Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort.

INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments. METHODS: A total of 135 sporadic (s-bvFTD; mean age 63.3 years; 34% female) and 99 familial (f-bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f-bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule-associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation. RESULTS: Participants with f-bvFTD were younger and had earlier age at onset. s-bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI-Q) scores due to more frequent endorsement of depression and irritability. DISCUSSION: f-bvFTD and s-bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

Positive crossmatch kidney transplant recipients treated with eculizumab: outcomes beyond 1 year.

This study examined outcomes beyond 1 year in eculizumab-treated (EC) positive crossmatch kidney transplants (+XMKTx) compared to a historical control group. +XMKTx received desensitization with either plasma exchange (PE) alone (N = 48) or PE and EC (N = 30). EC, given for at least 1 month, was continued in the setting of persistently high DSA (B flow cytometric crossmatch [BFXM] >200) including: 4 weeks (n = 14); 9 weeks (n = 6), 6 months (n = 2), and 12 months (n = 8). All patients had at least 2 years follow-up. The incidence of acute clinical ABMR was lower in the EC group than controls (6.7% vs. 43.8% p < 0.01). Death-censored allograft survival was similar between groups. Chronic ABMR was the main cause of graft loss. On 1-year protocol biopsies, no differences were noted between EC and controls including: cg score >0, 26.7% versus 31.9% (p = 0.62), ptc score ≥ 2, 60.0% versus 60.0% (p = 1.00), or C4d + , 33.8% versus 13.5% (p = 0.08). A persistently high BFXM in EC-treated patients was associated with cg score >0 at 1 year, while EC appeared to protect against cg if the BFXM remained low. We conclude that despite decreasing acute clinical ABMR rates, EC treatment does not prevent chronic ABMR in recipients with persistently high BFXM after +XMKTx.

Kidney allograft function and histology in recipients dying with a functioning graft.

Death with function (DWF) is a major cause of kidney allograft failure. Allograft dysfunction may contribute to DWF. The aim of this study was to examine the relationship between DWF and allograft function using estimated GFR (eGFR) and histology. We retrospectively analyzed 1842 kidney allografts transplanted at our center from 1996 to 2010. eGFR was estimated using the MDRD equation. Biopsies obtained 12 months posttransplant and within 1 year of DWF were analyzed. Proportional hazards models were used to examine the relationship between eGFR and DWF. During 68 ± 43 months of follow-up, 14% (n = 256) of recipients experienced DWF. Risk factors of DWF included increasing recipient age (hazard ratio [HR] = 2.07, confidence interval [CI] 1.77-2.43, p < 0.0001), diabetes (HR = 2.58, CI 1.81-3.69, p < 0.0001), prior dialysis (HR = 1.47, CI 1.05-2.06, p = 0.03) and eGFR <40 mL/min/1.73 m(2) (HR 2.26 per 10 mL/min/1.73 m(2) decrease in eGFR, CI 1.82-2.81, p < 0.0001). Prior to death, only 15.9% (n = 39) of DWF recipients had stage 4 chronic kidney disease (CKD) and only 4.9% (n = 12) had stage 5 CKD. Most biopsies performed within 1 year of DWF (68%) demonstrated benign histology and were comparable to biopsies from matched controls. In conclusion, allograft dysfunction is independently associated with DWF. However, the majority of DWF recipients have well-preserved allograft function and histology prior to death.

Urine high and low molecular weight proteins one-year post-kidney transplant: relationship to histology and graft survival.

Increased urinary protein excretion is common after renal transplantation and portends worse outcome. In this study we assessed the prognostic contribution of several urinary proteins. Urinary total protein, albumin, retinol binding protein (RBP), α-1-microglobulin, IgG and IgM were measured in banked urine samples from 221 individuals 1 year after renal transplantation (age 52 ± 13 years, 55% male, 93% Caucasian and 82% living donor). Levels of all proteins measured were higher than in normal nontransplant populations. Patients with glomerular lesions had higher urinary albumin than those with normal histology, while those with interstitial fibrosis and tubular atrophy plus inflammation (ci>0, cg = 0, i>0) had higher levels of IgG, IgM, α-1-microglobulin and RBP. Concomitant normal levels of urinary albumin, IgM and RBP identified normal histology (specificity 91%, sensitivity 15%,). Urinary levels of the specific proteins were highly correlated, could not differentiate among the histologic groups, and appeared to result from tubulointerstitial damage. Increased urinary excretion of the low molecular weight protein RBP was a sensitive marker of allografts at risk, predicting long-term graft loss independent of histology and urinary albumin. This study highlights the prognostic importance of tubulointerstitial disease for long-term graft loss.

