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.

The histology of solitary renal allografts at 1 and 5 years after transplantation.

Previous studies suggest that the majority of renal allografts are affected by progressive, severe chronic histologic injury, yet studies using current protocols are lacking. The goal of this study was to examine the prevalence and progression of histologic changes using protocol allograft biopsies at 1 and 5 years after solitary kidney transplantation in patients transplanted between 1998 and 2004. Chronic histologic changes generally were mild at both 1 and 5 years and were similar in deceased and living donor kidneys. The overall prevalence of moderate or severe fibrosis was 13% (60/447) at 1 year and 17% (60/343) at 5 years. In a subgroup of 296 patients who underwent both 1- and 5-year biopsies, mild fibrosis present at 1 year progressed to more severe forms at 5 years in 23% of allografts. The prevalence of moderate or severe arteriolar hyalinosis was similar in tacrolimus and calcineurin inhibitor-free immunosuppression. These results in the recent era of transplantation demonstrate fewer, less severe and less progressive chronic histologic changes in the first 5 years after transplantation than previously reported.

The outcome of patients with nephrogenic systemic fibrosis after successful kidney transplantation.

Nephrogenic systemic fibrosis (NSF) is a debilitating disease in patients with severely diminished kidney function. Currently, no standard treatment exists but improvement has been reported after restoration of kidney function. We retrospectively studied 17 NSF patients with and without successful kidney transplantation (KTx) to evaluate the effects of KTx on NSF. Nine of the 11 KTx developed NSF pretransplant whereas two developed NSF immediately after KTx with delayed graft function. Two of the six dialysis patients had previous failed kidney transplants. Age and sex were well matched. All but one patient was dialysis dependent at the time of NSF. Median follow-up was 35 months for KTx patients and 9 months for dialysis patients. Kidney transplants achieved adequate renal function with median serum creatinine of 1.4 (0.9-2.8) mg/dL and a glomerular filtration rate of 42 (19-60) mL/min/1.73 m(2). NSF improved in 54.6% of the transplanted patients and 50% of the nontransplanted patients (p = 0.86). Two KTx patients had complete resolution of their symptoms whereas four had partial improvement. Improvement in the dialysis patients was all partial. Successful KTx did not insure improvement in NSF and in fact appeared to have no significant benefit over dialysis.

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.

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.

Patterns of quantitative sensation testing of hypoesthesia and hyperalgesia are predictive of diabetic polyneuropathy: a study of three cohorts. Nerve growth factor study group.

OBJECTIVE: To test quantitative sensation testing (QST) patterns of hypoesthesia and hyperalgesia as indicators of diabetic polyneuropathy (DPN) and its severity RESEARCH DESIGN AND METHODS: We used Computer-Assisted Sensory Examination IV; characterized the QST results of the foot of each patient in three diabetic cohorts (approximately 1,500 patients) as hyperesthetic (< or = 2.5th percentile), low-normal (2.5th-50th percentiles), high-normal (50th-97.5th percentiles), or hypoesthetic (> or = 97.5th percentile); and tested associations with symptoms, impairments, and test abnormalities. RESULTS: Overall neuropathic impairment was most severe in the pancreas-renal transplant and nerve growth factor cohorts, but it was much less severe in the population-based Rochester Diabetic Neuropathy Study (RDNS) cohort. The frequency distribution of sensory abnormalities mirrored this difference. When the QST spectra of diabetic cohorts were compared with those of the control subject cohort for vibration and cooling sensations, the only abnormality observed was hypoesthesia, which was expressed as an increased number of subjects with values at or above the 97.5th percentile or by an increased percentage of cases with high-normal values. Symptoms and impairments of DPN were significantly more frequent in the subjects with values at or above the 97.5th percentile than in the subjects whose values were between the 50th and 97.5th percentiles. For heat pain (HP) sensation thresholds (intermediate pain severity [HP:5], pain threshold [HP:0.5], and pain-stimulus response slope [HP:5-0.5]), an increased frequency of both hypoalgesia and hyperalgesia was observed (especially in the RDNS cohort). Steeper pain-stimulus response slopes were significantly associated with sensory symptoms, including severity of pain. CONCLUSIONS: 1) Decreased vibratory sensation (hypoesthesia) appears to be characteristic of mild DPN, whereas panmodality hypoesthesia is characteristic of severe DPN. 2) A shift of vibratory and cold detection thresholds (and also of attributes of nerve conduction and a measure of autonomic dysfunction) from low-normal (2.5th-50th percentiles) to high-normal (50th-97.5th percentiles) appears to precede overt expression of DPN and to thereby provide evidence of subclinical abnormality 3) Heat stimulus-induced hyperesthesia (low thresholds) occurs especially in mild DPN, and, because it correlates with DPN symptoms and impairments, it must be attributed to hyperalgesia rather than to supersensitivity Therefore, hypoalgesia or hyperalgesia may be an indicator of early DPN.

