Prolonged curarisation following renal transplantation

A retrospective study of postoperative respiratory morbidity in 247 patients requiring renal transplantation between 1955 and 1973 showed that 7 patients required postoperative controlled ventilation for up to 6 days. The nondepolarising relaxants tubocurarine and pancuronium were used in only 65 patients, but all 7 cases of respiratory failure occurred in this group. This suggests that the use of these drugsin anephric patients is potentially hazardous so far as postoperative respiratory insufficiency is concerned.     

Temporary inactive status on renal transplant waiting list: causes, risk factors, and outcomes

Approximately 30% of all patients listed for a kidney transplant in the United States are on inactive status. The consequences of temporary inactivation and rates of transplantation in this group of patients have not been reported. We undertook a retrospective cohort study at our transplant center examining all patients listed between 2001 and 2007. We examined the rate of inactivation, risk factors, duration, and outcomes including transplantation rates and patient survival while on the waiting list and after transplantation. There were 436 patients included in the analysis; 322 (73.9%) were never inactivated and 114 patients (26.1%) were temporarily inactive. The most common causes for inactivation were cardiovascular and suspected malignancy. Time to reactivation was similar among different causes. Waiting times for transplantation (excluding time of inactivation) was 18.7 ± 0.9 versus 39.9 ± 2.3 months for active compared with temporarily inactive patients (log-rank P < .0001). Sixty-five percent of patients were reactivated within 24 months. Approximately one-third of patients were never reactivated. Patient survival was similar among both groups. Temporary inactivation is an independent risk factor for a prolonged waiting time even if time of inactivation is not accounted for. Effective strategies for monitoring patients temporarily inactive on the waiting list should be developed.     

Contemporary risk factors for ureteral stricture following renal transplantation

IntroductionAllograft ureteral strictures after renal transplantation impact graft function and increase patient morbidity. They can be challenging to treat and may require complex surgical repair. Therefore, the objective of this study was to identify contemporary risk factors for the development of post-renal transplant ureteral strictures.MethodsA retrospective analysis was performed on all renal transplant patients at Vancouver General Hospital from 2008–2019. Demographics, clinical parameters, and outcomes were compared between patients who did and did not develop ureteral strictures. Putative risk factors for ureteral stricture were analyzed using logistic regression.ResultsA total of 1167 patients were included with a mean followup of 61.9±40.8 months. Ureteral strictures occurred in 25 patients (2.1%). Stricture patients had no demographic differences compared to non-stricture patients but had significantly higher rates of postoperative complications, longer hospital stays, and decreased renal function one year post-transplant (all p<0.05). On multivariable analysis, cold ischemia time >435 minutes (odds ratio [OR] 43.9, confidence interval [CI] 1.6–1238.8, p=0.027), acute rejection (OR 3.0, CI 1.1–7.4, p=0.027), and postoperative complications (OR 112.4, CI 2.4–5332.6, p=0.016) were risk factors for stricture.ConclusionsRenal transplant patients with ureteral stricture experience greater morbidity and reduced post-transplant renal function compared to non-stricture patients. Our findings support attempts to reduce cold ischemia time, acute rejection, and postoperative complications to mitigate this potential complication. Our study is limited by the low incidence of ureteral stricture resulting in a small sample of stricture patients. Future research in a larger, multicenter setting is warranted.     

Hypertension, antihypertensive agents and outcomes following renal transplantation

