Older Donation After Circulatory Death Kidneys for Older Recipients: A Single-Center Experience.

The number of older patients is increasing on the transplant waiting list. Donation after circulatory death (DCD) kidney transplantation has increased, but there remains hesitancy in use of older DCD organs. The aim of this study was to evaluate outcomes of directing older DCD donor kidneys into older recipients. METHODS: Patients 60 years or older who received transplants from DCD donors 60 years or older, between February 2010 and January 2014, were identified from a prospectively maintained database. RESULTS: Over a 4-year period, 88 patients 60 years or older received DCD kidney transplants from donors 60 years or older. Of these 44 (55%) were 60 to 69 years old and 40 (45%) were 70 years or older. Median follow up was 63 months. Patient survival was 95% and 79% at 1 and 5 years, respectively, with a survival in those 70 years and older (69%) compared with those aged 60 to 69 (88%) years (P = .01). Censored for death graft survival was 94% and 80% at 1 and 5 years, respectively. Median estimated glomerular filtration rate at 12 months and 36 months was 36 mL/min (range, 11-70 mL/min) and 39.5 mL/min (range, 11-77 mL/min), respectively. CONCLUSIONS: Older DCD kidneys, when transplanted into older recipients, result in good patient and graft survival and an acceptable graft function, especially considering their age. This represents a good use of this organ resource.

Dual Kidney Transplantation Offers a Valuable Source for Kidneys With Good Functional Outcome.

BACKGROUND: Reasons for declining kidney donors are older age, with or without, hypertension, kidney dysfunction, and diabetes. Implantation of both kidneys into a single recipient from such donors may improve their acceptability and outcome. METHODS: Patients who underwent dual kidney transplantation (DKT) between June 2010 and May 2014 were identified from a prospectively maintained database. Single kidney transplantations (SKT) with matching donor criteria were also identified. Donors considered for DKT were the following: DBDs >70 years of age with diabetes and/or hypertension; DCDs >65 years of age with diabetes and/or hypertension; and DCDs >70 years of age. RESULTS: Over a 4-year period, 34 patients underwent adult DKT, and 51, with matching donor criteria, underwent SKT. The median estimated glomerular filtration rate (eGFR) at 12 and 36 months of DKT was 49 (range, 5-79) and 42 (range, 15-85) mL/min compared with SKT of 35 (range, 10-65) and 32 (range, 6-65), respectively. The 1-year graft survival for DKT and SKT was 88% and 96% (P = .52), and patient survival was 94% and 98%, respectively (P = .12). Median hospital stay, intensive care unit admission, and wound complications were more frequent in the DKT group. CONCLUSIONS: Graft function following DKT is significantly better compared with matched criteria SKT; graft and patient survival are similar. There is an increased rate of complications following DKT, with longer hospital stay and ICU admission.

The influence of socioeconomic deprivation on outcomes following renal transplantation in the United kingdom.

Socio-economic deprivation is an important determinant of poor health and is associated with a higher incidence of end-stage renal disease, higher mortality for dialysis patients and lower chance of being listed for transplantation. The influence of deprivation on outcomes following renal transplantation has not previously been reported in the United Kingdom. The Welsh Index of Multiple Deprivation was used to assess the influence of socio-economic deprivation on outcomes for 621 consecutive renal transplant recipients from a single centre in the United Kingdom transplanted between 1997 and 2005. Outcomes measured were rate of acute rejection and graft survival. Patients from the most deprived areas were significantly more likely to experience an episode of acute rejection requiring treatment (36% vs. 27%, p=0.01) and increasing overall deprivation correlated with increasing rates of rejection (p=0.03). Income deprivation was significantly and independently associated with graft survival (HR 1.484, p=0.046). Among patients who experienced acute rejection 5-year graft survival was 79% for those from the most deprived areas compared with 90% for patients from the least deprived areas (p = 0.018). Overall socio-economic deprivation is associated with higher rate of acute rejection following renal transplantation and income deprivation is a significant and independent predictor of graft survival.

Sotrastaurin, a novel small molecule inhibiting protein kinase C: first clinical results in renal-transplant recipients.

