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Background: The objective of this study was to evaluate the influence of recipient underweight on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT)., Patients and Methods: Three hundred thirty-three patients receiving primary KT in our department between 1993 and 2017 were included in the study. Patients were divided according to their body mass index (BMI) into underweight (BMI <18.5 kg/m 2 ; N = 29) and normal weight (BMI 18.5-24.9 kg/m 2 ; N = 304) groups. Clinicopathological characteristics, postoperative outcomes, and graft and patient survival were analyzed retrospectively., Results: The postoperative rate of surgical complications and renal function were comparable between the groups. One year and 3 years after KT, 70% and 92.9%, respectively, of the pre-transplant underweight patients reached a normal BMI (≥18.5 kg/m 2 ). The mean death-censored graft survival was significantly lower in pre-transplant underweight patients than in pre-transplant normal-weight patients (11.5 ± 1.6 years vs 16.3 ± 0.6 years, respectively; P = .045). Especially KT recipients with a moderate or severe pre-transplant underweight (BMI <17 kg/m 2 ; N = 8) showed an increased rate of graft loss (5- and 10-year graft survival: 21.4% each). No statistical difference could be observed between the 2 groups regarding causes of graft loss. In multivariate analysis, recipient underweight (P = .024) remained an independent prognostic factor for graft survival., Conclusion: Being underweight did not affect the early postoperative outcome after primary KT. However, underweight, and especially moderate and severe thinness, is associated with reduced long-term kidney graft survival, and therefore this group of patients should be monitored with special attention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Kidney transplantation with grafts procured after donation-after-cardiac death (DCD) has led to an increase in incidence of delayed graft function (DGF). It is thought that the warm ischemic (WI) insult encountered during DCD procurement is the cause of this finding, although few studies have been designed to definitely demonstrate this causation in a transplantation setting. Here, we use a large animal renal transplantation model to study the effects of prolonged WI during procurement on post-transplantation renal function. Kidneys from 30 kg-Yorkshire pigs were procured following increasing WI times of 0 min (Heart-Beating Donor), 30 min, 60 min, 90 min, and 120 min (n = 3-6 per group) to mimic DCD. Following 8 h of static cold storage and autotransplantation, animals were followed for 7-days. Significant renal dysfunction (SRD), resembling clinical DGF, was defined as the development of oliguria < 500 mL in 24 h from POD3-4 along with POD4 serum potassium > 6.0 mmol/L. Increasing WI times resulted in incremental elevation of post-operative serum creatinine that peaked later. DCD120min grafts had the highest and latest elevation of serum creatinine compared to all groups (POD5: 19.0 ± 1.1 mg/dL, p < 0.05). All surviving animals in this group had POD4 24 h urine output < 500 cc (mean 235 ± 172 mL) and elevated serum potassium (7.2 ± 1.1 mmol/L). Only animals in the DCD120min group fulfilled our criteria of SRD (p = 0.003), and their renal function improved by POD7 with 24 h urine output > 500 mL and POD7 serum potassium < 6.0 mmol/L distinguishing this state from primary non-function. In a transplantation survival model, this work demonstrates that prolonging WI time similar to that which occurs in DCD conditions contributes to the development of SRD that resembles clinical DGF., (© 2021. The Author(s).)

Background: Better preservation strategies for the storage of donation after circulatory death grafts are essential to improve graft function and to increase the kidney donor pool. We compared continuous normothermic ex vivo kidney perfusion (NEVKP) with hypothermic anoxic machine perfusion (HAMP) and static cold storage (SCS) in a porcine kidney autotransplantation model., Methods: Porcine kidneys were exposed to 30 minutes of warm ischemia and then reimplanted following either 16 hours of either SCS, HAMP (LifePort 1.0), or NEVKP before autotransplantation (n = 5 per group). The contralateral kidney was removed. Animals were followed for 8 days., Results: Grafts preserved by NEVKP demonstrated improved function with more rapid recovery compared with HAMP and SCS (mean peak serum creatinine: 3.66 ± 1.33 mg/dL [postoperative d 1 [(POD1)], 8.82 ± 3.17 mg/dL [POD2], and 12.90 ± 2.19 mg/dL [POD3], respectively). The NEVKP group demonstrated significantly increased creatinine clearance calculated on POD3 (63.6 ± 19.0 mL/min) compared with HAMP (13.5 ± 10.3 mL/min, P = 0.001) and SCS (4.0 ± 2.6 mL/min, P = 0.001). Histopathologic injury scores on POD8 were lower in both perfused groups (NEVKP and HAMP, score: 1-1.5) compared with SCS (score: 1-3, P = 0.3), without reaching statistical significance., Conclusions: NEVKP storage significantly improved early kidney function compared with both cold preservation strategies, although HAMP also demonstrates improvement over SCS. NEVKP may represent a novel, superior preservation option for donation after circulatory death renal grafts compared with conventional hypothermic methods.

