Cancer Incidence Among Canadian Kidney Transplant Recipients

A number of studies have observed increased cancer incidence rates among individuals who have received renal transplants. Generally, however, these studies have been limited by relatively small sample sizes, short follow-up intervals or focused on only one cancer site. We conducted a nationwide population-based study of 11,155 patients who underwent kidney transplantation between 1981 and 1998. Incident cancers were identified up to December 31, 1999, through record linkage to the Canadian Cancer Registry. Patterns of cancer incidence in the cohort were compared to the Canadian general population using standardized incidence ratios (SIRs). We examined variations in risk according time since transplantation, year of transplantation and age at transplantation. In our patient population, we observed a total of 778 incident cancers versus 313.2 expected (SIR = 2.5, 95% CI = 2.3-2.7). Site-specific SIRs were highest for cancer of the lip (SIR = 31.3, 95% CI = 23.5-40.8), non-Hodgkin's lymphoma (NHL) (SIR = 8.8, 95% CI = 7.4-10.5), and kidney cancer (SIR = 7.3, 95% CI = 5.7-9.2). SIRs for NHL and cancer of the lip and kidney were highest and among transplant patients. This study confirms previous findings of increased risks of posttransplant cancer. Our findings underscore the need for increased vigilance among kidney transplant recipients for cancers at sites where there are no population-based screening programs in place.     

Sirolimus Use and Cancer Incidence Among US Kidney Transplant Recipients

Sirolimus has anti‐carcinogenic properties and can be included in maintenance immunosuppressive therapy following kidney transplantation. We investigated sirolimus effects on cancer incidence among kidney recipients. The US transplant registry was linked with 15 population‐based cancer registries and national pharmacy claims. Recipients contributed sirolimus‐exposed time when sirolimus claims were filled, and unexposed time when other immunosuppressant claims were filled without sirolimus. Cox regression was used to estimate associations with overall and specific cancer incidence, excluding nonmelanoma skin cancers (not captured in cancer registries). We included 32 604 kidney transplants (5687 sirolimus‐exposed). Overall, cancer incidence was suggestively lower during sirolimus use (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.70–1.11). Prostate cancer incidence was higher during sirolimus use (HR = 1.86, 95% CI = 1.15–3.02). Incidence of other cancers was similar or lower with sirolimus use, with a 26% decrease overall (HR = 0.74, 95% CI = 0.57–0.96, excluding prostate cancer). Results were similar after adjustment for demographic and clinical characteristics. This modest association does not provide strong evidence that sirolimus prevents posttransplant cancer, but it may be advantageous among kidney recipients with high cancer risk. Increased prostate cancer diagnoses may result from sirolimus effects on screen detection.     

Incidence and Risk Factors for Cytomegalovirus Disease in a Colombian Cohort of Kidney Transplant Recipients

Incidence and risk factors for cytomegalovirus (CMV) disease in a Colombian cohort of kidney transplant recipients. CMV infection and disease are important causes of morbidity and mortality in kidney transplant recipients, and its prevalence varies with economic, geographic, and ethnic factors. Among 1620 records from a Colombian reference center, CMV immunoglobulin (Ig)G seroprevalence was found to be 90.9% among recipients and 90.2% among donors. In 86% (n = 264) of the cases, CMV disease occurred during the first 6 months after the transplantation, and the most frequent clinical presentation was CMV syndrome, followed by gastrointestinal disease. The following parameters were independent predictors of CMV disease: serological status of D+/R+ (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.03–2.63) and D+/R− (HR, 2.72; 95% CI, 1.49–4.93), age of the recipient (HR, 1.02; 95% CI, 1.01–1.03), and receiving more than 30 mg of prednisolone by the end of the first month after transplantation (HR, 1.59; 95% CI, 1.22–2.07). Acyclovir prophylaxis or other antiviral agents significantly decreased the risk of disease (HR, 0.41; 95% CI, 0.29–0.58 and HR, 0.34; 95% CI, 0.20–0.58, respectively). In conclusion, we found a high prevalence of CMV infection in a cohort of Latin American transplant recipients. In accord with findings from other regions, serological status is the main risk factor, prophylaxis with acyclovir is effective, and induction with alemtuzumab does not increase the risk of CMV disease.     

Incidence of Early Acute Kidney Injury in Lung Transplant Patients: A Single-Center Experience

Background

Acute kidney injury (AKI) is a common complication in the early period of lung transplantation (LTx). We aimed to describe the incidence and perioperative risk factors associated with AKI following LTx.

Deceased-Donor Acute Kidney Injury and Acute Rejection in Kidney Transplant Recipients: A Multicenter Cohort

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Risk Factors for Septic Complications in Kidney Transplant Recipients

Introduction

Septic complications following kidney transplantation are a leading cause of therapeutic failure. An early diagnosis may protect the recipient from the severe consequences of sepsis. We sought to determine the risk factors influencing the occurrence of septic complications among kidney transplant recipients.