Hypertension is common following renal transplantation and adversely affects graft and patient survival. However, strategies for antihypertensive drug therapy and target blood pressure have not been clearly defined. Aim: To assess the influence of achieved blood pressure and antihypertension drug therapy on graft and patient survival with the aim of identifying targets and event rates for future intervention studies. Methods: We undertook a longitudinal follow up study of 634 renal transplant patients. Patients were surveyed in December 1994 and followed up after 102 months. Blood pressure (BP) was determined from the mean of three clinic readings and antihypertensive drug therapy recorded. Results: Complete follow up data were available for analysis on 622 patients (57.2% male; mean age: 45.2 +/- 13.0 yr. There were 158 (25.4%) deaths and 115 (18.5%) death-censored graft failures. Lower systolic and diastolic blood pressure were associated with better graft survival in the Kaplan-Meier analysis. Univariate analysis showed serum creatinine (HR 1.012, p < 0.001), duration of renal replacement therapy (HR 0.946, p = 0.012), age (HR 0.979, p = 0.014) and pulse pressure (HR 1.017, p = 0.044) to be predictors of graft survival with serum creatinine and duration of renal replacement therapy as the only significant factors in the multivariate analysis. Lower systolic and pulse pressure were associated with better patient survival in the Kaplan-Meier analysis. Age (HR) 1.062, p < 0.0001), serum creatinine (HR 1.002, p = 0.021), diabetes (HR 3.371, p < 0.0001), and pulse pressure (HR 1.013, p = 0.036) were significant predictors of patient survival in the univariate and multivariate analysis. Patient survival was reduced with increasing number of antihypertensives (p < 0.05), as was graft survival (p < 0.05). Reduced patient and graft survival were seen in patients prescribed calcium channel antagonists (p < 0.01). There was no increased patient mortality in those patients on beta-blockers or angiotensin converting enzyme (ACE) inhibitors. Conclusion: Hypertension is a risk factor, which remains despite the use of anti-hypertensives, for reduced patient and graft survival. The risk was not significant when blood pressure was entered together with serum creatinine in the multivariate analysis. Beta-blockers may have a beneficial effect on cardiovascular mortality, and ACE inhibitors a beneficial effect on both patient and graft survival. There is a pressing need for interventional studies to assess the impact of blood pressure targets on patient and graft survival and the effect of individual agents on these outcomes.     

Cardiovascular events following renal transplantation: role of traditional and transplant-specific risk factors

Cardiovascular mortality is increased in transplant recipients. However, studies including non-fatal events are critical to assess the burden of disease and to identify novel risk factors. We described the incidence of fatal and non-fatal events, and explored associations and interactions among traditional and transplant-specific risk factors and cardiovascular events (CVE) in a cohort of 922 patients transplanted between 1993 and 1998. One hundred and seventy-six patients experienced 201 CVE (111 cardiac, 48 cerebrovascular, 42 peripheral-vascular). Most CVE were non-fatal. Factors associated with cardiac events were (adjusted hazard ratios) tobacco (3.53; P<0.001), obesity (2.92; P<0.001), diabetes (2.63; P<0.001), multiple rejections (2.19; P=0.008), prior CVE (2.0; P=0.004), dialysis >1 year (1.91; P=0.007), and overweight status (1.68; P=0.04); with cerebrovascular events: diabetes and peritoneal dialysis (11.95; P<0.001), age >45 (6.77; P<0.001), diabetes (4.87; P<0.001), prior CVE (3.73; P<0.001), creatinine >141 micromol/l (3.16; P=0.001), peritoneal dialysis (3.06; P=0.027), and obesity (0.32; P=0.046); with peripheral-vascular events: diabetes (8.48; P<0.001), tobacco and cytomegalovirus (3.88; P<0.001), age >45 (2.31; P=0.019), and prior CVE (2.25; P=0.016); with mortality: tobacco and deceased-donor (3.52; P<0.001), age >45 (1.81; P=0.002), diabetes (1.76; P=0.002), pulse pressure (1.64; P=0.029), prior CVE (1.52; P=0.04), and dialysis >1 year (1.47; P=0.04). The majority of CVE post-transplant were non-fatal. Previous CVE was strongly associated with CVE post-transplant. Interactions among transplant-specific and traditional risks impacted significantly the incidence of CVE. Modifiable factors such as duration of dialysis, deceased-donor transplantation, and acute rejection should be viewed as cardiovascular risks.     

