Uncertainty in forecasts of long-run economic growth.

Forecasts of long-run economic growth are critical inputs into policy decisions being made today on the economy and the environment. Despite its importance, there is a sparse literature on long-run forecasts of economic growth and the uncertainty in such forecasts. This study presents comprehensive probabilistic long-run projections of global and regional per-capita economic growth rates, comparing estimates from an expert survey and a low-frequency econometric approach. Our primary results suggest a median 2010-2100 global growth rate in per-capita gross domestic product of 2.1% per year, with a standard deviation (SD) of 1.1 percentage points, indicating substantially higher uncertainty than is implied in existing forecasts. The larger range of growth rates implies a greater likelihood of extreme climate change outcomes than is currently assumed and has important implications for social insurance programs in the United States.

Prospective randomized trial of maintenance immunosuppression with rapid discontinuation of prednisone in adult kidney transplantation.

Rapid discontinuation of prednisone (RDP) has minimized steroid-related complications following kidney transplant (KT). This trial compares long-term (10-year) outcomes with three different maintenance immunosuppressive protocols following RDP in adult KT. Recipients (n=440; 73% living donor) from March 2001 to April 2006 were randomized into one of three arms: cyclosporine (CSA) and mycophenolate mofetil (MMF) (CSA/MMF, n=151); high-level tacrolimus (TAC, 8-12 µg/L) and low-level sirolimus (SIR, 3-7 µg/L) (TACH/SIRL, n=149) or low-level TAC (3-7 µg/L) and high-level SIR (8-12 µg/L) (TACL/SIR(H) , n=140). Median follow-up was ∼7 years. There were no differences between arms in 10-year actuarial patient, graft and death-censored graft survival or in allograft function. There were no differences in the 10-year actuarial rates of biopsy-proven acute rejection (30%, 26% and 20% in CSA/MMF, TACH/SIRL and TACL/SIRH) and chronic rejection (38%, 35% and 31% in CSA/MMF, TACH/SIRL and TACL/SIRH). Rates of new-onset diabetes mellitus were higher with TACH/SIRL (p=0.04), and rates of anemia were higher with TACH/SIRL and TACL/SIRH (p=0.04). No differences were found in the overall rates of 16 other post-KT complications. These data indicate that RDP-based protocol yield acceptable 10-year outcomes, but side effects differ based on the maintenance regimen used and should be considered when optimizing immunosuppression following RDP.

Revisiting traditional risk factors for rejection and graft loss after kidney transplantation.

Single-antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single-antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third-party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death-censored graft survival (DCGS) and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization.

Diabetes after kidney donation.

Kidney donors, similar to the general population, are at risk for development of type 2 diabetes mellitus (T2DM). The course of donors who develop T2DM has not been studied. We surveyed 3777 kidney donors regarding the development of T2DM. Of the 2954 who responded, 154 developed T2DM 17.7 +/- 9.0 years after donation. The multivariable risk of development of T2DM was associated with type 1 DM in the recipient, male gender and body mass index >30 kg/m(2) at time of donation. Compared to age, gender, duration after donation and body mass index (BMI)-matched non-diabetic donor controls; diabetic donors were more likely to have hypertension (70.8% vs. 36.2%, p = 0.005), proteinuria (18.8% vs. 3.9%, p < 0.0001) but had a similar serum creatinine. eGFR change after T2DM development was -0.80 +/- 0.94 mL/min/year, -0.70 +/- 0.86 in nondiabetic donors with similar duration after donation and -0.61 +/- 0.76 mL/min/year in age, gender, BMI and duration after donation matched nondiabetic donor controls. These preliminary and short-term data demonstrate that factors associated with T2DM in kidney donors are similar to those in the general population and donors screened carefully at the time of donation do not appear to have an acceleration of diabetic kidney disease.

Selective retransplant after graft loss to nonadherence: success with a second chance.

