P Domagała

Machine Perfusion Preservation Improves Renal Allograft Survival

Machine perfusion (MP) has been used as the kidney preservation method in our center for over 10 years. The first, small (n = 74) prospective, single‐blinded randomized study comparing MP and Cold Storage (CS) showed that the incidence of delayed graft function was higher after CS. There have been no reports in the literature on the effect of storage modality on long‐term function of renal allografts. This paper presents an analysis of long‐term results of renal transplantation in 415 patients operated on between 1994 and 1999. Of those, 227 kidneys were MP‐stored prior to KTx. The control group consisted of 188 CS kidney transplants. Kidneys were not randomized to MP or to CS. Donor demographics, medical and biochemical data, cold ischemia time, HLA match and recipient data were collected. Standard triple‐drug immunosuppression was administered to both groups. Mortality, graft survival and incidence of return to hemodialysis treatment were analyzed. Despite longer cold ischemia time and poorer donor hemodynamics in MP group, 5‐year Kaplan‐Meier graft survival was better in MP‐stored than in CS‐stored kidneys (68.2% vs. 54.2%, p = 0.02). Conclusion: In this nonrandomized analysis, kidney storage by MP improved graft survival and reduced the number of patients who returned to dialysis.

One-year results of a prospective, randomized trial comparing two machine perfusion devices used for kidney preservation.

Studies have shown beneficial effects of machine perfusion (MP) on early kidney function and long‐term graft survival. The aim of this study was to investigate whether the type of perfusion device could affect outcome of transplantation of deceased donor kidneys. A total of 50 kidneys retrieved from 25 donors were randomized to machine perfusion using a flow‐driven (FD) device (RM3; Waters Medical Inc) or a pressure‐driven (PD) device (LifePort; Organ Recovery Systems), 24 of these kidneys (n = 12 pairs; 48%) were procured from expanded criteria donors (ECD). The primary endpoints were kidney function after transplantation defined using the incidence of delayed graft function (DGF), the number of hemodialysis sessions required, graft function at 12 months, and analyses of biopsy. DGF was similar in both groups (32%; 8/25). Patients with DGF in the FD group required a mean of 4.66 hemodialysis sessions versus 2.65 in the PD group (P = 0.005). Overall, 1‐year graft survival was 80% (20/25) vs. 96% (24/25) in the FD and PD groups. One‐year graft survival of ECD kidneys was 66% (8/12) in the FD group versus 92% (11/12) in the PD group. Interstitial fibrosis and tubular atrophy were significantly more common in the FD group – 45% (5/11) vs. 0% (0/9) (P = 0.03) in PD group. There were no differences in creatinine levels between the groups. Machine perfusion using a pressure‐driven device generating lower pulse stress is superior to a flow‐driven device with higher pulse stress for preserving kidney function.

Assessment of Kidneys Procured From Expanded Criteria Donors Before Transplantation

BACKGROUND Using expanded criteria donor (ECD) organs is 1 strategy to make more organs available for transplant. To reduce the number of posttransplant complications and failures, there is a need to create a comprehensive system of evaluation before transplantation, especially for kidneys harvested from ECD. The aim of this study was to assess the results of kidneys procured from ECD seeking to discover the most useful factors for kidney evaluation before transplantation. PATIENTS AND METHODS One hundred seventy-two patients received cadaveric renal transplants between January 1, 2006, and August 31, 2008. We collected data on donors, recipients, and perfusion parameters. We analyzed patient and graft survivals, as well as immediate, delayed, and slow graft function. Kidney recipient function was assessed by serum creatinine concentrations and by creatinine clearance calculated according to the Cockroft-Gault formula. Renal biopsy specimens were obtained in the perioperative periods 147 cases. RESULTS The overall 1-year graft survival was 86.9%. More than 25% of transplanted kidneys were harvested from ECD. There were no significant differences in patient survival between recipients of standard criteria donor kidneys (RSCDK) versus of expanded criteria donor kidneys (RECDK). One-year graft survival was higher among the RSCDK group than the RECDK group, namely, 94.4% versus 62.5%, (P = .004). There were no differences in the incidence of primary nonfunction or in delayed graft function between the groups. RECDK were more likely to show slow graft function (69.2% vs 37.8%; P = .033). A lower graft survival at 6 months after transplantation was observed among organs harvested from ECD compared with standard criteria donor (SCD) kidneys who showed histologic lesions or a flow at the fourth hour of machine perfusion below 0.4 mL/g. Using a logistic regression model, chronic histologic changes were shown to influence kidney survival at 6 months after transplantation. CONCLUSION There was no significant difference in patient survival between recipients of kidneys harvested from expanded versus standard criteria donors. ECD kidneys displayed lower graft survival rates. There was no significant difference in the incidence of delayed graft function between recipients of kidneys harvested from expanded versus standard criteria donors. Pretransplant evaluation of ECD kidneys should include 3 variables: donor parameters, histologic findings, and machine perfusion parameters.

