Acute rejection in kidney transplantation and the evaluation of associated polymorphisms (SNPs): the importance of sample size.

Background Acute rejection (AR) is one of the most frequent complications after kidney transplantation (KT). Scientific evidence reports that some single-nucleotide polymorphisms (SNPs) located in genes involved in the immune response and in the pharmacokinetics and pharmacodynamics of immunosuppressive drugs are associated with rejection in renal transplant patients. The aim of this study was to evaluate some SNPs located in six genes: interleukin-10 (IL-10), tumor necrosis factor (TNF), adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1), uridine diphosphate glucuronosyltransferase family 1 member A9 (UGT1A9), inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2. Methods We enrolled cases with at least one AR after KT and two groups of controls: patients without any AR after KT and healthy blood donors. Genetic analysis on DNA was performed. The heterozygosity (HET) was determined and the Hardy-Weinberg equilibrium (HWE) test was performed for each SNP. The sample size was calculated using the QUANTO program and the genetic associations were calculated using the SAS program (SAS Institute Inc., Cary, NC, USA). Results In our previous preliminary study (sample size was not reached for cases), the results showed that patients with the C allele in the SNP rs1045642 and the A allele in the SNP rs2032582 of the ABCB1 gene had more frequent AR. In contrast, with the achievement of sample size, the trend of the previous data was not confirmed. Conclusions Our study highlights a fundamental aspect of scientific research that is generally presumed, i.e. the sample size of groups enrolled for a scientific study. We believe that our study will make a significant contribution to the scientific community in the discussion of the importance of the analysis and the achievement of sample size to evaluate the associations between SNPs and the studied event.

Rationale for the Evaluation of Renal Functional Reserve in Living Kidney Donors and Recipients: A Pilot Study.

BACKGROUND: In living kidney transplantation, preoperative donors' renal functional reserve (RFR) may correlate with postoperative residual renal function in both donors and recipients. The aim of this study was to evaluate the donors' RFR before transplantation and to compare basal and stress renal function before and after transplantation in both donors and recipients. METHODS: Seven pairs of living kidney donors and recipients were considered for this observational study. RFR was measured with a renal stress test (RST) before and after the kidney transplantation through an oral protein loading test (1 g/kg of body weight). RFR was defined as the difference between the maximum value of creatinine clearance after protein load (stress glomerular filtration rate, sGFR) and baseline creatinine clearance (basal GFR, bGFR). RESULTS: Before transplantation, a significant difference between sGFR and bGFR (p = 0.04) was observed in donors, with an RFR = 30.6 (11.9-41.5) mL/min/1.73 m2. After kidney transplantation, sGFR was similar to bGFR for both donors and recipients (p = 0.13), with a limited RFR (7.9 [6.70-19.25] and 14.90 [-6.67 to 25.53] mL/min/1.73 m2, respectively). The sum of the donor's and recipient's post-transplant sGFR was similar to the pre-transplant donor's sGFR (p = 0.73). CONCLUSION: RST is a safe, feasible, easy, and an inexpensive tool that is able to quantify RFR. In living kidney transplantation, it can be used in clinical practice to measure the original global filtration capacity of the donor's kidneys (sGFR) and to quantify the susceptibility of donors and recipients in developing postoperative kidney dysfunction. However, further studies with an adequate sample size and follow-up period are needed to test this hypothesis.

Optimizing utilization of kidneys from deceased donors over 60 years: five-year outcomes after implementation of a combined clinical and histological allocation algorithm.

This 5 year observational multicentre study conducted in the Nord Italian Transplant programme area evaluated outcomes in patients receiving kidneys from donors over 60 years allocated according to a combined clinical and histological algorithm. Low-risk donors 60-69 years without risk factors were allocated to single kidney transplant (LR-SKT) based on clinical criteria. Biopsy was performed in donors over 70 years or 60-69 years with risk factors, allocated to Single (HR-SKT) or Dual kidney transplant (HR-DKT) according to the severity of histological damage. Forty HR-DKTs, 41 HR-SKTs and 234 LR-SKTs were evaluated. Baseline differences generally reflected stratification and allocation criteria. Patient and graft (death censored) survival were 90% and 92% for HR-DKT, 85% and 89% for HR-SKT, 88% and 87% for LR-SKT. The algorithm appeared user-friendly in daily practice and was safe and efficient, as demonstrated by satisfactory outcomes in all groups at 5 years. Clinical criteria performed well in low-risk donors. The excellent outcomes observed in DKTs call for fine-tuning of cut-off scores for allocation to DKT or SKT in high-risk patients.