Oral paricalcitol reduces the prevalence of posttransplant hyperparathyroidism: results of an open label randomized trial.

Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 µg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24-h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1-year posttransplant. Eighty-seven patients completed the trial. One-year posttransplant, 29% of paricalcitol-treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 µg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.

Kidney allograft inflammation and fibrosis, causes and consequences.

This study assessed the development of allograft interstitial fibrosis and inflammation (GIF+"i"), a histologic pattern associated with reduced graft survival. Included are 795 adults, recipients of kidney allografts from 2000 to 2006. GIF+"i" was diagnosed in surveillance and clinical biopsies that had no transplant glomerulopathy. With time, posttransplant increasing number of grafts showed GIF+"i" and these patients had reduced death-censored graft survival (HR = 4.33 (2.49-7.53), p < 0.0001). Development of GIF+"i" was related to prior acute cellular rejection (ACR), BK nephropathy (PVAN), increasing number of HLA mismatches, retransplantation and DGF. However, 46.4% of GIF+"i" cases had no history of ACR or PVAN. Anti-HLA antibodies at transplant did not relate to GIF+"i" and these patients had no increased frequency of new antibody formation posttransplant. Post-ACR biopsies showed that GIF+"i" developed more commonly after clinically and/or histologically more severe ACR. Graft inflammation persisted in 38.7 and 29.6% of grafts 2 and 12 months post-ACR. Twelve months post-ACR, 27.1% of biopsies developed moderate-severe GIF and 51.8% showed GIF and inflammation. Persistent inflammation and progressive GIF is often subclinical but may lead to graft failure. GIF+"i" can be initiated by multiple etiologies but it is often postinfectious or due to persistent cellular immune-mediated injury.

Prosthetic joint infection in solid organ transplant recipients: a retrospective case-control study.

BACKGROUND: The clinical features and outcome of prosthetic joint infection (PJI) among solid organ transplant (SOT) recipients have not been characterized. We performed a retrospective, matched case-control study to examine potential risk factors. METHODS: We reviewed cases of PJI among transplant recipients who were evaluated at the Mayo Clinic between 1989 and 2009. Cases were matched to non-infected controls based on transplant type, prosthetic joint type, and order of organ transplantation/joint implantation. RESULTS: Among 367 patients with both a joint prosthesis and an SOT, there were 12 cases of infection in those receiving immunosuppression. These occurred in 8 renal recipients, 3 liver recipients, and 1 heart transplant recipient. Six subjects had hip and 6 had knee arthroplasty infections. The observed time to prosthesis failure ranged from 0.5 to 148 months after implantation. Gram-positive bacteria (staphylococci and streptococci) caused the infection in 8 subjects. Two cases were caused by nontuberculous mycobacteria, whereas the remaining 2 cases were culture-negative in the setting of antimicrobial use. We did not find a statistically significant association between obesity, diabetes mellitus, or antimicrobial prophylaxis (given in the setting of immunosuppression) and development of PJI. A marginal association was seen between surgical site infection and the risk of PJI; however, this did not reach statistical significance. CONCLUSION: In our series, infection was mainly caused by gram-positive bacterial pathogens, similar to the commonly encountered organisms in the immunocompetent host, although opportunistic pathogens were also isolated.

Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study.