Employment outcomes following successful renal transplantation

Eng M, Zhang J, Cambon A, Marvin MR, Gleason J. Employment outcomes following successful renal transplantation.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01441.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: Data on employment outcomes after successful renal transplantation are few. We conducted this study to identify favorable factors for employment after transplantation. Methods: Adult patients <65 yr of age who underwent renal transplantation between January 1, 2002 and December 31, 2007 were surveyed. Patients with graft survival <1 yr were excluded. We also tested their knowledge of Medicare coverage after transplantation. Data were analyzed using chi‐squared and Fisher’s exact tests. p‐Value <0.05 was considered statistically significant. Results: A 55% response rate was obtained where 56% of respondents were employed after transplantation. Race, marital status, previous transplant, and complicated post‐operative course did not influence employment. Favorable factors include male gender (p = 0.04), younger age (<40 [p = 0.0003] or <50 yr [p < 0.0001]), having ≥1 dependent (p = 0.04), higher education (minimum high school degree [p = 0.003] or some college [p = 0.002]), live donor recipient (p = 0.004), wait time <2 yr (p = 0.03), dialysis <2 yr (p < 0.0001) or pre‐dialysis (p = 0.04), and pre‐transplantation employment (p < 0.0001). Mean time for employment was 4.9 ± 6.3 months (median three months). Common reasons for unemployment were disability (59%) and retirement (27%). Finally, 7% correctly responded that Medicare benefits end 36 months following transplantation. Conclusions: Potentially modifiable factors to improve employment are earlier referral and better education regarding Medicare eligibility.     

New-onset diabetes after renal transplantation: diagnosis, incidence, risk factors, impact on outcomes, and novel implications

Objective

New-onset diabetes after transplantation (NODAT) is a multifactorial, complex metabolic disorder associated with impaired long-term graft function, reduced recipient survival, and increased risks of cardiovascular disease and infectious complications. The impact of NODAT is generally underestimated partly due to the inconsistent criteria that have been previously used for its diagnosis and to the generally short observation periods. The aim of this article was to review the recent literature on NODAT and to highlight the novel implications.

Findings

The 2010 American Diabetes Association guidelines provide useful, simplified criteria to unify the diagnosis including application of hemoglobin A1C levels. We sought to establish the impact of various modifiable and nonmodifiable risk factors. A vast number of papers have examined the effects of immunosuppressive medications on the development of NODAT: Neither calcineurin inhibitor nor sirolimus (SRL) or steroids seems to be innocent of contributing to it. Immunosuppressants account for 74% of the occurrence of NODAT. Among modifiable risk factors, obesity is independent and significant, with great prevalence in the population. In additional to lifestyle modifications, the role of bariatric surgery (BS) either before or after transplantation is highlighted herein as a strategy to reduce disease in the view of the results among overweight, nontransplanted patients.

Summary

Because of the strong association between high glucose values in the early posttransplant period and the development of NODAT, the condition must be recognized early after (or even before) transplantation by intensive screening. Patients at risk for NODAT must modify appropriate risk factors and particularly undergo pretransplant planning and/or posttransplant adjustment individualizing immunosuppressive therapy to mitigate the risk of this serious complication.     

肾移植术后糖尿病的临床特性及高危因素

目的 研究肾移植术后糖尿病（ＰＴＤＭ）的临床特性及高危因素。方法 将５１２例肾移植患者分为２组,其中４８例ＰＴＤＭ患者为糖尿病组。其余４６４例患者为非糖尿病组。定期监测患者体重、用药情况、生化指标、病毒抗体,并用血清学方法及聚合酶链反应（ＰＣＲ）方法检测主要组织相容性抗原（ＨＬＡ）。结果 糖尿病组的平均年龄及术后６个月内激素的用量明显高于非糖尿病组。肾移植术后半年内易出现ＰＴＤＭ,且全部ＰＴＤＭ     

Long‐term evolution,secular trends,and risk factors of renal dysfunction following cardiac transplantation

Recent reports suggest that individuals who underwent heart transplantation in the last decade have improved post‐transplant kidney function. The objectives of this retrospective study were to describe the incidence and to identify fixed and time‐dependent predictors of renal dysfunction in cardiac recipients transplanted over a 25‐year period (1983–2008). To illustrate temporal trends, patients (n = 306) were divided into five groups based on year of transplantation. The primary endpoint was the estimated glomerular filtration rate (eGFR) at year 1. Secondary endpoints were time to moderate (eGFR <60 ml/min/1.73 m²) and severe renal dysfunction (eGFR <30 ml/min/1.73 m²). Risk factor analyses relied on multivariable regression models. Kidney function was mildly impaired before transplant (median eGFR=61.0 ml/min/1.73 m²), improved at discharge (eGFR=72.3 ml/min/1.73 m²; P < 0.001), decreased considerably in the first year (eGFR = 54.7 ml/min/1.73 m²; P < 0.001), and deteriorated less rapidly thereafter. At year 1, 2004–2008 recipients exhibited a higher eGFR compared with all other patients (P < 0.001). Factors independently associated with eGFR at year 1 and with moderate and severe renal dysfunction included age, gender, pretransplant eGFR, blood pressure, glycemia, and use of prednisone (P < 0.05). In summary, kidney function worsens constantly up to two decades after cardiac transplantation, with the greatest decline occurring in the first year. Corticosteroid minimization and treatment of modifiable risk factors (hypertension, diabetes) may minimize renal deterioration.     