Complications of Transplantation of Kidneys From Expanded-Criteria Donors

BACKGROUND Organ shortage is the primary barrier to kidney transplantation. To maximize organ use, organs from expanded-criteria donors (ECDs) have been used increasingly. Expanded-criteria donors are defined as individuals older than 60 years or older than 50 years with at least 2 of the following risk factors: hypertension, stroke as the cause of death, or serum creatinine concentration greater than 1.5 mg/dL. OBJECTIVE To assess the incidence of complications posttransplantation in ECD kidneys compared with kidneys from standard-criteria cadaveric donors (SCDs). PATIENTS AND METHODS One hundred seventy-two patients received cadaveric renal transplants between January 1, 2006, and August 31, 2008. Donor and recipient data were collected, as well as patient and graft survival and immediate, delayed, or slow graft function. Complication rates for lymphocele, urinary leak, thrombosis, hematoma, urinary tract infection, and cytomegalovirus infection were recorded. Follow-up was for 3 to 35 months, ending on November 30, 2008. RESULTS Overall, mean 1-year graft survival was 86.9%, and mean creatinine concentration was 1.58 mg/dL. One incidence of primary nonfunction (0.6%) was observed. More than 25% of transplanted kidneys were from ECDs. No significant differences were noted in postoperative complications between recipients of ECD or SCD organs. CONCLUSION The rate of complications in recipients of ECD and SCD kidneys is comparable.

The Assessment of Residual Kidney Function After Living Donor Nephrectomy

BACKGROUND The number of patients on the waiting list for kidney transplantation is increasing as a result of the cadaveric donor shortage. One way to expand the pool is living donor transplantation. However, only 2% of kidney transplants in Poland come from living-related donors. AIM We sought to assess residual renal function, incidence of hypertension, and proteinuria among living kidney donors. PATIENTS AND METHODS Between 2004 and 2007, we performed 46 living donor open nephrectomies. The mean age of the kidney donor was 39 years (range, 25-57). The donors were predominantly females (61%). Mean hospitalization time was 8 days (range, 4-22). Nine donors did not report for follow-up visits. The observation periods ranged from 1 to 24 months. Physical examination, blood and urine tests, as well as ultrasound scans were performed before nephrectomy and at every follow-up visit (1, 3, 12, and 24 months post operatively). RESULTS Mean creatinine concentration was higher at 3 months after nephrectomy than preoperatively (P < .05). Mean creatinine clearance according to Cockroft-Gault formula and mean creatinine clearance according to abbreviated modification of diet in renal disease equation (aMDRD) decreased after donation by 30% (P < .05). No cases of proteinuria were observed. Hypertension occurred in 1 donor (2.7%). CONCLUSION Living kidney donation resulted in a reduced creatinine clearance in the donor. Follow-up of living kidney donors is essential to determine risk factors for deterioration of residual kidney function.

Preservation of kidneys by machine perfusion influences gene expression and may limit ischemia/reperfusion injury

Context Machine perfusion improves graft survival. Histopathologic analysis reveals a lower incidence of chronic rejection and interstitial fibrosis in kidneys preserved with machine perfusion. Ischemic/reperfusion injury may help to explain these findings. Objective To assess the activation of genes correlated with ischemic/reperfusion injury in kidneys preserved under different conditions before transplant. Design/Patients Between 2005 and 2006, 69 kidney biopsy specimens were collected and patients were followed up for 5 years after that. Intervention Before transplant, kidneys were preserved with machine perfusion or cold storage. Donors from the machine perfusion and cold storage groups did not differ with regard to age, sex, or hemodynamic status. Recipients were divided into 5 groups: expanded criteria donor–machine perfusion (n = 16), standard criteria donor–machine perfusion (n = 10), expanded criteria donor–cold storage (n = 9), and standard criteria donor–cold storage (n = 27); 7 kidneys were retrieved from living related donors. Main Outcome Measures Biopsies were done 30 minutes after reperfusion. Interleukin-1β, vascular endothelial growth factor, heme oxygenase-1, and hypoxia-inducible factor–1 gene expression levels were analyzed. Results Mean expression levels of hypoxia-inducible factor–1α were significantly higher in the cold storage groups, and lower in the machine perfusion and living-related donor groups. Five-year graft survival was significantly (P < .05) lower in the expanded criteria donor–cold storage group (66%) than in the standard criteria donor–machine perfusion group (90%). Machine perfusion influences gene expression related to hypoxia during reperfusion and may improve the long-term results of kidney transplant.

Surgical site infections in the early posttransplant period after simultaneous pancreas-kidney transplantation.

