Gregory A. Knoll

Systematic Review: Kidney Transplantation Compared With Dialysis in Clinically Relevant Outcomes

Individual studies indicate that kidney transplantation is associated with lower mortality and improved quality of life compared with chronic dialysis treatment. We did a systematic review to summarize the benefits of transplantation, aiming to identify characteristics associated with especially large or small relative benefit. Results were not pooled because of expected diversity inherent to observational studies. Risk of bias was assessed using the Downs and Black checklist and items related to time‐to‐event analysis techniques. MEDLINE and EMBASE were searched up to February 2010. Cohort studies comparing adult chronic dialysis patients with kidney transplantation recipients for clinical outcomes were selected. We identified 110 eligible studies with a total of 1 922 300 participants. Most studies found significantly lower mortality associated with transplantation, and the relative magnitude of the benefit seemed to increase over time (p < 0.001). Most studies also found that the risk of cardiovascular events was significantly reduced among transplant recipients. Quality of life was significantly and substantially better among transplant recipients. Despite increases in the age and comorbidity of contemporary transplant recipients, the relative benefits of transplantation seem to be increasing over time. These findings validate current attempts to increase the number of people worldwide that benefit from kidney transplantation.

Enteric-Coated Mycophenolate Sodium can be Safely Administered in Maintenance Renal Transplant Patients: Results of a 1-Year Study

With the objective of enhancing upper gastrointestinal (GI) tolerability, enteric‐coated mycophenolate sodium (EC‐MPS, myfortic®, Novartis Pharma AG, Basel, Switzerland) has been developed. This double‐blinded, 12‐month study investigated whether renal transplant patients taking mycophenolate mofetil (MMF) can be safely converted to EC‐MPS. Stable kidney transplant patients were randomized to receive EC‐MPS (720 mg b.i.d.; n = 159) or continue receiving MMF (1000 mg b.i.d.; n = 163). The incidence of GI adverse events (AEs) was similar at 3 months (primary endpoint: EC‐MPS 26.4%; MMF 20.9%; p = NS) and at 12 months (EC‐MPS 29.6%; MMF 24.5%; p = NS). The increase from baseline in mean GI AE severity score, adjusted for duration, tended to be lower in EC‐MPS patients (3 months: 0.15 vs. 0.20; 12 months: 0.23 vs. 0.47; p = NS). Neutropenia (<1500 cells/mm3) within the first 3 months (coprimary endpoint) was low in both groups (EC‐MPS 0.6%; MMF 3.1%; p = NS). Although the overall incidence of infections was similar, the number of serious infections was significantly lower in EC‐MPS patients (8.8% vs. 16.0%; p < 0.05). Similar rates of efficacy failure (EC‐MPS 2.5%; MMF 6.1%; p = NS), biopsy‐proven acute rejection (EC‐MPS 1.3%; MMF 3.1%; p = NS) and biopsy‐proven chronic rejection (EC‐MPS 3.8%; MMF 4.9%; p = NS) were observed in both groups. In conclusion, renal maintenance patients can be converted from MMF to EC‐MPS without compromising the safety and efficacy profile associated with MMF.

Renin Angiotensin System Blockade in Kidney Transplantation: A Systematic Review of the Evidence

ACE‐inhibitors and angiotensin receptor blockers (ARB) slow the progression of renal disease in nontransplant patients. A systematic review of randomized trials (n = 21 trials with 1549 patients) was conducted to determine the effect of ACE‐inhibitor or ARB use following kidney transplantation. With a median follow‐up of 27 months, ACE‐inhibitor or ARB use was associated with a significant decrease in glomerular filtration rate (−5.8 mL/min; 95% CI −10.6 to −0.99). ACE‐inhibitor or ARB use resulted in a lower hematocrit (−3.5%; 95% CI −6.1 to −0.95), reduction in proteinuria (−0.47 gm/d; 95% CI −0.86 to −0.08) but no change in the serum potassium (0.18 mmol/L; 95% CI −0.03 to 0.40). ACE‐inhibitor or ARB use results in clinically important reductions in proteinuria, hematocrit and glomerular filtration rate in renal transplant recipients, but there are insufficient data to determine the effect on patient or graft survival. Randomized trials of sufficient power and duration that examine these hard outcomes should be conducted. Until such trials are completed, this study provides quantitative estimates of the risks and benefits of ACE‐inhibitor or ARB use that can be used by clinicians considering prescribing these medications to kidney transplant recipients or to researchers designing future trials.