Nonadherence (NA) is a difficult posttransplant problem that can lead to graft loss. A retransplant is controversial because of a fear of recurrent NA. We reviewed our center's data base and identified 114 kidney recipients who lost their graft to overt NA; of this group, 35 (31%) underwent a retransplant after a thorough reevaluation. We compared this NA retransplant group to a control group of second transplant recipients who did not lose their first graft to overt NA (non-NA) (n = 552). After 8 years of follow-up, we found no significant differences between the groups in actuarial graft or patient survival rates, renal function, or the incidence of biopsy-proven chronic rejection. However, 5 of 35 (14%) NA recipients versus 10 of 552 (2%) non-NA recipients lost their retransplant to NA (p = 0.0001). Twenty of 35 (57%) of the NA group exhibited repeat NA behavior after retransplant. We conclude that prior graft loss to NA is associated with increased graft loss to NA after retransplant. However, the majority of NA retransplant recipients did well-with overall long-term outcomes similar to those of the non-NA group. With careful patient selection and aggressive intervention, prior overt NA should not be an absolute contraindication to retransplantation.

Pregnancy outcomes after kidney donation.

The outcome of pregnancy in kidney donors has generally been viewed to be favorable. We determined fetal and maternal outcomes in a large cohort of kidney donors. A total of 2102 women have donated a kidney at our institution; 1589 donors responded to our pregnancy surveys; 1085 reported 3213 pregnancies and 504 reported none. Fetal and maternal outcomes in postdonation pregnancies were comparable to published rates in the general population. Postdonation (vs. predonation) pregnancies were associated with a lower likelihood of full-term deliveries (73.7% vs. 84.6%, p = 0.0004) and a higher likelihood of fetal loss (19.2% vs. 11.3%, p < 0.0001). Postdonation pregnancies were also associated with a higher risk of gestational diabetes (2.7% vs. 0.7%, p = 0.0001), gestational hypertension (5.7% vs. 0.6%, p < 0.0001), proteinuria (4.3% vs. 1.1%, p < 0.0001) and preeclampsia (5.5% vs. 0.8%, p < 0.0001). Women who had both pre- and post-donation pregnancies were also more likely to have these adverse maternal outcomes in their postdonation pregnancies. In this large survey of previous living donors in a single center, fetal and maternal outcomes and pregnancy outcomes after kidney donation were similar to those reported in the general population, but inferior to predonation pregnancy outcomes.

2202 kidney transplant recipients with 10 years of graft function: what happens next?

The ultimate goal of clinical transplantation is for the recipients to achieve long-term survival, with continuing graft function, that is equivalent to that of the age-matched general population. We studied subsequent outcome in kidney transplant recipients with 10 years of graft function. In all, 2202 kidney transplant recipients survived with graft function >10 years. For 10-year survivors, the actuarial 25-year patient survival rate for primary transplant living donor (LD) recipients was 57%; graft survival, 43%. For primary transplant deceased donor (DD) recipients, the actuarial 25-year patient survival rate was 39%; graft survival, 27%. The two major causes of late graft loss were death (with graft function) and chronic allograft nephropathy (tubular atrophy and interstitial fibrosis). The two major causes of death with function were cardiovascular disease (CVD) and malignancy. For nondiabetic recipients, the mean age at death with function from CVD was 54 +/- 13 years; for diabetic recipients, 53 +/- 7 years. By 20 years posttransplant, morbidity was common: >40% recipients had skin cancer (mean age for nondiabetic recipients, 53 +/- 13 years; for diabetics, 49 +/- 8 years), >10% had non-skin cancer (mean age for nondiabetic recipients, 53 +/- 16 years; for diabetics, 46 +/- 9 years), and >30% had CVD (mean age for nondiabetic recipients, 53 +/- 15 years; for diabetics, 47 +/- 9 years). We conclude that long-term transplant recipients have a high rate of morbidity and early mortality. As short-term results have improved, more focus is needed on long-term outcome.

In vitro biocompatibility of fluorcanasite glass-ceramics for bone tissue repair.

