Cytomegalovirus post kidney transplantation: prophylaxis versus pre‐emptive therapy?

Cytomegalovirus is the most important pathogen causing opportunistic infections in kidney allograft recipients. The occurrence of CMV disease is associated with higher morbidity, higher incidence of other opportunistic infections, allograft loss and death. Therefore, an efficient strategy to prevent CMV disease after kidney transplantation is required. Two options are currently available: pre‐emptive therapy based on regular CMV PCR monitoring and generalized antiviral prophylaxis during a defined period. In this review, we describe those two approaches, highlight the distinct advantages and risks of each strategy and summarize the four randomized controlled trials performed in this field so far. Taken this evidence together, pre‐emptive therapy and anti‐CMV prophylaxis are both equally potent in preventing CMV‐associated complications; however, the pre‐emptive approach may have distinct advantages in allowing for development of long‐term anti‐CMV immunity. We propose a risk‐adapted use of these approaches based on serostatus, immunosuppressive therapy and availability of resources at a particular transplant centre.     

Who can tolerate a marginal kidney? Predicting survival after deceased donor kidney transplant by donor–recipient combination

The impact of donor quality on post–kidney transplant (KT) survival may vary by candidate condition. Characterizing this variation would increase access to KT without sacrificing outcomes. We developed a tool to estimate post‐KT survival for combinations of donor quality and candidate condition. We studied deceased donor KT recipients (n = 120 818) and waitlisted candidates (n = 376 272) between 2005 and 2016 by using the Scientific Registry of Transplant Recipients. Donor quality and candidate condition were measured by using the Kidney Donor Profile Index (KDPI) and the Estimated Post Transplant Survival (EPTS) score. We estimated 5‐year post‐KT survival based on combinations of KDPI and EPTS score using random forest algorithms and waitlist survival by EPTS score using Weibull regressions. Survival benefit was defined as absolute reduction in mortality risk with KT. For candidates with an EPTS score of 80, 5‐year waitlist survival was 47.6%, and 5‐year post‐KT survival was 78.9% after receiving kidneys with a KDPI of 20 and was 70.7% after receiving kidneys with a KDPI of 80. The impact of KDPI on survival benefit varied greatly by EPTS score. For candidates with low EPTS scores (eg, <40), the KDPI had limited impact on survival benefit. For candidates with middle or high EPTS scores (eg, >40), survival benefit decreased with higher KDPI but was still substantial even with a KDPI of 100 (>16 percentage points). Our prediction tool ( www.transplantmodels.com/kdpi-epts ) can support individualized decision‐making on kidney offers in clinical practice.     

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.     

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.     

Intermediate-term outcomes with expanded criteria deceased donors in kidney transplantation: a spectrum or specter of quality?

OBJECTIVE: To compare intermediate-term outcomes in adult recipients of expanded criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney transplants at a single center using a standardized approach. SUMMARY BACKGROUND DATA: Expanded criteria donors (ECDs) are a source of kidneys that increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns regarding diminished survival and predicted poorer intermediate-term outcomes. METHODS: Over a 47-month period, we performed 244 deceased donor kidney transplants into adult recipients, including 143 from SCDs and 101 from ECDs. Management algorithms were implemented to preserve nephron function, and recipient selection for an ECD kidney transplant was based on low immunologic risk. All patients received depleting antibody induction in combination with tacrolimus and mycophenolate mofetil. A total of 188 patients (77%) had at least a 1-year follow-up. RESULTS: ECDs were older, had a higher BMI, had an increased incidence of cerebrovascular brain death and preexisting donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P < 0.01) compared with SCDs. Cold ischemic times were similar between groups, but more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates were similar between groups with a mean follow-up of 24 months. The rates of delayed graft function (DGF), acute rejection, readmissions, operative complications, major infections, and resource utilization were comparable between groups. Renal function followed longitudinally was consistently better in SCD patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection, and graft loss (P < 0.05), but the effects were less pronounced in the ECD group. CONCLUSIONS: By appropriate donor and recipient profiling and the use of management algorithms to project and protect renal function, excellent intermediate-term outcomes can be achieved with ECD kidney transplants that are comparable to SCD kidney transplants.     

Does mini‐incision donor nephrectomy improve quality of life in living kidney donors?