Trends in persistent proteinuria in adult-onset diabetes: a population-based study.

OBJECTIVE: This study investigates temporal trends in the prevalence and incidence of persistent proteinuria among people with adult-onset diabetes (age > or =40 years). RESEARCH DESIGN AND METHODS: The complete community-based medical records of all Rochester, Minnesota, residents with a diagnosis of diabetes or diabetes-like condition from 1945 through 1989 were reviewed to determine whether they met National Diabetes Data Group (NDDG) criteria. All confirmed diabetes cases residing in Rochester on 1 January 1970 (n = 446), 1980 (n = 647), and/or 1990 (n = 940) were identified. The medical records of these prevalence cases were reviewed from the time of the first laboratory urinalysis value to the last visit, death, or 1 April 1992 (whichever came first) for evidence of persistent proteinuria (two consecutive urinalyses positive for protein, with no subsequent negative values). Similarly, the medical records of all 1970-1989 diabetes incidence cases (n = 1,252) were reviewed to investigate temporal changes in 1) the likelihood of having persistent proteinuria before the date NDDG criteria was met, i.e., baseline; 2) the risk of persistent proteinuria after baseline; and 3) the relative risk of mortality associated with persistent proteinuria. RESULTS: The proportion of diabetes prevalence cases with persistent proteinuria on or before the prevalence date declined from 20% in 1970 to 11% in 1980 and 8% in 1990. Among the 1970-1989 diabetes incidence cases, 77 (6%) had persistent proteinuria on or before baseline; the adjusted odds declined by 50% with each 10-year increase in baseline calendar year (P<0.001). Among individuals free of persistent proteinuria at baseline, 136 subsequently developed persistent proteinuria; the estimated 20-year cumulative incidence was 41% (95% CI 31-59); the adjusted risk did not differ as a function of baseline calendar year. Survival of individuals with persistent proteinuria relative to those without was reduced but did not differ by baseline calendar year. CONCLUSIONS: The prevalence of persistent proteinuria among people with adult-onset diabetes in Rochester, Minnesota, declined 60% between 1970 and 1990. The decline appears because of a decrease in the proportion of diabetes incidence cases with persistent proteinuria before baseline rather than secular declines in the risk of persistent proteinuria after baseline or secular increases in the risk of mortality associated with persistent proteinuria. Similarity over time in age and fasting glucose at baseline, and at prevalence dates, is evidence that earlier detection of diabetes is not the sole explanation for the decline.

Increased weakness after pancreas and kidney transplantation.