Fluorcanasite glass-ceramics were produced by controlled two stage heat-treatment of as-cast glasses. These glasses were modified from stoichiometric fluorcanasite composition by either adding P(2)O(5) or altering the molar ratios of Na(2)O and CaO. Commercial bioactive 45S5 Bioglass(R) was also prepared in-house to evaluate the relative in vitro biocompatibility of fluorcanasite glass-ceramics. The scanning electron microscopy (SEM) images showed that cells had colonized the surfaces of fluorcanasite glass-ceramics to form a confluent sheet. Quantitative MTT assay results were in good agreement with the qualitative SEM observations. It was concluded that incorporation of excess calcium oxide or P(2)O(5) in stoichiometric glass composition improved in vitro biocompatibility. Controlled heat-treatment further improved the biological response of cultured bone cells to modified fluorcanasite glass-ceramics when compared with their parent glasses. Ion release and pH data suggested a strong correlation between solubility (in particular, Na ion release) and biocompatibility. Reduced solubility, Na ion release, and related pH effects appeared to be the principal mechanisms responsible for improvement in in vitro biocompatibility.

Biocompatibility of glass-ionomer bone cements.

Glass-ionomer cements (GIC) have been extensively used in dentistry for over 30 years. Due to their excellent biocompatibility in dental applications GIC have been formulated for medical applications. The past decade has seen some impressive advances in the development of medical GICs, however these advances have been matched by serious critical problems. This review examines the properties of GICs, which can influence their behaviour in a biological environment. The progress made and the problems encountered in the development of these bone cements will also be addressed. The review will conclude with the research currently being employed to optimise the biocompatibility of these important biomaterials. There is little doubt that GICs compare favourably with alternative bone cements for specific applications, based on in vitro and in vivo studies. There is however, a degree of risk inherent in the use of any medical device or biomaterial. GICs must therefore be used carefully and in accordance with the instructions that are based on a significant body of research data.

In vitro biocompatibility of a novel Fe2O3 based glass ionomer cement.

INTRODUCTION: Since their invention in the late 1960s, glass ionomer cements (GICs) have been used extensively in dentistry but recently they have also been utilised in ear nose and throat (ENT) surgery. Unfortunately, Al3+, a component of conventional ionomer glasses, has been linked to poor bone mineralisation and neurotoxicity. OBJECTIVE: The aim of the research was to modify a commercial ionomer glass composition by substituting Al2O3 with Fe2O3. METHODS: Glasses with the following molar compositions were fabricated: 4.5SiO2*3M2O3*XP2O5*3CaO*2CaF2 (M = Al or Fe, X = 0-1.5). The glasses were characterised using X-ray fluorescence (XRF) and X-ray powder diffraction (XRD). Cements were prepared using a standard ratio of; 1 g of glass powder: 0.2 g of dried polyacrylic acid: 0.3 g of 10% tartaric acid solution. Cement formation was assessed using a Gilmore needle and in vitro biocompatibility was investigated for novel cement formulations. RESULTS: XRF revealed that the Fe2O3-based glasses had Al2O3 contamination from the crucibles and also had undergone substantial F- losses. XRD gave peaks that corresponded to magnetite Fe3O4 (JCPDS # 19-629) in all compositions. Apatite Ca5(PO4)3(OH,F) (JCPDS # 15-876) was identified in P2O5 containing glasses. It was possible to fabricate cements from all of the Fe2O3-based ionomer glasses. Good in vitro biocompatibility was observed for the Fe2O3-based cements. CONCLUSION: Ionomer glasses may be prepared by entirely replacing Al2O3 with Fe2O3. Cement setting times appeared to be related to P2O5 content. Fe2O3-based cements showed good in vitro biocompatibility.

Mycobacterial infections after kidney transplant.