BACKGROUND: Living kidney donation helps to avoid or reduce the time period of dialysis and on waiting lists in patients requiring a new organ. Mini-incision donor nephrectomy (MIDN) shows to result in better clinical outcome in comparison with traditional open donor nephrectomy (ODN). This study was performed to evaluate the impact of different surgical procedures on the quality of life (QoL) in patients that underwent donor nephrectomy. METHODS: The aim of the study was to detect differences in QoL assessed with the Short Form-36 Version 2 (SF-36v2) questionnaire between MIDN (n = 34) and ODN (n = 36). Furthermore, the development of QoL from prior to surgery until one yr afterwards, as well as outcomes of QoL in comparison with norm-based scores was investigated. RESULTS: Sixty-one of 70 patients, which is 87% (MIDN: 86%, ODN: 88%) resent a whole set questionnaires. QoL was similar at all time-points (prior to surgery, one wk, three months and one yr) in both groups. A tendency of better QoL in MIDN (Bodily Pain) after one wk was detectable (p = 0.075). Physical Component Summaries (PCS) significantly decreased from prior to surgery until one wk after surgery (p = 0.001) and improved significantly until three months (MIDN: p = 0.006, ODN: p = 0.001) and also until one yr after surgery (p = 0.002). Mental Component Summaries (MCS) were stable throughout the whole investigated time period. In comparison with norm-based scores, MIDN (p = 0.005) and ODN (p = 0.001) showed significantly higher PCS prior to, lower scores one wk after (p = 0.001), similar scores three months after and better scores (MIDN: p = 0.023, ODN: 0.015) one yr after surgery. Mental Component Scores were similar in both prior to and one wk after surgery. After three months and one yr scores were significantly better in MIDN (three months: p = 0.049, one yr: p = 0.037) and ODN (three months: 0.020, one yr: 0.073). CONCLUSION: Quality of life after living donor nephrectomy is not influenced by the surgical technique. Nevertheless the standardized instrument of the SF-36v2 Health Survey is a useful, practicable and universally interpretable tool to gain and estimate recovery from surgical procedures in the perioperative period and its development thereafter.     

Does graft mass impact on pediatric kidney transplant outcomes?

Background

The aim of this study is to assess the evolution of renal size and function in pediatric transplant patients according to the graft mass/recipient size ratio.

Methods

Fifty pediatric renal transplant recipients were followed over 2 years. Grafts were weighed, and three different graft mass/m² ratios were determined: (1) low graft mass (58 g/m², range?31–57 g/m²), (2) median (142 g/m², range?59–141 g/m²) and high (267 g/m², range?143–353 g/m²). Patients underwent repeated ultrasound Doppler scans and repeated measurements of estimated glomerular filtration rate (eGFR; 1 week and 1, 6, 12 and 24 months), urinary retinol-binding protein (RBP) and proteinuria (1 week and 6, 12 and 24 months).

Results

The volume of renal tissue increased by 12?±?5.6 cm³ at 24 months (p?=?0.035) in the low graft mass and decreased by ?14?±?7 cm³ (p?=?0.046) in the high graft mass. The eGFR increased when either low (30?±?5 ml/min/1.73 m², p?<?0.001) or median (19?±?4 ml/min/1.73 m², p?<?0.001) graft mass was transplanted but remained stable when high graft mass was transplanted. The resistive index (RI) presented a significant decrease throughout early follow-up in the transplants involving low and median graft mass, whereas a slight rise was observed in those involving high graft mass. A significant difference was apparent 6 months post-transplant. Transplants of low and median graft mass were associated with an initial higher urinary RBP. No significant differences in proteinuria were detected.

Conclusions

Small kidneys undergo increases in volume and function without escalation of either proteinuria or urinary RBP, characterizing an adequate adaptation to the recipient. Children receiving larger kidneys present a reduction in volume, stable GFR and higher RI at 6 months.     

Does cadaveric donor renal transplantation ever provide better outcomes than live-donor renal transplantation?