Although mortality rates following liver transplantation (LT) are well described, there is a lack of detailed, prospective studies determining patterns of and risk factors for long-term mortality. We analyzed the multicenter, prospectively obtained The National Institute of Diabetes and Digestive and Kidney Diseases LT Database of 798 transplant recipients from 1990 to 1994 (follow-up 2003). Overall, 327 recipients died. Causes of death >1 year: 28% hepatic, 22% malignancy, 11% cardiovascular, 9% infection, 6% renal failure. Renal-related death increased dramatically over time. Risk factors for death >1 year (univariate): male gender, age/decade, pre-LT diabetes, post-LT diabetes, post-LT hypertension, post-LT renal insufficiency, retransplantation >1 year, pre-LT malignancy, alcoholic disease (ALD) and metabolic liver disease, with similar risks noted for death >5 years. Hepatitis C, retransplantation, post-LT diabetes, hypertension and renal insufficiency were significant risk factors for liver-related death. Cardiac deaths associated with age, male gender, ALD, cryptogenic disease, pre-LT hypertension and post-LT renal insufficiency. In summary, the leading causes of late deaths after transplant were graft failure, malignancy, cardiovascular disease and renal failure. Older age, diabetes and renal insufficiency identified patients at highest risk of poor survival overall. Diligent management of modifiable post-LT factors including diabetes, hypertension and renal insufficiency may impact long-term mortality.

Longitudinal Comparison of in Clinic and at Home Administration of the Cogstate Brief Battery and Demonstrated Practice Effects in the Mayo Clinic Study of Aging.

BACKGROUND: The Cogstate Brief Battery (CBB) is a computerized cognitive assessment that can be completed in clinic or at home. Design/Objective: This retrospective study investigated whether practice effects / performance trajectories of the CBB differ by location of administration. PARTICIPANTS/SETTING: Participants included 1439 cognitively unimpaired individuals age 50-75 at baseline participating in the Mayo Clinic Study of Aging (MCSA), a population-based study of cognitive aging. Sixty three percent of participants completed the CBB in clinic only and 37% completed CBB both in clinic and at home. MEASUREMENTS: The CBB consists of four subtests: Detection, Identification, One Card Learning, and One Back. Linear mixed effects models were used to evaluate performance trajectories in clinic and at home. RESULTS: Results demonstrated significant practice effects between sessions 1 to 2 for most CBB measures. Practice effects continued over subsequent testing sessions, to a lesser degree. Average practice effects/trajectories were similar for each location (home vs. clinic). One Card Learning and One Back accuracy performances were lower at home than in clinic, and this difference was large in magnitude for One Card Learning accuracy. Participants performed faster at home on Detection reaction time, although this difference was small in magnitude. CONCLUSIONS: Results suggest the location where the CBB is completed has an important impact on performance, particularly for One Card Learning accuracy, and there are practice effects across repeated sessions that are similar regardless of where testing is completed.

Identifying specific causes of kidney allograft loss.

The causes of kidney allograft loss remain unclear. Herein we investigated these causes in 1317 conventional kidney recipients. The cause of graft loss was determined by reviewing clinical and histologic information the latter available in 98% of cases. During 50.3 +/- 32.6 months of follow-up, 330 grafts were lost (25.0%), 138 (10.4%) due to death with function, 39 (2.9%) due to primary nonfunction and 153 (11.6%) due to graft failure censored for death. The latter group was subdivided by cause into: glomerular diseases (n = 56, 36.6%); fibrosis/atrophy (n = 47, 30.7%); medical/surgical conditions (n = 25, 16.3%); acute rejection (n = 18, 11.8%); and unclassifiable (n = 7, 4.6%). Glomerular pathologies leading to failure included recurrent disease (n = 23), transplant glomerulopathy (n = 23) and presumed nonrecurrent disease (n = 10). In cases with fibrosis/atrophy a specific cause(s) was identified in 81% and it was rarely attributable to calcineurin inhibitor (CNI) toxicity alone (n = 1, 0.7%). Contrary to current concepts, most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or CNI toxicity. Glomerular pathologies cause the largest proportion of graft loss and alloinmunity remains the most common mechanism leading to failure. This study identifies targets for investigation and intervention that may result in improved kidney transplantation outcomes.

Posttransplant lymphoproliferative disorder following pancreas transplantation.