Normothermic ex vivo kidney perfusion (NEVKP) represents a novel approach for graft preservation and functional improvement in kidney transplantation. We investigated whether NEVKP also allows graft quality assessment before transplantation. Kidneys from 30-kg pigs were recovered in a model of heart-beating donation (group A) after 30 minutes (group B) or 60 minutes (group C) (n = 5/group) of warm ischemia. After 8 hours of NEVKP, contralateral kidneys were resected, grafts were autotransplanted, and the pigs were followed for 3 days. After transplantation, renal function measured based on peak serum creatinine differed significantly among groups (P < .05). Throughout NEVKP, intrarenal resistance was lowest in group A and highest in group C (P < .05). intrarenal resistance at the initiation of NEVKP correlated with postoperative renal function (P < .001 at NEVKP hour 1). Markers of acid-base homeostasis (pH, HCO 3 - , base excess) differed among groups (P < .05) and correlated with posttransplantation renal function (P < .001 for pH at NEVKP hour 1). Similarly, lactate and aspartate aminotransferase were lowest in noninjured grafts versus donation after circulatory death kidneys (P < .05) and correlated with posttransplantation kidney function (P < .001 for lactate at NEVKP hour 1). In conclusion, assessment of perfusion characteristics and clinically available perfusate biomarkers during NEVKP allows the prediction of posttransplantation graft function. Thus, NEVKP might allow decision-making regarding whether grafts are suitable for transplantation., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Kidney transplantation is the treatment of choice for end-stage renal disease. Despite its superiority over dialysis, the persisting organ shortage remains a major drawback. Additional sources to increase the donor pool are grafts recovered from extended criteria donors (ECD) and donation after circulatory death (DCD). Although transplantation of marginal grafts demonstrates promising outcomes, increased rates of primary non-function, delayed graft function, and reduced graft survival have been reported. Cold ischemic injury, caused by static cold storage is a significant risk factor for poor outcome. Machine perfusion (MP) at various temperatures bears the potential to improve organ preservation, assessment, and repair. While hypothermic machine perfusion (HMP) is well established in clinical practice, modified HMP, subnormothermic machine perfusion (SMP), and normothermic machine perfusion (NMP) are novel emerging strategies with the potential to significantly improve the outcome of marginal kidney grafts. This review summarizes findings and recent advances from pre-clinical and clinical machine perfusion studies, organized by temperature, and discusses potential future developments for graft assessment and repair., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Normothermic ex vivo kidney perfusion (NEVKP) demonstrated superior results compared to hypothermic storage in donation after circulatory death (DCD) kidney transplantation. It is unknown whether an optimal perfusion time exists following hypothermic storage to allow for the recovery of renal grafts from cold ischemic injury. In a porcine model of DCD kidney autotransplantation, the impact of initial static cold storage (SCS) (8 h) followed by various periods of NEVKP recovery was investigated: group A, 8 hSCS only (control); group B, 8 hSCS + 1 hNEVKP (brief NEVKP); group C, 8 hSCS + 8 hNEVKP (intermediate NEVKP); and group D, 8 hSCS + 16 hNEVKP (prolonged NEVKP). All grafts were preserved and transplanted successfully. One animal in group D was sacrificed and excluded by postoperative day 3 due to hind limb paralysis, but demonstrated good renal function. Postoperative graft assessment during 8 days' follow-up demonstrated lowest levels of peak serum creatinine for intermediate (C) and prolonged (D) NEVKP (p = 0.027). Histological assessment on day 8 demonstrated a significant difference in tubular injury (p = 0.001), with highest values for group B. These results suggest that longer periods of NEVKP following SCS are feasible and safe for postponing surgical transplant