BACKGROUND: Live donor renal transplantation (LRT) now comprises more than 40% of all kidney transplants performed in the United States. Many patients on the cadaveric waiting list have a prospective live kidney donor. This study determines whether cadaveric donor renal transplantation (CRT) can demonstrate better outcomes than LRT. METHODS: From the United States Renal Data System registry, 31,909 adult recipients of a first-time kidney transplant from 1995 to 1998 were analyzed. Recipients were followed until December 31, 2000. RESULTS: CRT, more human leukocyte antigen (HLA) mismatches, increased donor age, cold ischemia time greater than 24 hr, African American recipient, and a history of diabetic nephropathy all increased the risk of graft failure, return to dialysis, and death. Nevertheless, in specific circumstances, CRT could provide better outcomes than LRT. For example, in recipients aged 18 to 59 years with a hypothetical live kidney donor aged 50 years and four HLA mismatches, the relative risk of graft loss with LRT is comparable or increased compared with CRT if the cadaveric kidney donor is much younger or with fewer HLA mismatches. On the other hand, for recipients aged 60 years or older, CRT never provides better outcomes than LRT. All analyses were adjusted for recipient race, gender, and history of diabetic nephropathy. There were no significant interactions among donor type, HLA mismatches, donor age, and cold ischemia time. CONCLUSIONS: The elderly recipient with an imminent LRT should never be offered CRT. A combination of recipient and donor factors can make CRT preferable to LRT in younger patients.     

Does donor brain death influence acute vascular rejection in the kidney transplant?

BACKGROUND: There is increasing experimental evidence to suggest that donor brain death enhances susceptibility to early inflammatory responses such as acute rejection in the kidney transplant. The aim of the present study was to establish whether the injury induced or aggravated by donor brain death could exert an effect on recipient immunologic tolerance by comparing data from patients receiving a kidney from non-heart-beating donors (NHBD) or from brain-dead donors (BDD). METHODS: We reviewed data corresponding to 372 renal transplants performed from January 1996 to May 2002. The data were stratified according to donor type as 197 (53%) brain-dead and 175 (47%) non-heart-beating donors, and the two groups were compared in terms of acute vascular rejection by Cox's regression analysis. RESULTS: The rate of vascular rejection was 28% in the BDD group and 21.7% in the NHBD (P=0.10). The following predictive variables for acute vascular rejection were established: brain death [RR 1.77 (95% CI 1.06-3.18)], presence of delayed graft function [RR 3.33 (1.99-5.55)], previous transplant [RR 2.35 (1.34-4.13)], recipient age under 60 years [RR 1.86 (0.99-2.28)], female recipient [RR 1.50 (0.99-2.28)], cerebrovascular disease as cause of donor death [RR 1.72 (1.02-2.91)], and triple therapy as immunosuppressive treatment. CONCLUSION: Donor brain death could be a risk factor for the development of vascular rejection in kidney recipients. This process could affect the quality of the graft and host alloresponsiveness. Delayed graft function in transplants from dead brain donors could be a reflection of severe autonomic storm, leading to a higher incidence of vascular rejection in these patients.     

Does kidney transplantation with multiple arteries affect graft survival?

Introduction

We compared short- and long-term outcomes of renal transplants with single versus multiple arteries.

Patients and methods

We retrospectively analyzed data from kidney transplants from 208 living donors performed between 1994 and 2010. Renal grafts were divided into two groups: single renal artery (n = 164) versus multiple renal arteries (n = 44). The groups were compared regarding early and late vascular and urological complications. Patient and graft survivals were compared using Kaplan-Meier survivorship curves with comparisons using the log-rank test.

Results

Both groups were comparable regarding acute rejection episodes, posttransplant hypertension, postsurgery renal artery stenosis, and urologic complications. Only hemorrhagic complications and renal artery thrombosis were significantly higher in the multiple renal arteries group (P = .027 and .03, respectively). Warm ischemia time was significantly longer in the multiple renal arteries group without any influence on the incidence of acute tubular necrosis (P = .2). Mean creatinine clearance at 1 year was 65 versus 50 mL/min/1.73 m² (P = .5) and at 5 years, 60 versus 55 mL/min/1.73 m² (P = .1) for the single versus multiple renal arteries groups, respectively. Return to hemodialysis was necessary for 18.8% of the single and 16.1% of the multiple renal arteries group.

Conclusion

The use of an allograft with multiple renal arteries is a safe, successful surgical procedure, that does not influence patient or graft survivals or increase surgical complication rates provided the surgical team is evolved with technical skill.