Hypertension in renal transplantation: donor and recipient risk factors

AIMS: To determine the respective roles of donor and recipient factors in the subsequent development of hypertension after renal transplantation. PATIENTS AND METHODS: All the patients transplanted between January 1990 and December 1999 who still had a functioning graft 1 year post-transplant (n = 321) were retrospectively studied. Blood pressure was assessed at 1 year post-transplant. Hypertension was defined as a systolic BP > or equal 140 mmHg or diastolic BP > or equal 90 mmHg, or use of antihypertensive medication. Relevant donor and recipient characteristics were recorded. RESULTS: Two-hundred-and-sixty-three patients (82%) were hypertensive. In multivariate analysis, pretransplant hypertension (RR, 1.74, 95% CI, 1.07 to 2.87), anticalcineurin use (RR, 2.59, 95% CI, 1.13 to 5.92), urinary protein excretion (RR, 1.84, 95% CI, 1.06 to 3.18), BMI (RR, 1.08, 95% CI, 1.01 to 1.16), donor age (RR, 1.28,95% CI, 1.05 to 1.59, for each 10-year increase in donor age) and donor aortorenal atheroma (OR, 2.34; 95% CI, 1.24 to 4.46) were associated with hypertension. Among patients under calcineurin inhibitors, those receiving cyclosporine were more prone to have hypertension than those receiving tacrolimus (88.7% vs 78%; p = 0.04). CONCLUSION: Both recipient and donor factors contribute to hypertension in RTR.     

Liver transplantation: role of immunosuppression, renal dysfunction and cardiovascular risk factors

In the past decades, advances in immunosuppression, organ preservation, surgical techniques and better management of post-transplantation complications have led to improvement in survival of liver transplant patients. Such extended survival of liver graft recipients in their fifties and sixties has resulted in a greater prevalence of complications, in particular chronic kidney (CKD) and cardiovascular diseases (CVD). Renal failure and cardiovascular complications in the setting of liver transplantation are associated to an increase of morbidity and mortality. A 4-fold increased risk of death is reported among patients developing post-transplant CKD, and CVD is the leading cause of death with a functioning allograft, accounting for as much as 30% of post-transplant mortality. The onset is multifactorial, with pre-transplant conditions involved, including pre-transplant renal insufficiency, hepatitis C virus infection and pretransplant diabetes. Acute renal dysfunction in the setting of transplantation is also responsible of post-transplant CKD. Immunosuppressive therapy is primarily responsible for the development of CKD. Metabolic syndrome and its individual components, including diabetes mellitus, systemic hypertension, dyslipidemia, and obesity, are increasingly being identified as closely related to immunosuppressive therapy and actively contribute to cardiovascular morbidity and mortality in transplant patients. Treatment of modifiable risk factors is mandatory aiming to prevent the development and progression of serious complications. Early recognition, prevention and treatment of these conditions may further improve long-term survival after liver transplantation.     