Materials and methods

The 146 potential donors included in the study were evaluated for brain stem death criteria. Supportive management included mechanical ventilation to normocapnia, rewarming, as well as fluid and electrolyte replacement. Dopamine infusions and desaminovasopressin were titrated to predetermined mean arterial pressure (MAP). Central venous pressure (CVP) was maintained at 8 to 11 mm Hg. Hemodynamic data were acquired by the thermodilution method prior to organ procurement: MAP, CVP, pulmonary capillary wedge pressure (PCWP), and systemic vascular resistance index (SVRI). Recipient data included age, gender, period of prior hemodialysis, panel reactive antibodies, cold ischemia time, and cause of renal insufficiency. The 232 kidney recipients were examined for occurrence of septic complications including septicemia, pneumonia, peritonitis, or graft infection.

Results

Kidney transplants from donors with MAP < 70 mm Hg and SVRI < 1200 dyne × s/cm⁵ × m² showed a significantly higher occurrence of septic complications in recipients (P < .05) where mortality rate was also significantly greater (P < .01).

Conclusions

MAP < 70 mm Hg and SVRI < 1200 dyne × s/cm⁵ × m² among organ donors predicted greater occurrence of septic complications and increased mortality among kidney transplant recipients.     

Pregnancy and Maternal Outcomes Among Kidney Transplant Recipients

Fertility rates, pregnancy, and maternal outcomes are not well described among women with a functioning kidney transplant. Using data from the Australian and New Zealand Dialysis and Transplant Registry, we analyzed 40 yr of pregnancy-related outcomes for transplant recipients. This analysis included 444 live births reported from 577 pregnancies; the absolute but not relative fertility rate fell during these four decades. Of pregnancies achieved, 97% were beyond the first year after transplantation. The mean age at the time of pregnancy was 29 ± 5 yr. Compared with previous decades, the mean age during the last decade increased significantly to 32 yr (P < 0.001). The proportion of live births doubled during the last decade, whereas surgical terminations declined (P < 0.001). The fertility rate (or live-birth rate) for this cohort of women was 0.19 (95% confidence interval 0.17 to 0.21) relative to the Australian background population. We also matched 120 parous with 120 nulliparous women by year of transplantation, duration of transplant, age at transplantation ±5 yr, and predelivery creatinine for parous women or serum creatinine for nulliparous women; a first live birth was not associated with a poorer 20-yr graft or patient survival. Maternal complications included preeclampsia in 27% and gestational diabetes in 1%. Taken together, these data confirm that a live birth in women with a functioning graft does not have an adverse impact on graft and patient survival.One of the many perceived benefits of kidney transplantation has been restoration of pituitary-ovarian function and fertility in women of reproductive age. Prenatal advice for women with a functioning kidney transplant has been primarily based on data derived from observational research,^1–13 and the reported live-birth rates achieved in such women range from 43.2¹⁴ to 82%.¹⁵Although an increased pregnancy event number has been reported for women with a functioning kidney transplant,¹⁶ little is actually known about “pregnancy rate changes” during the past 40 yr. More importantly, long-term graft and maternal survival analyses, referred to when advising women who have undergone transplantation and are considering a pregnancy, have been mostly performed without adequate matching,¹² or, alternatively, matching has been used but outcomes followed up for only brief intervals^14,17,18 and in small cohorts.^19–22 Published graft matching studies to date suggest no adverse impact 10 yr after a live birth.¹⁴In most instances, pregnancies in women with a kidney graft have been encouraged. Historically, renal function,^8,15,17,18 baseline proteinuria,²³ intercurrent hypertension,^1,24 and time from transplantation^{1,3,5,8,14,15,18,24,25} have been used to predict adverse event risks to the mother, kidney, and offspring. To this are added the often unquantifiable inherent risks for genetically transmitted diseases or the problems associated with prematurity.^26,27 More recently, epidemiologic evidence suggests low birth weight may be associated with the development of hypertension,²⁸ cardiovascular disease,²⁹ insulin resistance,³⁰ and end-stage renal failure.³¹ Moreover, low birth weight is associated with an increased risk for hypertension, independent of genetic and shared environmental factors.³²Series published to date have not captured all pregnancy events or their outcomes. Limitations of some of the published studies include short duration of follow-up and studies with no adequate or long-term matching for decade and renal function.We examined fertility rates, pregnancy rates, and pregnancy outcomes over 40 yr in an at-risk population, defined as women who were aged between 15 and 49 and had a functioning kidney transplant, using ANZDATA registry data. In addition, maternal and graft outcomes were analyzed, and, uniquely, a matched cohort analysis of 120 nulliparous and 120 parous women who had undergone transplantation enabled analysis of outcomes at 20 yr.     