BACKGROUND: Already there is evidence that simultaneous pancreas and kidney (SPK), or pancreas after kidney (PAK) transplantation, in patients with type 1 diabetes mellitus and end-stage kidney disease prevents worsening of diabetic polyneuropathy, but neuropathic improvement is delayed and incomplete. METHODS: In 85 patients with type 1 diabetes mellitus who underwent SPK or PAK transplantations, we performed sequential neuromuscular evaluations before, every 3 months after, and yearly after transplantation, quantitating muscle weakness separately from overall severity of polyneuropathy. RESULTS: We found that, on average, the weakness subscore of the Neuropathy Impairment Score of the lower limbs [NIS(LL)-W] was significantly worse at 3, 6, 9, and 12 months (by about 5 points) than at baseline. By contrast, for these times after transplantation, a composite score of nerve conduction abnormalities, an independent measure of severity of polyneuropathy, was not significantly worse and, in fact, was significantly improved. In multivariate analysis, length of hospital stay correlated with the increased weakness. CONCLUSIONS: We conclude that: (1) increased neuromuscular impairment after transplantation is mainly due to muscle weakness and not to worsening polyneuropathy; (2) in multivariate analysis, duration of hospitalization after transplantation was significantly associated with this increased weakness; (3) increased weakness is probably due to development of myopathy, which may be related to graft rejection, immunosuppression, sepsis, and intercurrent infections; (4) in future transplantation trials, weakness should be evaluated separately from neuropathic status, and the lowest efficacious dosages of immunotherapy should be used; and (5) essentially all diabetic patients reported that SPK or PAK transplantation was worthwhile because it freed them from diabetic lifestyle concerns.

Thymoglobulin induction decreases rejection in solitary pancreas transplantation.

BACKGROUND: Solitary pancreas transplants, both pancreas transplant alone (PTA) and pancreas after kidney (PAK), have higher rejection rates and lower graft survivals than simultaneous pancreas-kidney transplants (SPK). The aim of this study is to compare three different antibody induction regimens in solitary pancreas transplant recipients and to assess the role of surveillance pancreas biopsies in the management of these patients. METHODS: Solitary pancreas transplant recipients between 01/98 to 02/00 (n=29) received induction with either daclizumab (1 mg/kg on day 0, 7, 14), OKT 3 (5 mg/day x0-7), or thymoglobulin (1.5 mg/kg/day x0-10). Maintenance immunosuppression was similar for the three groups. All rejections were biopsy-proven either by surveillance/protocol or when clinically indicated. RESULTS: The 1-year graft survival was 89.3% overall and 91.7% in the thymoglobulin group. Thymoglobulin significantly decreased rejection in the first 6 months when compared with OKT3 or daclizumab (7.7 vs. 60 vs. 50%). Acute rejections were seen on surveillance biopsies in the absence of biochemical abnormalities in 40% of patients. CONCLUSIONS: Thymoglobulin induction regimen led to a low incidence of acute rejection and a high rate of graft survival in solitary pancreas transplants. In addition, surveillance biopsies were useful in the detection of early acute rejection in the absence of biochemical abnormalities.

Cyclosporine elimination in the presence of TOR inhibitors: effects on renal function, acute rejection, and safety.

Sirolimus in combination with cyclosporine reduces the incidence of acute rejection in renal transplant recipients when administered in double- or triple-therapy immunosuppressive regimens. Sirolimus administered as primary therapy has a beneficial effect on renal function, and the frequency of rejection episodes is similar to that of primary immunosuppression with cyclosporine. A strategy that may result in a more benign immunologic course with a substantially beneficial effect on renal function is to administer sirolimus and a calcineurin inhibitor early after transplantation, thereby promoting immunologic adaptation, and then to withdraw the calcineurin inhibitor at some point after transplantation to prevent nephrotoxicity. This article examines the results of this approach in recent studies that evaluated the effect of cyclosporine withdrawal on renal function, acute rejection, and safety in patients treated with sirolimus. Two open-label randomized trials of cyclosporine withdrawal were conducted in the United States, Canada, Europe, and Australia. In one of the studies, graft survival, patient survival, and the incidence of acute rejection at 6 months posttransplantation were not statistically significantly different between the patients receiving cyclosporine and the group that had undergone cyclosporine withdrawal. Furthermore, significantly better renal function was observed in the patients who underwent cyclosporine withdrawal compared with patients who continued to receive full-dose cyclosporine. These studies indicate that cyclosporine withdrawal has a beneficial effect on renal function without a significant increase in the incidence of acute rejection episodes.

Evaluation of proteinuria.