Oxidative stress and 'monocyte reprogramming' after kidney transplant: a longitudinal study.

Uremia has been implicated in increased oxidative stress (OS) and decreased monocyte HLA-DR expression in chronic kidney disease (CKD) patients. Thus, one would expect normalization of these parameters after successful kidney transplant (KTx). Our aim was to describe patterns of OS and HLA-DR expression after KTx and to explore the effect of renal function and different immunosuppression regimens. 30 KTx patients (20 male; 48 +/- 11 years) were enrolled and compared with 20 healthy controls. We measured advanced oxidation protein products (AOPP) and the percentage of monocytes expressing HLA-DR (%DR+) before (preKTx) and after KTx (on days 2, 30, 90, 180 and after 1 year). Compared to controls, patients had a higher preKTx AOPP (152.6 vs. 69.3 micromol/l; p < 0.001). AOPP decreased at 48 h after KTx, achieving values similar to controls. Thereafter, it increased again and remained significantly higher compared to controls, returning to preKTx levels at 90 days. Prior to KTx there was a trend for lower %DR+ in KTx patients compared to controls (96 vs. 98%; NS). Following KTx, patients had a lower %DR+ in the 1st month; then it gradually returned to preKTx levels during the 1st year; at no time did it reach a value similar to controls. Cyclosporine (CyA)-treated patients had a significantly higher AOPP (161.5 vs. 99.5 micromol/l; p = 0.03) and a lower %DR+ (91.7 vs. 96.4; p < 0.05) at 30 days than patients on tacrolimus (FK). Patients on mycophenolate mofetil (MMF) showed a low AOPP (106.9 vs. 168.1 micromol/l; p = 0.05) and a high %DR+ (96.7 vs. 88.2%; p = 0.001) than those on everolimus. After 3 months, CyA-treated patients had a non-significant increase in AOPP levels, whereas those on FK showed a decrease (p < 0.05) as did those treated with MMF (p < 0.05). Successful KTx reduced but did not normalize AOPP, suggesting ongoing OS, perhaps due to persistent mild renal dysfunction and the effects of immunosuppression. HLA-DR expression remained low after KTx, which may be a possible contributing factor to infectious complications after transplantation. Immunosuppressive agents appear to have diverse effects on OS and HLA-DR expression.

Rational choice of peritoneal dialysis catheter.

The peritoneal catheter should be a permanent and safe access to the peritoneal cavity. Catheter-related problems are often the cause of permanent transfer to hemodialysis (HD) in up to 20% of peritoneal dialysis (PD) patients; in some cases, these problems require a temporary period on HD. Advances in connectology have reduced the incidence of peritonitis, and so catheter-related complications during PD have become a major concern. In the last few years, novel techniques have emerged in the field of PD: new dialysis solutions, better connectology, and cyclers for automated PD. However, extracorporeal dialysis has continued to improve in terms of methods and patient survival, but PD has failed to do so. The main reason is that peritoneal access has remained problematical. The peritoneal catheter is the major obstacle to wide-spread use of PD. Overcoming catheter-related problems means giving a real chance to development of the peritoneal technique. Catheters should be as efficient, safe, and acceptable as possible. Since its introduction in the mid-1960s, the Tenckhoff catheter has not become obsolete: dozens of new models have been proposed, but none has significantly reduced the pre-dominance of the first catheter. No convincing prospective data demonstrate the superiority of any peritoneal catheter, and so it seems that factors other than choice of catheter are what affect survival and complication rates. Efforts to improve peritoneal catheter survival and complication rates should probably focus on factors other than the choice of catheter. The present article provides an overview of the characteristics of the best-known peritoneal catheters.

Kidney transplantation from anti-HBc+ donors: results from a retrospective Italian study.

BACKGROUND: The risk of transmitting a hepatitis B virus (HBV) infection from donor kidneys with a past HBV serological profile may be negligible. Data on HBV transmission to kidney transplant recipients from donor organs that were anti-HBc/HBsAg in Italy has not been previously reported. Anti-HBc testing in cadaver organ donors has been mandatory in Italy since 2002, when anti-HBc determinations were included in the National Guidelines for donor evaluation. Therefore, prior to that date kidney recipients from anti-HBc/HBsAg donors can be identified retrospectively where stored serum is available for testing. METHODS: The prevalence of anti-HBc Italian organ donors, the incidence of HBV transmission according to the recipients' HBV status (vaccinated, recovered, or naive), and the clinical impact (5-year graft and patient survival rates) in the North Italy Transplant program was evaluated by retrospectively screening for anti-HBc antibodies in the sera of cadaver kidney donors used in transplants from 1997 to 1999. RESULTS: Two hundred and ten donors were found to have been anti-HBc. At the time of the study, no active infection was observed in any of the 344 HBsAg recipients, but 4/140 (2.86%) of the vaccinated recipients were found to have been anti-HBc/HBsAg. None of these patients, however, had any biochemical or clinical history of HBV infection. Patient and graft survival rates of anti-HBc or anti-HBc kidney recipients did not differ statistically. CONCLUSION: Kidney grafts from anti-HBc donors should be considered in all recipients because the benefit obtained from the transplantation out weighs the negligible risk of HBV transmission.