We looked at mycobacterial infections occurring after a kidney transplant to determine incidence, risk factors, and outcomes. Of 3921 kidney transplants performed between 1984 and 2002, 18 (0.45%) (10 men, eight women; 11 cadaveric donor, seven living donor graft) were identified as having mycobacterial infection at some time posttransplant. Mean age at transplant was 38.3 years. Racial background was: Caucasian (n = 12), African-American (n = 2), Native Indian (n = 2), Hispanic (n = 1), and Middle Eastern (n = 1). The majority had a kidney alone (n = 14). Four recipients had simultaneous transplant of a second organ: pancreas (n = 2), islets (n = 1), and liver (n = 1). None of the 18 recipients had documented mycobacterial infection pretransplant. One recipient had a positive Mantoux test at the time of transplant and then developed pulmonary tuberculosis 4 months posttransplant; the remaining 17 patients had either negative (n = 10) or unavailable (n = 7) pretransplant Mantoux results. Mean time to infection was 3.2 years (range 1 week to 12 years). The most common site of infection was respiratory (n = 8). Other sites included musculoskeletal (n = 4), skin (n = 3), gyn (n = 1), and other (n = 2). Only three of the infections were with mycobacterial tuberculi; the others were with avium (n = 5), chelonae (n = 2), or other nontuberculous mycobacteria. Risk factors included previous TB exposure, occupational exposure, or accidental soft tissue injury. Soft tissue infections often presented as chronic unhealed wounds and required extensive surgical debridements. With mean follow-up of 12.5 years since transplant and 9.2 years since infection, 13 of the recipients are alive and well; causes of death included cardiovascular (n = 3) and sepsis (n = 2).

Half-life and risk factors for kidney transplant outcome--importance of death with function.

Transplant center outcome is being increasingly scrutinized, so it is critical to have a consistent approach to data analysis. Standard practice has been to include death with function as a graft loss. But doing so may obscure other important risk factors and make it difficult to compare centers. To document this data analysis problem, we studied half-life and risk factors for long-term graft survival in 2230 kidney transplant recipients who had > or = 1 year of function. Four separate Cox regression analyses were done, differing in how death with function is considered: death with function considered a graft loss (analysis 1); all deaths censored (analysis 2); definitively non-transplant-related deaths censored, i.e., deaths from infection, malignancy, or cardiac problems analyzed as a graft loss (analysis 3); and definitively non-transplant-related as well as cardiac deaths censored (analysis 4). For each analysis, variables included immunosuppressive protocol, age at transplant, donor source, diabetes, gender, transplant number (primary vs. retransplant), and HLA ABDR mismatches (0 vs. > or = 1 mismatch). There were important differences in risk factors, depending on how death with function is considered. For example, when all deaths are considered a graft loss, age > 50, cadaver donor source, diabetes, retransplantation, and > 0 antigen mismatch were found to be risk factors for long-term graft survival. However, when all deaths are censored, age > 50, cadaver donor source, retransplantation, and diabetes were no longer risk factors. In fact, age > 50 was associated with significantly better graft survival when all deaths are censored (analysis 2), suggesting that the increased graft loss seen in these patients is nonimmunologic. Similarly, t1/2 is markedly different for different patient subgroups depending on how death with function is considered. For example, nondiabetic living donor (non-HLA-identical) recipients > 50 have a t1/2 of 9 +/- 1 years when death with function is considered a graft loss; for the same group, t1/2 is 62 +/- 28 years when death with function is considered. For diabetic patients < or = 50, when death with function is considered a graft loss, t1/2 is 9 +/- 0.9 years for living donor recipients and 7 +/- 0.7 years for cadaver donor recipients. For the same patients, when death with function is censored, t1/2 is 27 +/- 4 years for living donor recipients and 24 +/- 4 years for cadaver donor recipients. Our analysis suggests that death with function needs to be considered in analyzing kidney transplant outcomes.(ABSTRACT TRUNCATED AT 400 WORDS)

Features of acute rejection that increase risk for chronic rejection.

