw/Rw) ratio on long-term graft function and survival. We investigated retrospectively whether there was any association between Kw/Rw ratio and long-term graft survival and function after a follow-up of >10 years. We studied a consecutive series of 123 adult-to-adult living kidney transplants. According to the Kw/Rw ratio, patients were divided into 3 groups: “low” (Kw/Rw <2.85; n = 29), “medium” (2.85 ≤ Kw/Rw < 4.04; n = 63), and “high” (≥4.04; n = 31). Among the 3 groups, the mean serum creatinine levels at 1 and 6 months as well as 1 year after transplantation were significantly lower among patients with a high Kw/Rw ratio than in those with a medium or low ratio, but serum creatinine levels at 3 and 5 years did not differ significantly (P = .394 and 0.620, respectively). Graft survival rates at 5 and 10 years after transplantation were significantly lower in the “low” group. We observed a significant association between Kw/Rw ratio and graft survival (P = .018). The Kw/Rw ratio is an important factor for long-term graft survival and early graft function. However, it did not significantly affect subsequent renal function.     

Does the difference in donor and recipient weight influence renal graft survival?

Introduction

Grafts from older donors or those in recipients with a greater body mass index (BMI) as compared with the donor may develop hyperfiltration syndrome that shortens renal graft survival.

Objectives

To assess whether the differences in weight and BMI between donor and recipient correlated with renal function, proteinuria, or graft survival among recipients of grafts from expanded criteria donors.

Materials and methods

We undertook a prospective, observational study in 180 recipients of grafts from expanded criteria donors performed between 1999 and 2006. All grafts had been biopsied previously for viability. The recipients underwent immunosuppression with basiliximab, late introduction of tacrolimus, mycophenolate mofetil and steroids. The study population was divided into three groups, depending on the tertile of the donor-to-recipient weight ratio (<1, n = 64; 1-1.2, n = 56; >1.2, n = 60), and the donor-to-recipient BMI ratio (<0.97, n = 59; 0.97-1.13, n = 60; >1.13, n = 60). The glomerular filtration rate was estimated from the modified diet in renal disease (MDRD) equation.

Results

The mean age of the donors was 63.54 years and of the recipients, 58.38 years. The proportion of male-to-female donors was 52:48 and recipients 57.8:42.2 (P = NS). No significant differences in overall graft survival were observed between the tertiles. There was a negative correlation between the donor-to-recipient weight ratio and serum creatinine value at 1 (P < .001), 3 (P = .013), and 12 months (P = .005) after transplantation, and a positive correlation with the MDRD at 1 month (P < .001). No relation was noted between weight and proteinuria at 1 (P = .25), 3 (P = .51), or 12 months (P = .90). The results were similar after analyzing the ratio of the BMI to creatinine, MDRD or proteinuria, as well as in cases of a female donor to a male recipient.

Conclusions

Differences in weights between the donor and the recipient did not appear to affect graft survival or proteinuria among patients receiving grafts from expanded criteria donors, though it may be related to renal function during the early posttransplant stages.     

Does histologic acute rejection in lung allografts predict the development of bronchiolitis obliterans?

Clinical acute lung rejection (AR) occurs in lung allografts usually within 50 days after transplantation. While perivascular infiltrates characterize AR, with moderate-to-severe acute rejection small airway injury occurs. We investigated the significance of small airway injury in AR and its relationship to the development of bronchiolitis obliterans (OB) in 11 recipients of combined heart-lung or double-lung allografts. In general, the intensity and persistence of early acute rejection episodes associated with injury to bronchioles correlated with the development of histologic bronchiolitis obliterans. Early AR may "prime" lymphocytes for subsequent respiratory epithelial injury and airway fibrosis late in the postoperative period.     

How important is the duration of the brain death period for the outcome in kidney transplantation?

In kidney transplantation, graft survival using grafts from donation after brain death (DBD) donors is inferior to results after living donation. However, little is known about the effect of the duration of brain death (BDdur) on outcome after transplantation. This is a retrospective Organ Procurement and Transplant Network analysis using kidney donor and recipient data from 1994 to 2006. BDdur was calculated as the period between brain death declaration and aortic cross clamp. Effects of BDdur on delayed graft function (DGF), acute rejection and graft failure were calculated using binary logistic regression and Cox regression models. Median BDdur was 23.8 h. Longer BDdur decreased the risk for DGF and 1‐ and 3‐year graft failure slightly, but not for acute rejection. In multivariate analysis, donor age and acute rejection were confounders. However, in a multivariate subgroup analysis of donors aged ≤55 years BDdur independently predicted DGF; each hour of BDdur decreasing the risk of DGF with 0.4% (P = 0.008). Longer BDdur is not detrimental and in fact slightly beneficial in DBD donors ≤55 years of age, reducing the chance of DGF in the recipient. This finding may have an impact on organ retrieval procedures, as no rush but rather an improved donor management prior to retrieval will benefit donor kidney viability.     

Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation?