Sotrastaurin, a novel protein-kinase-C inhibitor, blocks early T-cell activation. In this 12-month, Phase II study, de novo renal-transplant patients were randomized to sotrastaurin (200 mg b.i.d.) + standard-exposure tacrolimus (SET) or reduced-exposure tacrolimus (RET) (SET: n = 76; RET: n = 66), or control (SET + mycophenolic acid [MPA, 720 mg b.i.d.]; n = 74). In both sotrastaurin groups, patients were converted from tacrolimus to MPA after Month 3, achieving calcineurin inhibitor-free immunosuppression. The primary endpoint was composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death or loss to follow-up). The key secondary endpoint was glomerular filtration rate (GFR). Composite efficacy failure rates were: 4.1%, 5.4% and 1.5% at Month 3 (preconversion) and 7.8%, 44.8% and 34.1% at study end in the control, sotrastaurin + SET and sotrastaurin + RET groups, respectively; these results led to premature study discontinuation. Median GFR at Month 6 was: 57.0, 53.0 and 60.0 mL/min/1.73 m(2), respectively. Study-drug discontinuations due to adverse events occurred in 16.2%, 18.4% and 12.1%, respectively. Leukopenia and neutropenia occurred more frequently preconversion in control versus sotrastaurin groups: 13.7%, 5.6%, and 4.6%; and 11.1%, 4.3% and 3.1%, respectively. The initial sotrastaurin + tacrolimus regimen was efficacious and well tolerated but the postconversion sotrastaurin + MPA regimen showed inadequate efficacy. Longer-term evaluation of sotrastaurin + tacrolimus is warranted.

Infective complications associated with ureteral stents in renal transplant recipients.

OBJECTIVE: Stenting of the ureter is commonly performed during renal transplantation to avoid early complications. However, it predisposes to infections that may pose a significant threat to the graft and patient. Our study sought to investigate the incidence of infections associated with stents in renal transplant recipients. PATIENTS AND METHODS: A retrospective analysis of 100 consecutive renal transplant recipients performed over 1 year with 6 months follow-up. RESULTS: The median recipient age was 46 years (range, 19-71 years). Among the study group, 75 patients received an organ from deceased donor and 25 from live donor. In our study, there were 79 patients with a stent (ST) and 18 without a stent (WOST); 3 patients who required nephrectomy were excluded from the study. There were 2 ureteric stenoses that occurred following stent removal: 1 required surgical correction and 1 was treated radiologically. There were no cases of urinary leak. The incidence of urinary tract infection (UTI) was significantly greater among ST compared with WOST subjects (71% vs 39%; P = .02). New episodes of UTI following removal of the stent were more common among patients who had experienced infections while having a stent compared with infection-free stented patients (54% vs 30%; P = .04). CONCLUSIONS: A ureteric stent may help to reduce early postoperative complications (leak and stricture), but increased the likelihood of UTI. Infection while having a ureteric stent was associated with a high recurrence rate of UTI even after stent removal.

Effect of degree of obesity on renal transplant outcome.

Obesity in renal transplantation has proven to affect both patient and graft survival. The scientific community seems to be split into 2 groups: one claims similar outcomes among obese and nonobese, showing only marginally increased postoperative complications; whereas the other group report a higher rate of complications, including graft loss and mortality. These results did not provide sufficient evidence to be applied in practice. In this study we analyzed the outcomes of obese recipients of renal transplant in our institution. One hundred fourteen renal transplantations were performed between January 1993 and December 2003. To estimate the impact of various degrees of obesity, the patients were allocated into 2 cohorts: Group A (body mass index [BMI] 30-34.9) and Group B (BMI 35 and greater). We analyzed patient and donor characteristics. Wound infection rates were similar in the 2 groups. The aggregate Group A and B patient survival rate was 95.6% at 1 year and 93% at 5 years. Graft survival rate was 93.9% at 1 year and 88% at 5 years. However, the analysis of the outcomes in the 2 groups with different degrees of obesity showed that the patient survival rate at 1 year in Group A was 98.9% (1 death) and 95.6% at 5 years (4 deaths). In Group B the patient survival rate at 1 year was 87.5% (3 deaths; P = .007) and at 5 years was 79.2% (P = .006). Graft survival rate in Group A was 98.9% (1 graft loss) at 1 year and 94.5% (5 graft losses) at 5 years; in Group B the graft survival rate was 75% (6 graft loss) at 1 year and 63% (9 graft losses) at 5 years (P < .0001 both at 1 and 5 years). The present study showed that overall obese recipient outcomes were as expected when evaluating the obese as a single group of recipients with a BMI >30. The overall patient and graft survival did not show particularly different results from already published studies claiming similar outcomes. However, this series showed different outcomes when we divided them into 2 groups by BMI. There was a remarkable difference between moderate obese (Group A) and morbid obese (Group B) recipients as regards patient and graft survival. It is possible that the excellent outcome in Group A may be the result of super-selection and stringent cardiovascular risk screening that is implemented for this category of potential recipients. Obese recipients with a BMI of >35 are a high-risk category. Because of the difference in the outcomes of the 2 groups, it does not seem reasonable to address obese recipients as a single group. We believe that obese patients should not be discriminated simply on the basis of the BMI. A strict evaluation should be performed before denying the opportunity to receive a renal transplant to these patients.