BACKGROUND: Acute rejection (AR) has been shown to be a significant risk factor for chronic rejection (CR) in kidney transplant recipients, yet many recipients with AR do not progress to CR. The purpose of this study was to determine if certain AR episodes are associated with a worse prognosis. METHODS: The study group consisted of 279 kidney transplant recipients, all treated for a single episode of biopsy-proven AR. All AR episodes were initially treated with steroids; steroid-resistant rejection was managed with an antibody preparation. RESULTS: First, by univariate techniques, we determined the clinical impact of severity of AR (as estimated by delta creatinine [dCr], defined as the change in baseline serum creatinine level 6 weeks after AR treatment) on two different endpoints--biopsy-proven CR and graft survival. Irrespective of 6-week dCr, all recipients with AR had a significantly increased risk of CR vs. those with no AR (P<0.01). Recipients with dCr between 0.5 and 1.0 mg/dl had a significantly higher incidence of CR vs. those with dCr <0.5 mg/dl (P<0.05), but a significantly lower incidence vs. those with dCr >1.0 mg/dl (P<0.05). We then performed multivariate analysis. We used severity of AR in addition to other variables (e.g., timing of AR, donor age) to determine which factors were most associated with risk for CR and graft loss. Risk for CR increased with AR episodes occurring >6 months after transplant (relative risk [RR] = 3.8, P = 0.005); with moderate or severe (vs. mild) AR episodes (RR = 2.7, P = 0.05); and with dCr >0.5 mg(dl (vs. <0.5 mg/dl) at 6 weeks after AR treatment (RR = 2.3, P = 0.1). Findings were similar when graft survival (death-censored) was the endpoint instead of CR. CONCLUSIONS: All AR episodes are associated with some increase in the risk for CR. But AR episodes occurring >6 months after transplant and those of increased severity (as assessed qualitatively by histologic grading and quantitatively by dCr) confer the greatest risk. Recipients with these risk factors could be targeted with measures to decrease their risk for CR, including trials of novel immunosuppressive regimens.

Living unrelated donors in kidney transplants: better long-term results than with non-HLA-identical living related donors?

BACKGROUND: Given the severe organ shortage and the documented superior results obtained with living (vs. cadaver) donor kidney transplants, we have adopted a very aggressive policy for the use of living donors. Currently, we make thorough attempts to locate a living related donor (LRD) or a living unrelated donor (LURD) before proceeding with a cadaver transplant. METHODS: We compared the results of our LURD versus LRD transplants to determine any significant difference in outcome. RESULTS: Between 1/1/84 and 6/30/98, we performed 711 adult kidney transplants with non-HLA-identical living donors. Of these, 595 procedures used LRDs and 116 used LURDs. Immunosuppression for both groups was cyclosporine-based, although LURD recipients received 5-7 days of induction therapy (antilymphocyte globulin or antithymocyte globulin), whereas LRD recipients did not. LURD recipients tended to be older, to have inferior HLA matching, and to have older donors than did the LRD recipients (all factors potentially associated with decreased graft survival). Short-term results, including initial graft function and incidence of acute rejection, were similar in the two groups. LURD recipients had a slightly higher incidence of cytomegalovirus disease (P=NS). We found no difference in patient and graft survival rates. However, the incidence of biopsy-proven chronic rejection was significantly lower among LURD recipients (16.7% for LRD recipients and 10.0% for LURD recipients at 5 years posttransplant; P=0.05). LRD recipients also had a greater incidence of late (>6 months posttransplant) acute rejection episodes than did the LURD recipients (8.6% vs. 2.6%, P=0.04). The exact reason for these findings is unknown. CONCLUSION: Although LURD recipients have poorer HLA matching and older donors, their patient and graft survival rates are equivalent to those of non-HLA-identical LRD recipients. The incidence of biopsy-proven chronic rejection is lower in LURD transplants. Given this finding and the superior results of living donor (vs. cadaver) transplants, a thorough search should be made for a living donor-LRD or LURD-before proceeding with a cadaver transplant.

Are wound complications after a kidney transplant more common with modern immunosuppression?