OBJECTIVE Urinary tract infection (UTI) is among the common infection in simultaneous pancreas-kidney transplantation (SPKT). PATIENTS AND METHODS The study included 26 adult patients undergoing SPKT between September 2001 and December 2006. All the patients were followed prospectively for UTI during the first 4 weeks after surgery. Urine samples were investigated for bacteriologic cultures. The micro-organisms were identified in accordance with standard bacteriologic procedures. Susceptibility testing was carried out using Clinical and Laboratory Standards Institute (CLSI) procedures. RESULTS Among 77 urine specimens obtained from all recipients during the first month, there were 30 isolated bacterial strains. The most common were Gram-positive bacteria (53.3%) with predominance of enterococci (75%) associated with high levels of aminoglycoside resistant strains (HLAR; 58.3%) and vancomycin-resistant strains (VRE; 25%). Gram-negative bacteria were detected in 46.7% of positive cultures. CONCLUSIONS In our study, enterococci predominated as 75% of Gram-positive isolates. The increased proportion of multi-drug-resistant bacteria, which can caused severe UTI in patients after SPKT, may be due to the frequent use of prophylaxis of bacterial infections in patients.

Etiologic agents of bacteremia in the early period after simultaneous pancreas-kidney transplantation.

BACKGROUND Bacteremia is among the known complications in simultaneous pancreas-kidney transplantation (SPKT). This study evaluated the frequency of microbial isolates and their susceptibility profiles among cultures of clinical samples obtained from blood and from the tips of blood vessel catheters of 26 SPKT recipients suspected of bacteremia in the early posttransplant period. PATIENTS AND METHODS Data on microbiologic blood cultures of 26 adult patients undergoing SPKT were collected prospectively from 2001 to the end of 2006. The isolation and identification of cultured microorganisms were performed according to standard microbiological procedures and commercially available tests. The susceptibility of the strains to antibacterial agents was established by the Clinical and Laboratory Standards Institute guidelines. RESULTS All patients were followed prospectively for the first 4 weeks after surgery. Among 66 clinical samples, there were 23 microbial isolates from blood samples of 17 recipients and catheter tips of 12 recipients. The most common isolates were Gram-positive bacteria (73.9%) with domination of staphylococci (64.7%) and MRCNS strains (81.8%). Gram-negative bacteria comprised 17.4% of positive cultures, whereas yeast-like fungi, 8.7% with a predominance of Candida glabrata. CONCLUSION Our study showed predominately Gram-positive bacteria in 73.9% of isolates. The increased proportion of multi-drug-resistant bacteria and fungi to antimicrobial agents may be due to the frequent use of these agents for prophylaxis of bacterial infections in patients.

Serum concentration of vitamin D and parathyroid hormone after living kidney donation.

BACKGROUND Metabolic consequences resulting from loss of renal mass in living kidney donors remain uncertain. There is recent focus on the changes in the active form of vitamin D because it is an agent for cancer regulation. The objective of the study was to measure serum concentrations of 1,25-dihydroxycholecalciferol, parathyroid hormone and insulin-like growth factor-1 (IGF-1) in living donors after kidney donation. PATIENTS AND METHODS Forty living kidney donors reported for follow-up visits. Their mean age was 46.14 years. They were women in 52.5% of cases. The mean observation period was 65.6 months. Serum 1,25(OH)2D3 and IGF-1 concentrations were measured by radioimmunoassay after extraction. Serum intact parathyroid hormone (PTH) was quantified using an enhanced chemiluminescence immunoassay system. RESULTS 1,25-dihydroxycholecalciferol deficiency in 57.5% patients after nephrectomy was the most important change we noted. No correlation was observed between 1,25(OH)2D3 and PTH. A decreased serum IGF-1 concentration was observed in 17.5% of donors. However, decreases in both serum IGF-1 and 1,25(OH)2D3 concentrations were observed in 12.5% of donors. CONCLUSION Prospective studies may be essential to determine metabolic changes after nephrectomy among living kidney donors.

The effect of the use of a TNF-alpha inhibitor in hypothermic machine perfusion on kidney function after transplantation

One of the most important problems in transplantation medicine is the ischemia/reperfusion injury of the organs to be transplanted. The aim of the present study was to assess the effect of tumor necrosis factor-alpha (TNF-alpha) inhibitor etanercept on the machine perfusion hypothermia of renal allograft kidney function and organ perfusion. No statistically significant differences were found in the impact of the applied intervention on kidney machine perfusion during which the average flow and vascular resistance were evaluated. There were no statistically significant differences in the occurrence of delayed graft function (DGF). Fewer events in patients who received a kidney from the etanercept treated Group A compared to the patients who received a kidney from the control Group B were observed when comparing the functional DGF and occurrence of acute rejection episodes, however, there was no statistically significant difference. In summary, no effect of treatment with etanercept an inhibitor of TNF-alpha in a hypothermic machine perfusion on renal allograft renal survival and its perfusion were detected in this study. However, treatment of the isolated organ may be important for the future of transplantation medicine.