Clinical significance of a positive flow crossmatch on the outcomes of cadaveric renal transplants.

Pretransplantation crossmatching is an integral part of kidney transplantation. Flow cytometric crossmatch (FCXM) is more sensitive than complement-dependent cytotoxic crossmatch (CDC-XM). However, the clinical significance of positive FCXM with negative CDC-XM is controversial. We evaluated FCXM in 455 consecutive deceased donor renal transplants. All had a negative CDC-XM. There were 341 T-cell and B-cell FCXM negative and 38 T-cell and B-cell positive. There was a higher percentage of retransplantations and HLA mismatches (26.3% vs 8.2%, P= .002 and 2.45 vs 1.99, P= .02, respectively) in the FCXM-positive group compared with the FCXM-negative group; 65.8% of the FCXM-positive patients had rejection compared with 49.3% of the FCXM-negative patients (odds ratio [OR]=1.89, P= .06). FCXM-positive patients had a higher incidence of vascular rejection (28.9% vs 12.6%, OR=2.68, P= .008). One- and 5-year graft survivals were 84% and 66% in the FCXM-positive group vs 90% and 75% in the FCXM-negative group. Censoring for patient death, 1- and 5-year graft survivals were 84% and 73% in the FCXM-positive group vs 94% and 82% in the FCXM-negative group. There was no difference in renal function between the 2 groups. In conclusion, a positive T-cell and B-cell FCXM transplant with a negative CDC-XM is associated with a higher incidence of rejection, twice the risk of vascular rejection, and a trend toward poorer graft survival.

Efficacy of early biopsy in kidney allograft recipients with delayed graft function.

It is accepted that kidney transplants that display delayed graft function (DGF) show poorer survival and function, particularly when an acute rejection episode (ARE) occurs. A diagnostic biopsy to establish the reason for DGF, or acknowledge an ARE, even if borderline, can improve short- and long-term graft survivals. From January 2002 to September 2006 we retrospectively evaluated 358 kidney transplant recipients. We performed a biopsy to evaluate the cause of DGF in all patients who required dialysis, or had serum creatinine levels that increased, remained unchanged, or decreased less than 10% per day on three consecutive days during the first week after transplantation. An ARE was found in 18.8% (n = 19) of the biopsies. Early biopsy for patients with DGF is a safe method that allows uncovering of an ARE that would otherwise be undetected. The immediate recognition and treatment of rejection episodes can certainly increase long-term survival and function of renal transplants.

Cyst infection in renal allograft recipients with adult polycystic kidney disease: the diagnostic value of labeled leukocyte scanning: case reports.

Occult infection following renal transplantation is a common diagnostic problem facing nephrologists and transplant surgeons. Patients with adult polycystic kidney disease (APKD) are prone to recurrent infections in their native kidneys and this can present with little if any localizing signs. Conventional radiological imaging with computed tomography or ultrasonography has a low sensitivity and specificity in such patients due to anatomic distortion and poor native renal function, and therefore identifying the source of sepsis can be difficult. Two cases are presented where patients with APKD who had received kidney transplants were investigated unsuccessfully for occult sepsis. White cell-labeled scanning identified the location of the infection in the patients' native polycystic kidney in both cases, allowing targeted treatment in the form of native nephrectomy. White cell-labeled scanning has an important role in the investigation of occult infection in renal allograft recipients with APKD.