BACKGROUND: The most common surgical complication after a kidney transplant is likely related to the wound. The purpose of this analysis was to determine the incidence of, and risk factors for, wound complications (e.g., infections, hernias) in kidney recipients and to assess whether newer immunosuppressive drugs increase the risk for such complications. METHODS: Between January 1, 1984 and September 30, 1998, we performed 2013 adult kidney transplants. Of these 2013 recipients, 97 (4.8%) developed either a superficial or a deep wound infection. Additionally, 73 (3.6%) recipients developed either a fascial dehiscence or a hernia of the wound. We used univariate and multivariate techniques to determine significant risk factors and outcomes. RESULTS: Mean time to development of a superficial infection (defined as located above the fascia) was 11.9 days posttransplant; to development of a deep infection (defined as located below the fascia), 39.2 days; and to development of a hernia or fascial dehiscence, 12.8 months. By multivariate analysis, the most significant risk factor for a superficial or deep wound infection was obesity (defined as body mass index>30 kg/m2) (RR=4.4, P=0.0001). Other significant risk factors were a urine leak posttransplant, any reoperation through the transplant incision, diabetes, and the use of mycophenolate mofetil (MMF) (vs. azathioprine) for maintenance immunosuppression (RR=2.43, P=0.0001). Significant risk factors for a hernia or fascial dehiscence were any reoperation through the transplant incision, increased recipient age, obesity, and the use of MMF (vs. azathioprine) for maintenance immunosuppression (RR=3.54, P=0.0004). Use of antibody induction and treatment for acute rejection were not significant risk factors for either infections or hernias. Death-censored graft survival was lower in recipients who developed a wound infection (vs. those who did not); it was not lower in recipients who developed an incisional hernia or facial dehiscence (vs. those who did not). CONCLUSIONS: Despite immunosuppression including chronic steroids, the incidence of wound infections, incisional hernias, and fascial dehiscence is low in kidney recipients. As with other types of surgery, the main risk factors for postoperative complications are obesity, reoperation, and increased age. However, in kidney recipients, use of MMF (vs. azathioprine) is an additional risk factor -one that potentially could be altered, especially in high-risk recipients.

The impact of an acute rejection episode on long-term renal allograft survival (t1/2).

An acute renal transplant rejection episode has been shown to be associated with decreased 1-year graft survival. The impact on long-term outcome is undefined. We studied the impact of an acute rejection episode on t1/2, the time it takes for 1/2 of the grafts functioning at 1 year to fail. Use of t1/2 avoids inclusion of early graft loss to acute rejection or complications of treatment. Since 1/1/86, a total of 653 patients have received a primary kidney transplant and had at least 1 year of function. Recipients were divided by the incidence and timing of rejection: no rejection; 1 rejection within the first year; > 1 rejection, the first episode in the first year; and > or = 1 rejection, the first episode after the first year. A single rejection episode in the first year reduced t1/2 (45 +/- 11 years in those with no rejection vs. 25 +/- 8 years in those with 1 in the first year). Multiple rejections (t1/2 = 5 +/- 11 years) and a first rejection after the first year (t1/2 = 3 +/- 1 years) have a significant effect (P < .05). Both living and cadaver donor recipients with rejection had shortened t1/2. For those with > 1 rejection, the first episode in the first year, and those with > or = 1 rejection, the first episode after the first year, chronic rejection was the predominant cause of graft loss; noncompliance also played a role. We conclude that a single rejection episode shortens t1/2. Those with > 1 rejection, the first episode within the first year, and those with > or = 1 rejection, the first episode after the first year, are at high risk for late graft loss.

Increased incidence of cardiac complications in kidney transplant recipients with cytomegalovirus disease.

BACKGROUND: The transplant literature has not shown cytomegalovirus (CMV) disease to be a significant risk factor for posttransplant cardiac complications. A large number of nontransplant studies have, however, reported an association between coronary heart disease (CHD) and CMV disease. Pathology studies have demonstrated a high incidence of CMV in atheromatous plaques from the coronary circulation. METHODS: We performed multivariate analysis to determine if posttransplant CMV disease was a significant risk factor for cardiac complications in kidney transplant recipients. We also performed univariate analysis to determine which cardiac complications were more common in the recipients with CMV disease. RESULTS: Between January 1, 1984 and June 30, 1997, 1859 adults underwent kidney transplants at our institution. Of these, 377 developed one of the following cardiac complications posttransplant: myocardial infarction, angina, arrhythmia, congestive heart failure, and angiographic vessel occlusion. By multivariate analysis, significant risk factors for one of the above cardiac complications were recipient age >50 years [odds ratio (OR)=2.5, P=0.0001], diabetes (OR=1.99, P=0.0001), a history of cardiac disease pretransplant (OR= 1.34, P=0.04), and CMV disease (OR=1.5, P=0.01). Univariate analysis demonstrated that recipients with CMV disease had a higher overall incidence of cardiac complications. Arrhythmias, congestive heart failure, and vessel occlusion were more common in those with CMV disease. The incidence of myocardial infarction, angina, and cardiac arrest did not differ between the two groups (recipients with versus without CMV disease). CONCLUSIONS: CMV disease is associated with an increased risk of cardiac complications in kidney transplant recipients. In our series, angiographic vessel occlusion was more common in recipients with CMV disease. This interesting finding may support the theory that CMV plays some role in the pathogenesis of CHD.

