G. Feliciangeli

The Kidney Donor Profile Index (KDPI) of marginal donors allocated by standardized pretransplant donor biopsy assessment: distribution and association with graft outcomes.

Pretransplant donor biopsy (PTDB)‐based marginal donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the highest range (e.g. >80 or >90), whose discard rate approximates 50% in the United States. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score <4 [median KDPI: 87; interquartile range (IQR): 78–94] and 62 with a score = 4 [median KDPI: 87; IQR: 76–93]; 102 dual transplants [median KDPI: 93; IQR: 86–96]) and 248 single standard transplant controls (median KDPI: 36; IQR: 18–51). PTDB‐based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80–90 and of 37% for kidneys with a KDPI of 91–100. Although 1‐year estimated GFRs were significantly lower in recipients of marginal kidneys (−9.3, −17.9 and −18.8 mL/min, for dual transplants, single kidneys with PTDB score <4 and =4, respectively; p < 0.001), graft survival (median follow‐up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 [95% confidence interval: 0.80–1.79; p = 0.38]). In conclusion, PTDB‐based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.

Validity of flow cytometry for cross-match evaluation in clinical renal transplantation.

This paper reports a 2-year experience of more than 5,000 cross-match tests for renal transplantation. Tests were performed by means of both standard light microscopy and an innovatory method based on flow cytometry, an up-to-date investigative technique for computerized analysis of individual cell characteristics. Flow cytometry allowed a better detection of weak positive reactions (false-negative cross-matches) than light microscopy, thus reducing the risk of selecting candidates with donor presensitization. Transplant clinical outcome supported the value of this original and advanced technological method.

Renal transplant in patients with polycystic disease: the Italian experience.

We analyzed the results of kidney transplantation in autosomal dominent polycystic kidney disease (ADPKD) patients in Italy, including 14,305 transplantations performed from January 2002 to December 2010, including: 12,859 first single or double kidneys from cadaveric donors (13% polycystic), 172 combined liver-kidney cases (22% polycystic), and 1,303 living-donor organs (7% polycystic). Among the first transplantations (12,008 single, 851 double), with follow-ups ranging from 16 to 120 months, polycystic patients demonstrated better graft survival compared with other kidney diseases (86% vs 82% at 5 years; P < .01); mortality was not different (92% vs 79% at 1 year). A better trend was obtained also among combined liver-kidney transplantations in ADPKD. Regarding pretransplantation management of polycystic patients, we noticed a conservative attitude in 32/35 transplant centers. The main indication for nephrectomy was for the lack of abdominal space. Regarding instrumental studies, 86% of centers asked for second-level investigations computerized tomography for kidney dimensions. Radiologic investigations for vasculocerebral malformations were required in 97% of the centers: 74% as a routine and 23% in the presence of familial history of cerebral hemorrhage. Polycystic patients are good candidates for kidney transplantation with correct management before transplantation.

Kidney preservation: review of present and future perspective.

One of the main problems in transplant surgery is the preservation of the organ during the cold ischemic time. The interrupted blood supply triggers a cascade of biological modifications resulting in cell death, which predisposes to discharge of a large quantity of toxic metabolites at the moment of organ reperfusion. Many approaches have been studied to prevent the toxic processes. Immediately after procurement, kidneys are flushed with these solutions. Two main: techniques of organ preservation are cold static storage and hypothermic machine perfusion (HMP). Based on age and comorbidities, individuals can be generally divided into 2 groups: ideal and marginal donors. Characteristics of organs from marginal donors are associated with an increased rate of delayed graft function and primary graft nonfunction (PNF), which reduce transplant survival and increase the acute rejection risk. In the last 20 years, the United Network of Organ Sharing has reported a 170% increase in deceased donors older than 50 years of age. Techniques of perfusion have been demonstrated to play a pivotal role in graft function after transplantation. Some studies suggest that HMP may improve outcomes after transplantation.