Immunosuppression and the Risk of Post-Transplant Malignancy Among Cadaveric First Kidney Transplant Recipients

The success of renal transplantation may be counterbalanced by serious adverse medical events. The effect of immunosuppression on the incidence of de novo neoplasms among kidney recipients should be monitored continuously. Using data from the Scientific Registry of Transplant Recipients, we studied the association of induction therapy by immunosuppression with antilymphocyte antibodies, with the development of de novo neoplasms. The study population included more than 41 000 recipients who received a cadaveric first kidney transplant after December 31, 1995, and were followed through February 28, 2002. Using Cox regression models, we estimated time to development of two types of malignancy: de novo solid tumors and post-transplant lymphoproliferative disorder (PTLD). We made adjustments for several patient demographic factors and comorbidities. Induction therapy was significantly associated with a higher relative risk (RR) of PTLD (RR = 1.78, p < 0.001), but not with a greater likelihood of de novo tumors (RR = 1.07, p = 0.42). Treatment with maintenance tacrolimus vs. cyclosporine showed a significantly different RR of developing de novo tumors for recipients with induction than for those not receiving induction (p = 0.024). These new estimates of the magnitude of malignancy risk associated with induction therapy may be useful for clinical practice.     

Risk of Renal Cell Carcinoma Among Kidney Transplant Recipients in the United States

Renal cell carcinoma (RCC) is a common malignancy following kidney transplantation. We describe RCC risk and examine RCC risk factors among US kidney recipients (1987–2010). The Transplant Cancer Match Study links the US transplant registry with 15 cancer registries. Standardized incidence ratios (SIRs) were used to compare RCC risk (overall and for clear cell [ccRCC] and papillary subtypes) to the general population. Associations with risk factors were assessed using Cox models. We identified 683 RCCs among 116 208 kidney recipients. RCC risk was substantially elevated compared with the general population (SIR 5.68, 95% confidence interval 5.27–6.13), especially for papillary RCC (SIR 13.3 versus 3.98 for ccRCC). Among kidney recipients, RCC risk was significantly elevated for blacks compared to whites (hazard ratio [HR] 1.50) and lower in females than males (HR 0.56). RCC risk increased with prolonged dialysis preceding transplantation (p‐trend < 0.0001). Risk was variably associated for RCC subtypes with some medical conditions that were indications for transplantation: ccRCC risk was reduced with polycystic kidney disease (HR 0.54), and papillary RCC was increased with hypertensive nephrosclerosis (HR 2.02) and vascular diseases (HR 1.86). In conclusion, kidney recipients experience substantially elevated risk of RCC, especially for papillary RCC, and multiple factors contribute to these cancers.     

Cytomegalovirus Status of Kidney Transplant Recipients and Cardiovascular Risk

Background

Cytomegalovirus (CMV) infection is associated with an increased risk of cardiac complications in kidney transplant recipients (KTRs). Some data suggest that CMV may be involved in atherogenesis. The aim of the study was the analysis of CMV medical history in KTRs and its influence on cardiovascular (CV) incidents.

Risk Factors and Outcomes Associated With Posttransplant Diabetes Mellitus in Kidney Transplant Recipients

Background

Although our understanding of the risk factors involved in the occurrence of posttransplant diabetes mellitus (PTDM) as well as its outcomes has improved, it still remains incomplete. Our study attempts to analyze the risk factors as well as the outcomes associated with PTDM in the renal transplant patients at the Cleveland Clinic.

Methods

Our study is a retrospective, case-control study. We screened 209 charts of 217 patients who received single-organ kidney transplant at the Cleveland Clinic between January 1996 and December 1998. PTDM was defined by the American Diabetes Association criteria of either a fasting blood glucose ≥126 mg/dL or random blood sugars ≥200 mg/dL confirmed on a second occasion. Kidney transplant recipients who developed PTDM (cases) were compared with kidney transplant recipients who did not develop diabetes but were matched for the time of transplant (controls).

Results

Forty-nine patients (23%) developed PTDM. The data of 47 cases and 47 controls were analyzed. Age ≥40 years, body mass index ≥30, pretransplant triglyceride levels >150 mg/dL, and presence of graft rejection were significant risk factors for developing PTDM. Smoking was associated with increased risk of PTDM but failed to achieve statistical significance. Compared with controls, PTDM patients had higher risk of cardiovascular disease, infections, and graft rejection.

Conclusion

Our results show that PTDM is a significant problem after kidney transplantation, and those who have high risk should be closely monitored after transplant and aggressively treated if they develop diabetes to minimize the risk of complications.