Proteinuria, a common finding on urinalysis, may indicate the presence of a wide variety of medical conditions, some of which are benign and associated with a favorable prognosis (such as orthostatic proteinuria) and others of which have more serious implications (such as glomerular disease or multiple myeloma). The amount of protein excreted in the urine may be increased by several factors, including increases in glomerular hydraulic pressure, pathologic changes of the glomeruli, decreases in tubular reabsorption and catabolism of protein, and increases in production or concentration of plasma proteins normally filtered by the glomerulus. Because proteinuria may reflect a severe renal pathologic condition, further evaluation should be undertaken to determine the most likely cause of the proteinuria.

Magnetic resonance angiography and detection of renal artery stenosis in a patient with impaired renal function.

Diagnosing renovascular disease in patients with renal insufficiency has challenged physicians for many years. Although contrast angiography is the "gold standard," it is associated with major risks in patients with preexisting renal failure. Other noninvasive tests have not proved to have sufficient sensitivity and specificity to supplant angiography. Developments in magnetic resonance (MR) angiographic technology, however, now enable physicians to assess the vasculature noninvasively and without use of potentially nephrotoxic agents. Herein we describe a patient with hypertension and renal failure in whom MR angiography proved to be the only effective noninvasive test for diagnosing renal artery stenosis. In addition, we review the current literature on MR angiography for renovascular disease. In the setting of renal impairment, MR angiography may be useful in screening patients for renovascular disease. More studies are needed in order to refine MR angiographic techniques and, ultimately, to determine specific situations in which MR angiography may be useful.

1,25-dihydroxyvitamin D-mediated hypercalcemia in a renal transplant recipient.

Hypercalcemia occurs in 10 to 30% of renal transplant recipients and is most often due to persistent hyperparathyroidism. Herein we describe a patient with a history of hyperparathyroidism who sought medical assessment because of recurrence of hypercalcemia 7 years after a successful renal transplantation. The hypercalcemia was associated with a normal serum phosphate level, a low to normal parathyroid hormone level, virtually undetectable levels of parathyroid hormone-related protein, and increased 1,25-dihydroxyvitamin D levels. Further assessment led to the diagnosis of an underlying lymphoma. To our knowledge, this is the first report of 1,25-dihydroxyvitamin D-mediated hypercalcemia in a renal transplant recipient with lymphoma. The possibility of an underlying lymphoproliferative disorder should be considered in the differential diagnosis of hypercalcemia in a renal transplant recipient.

Patient survival and renal recovery in acute renal failure: randomized comparison of cellulose acetate and polysulfone membrane dialyzers.

OBJECTIVE: To investigate survival and renal recovery after dialysis in patients with acute renal failure with use of synthetic membranes compared with substituted cellulose membranes. PATIENTS AND METHODS: We prospectively studied survival and recovery of renal function of 66 patients with acute renal failure who required intermittent hemodialysis. Patients were randomized to exclusive treatment with either cellulose acetate (CA) or polysulfone (PS) hemodialysis membranes. Additionally, markers of biocompatibility (complement, leukocyte counts, cytokine concentration) were measured at initiation and 1 hour after initiation of dialysis among 10 patients equally distributed between the CA and PS groups. RESULTS: The cohorts were indistinguishable with respect to age, sex, presence of diabetes mellitus, Acute Physiology and Chronic Health Evaluation II scores, percentage in the intensive care unit (ICU), and adequacy of dialysis. Survival (76% CA, 73% PS; P=.78) and recovery of renal function at 30 days (58% CA, 39% PS; P=.14) were not statistically different in the 2 groups. Among 26 CA patients and 27 PS patients treated in the ICU, survival was not statistically different (73% CA, 67% PS; P=.61); however, the proportion of patients recovering renal function suggested a benefit favoring CA membranes (65% CA, 37% PS; P=.04). Additionally, markers of biocompatibility were not significantly different between groups among the 10 patients equally distributed between the CA and PS groups. CONCLUSIONS: Overall clinical outcomes among patients with acute renal failure treated with CA hemodialysis membranes and those treated with PS membranes were not significantly different. The observed advantage favoring renal recovery among this ICU population treated with CA hemodialysis membranes warrants further investigation.