procedure and superior to brief NEVKP, reducing the damage caused during cold ischemic storage of renal grafts., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Donation after circulatory death (DCD) is current clinical practice to increase the donor pool. Deleterious effects on renal graft function are described for hypothermic preservation. Therefore, current research focuses on investigating alternative preservation techniques, such as normothermic perfusion., Methods: We compared continuous pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) with static cold storage (SCS) in a porcine model of DCD autotransplantation. After 30 minutes of warm ischemia, right kidneys were removed from 30-kg Yorkshire pigs and preserved with 8-hour NEVKP or in 4°C histidine-tryptophan-ketoglutarate solution (SCS), followed by kidney autotransplantation., Results: Throughout NEVKP, electrolytes and pH values were maintained. Intrarenal resistance decreased over the course of perfusion (0 hour, 1.6 ± 0.51 mm per minute vs 7 hours, 0.34 ± 0.05 mm Hg/mL per minute, P = 0.005). Perfusate lactate concentration also decreased (0 hour, 10.5 ± 0.8 vs 7 hours, 1.4 ± 0.3 mmol/L, P < 0.001). Cellular injury markers lactate dehydrogenase and aspartate aminotransferase were persistently low (lactate dehydrogenase < 100 U/L, below analyzer range; aspartate aminotransferase 0 hour, 15.6 ± 9.3 U/L vs 7 hours, 24.8 ± 14.6 U/L, P = 0.298). After autotransplantation, renal grafts preserved with NEVKP demonstrated lower serum creatinine on days 1 to 7 (P < 0.05) and lower peak values (NEVKP, 5.5 ± 1.7 mg/dL vs SCS, 11.1 ± 2.1 mg/dL, P = 0.002). The creatinine clearance on day 4 was increased in NEVKP-preserved kidneys (NEVKP, 39 ± 6.4 vs SCS, 18 ± 10.6 mL/min; P = 0.012). Serum neutrophil gelatinase-associated lipocalin at day 3 was lower in the NEVKP group (1267 ± 372 vs 2697 ± 1145 ng/mL, P = 0.029)., Conclusions: Continuous pressure-controlled NEVKP improves renal function in DCD kidney transplantation. Normothermic ex vivo kidney perfusion might help to decrease posttransplant delayed graft function rates and to increase the donor pool.

Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) versus short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS versus prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 min of warm ischemia, kidneys were removed from 30-kg Yorkshire pigs and preserved for 16 h with (A) 16 h SCS, (B) 15 h SCS + 1 h NEVKP, (C) 8 h SCS + 8 h NEVKP, and (D) 16 h NEVKP. After contralateral kidney resection, grafts were autotransplanted and pigs followed up for 8 days. Perfusate injury markers such as aspartate aminotransferase and lactate dehydrogenase remained low; lactate decreased significantly until end of perfusion in groups C and D (p < 0.001 and p = 0.002). Grafts in group D demonstrated significantly lower serum creatinine peak when compared to all other groups (p < 0.001) and 24-h creatinine clearance at day 3 after surgery was significantly higher (63.4 ± 19.0 mL/min) versus all other groups (p < 0.001). Histological assessment on day 8 demonstrated fewer apoptotic cells in group D (p = 0.008). In conclusion, prolonged, continuous NEVKP provides superior short-term outcomes following DCD kidney transplantation versus SCS or short additional NEVKP following SCS., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Hypothermic kidney storage causes preservation injury and is poorly tolerated by renal grafts. We investigated whether static cold storage (SCS) can be safely replaced with a novel technique of pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) in heart-beating donor kidney transplantation., Methods: Right kidneys were removed from 30 kg Yorkshire pigs in a model of heart-beating donation and either preserved in cold histidine-tryptophan-ketoglutarate solution for 8 hours (n = 5), or subjected to 8 hours of pressure-controlled NEVKP (n = 5) followed by renal heterotopic autotransplantation., Results: During NEVKP, physiologic perfusion conditions were maintained with low intrarenal resistance and normal electrolyte and pH parameters. Aspartate aminotransferase and lactate dehydrogenase as injury markers were below the