Polar nephrectomy in a transplanted kidney: a case report.

After renal transplantation, infarction of the lower pole may be observed. We report an unusual case of lower pole infarction and perforation of the lower calyx due to thrombosis of a lower polar artery. This was managed successfully with partial nephrectomy (nephron-sparing surgery).

Effect of cold ischemic time and HLA matching in kidneys coming from "young" and "old" donors: do not leave for tomorrow what you can do tonight.

BACKGROUND: Kidneys from older donors are likely to have a lower nephron mass. Nevertheless they constitute a valuable source of kidney allografts. Long cold ischemic time (CIT), with or without delayed graft function (DGF), has been associated with reduced graft survival. The aim of this study was to review the experience of a single UK center to assess the interaction of cold storage time, donor age, organ exchange, and HLA-DR mismatching on short- and long-term survival. METHODS: We analyzed 788 first cadaver kidney transplants that were performed in our center from 1990 to 1997 and had complete data available. A donor age of 55 years was the cutoff age for "old" and "young" donor kidneys. The primary outcome measured was graft failure from any cause. RESULTS: There were 132 grafts from donors 55 years or older (16.7%), with 76.8% of the kidneys implanted after >20 hr of CIT. Kidney grafts from donors older than 55 years had worse graft survival than grafts from donors younger than 55 (87% vs. 78% at 1 year and 80% vs. 58% at 5 years after transplant, P=0.0001). A CIT of >20 hr significantly reduced graft survival (91% vs.74.3% at 5 years after transplant, P=0.0002) in the young donor group and was associated with an overall graft survival in the old donor group of 57.5% at 5 years. In the same group, ignoring the HLA-DR mismatching to achieve shorter CIT, the predicted initial cost on graft survival at 1 year would have been 3.7% but would have increased to 9% 5 years after transplant. For young donors a CIT of >20 hr had a cost of approximately 18% at 5-year graft survival, far higher than a single DR mismatch. Occurrence of DGF decreased survival in both short (P=0.001) and long (P=0.00001) CIT groups. CONCLUSION: Forming local alliances (common recipient lists) and minimizing delays within the hospital might reduce CIT and DGF while achieving excellent HLA matching. This should improve significantly the outcome of both old and young donor kidney grafts.

Association of polymorphisms in the human interferon-gamma and interleukin-10 gene with acute and chronic kidney transplant outcome: the cytokine effect on transplantation.

BACKGROUND: Our group has previously described five different size alleles of an interferon (IFN)-gamma microsatellite. Analyzing this polymorphism, this study correlated high IFN-gamma production with a 12 CA repeat allele (allele 2). Further, our group has described interleukin (IL)-10 polymorphism defining in vitro high and low IL-10 producer status. METHODS: Samples from 88 of 115 consecutive cadaveric renal transplants were used to define polymorphism of both IFN-gamma and IL-10. Patients were separated into high and low genotypes based on the previously reported association between certain genotypes and in vitro production. Graft survival, acute rejection, and serum creatinine at 5 years were analyzed for comparison between groups. RESULTS: The genotype associated with high IFN-gamma production was found in 70 patients. The incidence of acute rejection was 54.3% in the high IFN-gamma genotype group, compared with 44.4% in the low IFN-gamma group. Requirement for antithymocyte globulin therapy was greater in the high IFN-gamma group (odds ratio [OR]=2.5). Among HLA-DR-mismatched patients, IFN-gamma genotype was more strongly associated with rejection (OR=2.86). In the cyclosporine monotherapy subgroup, patients with high IFN-gamma genotype had a 61% incidence of rejection compared with only 20% in the low IFN-gamma genotype patients (OR=3.06). Graft survival was similar between the two groups. When the analysis was controlled for the presence of delayed graft function, 40.5% of the high IFN-gamma genotype patients had serum creatinine levels above 200 micromol/L compared with only 14.3% of the low IFN-gamma genotype recipients at 5 years after transplantation (P=0.05). The high IL-10 genotype was shown to be associated with better graft function at 5 years (75 vs. 50%, P=0.09). CONCLUSION: In this study we have shown that high producer genotype for IFN-gamma may have an influence on acute rejection of kidney transplants, particularly in patients on cyclosporine monotherapy. It is also associated with worse long-term graft function. On the contrary high IL-10 production may have a long-term protective effect.