Incidence of Late Deep Venous Thrombosis Among Renal Transplant Patients

BACKGROUND Kidney transplant recipients (KTRs) manifest hypercoagulable state that contributes to an increased incidence of deep vein thrombosis (DVT), not only early but also late in their course. KTRs display an imbalance of hemostatic mechanisms with a multifactorial rise in procoagulant factors, partly related to traditional risk factors and partly to transplantation. The aim of this study was to evaluate the incidence of first episodes of DVT among KTRs, focusing on risk factors. METHODS From 2008 to 2011, we evaluated 30 kidney transplant patients who ≥4 months there after transplantation developed DVT in the lower limbs only, lower limbs complicated by pulmonary embolism or retinal thrombosis. We analyzed causes of primary nephropathy, immunosuppressive regimen, post-transplantation infections, and erythrocytosis. DVT was diagnosed by color Doppler ultrasound or eye examination. RESULTS A significantly increased incidence of DVT was observed among patients receiving cyclosporine or cyclosporine + mammalian target of rapamycin inhibitors, affected by polycystic kidney diseases, systemic lupus erythematosus or nephrotic syndrome, or displaying rapid and/or excessive correction of hematocrit values. DVT was not significantly related to an acute infection (cytomegalovirus) or to the prior dialysis modality. CONCLUSIONS Hypercoagulability is a multifactorial condition in KTRs, representing a severe complication in stable patients. Prevention may consist of either accurate pretransplantation screening for thrombophilia or identification of patients at higher DVT risk.

Use of Combined Hemodialysis/Hemoperfusion in Chronic Uremia1

The capacity of charcoal to absorb endogenous and exogenous toxins is well established. It removes substances of higher molecular weight than standard dialysis membranes. The regular use of charcoal hemoperfusion as an adjunct to hemodialysis in chronic uremia is a real prospect capable of improving the patients clinical and laboratory condition and/or reducing the weekly time of treatment. In line with our previous experience, 5 consenting informed patients on regular dialysis treatment from 9 to 35 months (residual creatinine clearance 0-1.8 ml/min, mean diuresis 350 ml) were treated without interruption for 5-8 months according to a schedule including two combined hemodialysis/hemoperfusion procedures instead of the previous three hemodialysis sessions. Patients were on adequate dialysis and their clinical, metabolic and laboratory conditions were stable. In the hemodialysis/hemoperfusion procedure a cartridge containing 150 g of methacrylate-coated activated charcoal with high biocompatibility was inserted in the dialysis circuit in series with a flat plate or hollow fiber dialyzer. Clinical, laboratory and metabolic conditions remained unchanged in all patients despite the one third reduction in dialysis hours per week. The tolerance of treatment was good: platelets, white cells and fibrinogen were unaffected. The marked reduction in weekly time of treatment led to a more satisfactory personal and social rehabilitation, enabling more patients to be treated with the same facilities.

The impact of apoptosis and inflammation gene polymorphisms on transplanted kidney function

BACKGROUND The progressive deterioration of kidney allograft function leads in most cases to transplant failure. Polymorphisms in genes encoding for inflammatory and apoptosis molecules may be one possible explanation for interindividual differences in kidney transplant outcomes. The objective of our work was to identify the possible effect of interleukin 6 (IL-6), transforming growth factor beta 1 (TGFB1), and Fas on graft function. MATERIAL AND METHODS A case-control study was carried out to assess potential associations between polymorphisms in inflammation- and apoptosis-related genes and the risk for chronic impairment of kidney graft function. The study included 376 cadaveric kidney recipients, 256 of them with stable graft function and 120 who experienced renal deterioration during the follow-up period of 2.6 ± 1.4 years. Genotyping of IL-6/G-174C, TGFB1/L10P, TGFB1/R25P, and Fas/G-670A polymorphisms was performed by PCR-RFLP and direct sequencing. RESULTS Considering the single IL-6, TGFB1, and Fas polymorphisms, we found similar allelic and genotype frequencies between the 2 groups. To test the hypothesis of mutual effects of polymorphisms, multiple logistic regression was performed incorporating data for all the possible dual genotypic associations. The association of IL-6 high producer and Fas low producer genotype resulted in a protective effect against graft dysfunction (OR=0.79; 95% C.I.=0.72-0.86). CONCLUSIONS This study did not find significant associations of apoptosis and inflammation gene polymorphisms with transplanted kidney function in Italian renal transplant recipients. However, our data seem to indicate that the carriage of IL-6 high producer/Fas low producer genotype has a protective effect against graft function loss.