detectable analyzer range (<4 and <100 U/L, respectively). Perfusate lactate concentration decreased from baseline until the end of perfusion (10.38 ± 0.76 mmol/L vs 1.22 ± 0.26 mmol/L; P < 0.001). Posttransplantation, animals transplanted with NEVKP versus SCS grafts demonstrated similar serum creatinine peak levels (NEVKP, 2.0 ± 0.5 vs SCS 2.7 ± 0.7 mg/dL; P = 0.11) and creatinine clearance on day 10 (NEVKP, 65.9 ± 18.8 mL/min vs SCS 61.2 ± 15.6 mL/min; P = 0.74). After 10 days of follow-up, animals transplanted with NEVKP grafts had serum creatinine and blood urea nitrogen values comparable to their basal levels (P = 0.49 and P = 0.59), whereas animals transplanted with SCS grafts had persistently elevated serum creatinine and blood urea nitrogen when compared with basal levels (P = 0.01 and P = 0.03)., Conclusions: Continuous pressure-controlled NEVKP is feasible and safe in good quality heart-beating donor kidney grafts. It maintains a physiologic environment and excellent graft function ex vivo during preservation without causing graft injury.

Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration. Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre- and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication.

Kidney transplantation has become a well-established treatment option for patients with end-stage renal failure. The persisting organ shortage remains a serious problem. Therefore, the acceptance criteria for organ donors have been extended leading to the usage of marginal kidney grafts. These marginal organs tolerate cold storage poorly resulting in increased preservation injury and higher rates of delayed graft function. To overcome the limitations of cold storage, extensive research is focused on alternative normothermic preservation methods. Ex vivo normothermic organ perfusion is an innovative preservation technique. The first experimental and clinical trials for ex vivo lung, liver, and kidney perfusions demonstrated favorable outcomes. In addition to the reduction of cold ischemic injury, the method of normothermic kidney storage offers the opportunity for organ assessment and repair. This manuscript provides information about kidney retrieval, organ preservation techniques, and isolated ex vivo normothermic kidney perfusion (NEVKP) in a porcine model. Surgical techniques, set up for the perfusion solution and the circuit, potential assessment options, and representative results are demonstrated.

Introduction: Simultaneous pancreas-kidney transplantation (SPK) is a standardized and life-saving procedure for a patient suffering from both insulin-dependent diabetes mellitus type 1 (IDDM 1) and end-stage diabetic nephropathy. To expand the donor pool and to determine the influence of the preprocurement pancreas suitability scoring system (P-PASS) on pancreas graft survival we retrospectively analyzed our data on SPK., Patients and Methods: From 1999 to 2010 we performed 55 SPKs, using systemic-enteric drainage as surgical approach. The immunosuppressive therapy was induced with basiliximab; maintenance therapy was based on tacrolimus, mycophenolate mofetil, and steroids. Data were prospectively obtained, analyzed, and correlated to the P-PASS., Results: The overall 10-year patient survival rate was 78% with a 10-year pancreas survival rate of 53%. Three patients needed retransplantation of SPK and 6 patients needed singular pancreas retransplantation. Seventeen patients showed acute rejection episodes and 14 patients suffered from cytomegalovirus (CMV) infections. We compared 43 patients receiving organs from an "ideal" donor (P-PASS <17) with 12 patients receiving grafts from "marginal" donors (P-PASS ≥17). Neither P-PASS nor donor age demonstrated significant influence on pancreas graft survival. However, the body mass index (BMI) of the donor showed a negative tendency (P = .059)., Conclusion: The P-PASS showed no significant prediction of pancreas graft survival. In view of our data, expansion of the German donor pool is possible. A multicenter study of SPK using "marginal" pancreas grafts is mandatory to define a realistic "cut-off" value for P-PASS., (Copyright © 2011 Elsevier Inc. All rights reserved.)