Cytokine gene polymorphisms predict acute graft rejection following renal transplantation.

BACKGROUND: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of acute rejection, while animal models suggest a role for interleukin-10 (IL-10) in promoting graft survival. It has also been shown that polymorphisms in the TNFA gene promoter (position -308) and in the IL-10 gene promoter (position -1082) correlate with differential production of these cytokines in vitro. The aim of this study was to determine whether TNF-alpha and IL-10 gene polymorphisms influence the incidence and severity of acute rejection in the first six months following renal transplantation. METHODS: The cytokine genotypes of 115 consecutive first cadaveric kidney allograft recipients and their donors were screened. The rejection episodes (REs) were defined clinically and confirmed histologically where possible and further classified according to severity (RS), namely steroid-resistant or responsive REs. The genotypes were then correlated with the REs and RS. RESULTS: The recipient TNF-alpha high producer genotype and IL-10 high producer genotype were significantly associated with multiple REs (>/=2) in human leukocyte antigen (HLA)-DR mismatched transplants (P = 0.0047 and P = 0.045, respectively), whereas only the TNF-alpha high producer genotype was associated with steroid-resistant REs (P = 0.025). When recipient cytokines were analyzed together, the TNF-alpha high/IL-10 high producer genotype had the worst prognosis, whereas TNF-alpha low/IL-10 low producer genotype was protective. CONCLUSIONS: We conclude that recipient TNF-alpha and IL-10 gene polymorphisms are determinants of REs and RS following kidney transplantation. Routine screening of these gene polymorphisms may have a clinical role in identifying patients at risk of multiple REs and severe rejections.

In vitro production of IFN-gamma correlates with CA repeat polymorphism in the human IFN-gamma gene.

The DNA sequence of the human IFN-gamma gene shows the presence of a variable-length CA repeat in the first intron of the gene. We investigated the allele distribution of this microsatellite region in 164 unrelated healthy individuals, and the association with interferon-gamma (IFN-gamma) production. In vitro production of IFN-gamma showed a significant correlation with the presence of allele #2.

Pre-emptive kidney transplantation: the attractive alternative.

BACKGROUND: Dialysis can be life-saving for patients with end-stage renal failure. However, not only is it associated with significant morbidity and a greater mortality than transplantation, but it is also expensive. Therefore renal transplantation is generally regarded as the treatment of choice for patients in whom this form of renal replacement therapy is appropriate. Transplantation usually takes place after a variable period of dialytic therapy, but pre-emptive kidney transplantation (PKT) has established itself as an attractive alternative. MATERIALS AND METHODS: 1463 consecutive first kidney transplants performed between January 1980 and December 1995 in a single centre were analysed. The 161 patients (11%) transplanted without prior dialysis were compared with the 1302 patients who had been dialysed prior to being transplanted. The pre-emptive group did not differ from the dialysis group in respect of donor age, donor and recipient gender, HLA mismatch, or cold ischaemic time, although there were more live donor transplants within the pre-emptive group. RESULTS: Delayed graft function occurred more frequently in the dialysis group (25% vs 16%) but more patients experienced an acute rejection episode in the pre-emptive group (67 vs 55%). The actuarial graft survival in the pre-emptive group at 1, 5, and 10 years (84, 76 and 67%) was significantly higher than the respective values in the dialysis group (83, 69, and 56%). Within the live donor recipient cohort the survival advantage for the pre-emptive group was even more striking. CONCLUSION: Pre-emptive kidney transplantation not only avoids the risks, cost, and inconvenience of dialysis, but is also associated with better graft survival than transplantation after a period of dialysis, particularly within the live donor cohort.

Factors influencing kidney transplantation in Manchester, UK: 1989-1996.

The Manchester renal transplant center has the highest single center activity in the UK at present and has managed to achieve high posttransplant survival rates. We believe that this success is due to a combination of factors including a conservative approach to patient management; changes in clinical practice are only made after the evidence base has been established. This center is committed to the philosophy of prolonged survival of all transplanted kidneys. We believe that transplanting kidneys into clinically high-risk patients is not the best use of available resources.