The incidence, risk factors and impact on patient and graft survival were evaluated for posttransplant lymphoproliferative disorder (PTLD) among 212 pancreas transplant recipients. Thirteen (6.1%) developed PTLD during 71 +/- 27 months follow-up. Cumulative incidences of PTLD at 1, 3, 5 and 10 years posttransplant were 4.2%, 5.3%, 6.0% and 7.0%, respectively. Incidence of PTLD was lower for recipients of simultaneous pancreas kidney compared to pancreas after kidney transplant or pancreas transplant alone, though not significantly so. Recipient Epstein-Barr virus (EBV) seronegativity and number of doses of depleting antibody therapy administered at transplant were associated with increased risk of PTLD, while recipient age, gender, transplant type, cytomegalovirus mismatch maintenance immunosuppression type and treated acute rejection were not. All 13 cases underwent immunosuppression reduction, and 10 received anti-CD20 monoclonal antibody. During follow-up, 10/13 (77%) responded to treatment with complete remission, while 3 (23%) died as a result of PTLD. Patient and graft survivals did not differ for recipients with and without PTLD. The strong association of PTLD with EBV-seronegativity requires considering this risk factor when evaluating and monitoring pancreas transplant recipients. With reduction of immunosuppression and anti-CD20 therapy, survival for pancreas transplant recipients with PTLD was substantially better than previously reported.

Cardiac allograft remodeling after heart transplantation is associated with increased graft vasculopathy and mortality.

The aim of this study was to assess the patterns, predictors and outcomes of left ventricular remodeling after heart transplantation (HTX). Routine echocardiographic studies were performed and analyzed at 1 week, 1 year and 3-5 years after HTX in 134 recipients. At each study point the total cohort was divided into three subgroups based on determination of left ventricle mass and relative wall thickness: (1) NG-normal geometry (2) CR-concentric remodeling and (3) CH-concentric hypertrophy. Abnormal left ventricular geometry was found as early as 1 week after HTX in 85% of patients. Explosive mode of donor brain death was the most significant determinant of CH (OR 2.9, p = 0.01) at 1 week. CH at 1 week (OR 2.72, p = 0.01), increased body mass index (OR 1.1, p = 0.01) and cytomegalovirus viremia (OR - 4.06, p = 0.02) were predictors of CH at 1 year. CH of the cardiac allograft at 1 year was associated with increased mortality as compared to NG (RR 1.87, p = 0.03). CR (RR 1.73, p = 0.027) and CH (RR 2.04, p = 0.008) of the cardiac allograft at 1 year is associated with increased subsequent graft arteriosclerosis as compared to NG.

Predictors of early re-bleeding and mortality after acute variceal haemorrhage in patients with cirrhosis.

BACKGROUND AND AIMS: Risk factors for mortality and re-bleeding following acute variceal haemorrhage (AVH) are incompletely understood. The aim of this study was to determine risk factors for 6-week mortality, and re-bleeding within 5 days in patients with cirrhosis and AVH. METHODS: Kaplan-Meier and Cox proportional hazards regression analyses were used to determine risk factors among 256 patients with AVH entered into a randomised, prospective trial. RESULTS: Thirty-five patients (14%) died within 6 weeks of AVH; 14 deaths (40%) occurred within 5 days. Only the Model for End-stage Liver Disease (MELD) score and units of packed red blood cells (PRBCs) transfused in the first 24 h were associated with 6-week mortality univariately (HR 1.11, p < 0.001; HR 1.22, p < 0.001) and bivariately (HR MELD = 1.10, p < 0.001; HR per unit of PRBCs transfused = 1.15, p = 0.005). Re-bleeding within 5 days occurred in 37 patients (15%); MELD score (p = 0.01) and a clot on a varix (p = 0.05) predicted re-bleeding. Patients with a MELD score > or = 18; both MELD score > or = 18 and > or = 4 units of PRBCs transfused; both MELD score > or = 18 and active bleeding at index endoscopy; and variceal re-bleeding had increased risk of death 6 weeks post-AVH (HR = 7.4, p < 0.001; 11.3, p < 0.001; 9.9, p < 0.001; 10.2, p < 0.001 respectively). CONCLUSIONS: Patients with AVH and MELD score > or = 18, requiring > or = 4 units of PRBCs within the first 24 h or with active bleeding at endoscopy are at increased risk of dying within 6 weeks. MELD score > or = 18 is also a strong predictor of variceal re-bleeding within the first 5 days.

Posttransplant diabetes mellitus after pancreas transplantation.