Pre-emptive transplants for patients with renal failure: an argument against waiting until dialysis.

BACKGROUND: Pre-emptive kidney transplants have not been favored in some centers because of concern about possible increased noncompliance and allegedly inferior long-term results. We analyzed our experience with pre-emptive kidney transplants to determine whether such concerns are justified. PATIENTS AND METHODS: Between January 1, 1984, and June 30, 1998, we performed 1849 adult primary kidney transplants: 385 pre-emptive (recipients not undergoing dialysis, ND) and 1464 non-pre-emptive (recipients undergoing dialysis, D). Results were subdivided by donor source: cadaver (CAD) and living donor (LD). ND recipients tended to be younger, but otherwise, the two groups were similar. Posttransplantation quality of life in recipients was evaluated using the nationally standardized Short Form Health Survey (SF-36). The posttransplantation employment status of the recipients was also evaluated. RESULTS: The patient survival rate 5 years posttransplantation was significantly better for ND (vs. D) recipients for both CAD (92.6% vs. 76.6%, P=0.001) and LD (93.3% vs. 89.5%, P=0.02) transplants. The 5-year patient survival rate was significantly higher for ND recipients compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation for both CAD (P=0.0005) and LD (P=0.0001) transplants. The graft survival rate 5 years posttransplantation was similar between ND and D recipients for CAD transplants, but significantly better for ND (vs. D) recipients of LD transplants (92.3% vs. 84.8%, P=0.006). For CAD transplants, the 5-year graft survival rate was not different when ND recipients were compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation; for LD transplants it was significantly higher for ND recipients compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation (P=0.04). The incidence of acute and chronic rejection was no different between ND and D recipients for either CAD or LD transplants, and it was also not affected by the pretransplantation time undergoing dialysis. Graft loss secondary to the recipient's discontinuation of immunosuppressive therapy (a crude estimate of compliance) was similar between ND and D recipients. Five years posttransplantation, the SF-36 scores regarding the recipient's quality of life and the employment status were similar for ND compared with D recipients, regardless of donor source. CONCLUSIONS: ND recipients do not seem to have higher rates of noncompliance than D recipients. Results for ND recipients seem to be superior than for D recipients, supporting the contention that renal failure patients should, if possible, undergo transplantation before dialysis.

Living donors >55 years: to use or not to use?