Role of adenosine in contrast media-induced acute renal failure in diabetes mellitus.

Increased release of renal adenosine and stimulation of renal adenosine receptors have been proposed to be major mechanisms in the development of contrast media-induced acute renal failure (CM-ARF). Patients with diabetes mellitus or preexisting renal disease who have reduced renal function have a markedly increased risk to develop CM-ARF. This increased risk to develop CM-ARF in patients with diabetes mellitus is linked to a higher sensitivity of the renal vasculature to adenosine, since experimental studies have shown increased adenosine-induced vasoconstriction in the kidneys of diabetic animals. Furthermore, recent evidence suggests that administration of adenosine receptor antagonists reduces the risk of development of CM-ARF in both diabetic and nondiabetic patients. The purpose of this review is to discuss the role of adenosine in the development of CM-ARF, particularly in the kidneys of diabetic patients, and to evaluate the therapeutic potential of adenosine receptor antagonists in the prevention of CM-ARF. Selective adenosine A1 receptor antagonists may provide a therapeutic tool to prevent CM-ARF in patients with diabetes mellitus and reduced renal function.

Pancreas transplantation for the prevention of diabetic nephropathy.

Diabetic nephropathy is the leading cause of kidney failure in the United States. Poor glycemic control, hypertension, and smoking have been implicated as risk factors for the development and progression of diabetic nephropathy in patients with type 1 diabetes mellitus. Improved medical therapy including angiotensin-converting enzyme inhibitors and tight glycemic control with use of intensive insulin therapy have been shown to reduce the progression of diabetic nephropathy substantially based on albumin excretion rates. Despite these improvements in medical management, many patients still experience progression from early diabetic nephropathy to end-stage renal disease. Successful pancreas transplantation leads to normal glycemic control in patients with type 1 diabetes, but historically it has generally been limited to patients with both kidney failure and diabetes. In this review of the current treatment of diabetic nephropathy, we examine the potential role of preemptive pancreas transplantation in patients with diabetic nephropathy.

Kidney transplantation without calcineurin inhibitors using sirolimus.

INTRODUCTION: With the introduction of new immunosuppressive medicines, it has become possible to determine the extent to which nephrotoxic medicines contribute to CAN. The aim of this study is to compare the safety and efficacy of calcineurin inhibitor (CI) free immunosuppression in a prospective, randomized trial comparing sirolimus-mycophenolate mofetil (MMF)-prednisone to tacrolimus- MMF-prednisone. METHODS: Patients are randomized at the time of transplant to receive either tacrolimus (target level 12 to 15 ng/mL in the first month) or sirolimus (target level 12 to 18 ng/mL in the first month). All patients also receive MMF (750 mg bid) and prednisone tapered to 10 mg/d by 3 months and thymoglobulin induction (1.5 mg/kg/d on days 0, 1, 2, 4 and 6). RESULTS: At this point we have 4-month follow-up in 85 patients. The acute rejection rate is 7.5% (3/40) in the tacrolimus group and 6.7% (3/45) in the sirolimus group. We have discontinued sirolimus in eight patients so far, with wound complications being the most common indication. Renal function appears to be better in the sirolimus group at 1 month after transplantation, but the difference is not statistically significant. CONCLUSIONS: While longer follow-up is needed, these results demonstrate that total avoidance of CI can be achieved with extremely low acute cellular rejection rates using sirolimus-based immunosuppression in combination with thymoglobulin, MMF, and prednisone.

Drug-induced renal toxicity. Help in recognizing offending agents.

Drug-induced kidney disease is common, especially in hospitalized patients, and prompt recognition of the various nephrotoxic syndromes is important because many are reversible. Risk factors should be assessed before patients are given an agent that may cause acute renal failure (eg, nonsteroidal anti-inflammatory drug, aminoglycoside antibiotic, angiotensin-converting enzyme inhibitor, radiocontrast agent). Discontinuation of the responsible drug is often the only necessary therapy.

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.