Nucleic acid testing (NAT) of organ donors: is the 'best' test the right test? A consensus conference report.

Nucleic acid testing (NAT) for HIV, HBV and HCV shortens the time between infection and detection by available testing. A group of experts was selected to develop recommendations for the use of NAT in the HIV/HBV/HCV screening of potential organ donors. The rapid turnaround times needed for donor testing and the risk of death while awaiting transplantation make organ donor screening different from screening blood‐or tissue donors. In donors with no identified risk factors, there is insufficient evidence to recommend routine NAT, as the benefits of NAT may not outweigh the disadvantages of NAT especially when false‐positive results can lead to loss of donor organs. For donors with identified behavioral risk factors, NAT should be considered to reduce the risk of transmission and increase organ utilization. Informed consent balancing the risks of donor‐derived infection against the risk of remaining on the waiting list should be obtained at the time of candidate listing and again at the time of organ offer. In conclusion, there is insufficient evidence to recommend universal prospective screening of organ donors for HIV, HCV and HBV using current NAT platforms. Further study of viral screening modalities may reduce disease transmission risk without excessive donor loss.

The Long-Term Quality of Life of Living Kidney Donors: A Multicenter Cohort Study

Previous studies that described the long‐term quality of life of living kidney donors were conducted in single centers, and lacked data on a healthy nondonor comparison group. We conducted a retrospective cohort study to compare the quality of life of 203 kidney donors with 104 healthy nondonor controls using validated scales (including the SF36, 15D and feeling thermometer) and author‐developed questions. Participants were recruited from nine transplant centers in Canada, Scotland and Australia. Outcomes were assessed a median of 5.5 years after the time of transplantation (lower and upper quartiles of 3.8 and 8.4 years, respectively). 15D scores (scale of 0 to 1) were high and similar between donors and nondonors (mean 0.93 (standard deviation (SD) 0.09) and 0.94 (SD 0.06), p = 0.55), and were not different when results were adjusted for several prognostic characteristics (p = 0.55). On other scales and author‐developed questions, groups performed similarly. Donors to recipients who had an adverse outcome (death, graft failure) had similar quality of life scores as those donors where the recipient did well. Our findings are reassuring for the practice of living transplantation. Those who donate a kidney in centers that use routine pretransplant donor evaluation have good long‐term quality of life.

Economic consequences incurred by living kidney donors: A canadian multi-center prospective study

Some living kidney donors incur economic consequences as a result of donation; however, these costs are poorly quantified. We developed a framework to comprehensively assess economic consequences from the donor perspective including out‐of‐pocket cost, lost wages and home productivity loss. We prospectively enrolled 100 living kidney donors from seven Canadian centers between 2004 and 2008 and collected and valued economic consequences (

Impact of immunosuppressive medication on the risk of renal allograft failure due to recurrent glomerulonephritis.

CAD 2008) at 3 months and 1 year after donation. Almost all (96%) donors experienced economic consequences, with 94% reporting travel costs and 47% reporting lost pay. The average and median costs of lost pay were

Accepting Kidneys from Older Living Donors: Impact on Transplant Recipient Outcomes

2144 (SD 4167) and

Bone and Mineral Metabolism and Fibroblast Growth Factor 23 Levels After Kidney Donation

0 (25th–75th percentile 0, 2794), respectively. For other expenses (travel, accommodation, medication and medical), mean and median costs were

Effect of intracoronary diltiazem on infarct size and regional myocardial function in the ischemic reperfused canine heart

1780 (SD 2504) and