Renal transplantation. Strategies to prevent organ rejection--the role of an inter-regional reference center.

This paper summarizes the role of the Inter-Regional Reference Center (RC) of the North Italy Transplant program (NITp), in coordinating a donor procurement and organ transplantation network, with a special focus on the strategies to minimize immunological risk and complications after transplantation. In the NITp, patients enrolled on the renal transplantation (RT) waiting list are typed for HLA-A,B,DRB1 antigens with a genomic method. They are periodically screened for the presence of lymphocytotoxic antibodies in their serum by the RC and their suitability to receive the transplant is checked periodically. Cadaver kidney allocation is ruled by a computerized algorithm, named NITK3, established in 1997, which aims at ensuring quality, equity, transparency and traceability during all the phases of the allocation decision-making process. NITK3 has been set up by the NITp Working Group on the basis of biological, medical and administrative criteria and it is periodically reviewed after the analysis of transplant results. In this paper, we show the results of a preliminary analysis of RTs performed from 1998 to 2002 in nine out of sixteen centers of the NITp area, which demonstrates the general quality of the NITp program in terms of patients and graft survival and the special attention to the patients at higher immunological risk.

A comparative prospective study of two available solutions for kidney and liver preservation.

BACKGROUND: Viaspan (University of Wisconsin [UW]) solution is the gold standard for abdominal organ preservation. Celsior (CEL) is an extracellular-type, low-potassium, low-viscosity solution, initially used for heart and lung preservation. We have performed a prospective multicenter study to compare the role of these cold-storage solutions on kidney and liver recovery after transplantation. PATIENTS AND METHODS: From March 15, 2000 to December 31, 2001, 441 (172 CEL and 269 UW) renal transplants (RT) and 175 (79 CEL and 96 UW) liver transplants (LT) were included in the study. RESULTS: Perfusate volume used was significantly lower in the UW group, being 4,732 +/- 796 mL versus 5,826 + 834 mL in the CEL group (P < 0.001). In LT, median total bilirubin serum levels were significantly higher at 5 and 7 posttransplant days in the UW group (90.6 and 92.3 micromol/L, respectively) as compared with CEL (51.3 and 63.4 micromol/L, respectively). After LT, primary nonfunction (PNF) rates in the CEL and UW groups were 3.8% and 4.2% (P = NS) respectively, with 1-year graft and patient survival being 83.3% versus 85.4% (P = NS) and 89.9% versus 90.6% (P = NS). After RT, delayed graft function (DGF) rates were 23.2% and 22.7% (P = NS), respectively; PNF rates were 1.9% and 1.7% (P = NS) respectively, with 1-year graft and patient survival being 92.3% versus 94.2% (P = NS) and 99.4% versus 97.7% (P = NS). CONCLUSIONS: CEL solution was shown to be as effective as UW in both liver and kidney preservation. In LT patients, biliary function recovery is significantly better in the CEL group. CEL solution represents an efficacious option in multiorgan harvesting.

Epidemiologic study on the origin of cancer after kidney transplantation.

BACKGROUND: Subjects who underwent solid organ transplantation are at higher risk for a wide variety of cancers. METHODS: The authors investigated the origin of cancer in a cohort of 2,526 patients followed up for 60.7 +/- 35.6 months after kidney transplantation between 1990 and 2000 in seven transplant centers. RESULTS: One hundred four of them developed cancer. All subjects who developed solid cancer within 6 months after transplantation (n=10) and a group of subjects who developed solid cancer after 6 months posttransplant (n=10) were selected. Short tandem repeat analysis was performed on paraffin-embedded biopsy specimens of tumors and on both donor and recipient pretransplant peripheral blood. Biologic material was obtained in 17 of the 20 selected patients (85.0%). The analysis showed that 16 of 17 tumors were genetically identical to the recipient. CONCLUSIONS: The authors' results suggest that donor transmission of solid cancer is an unlikely event in their population.