Some patients do not achieve normoglycemia after an otherwise successful pancreas transplant. The aim of this study was to define the incidence and risk factors for the development of persistent diabetes mellitus after pancreas transplantation. We studied the outcomes of 144 pancreas transplants performed at our institution between January 2001 and December 2005. Diabetes mellitus was defined as the persistent need for pharmacologic treatment of diabetes mellitus despite evidence of allograft function. Data are expressed as median (25-75% inter-quartile range). Median follow-up was 39 months (IQR 26-55 months). During the follow-up period, 28 patients (19%) developed diabetes mellitus with a functioning allograft. Factors predicting hyperglycemia included: pretransplant insulin dose, BMI and acute rejection episodes (p < 0.0001, p = 0.0002 and p < 0.02, respectively). The median pretransplant hemoglobin A1c for patients developing diabetes was 8.3% (IQR 7.0-9.4%) compared to 6.2% (IQR 5.8-7.4%) at 2 years after transplant (p = 0.0069). In conclusion, persistent diabetes mellitus can occur despite the presence of a functioning pancreas allograft and is due to increased pretransplant BMI, high pretransplant insulin requirements and episodes of acute rejection.

Survival of patients on the kidney transplant wait list: relationship to cardiac troponin T.

Patients waiting for a kidney transplant have high mortality despite careful preselection. Herein, we assessed whether cardiac troponin T (cTnT) can help stratify risk in patients selected for kidney transplantation. cTnT levels were measured in all kidney transplant candidates but the results were not used for patient selection. Among 644 patients placed on the kidney waiting list from 9/2004 to 12/2006, 61% had elevated cTnT levels (>0.01 ng/mL). Higher levels related to diabetes, longer time on dialysis, history of cardiovascular disease and low serum albumin. High cTnT also related to cardiac anomalies, including left ventricular hypertrophy (LVH), wall motion abnormalities and stress-inducible ischemia by dobutamine echo (DSE). However, 54% of patients without these cardiac findings had elevated cTnT. Increasing cTnT levels were associated with reduced survival (HR = 1.729, CI (1.25-2.39), p = 0.01) independently of low serum albumin (0.449 (0.24-0.83), p = 0.011) and history of stroke (3.368 (1.47-7.73), p = 0.0004). The results of the DSE and/or coronary angiography did not relate significantly to survival. However, high cTnT identified patients with abnormal echo findings and poor survival. Wait listed patients with normal cTnT have excellent survival irrespective of other factors. In contrast, high cTnT levels are strongly predictive of poor survival in the kidney transplant waiting list.

Impact of pegylated interferon and ribavirin treatment on graft survival in liver transplant patients with recurrent hepatitis C infection.

Recurrent hepatitis C virus (HCV) infection is a major cause of morbidity and mortality after liver transplantation for HCV-related end stage liver disease. Although previous studies have shown a short-term effect of interferon-based treatment on fibrosis progression, it is unclear whether this translates to improved graft survival. We evaluated whether treatment of recurrent HCV leads to an improved graft survival. Cohort study included consecutive HCV patients who underwent liver transplantation between 1 January 1995 and 1 January 2005 in the Mayo Clinic, Rochester, MN. Two hundred and fifteen patients were included in the study. During a median follow-up of 4.4 years (interquartile range 2.2-6.6), 165 patients (77%) had biopsy-proven recurrent HCV infection confirmed by serum HCV RNA testing. Seventy-eight patients were treated. There were no differences in MELD-score, fibrosis stage or time towards HCV recurrence between treated and untreated patients at time of recurrence. There was a trend for greater frequency of acute cellular rejection among untreated patients. The incidence of graft failure was lower for patients treated within 6 months of recurrence compared to patients not treated within this time-period (log rank p = 0.002). Time-dependent multivariate Cox regression analysis showed that treatment of recurrent HCV infection was statistically significantly associated with a decreased risk of overall graft failure (hazard ratio 0.34; CI 0.15-0.77, p = 0.009) and a decreased risk of graft failure due to recurrent HCV (hazard ratio 0.24; CI 0.08-0.69, p = 0.008). In conclusion, although a cause and effect relationship cannot be established, treatment of recurrent HCV infection after liver transplantation is associated with a reduced risk of graft failure.

Alloantibody levels and acute humoral rejection early after positive crossmatch kidney transplantation.