Induction Therapy With Alemtuzumab (Campath) in Combined Liver-Kidney Transplantation: University of Bologna Experience

BACKGROUND Combined liver-kidney transplantation (LKT) is considered to be a safe procedure, but the appropriate immunosuppressive regimen is unclear. PATIENTS AND METHODS Between January 1997 and October 2011, 55 patients were listed for LKT: 45 (82%) were effectively transplanted, 5 (9.2%) died whereon here the waiting list, 3 (5.5%) temporarily out of waiting list, 1 (1.8%) was on waiting list and 1 (1.8%) refused LKT. Five LKTs treated with cyclosporine (CyA) were excluded from the analysis. Mean recipient age was 50.32 ± 10.32 years (14-65), MELD score at time of LKT was 19.22 ± 4.69 (8-29), mean waiting list time was 8.14 ± 9.50 months (0.1-35.76), and follow-up, 4.09 ± 3.02 years (0.01-10.41). Main indications for LKT were policystic disease (n = 15; 37%), hepatitis virus C (HCV)-related cirrhosis (n = 9; 22%) metabolic disease (n = 5; 13%), hepatitis virus B (HBV) cirrhosis (n = 4; 10%), alcoholic cirrhosis (n = 4; 10%), and cholestatic disease (n = 3; 8%). Immunosuppressive regimen was based on tacrolimus and steroids in 40 cases with induction therapy with alemtuzumab (Campath; 0.3 mg/kg) in 13 of 40 instances cases administered on day 0 and day 7. RESULTS Postoperative mortality was 2.5%. Acute cellular rejection episodes were biopsy-proven in 2 (5%) cases, post-LKT infections developed in 17 cases (42.5%), and de novo cancer developed in 3 (7.5%) cases. Similar 5-year overall survivals were obtained irrespective of the LKT indication: 100% in cholestatic and alcoholic cirrhosis patients, 86% in policystic disease, 75% in metabolic disease and HBV patients, and 66% in HCV cirrhosis. Overall survivals for the alemtuzumab vs without-induction therapy groups at 1, 3, and 5-years were 100%, 85.7%, and 85.7% vs 76%, 76%, and 70%, respectively (P = .04). CONCLUSION An immunosuppressive regimen based on tacrolimus and steroids with induction therapy with alemtuzumab was safe, with excellent long-term results for combined LKT.

Prediction of Three-Year Outcome of Renal Transplantation from Optimal Donors versus Expanded Criteria Donors

Background/Aims: The shortage in organ supply has required the use of expanded criteria donors (ECD) for kidney transplantation. Current pre-transplant evaluations of ECD organs are based on histological, clinical or mixed criteria. This monocentric study investigates the predictivity of Karpinski’s histological score on 3-year graft function in renal transplant. Ex-post classification using Nyberg’s score was carried out to assess the reliability of a purely clinical score and its applicability for organ allocation. Methods: We evaluated 407 deceased donors (251 optimal and 156 ECD) for renal transplants performed between 2001 and 2006. The differences in creatinine levels and MDRD-GFR at transplant and 1, 2 and 3 years post-transplant between optimal donors and ECD were recorded. Amongst ECD organs, the effect of different Karpinski score classes (0–1, 2, 3, 4, double transplants) on 3-year graft outcomes was analyzed. We then compared renal function over time across the Nyberg grades (A, B, C, and D). Results: Karpinski scores 0–1 and 2 and double transplants were associated with improved graft function compared to scores 3 and 4. Nyberg’s clinical score shows a good fit with medium-term outcome and Karpinski’s score, but among the donors with a high Nyberg grade (C and D), it fails to differentiate between allocable or non-allocable organs (due to Karpinski’s score ≥7). Conclusions: Our data demonstrate a correlation of histological damage at the time of transplant with 3-year graft function, but at present we are unable to provide any supposition on the possible outcome of the discarded kidneys.

Importance of Renal Mass on Graft Function Outcome After 12 Months of Cadaveric Donor Kidney Transplantation

BACKGROUND Few studies have measured cadaveric kidney weight to investigate its relation to recipient kidney function related to it. The aim of this study was to evaluate kidney weight (cadaveric donor) and its relationship to creatinine clearance (CrCl) after 12 months posttransplantation. METHODS We evaluated 81 renal transplantation recipients from cadaveric donors. We collected donor and recipient demographic, clinical and anthropometric data. Data about kidney weight were obtained through kidney measurement using an electronic machine at the moment of transplantation. RESULTS The mean kidney weight was 201.4 +/- 10.2 g (200.5 +/- 11.6 g in women and 210.3 +/- 14.1 g in men). Kidney weight correlated with CrCl at 12 months (0.001). The CrCl at 12 months showed a significant correlation of graft weight/recipient weight ratio (P < .01). CONCLUSION The cadaveric donor kidney weight significantly influenced the CrCl at 12 months after transplantation.