The Banff schema incorporates a semiquantitative scoring system for grading of acute cellular rejection (ACR) of the liver allograft. The Banff rejection activity index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation (E); bile duct damage (B); and portal inflammation (P); the scores are combined to an overall score (the RAI). The purpose of this research was to determine the prognostic value of the Banff RAI score in predicting the response to increased immunosuppression and the long-term outcome of the graft. A retrospective study was done of patients undergoing primary liver transplantation between January 2000 and October 2004 with tacrolimus-based immunosuppression; 495 patients were included, 231 had histologically-confirmed ACR, 193 responded to 1 cycle of high-dose steroids. There was no correlation between the total RAI score and response to steroids, resistant rejection, development of chronic rejection, or graft survival. The E score was related to patient survival, a lower score being associated with a worse outcome (P = 0.048). In multivariable analysis, serum bilirubin, serum aspartate aminotransferase, and E score were significant predictors of death (P = 0.012). In univariable analysis, B score and bilirubin were significantly related to "resistant rejection" (P = 0.018 and 0.002, respectively), but only bilirubin was significant in multivariable analysis (logistic regression). In conclusion, although the Banff RAI score is a useful marker of the severity of rejection, neither the total RAI score nor any of the individual components correlated with response to steroids or graft survival.     

Ureteral length in live donor kidney transplantation; Does size matter?

The aim of this study was to evaluate the role of ureteral length on urological complications. Data were retrospective collected from the INEX‐trial database, a RCT to compare the intravesical to the extravesical ureteroneocystostomy. Ureteral length was measured in 198 recipients and used to divide recipients into three categories based on interquartile ranges: short (≤8.5 cm), medium (8.6–10.9 cm) and long ureters (≥11 cm). Urological complications were defined as the number of percutaneous nephrostomy placements (PCN). Fifty recipients fell into the short, 98 into the medium and 50 recipients into the long ureter category. Median follow‐up was 26 (range 2–45) months. There was no significant difference in number of PCN placements between the categories. There were 9 (18%) PCN placements in the short ureter category, 21 (20%) in medium ureter category and 10 (21%) in the long ureter category, P = 0.886. Risk factor analysis for gender, arterial multiplicity and type of ureteroneocystostomy showed no differences in PCN placements between the three ureteral length categories. We conclude that ureteral length alone does not seem to influence the number of urological complications.     

Does donor cause of death affect the outcome of lung transplantation?

BACKGROUND: Accumulating evidence suggests that the donor's cause of death may influence posttransplantation allograft function. We conducted a retrospective analysis of our adult lung transplant experience to investigate the influence of donor traumatic brain injury versus nontraumatic brain injury on posttransplantation outcome. METHODS: We retrospectively reviewed donor records and recipient medical charts for 500 consecutive lung transplants performed between July 1988 and December 1999. Recipient follow-up was complete, with a minimum follow-up of 1 year of survival. RESULTS: There were 295 and 205 donors in the traumatic and nontraumatic brain injury groups, respectively. Young male donors predominated in the traumatic brain injury group. Recipients receiving donor lungs from the traumatic and nontraumatic brain injury groups did not differ by age, sex, diagnosis, type of transplant (single-lung versus double-lung) or requirement for pretransplantation mechanical ventilatory assistance. Recipients did not differ in immediate or 24-hour PaO (2)/inspired oxygen ratio, ventilation time, hospital stay, hospital mortality, or overall survival. Recipients of organs from donors who died of traumatic brain injury showed a higher severity and frequency of rejection episodes during the first year after transplantation. Freedoms from bronchiolitis obliterans syndrome at 5 years were 34.5% and 50.8% for recipients of organs from donors who died of traumatic and nontraumatic brain injury, respectively (P =.002). CONCLUSIONS: The cause of donor brain death does not appear to influence early results of lung transplantation. Traumatic brain injury, or some phenomenon associated with it, may predispose a transplanted lung and its recipient toward more severe early rejection episodes and subsequent development of bronchiolitis obliterans syndrome.     

Does the risk of acute rejection really decrease with increasing recipient age?

Abstract In corneal transplants the risks of acute rejection and graft failure decrease with increasing recipient age, but kidney graft survival analyses tend to show the opposite effect. Why is this? Cadaveric kidney transplants performed in the UK and Republic of Ireland between 1985 and 1993 (UKTSSA database) were analysed by multifactorial methods to identify major factors affecting graft survival. In a study database that had been censured for technical failure and death with a functioning transplant, it was shown that increasing recipient age was associated with decreasing risk of graft failure at 1 year. This is consistent with the view that kidney transplants, like corneal transplants, are less likely to be acutely rejected as the age of the recipient increases.     

Does repeated Ramadan fasting adversely affect kidney function in renal transplant patients?

This is a prospective cohort study in renal transplant patients who fasted or who did not fast for three consecutive Ramadans. The baseline estimated glomerular filtration rate (GFR), mean arterial pressure (MAP), and urinary protein excretion before the first Ramadan were compared to those after the third Ramadan in 35 fasters and 33 nonfasters. The effect of age, time after transplantation, presence of diabetes mellitus (DM), and proteinuria on changes in the GFR were studied. The two groups were comparable in gender, age, donor source, time posttransplantation, presence of DM, hypertension, proteinuria, serum creatinine, and MAP. Among the fasters, there was no change in estimated GFR after fasting for three Ramadans (56.4 mL/min versus 55.4 mL/min, P=0.8) even after adjusting for age, DM, baseline GFR, proteinuria, or time after transplantation. There were no significant differences between the fasters and the nonfasters in the changes in GFR, MAP, and urinary protein excretion between baseline and the third Ramadan.