We examined the course of donor-specific alloantibody (DSA) levels early after transplant and their relationship with acute humoral rejection (AHR) in two groups of positive crossmatch (+XM) kidney transplant recipients: High DSA group-41 recipients with a baseline T- or B-cell flow crossmatch (TFXM, BFXM) channel shift >or=300 (molecules of equivalent soluble fluorochrome units (MESF) of approximately 19 300) who underwent pretransplant plasmapheresis (PP), and Low DSA group-29 recipients with a baseline channel shift <300 who did not undergo PP. The incidence of AHR was 39% (16/41) in the High DSA group and 31% (9/29) in the Low DSA group. Overall, mean DSA levels decreased by day 4 posttransplant and remained low in patients who did not develop AHR. By day 10, DSA levels increased in patients developing AHR with 92% (23/25) of patients with a BFXM >359 (MESF of approximately 34 000) developing AHR. The BFXM and the total DSA measured by single antigen beads correlated well across a wide spectrum suggesting that either could be used for monitoring. We conclude that AHR is associated with the development of High DSA levels posttransplant and protocols aimed at maintaining DSA at lower levels may decrease the incidence of AHR.

Effect of pretransplant human leukocyte antigen antibodies detected by solid-phase assay on heart transplant outcomes.

INTRODUCTION: The significance of pretransplant human leukocyte antigen antibodies (HLA-Abs), especially donor-specific HLA-Abs (DSA), as detected by single antigen bead assay (SAB), is not well characterized in cardiac transplantation (CTX). We analyzed the significance of DSA detected by SAB in predicting crossmatch (XM) results and post-transplant rejection. MATERIALS AND METHODS: We performed a retrospective study of 85 CTX with negative cytotoxicity XM. We tested pretransplant sera collected within 24 hours of transplantation by flow cytometric XM (FXM) and SAB. DSA identified by SAB were utilized to perform a virtual crossmatch (VXM). Positive VXM was defined as the presence of DSA at mean fluorescence intensity (DMFI)>1500. Additionally, to analyze the significance of low-level DSA weakly positive VXM was DMFI 300 to 1500. We defined a negative VXM as MFI<300. VXM results were correlated with FXM results and with posttransplant rejection. RESULTS: Patients in the weakly positive and negative VXM had similar posttransplant rejections. DMFI>1500 correlates well with FXM results (accuracy=90%). Patients with DMFI>1500 had a higher incidence of antibody-medicated rejection (AMR; P=.0052), AMR grade I (P<.0001), cell-mediated rejection (CMR) grade>1R/1A (P=.018), and CMR grade>2R/3A (P=.057). Similarly patients with positive FXM had a higher incidence of AMR (P=.091), AMR grade 1 (P<.0001), CMR grade>1R/1A (P=.05), and CMR grade>2R/3A (P=.56). CONCLUSIONS: In conclusion, SAB defined DMFI>1500 can be used as a surrogate for FXM. Recipients with DMFI>1500 pretransplant and positive FXM have significantly higher rates of AMR and CMR compared to recipients with DMFI<1500 or negative FXM.

Combined heart and kidney transplantation provides an excellent survival and decreases risk of cardiac cellular rejection and coronary allograft vasculopathy.

BACKGROUND: We analyzed the results of combined heart-kidney transplantation (CHKTx) over a 10-year period. METHODS: Between September 1996 and May 2007 at Mayo Clinic, 12 patients (age 52 ± 12.2 years) underwent CHKTx as a simultaneous procedure in 10 recipients and as a staged procedure in two recipients with unstable hemodynamics after heart transplantation. RESULTS: There was no operative mortality. Patient survival rates for the CHKTx recipients at 1 and 3 months and 6 years were 91%, 83%, and 83% and did not differ from isolated heart transplantation (IHTx) recipients (97%, 95%, and 79%, P = 0.61). The freedom from cardiac allograft rejection (≥ grade 2) at 3 months was 73% for CHKTx and had not changed during further follow-up; for IHTx, freedom from rejection at 3 months and 1 and 6 years was 61%, 56%, and 42% (P = .08). Heart and renal allograft survival was 100% with and left ventricular ejection fraction 66% ± 8.4% and glomerular filtration rate 61 ± 25 at last follow-up. There were no signs of cardiac allograft vasculopathy in the CHKTx recipients. CONCLUSION: CHKTx yields favorable long-term outcome, with a low incidence of cardiac rejection and vasculopathy. Simultaneous CHKTx appears feasible, if hemodynamics is satisfactory. This approach expands the selection criteria for transplantation in patients with coexisting end-stage cardiac and renal disease.