BACKGROUND: Kidney transplants using older donors are becoming increasingly accepted as a strategy for alleviating the growing donor organ shortage. Most studies to date have shown decreased graft survival associated with the use of older cadaver donors; however, studies on the effect of living donor age on graft survival are less clear-cut. METHODS: We studied the effect of donor age on patient and graft survival after 1126 consecutive cyclosporine-treated primary kidney transplants performed between January 1, 1985 and December 31, 1995. Of these grafts, 598 were from living donors (74 from donors >55 years old) and 528 from cadaver donors (54 from donors >55 years). We calculated actuarial patient survival, graft survival, and death-censored graft survival for recipients of both living donor and cadaver kidneys. Living donors were then further divided by HLA mismatch (0 vs. 1 - 6) and the presence or absence of an acute rejection episode. Multivariate analysis of factors associated with decreased graft survival was performed for recipients of both living and cadaver donor kidneys. Factors included for analysis were donor age >55 years, recipient age >50 years, the presence of diabetes mellitus, HLA mismatch (0 vs. 1 - 6), and the presence of an acute rejection episode. RESULTS: For cadaver kidneys, univariate analysis indicates that both overall (P=0.004) and death-censored (P=0.001) graft survival was significantly better with younger cadaver kidneys. This is supported by our multivariate analysis, which shows that cadaver donor age >55 years is an independent predictor of poor actuarial graft survival (P=0.0003). For living donor kidneys, univariate analysis also indicates that both overall (P=0.045) and death-censored (P=0.005) graft survival was significantly better with younger living donor kidneys. However, in the absence of acute rejection, 10-year death-censored graft survival for patients with older vs. younger living donor kidneys was 93% vs. 94%, whereas in the presence of one or more acute rejection episodes, 10-year death-censored graft survival dropped markedly to 39% with older and 54% with younger living donors. Kidneys from living donors >55 years had significantly better long-term graft survival than cadaver donors >55 years (P=0.012) and had comparable graft survival to younger cadaver donors. In contrast to our univariate analysis, multivariate analysis of our living donor data shows that decreased actuarial living donor death-censored graft survival was significantly associated only with the presence of one or more acute rejection episodes (P<0.0001). Living donor age >55 years was not independently associated with decreased graft survival. CONCLUSIONS: Ours is the largest single-center study of outcome for recipients of kidneys from living donors >55 years. Using univariate analysis, we have shown that graft survival of kidneys from older living donors is significantly better than that of kidneys from older cadaver donors and is comparable to that of kidneys from younger cadaver donors. Using multivariate analysis, we have shown that the presence of one or more acute rejection episodes significantly shortens both cadaver and living donor long-term graft survival. Most significantly, we have shown that, although the use of kidneys from cadaver donors >55 years is associated with significantly decreased long-term graft survival, no such association exists for recipients of kidneys from living donors >55 years. We feel that our data support the continued use of kidneys from older living donors.

Complications and risks of living donor nephrectomy.

BACKGROUND: Short- and long-term patient and graft survival rates are better for living donor (vs. cadaver) kidney transplant recipients. However, donor nephrectomy is associated with at least some morbidity and mortality. We have previously estimated the mortality of living donor nephrectomy to be 0.03%. In our present study, to determine associated perioperative morbidity, we reviewed donor nephrectomies performed at our institution from January 1, 1985, to December 31, 1995. METHODS: The records of 871 donors were complete and available for review. Of these donors, 380 (44%) were male and 491 (56%) were female. The mean age at the time of donation was 38 years (range: 17-74 years), and mean postoperative stay was 4.9 days (range: 2-14 days). RESULTS: We noted two (0.2%) major complications: femoral nerve compression with resulting weakness, and a retained sponge that required reexploration. We noted 86 minor complications in 69 (8%) donors: 22 (2.4%) suspected wound infections (only 1 wound was opened), 13 (1.5%) pneumothoraces (6 required intervention, 7 resolved spontaneously), 11 (1.3%) unexplained fevers, 8 (0.9%) instances of operative blood loss > or = 750 ml (not associated with other complications), 8 (0.9%) pneumonias (all of which resolved quickly with antibiotics alone), 5 (0.6%) wound hematomas or seromas (none were opened), 4 (0.5%) phlebitic intravenous sites, 3 (0.3%) urinary tract infections, 3 (0.3%) readmissions (2 for pain control and 1 for mild confusion that resolved with discontinuation of narcotics), 3 (0.3%) cases of atelectasis, 2 (0.2%) corneal abrasions, 1 (0.1%) subacute epididymitis, 1 (0.1%) Clostridium difficile colitis, 1 (0.1%) urethral trauma from catheter placement, and 1 (0.1%) enterotomy. At our institution, no donor died or required ventilation or intensive care. We noted no myocardial infarctions, deep wound infections, or reexplorations for bleeding. Analysis, by logistic regression, identified these significant risk factors for perioperative complications: male gender (vs. female, P<0.001), pleural entry (vs. no pleural entry, P<0.004), and weight > or = 100 kg (vs. < 100 kg, P<0.02). Similar analysis identified these significant risk factors for postoperative stay > 5 days: operative duration > or = 4 hr (vs. < 4 hr, P<0.001) and age > or = 50 years (vs. < 50 years, P<0.001). CONCLUSIONS: Living donor nephrectomy can be done with little major morbidity. The risks of nephrectomy must be balanced against the better outcome for recipients of living donor transplants.