Cardiovascular risk factors and diseases after renal transplantation

Cardiovascular disease is a leading cause of death after renal tranpslantation (tpx), and the incidence is considerably higher than in the general population. Objective To evaluate the incidence of atherosclerotic cardiovascular complications after tpx, the prevalence of cardiovascular risk factors, prior to and following tpx, and the association between the risk factors and complications. Patients and methods Analysis of atherosclerotic cardiovascular diseases (coronary artery disease, cerebral and peripheral vascular disease) and cardiovascular risk factors before and after transplantation in 427 renal transplant recipients between 1987 and 1992 (mean age at transplantation 45±12 years, 58% male, 7% diabetics) with a mean post-transplant follow-up of 29±20 months. Results Following tpx 11.7% developed atherosclerotic cardiovascular diseases, the majority coronary artery disease (9.8%). The comparison of risk factors 12 months before and 24 months following transplantation showed: prevalence of systemic hypertension (from 73% to 85%), diabetes mellitus (from 7% to 16%) and obesity with a body mass index >25 kg/m² (from 26% to 48%) had increased significantly whereas the number of smokers halved to 20%. Triglycerides decreased significantly (from235 mg/dl to 217 mg/dl). Totaland HDL cholesterol rose significantly (from 232 mg/dl to 273 mg/dl and from 47 mg/dl to 56 mg/dl, respectively). LDL cholesterol increase was significant (from 180 mg/dl to 189 mg/dl). In the univariate analysis, cardiovascular diseases were significantly associated with male gender, age over 50 years, diabetes mellitus (DM), smoking, total cholesterol ≥200 mg/dl, LDL cholesterol>180 mg/dl, HDL cholesterol ≤55 mg/dl, fibrinogen ≥350 mg/dl, body mass index>25 kg/m², serum uric acid >6.5 mg/dl and with more than two antihypertensive agents per day. The Cox proportional hazards model revealed DM with a relative risk (RR) of 4.3, age>50 years (RR=2.7), body mass index>25kg/m² (RR=2.6), smoking (RR=2.5), LDL cholesterol>180 mg/dl (RR=2.3) and uric acid>6.5 mg/dl as independent risk factors. Conclusions The high incidence of cardiovascular disease following renal transplantation is mianly due to a high prevalence and accumulation of classical risk factors before and following transplantation. Future prospective studies should evaluate the success of treatment regarding reduction of cardiovascular morbidity and mortality in this high risk population.     

Donor-specific HLA antibodies: risk factors and outcomes after kidney transplantation

Background

Anti-human leukocyte antigen antibodies (HLA Abs) have been associated with reduced kidney allograft survival. Our aim was to analyze the prevalence and impact on allograft function of donor-specific HLA antibodies (DSA) among a cohort of kidney transplant recipients.

Patients and Methods

The 321 recipients had received deceased-donor kidneys followed for a median of 70 ± 43 months. We performed a cross-sectional analysis of the presence of HLA Abs with the use of Luminex technology.

Results

Fifty patients (15.6%) displayed HLA Abs after transplantation including 21 (6.7%) as de novo HLA Abs. Eight patients (2.5%) developed DSA, and 42 (13%) showed no DSA. We compared 3 groups of patients: with DSA, without DSA, and without HLA sensitization. The DSA patients were younger (P = .03) with a higher percentage of men (P = .00), and having received less frequent induction treatment with basiliximab or thymoglobulin (P = .02). Patients without DSA revealed a higher percentage of pretransplantation HLA sensitization (P = .00), more pretransplantation transfusions (P = .08), and more frequent retransplantations (P = .00). The incidence of acute rejections was higher for DSA patients (P = .02) than for the other 2 groups, behaving as an independent risk factor (relative risk, 4.7; 95% confidence interval, 1.1-18.8; P = .03). Graft survival at 5 years was lower among patients with compared to those without HLA Abs (P = .00).

Conclusions

HLA donor-specific sensitization, an uncommon situation in our study, was associated with younger male recipients and less induction treatment. An acute rejection episode was an independent risk factor for the development of DSA; therefore, we think that monitoring of HLA Abs should be included in evaluation of the early postransplantation period.     

Non-immunological risk factors in paediatric renal transplantation

In paediatric renal transplantation, non-immunological risk factors account for about one-third of graft losses. Recurrence of original disease is observed mainly in primary hyperoxaluria and glomerulopathies such as steroid-resistant nephrotic syndrome and membranoproliferative glomerulonephritis. In both glomerulopathies, 20% of grafts are lost from recurrence. Vascular thrombosis is, in most series, the second cause of graft loss in children, particularly in young recipients or with young donors (under 5 years of age). Non-compliance with treatment is a common non-immunological factor in adolescent recipients, which may trigger a severe rejection process resulting in graft loss. The role of factors related to graft preservation and intra- and post-operative management (ischaemia time, delayed graft function) or to cytomegalovirus infection is less obvious in our series. Prevention of vascular thrombosis and of non-compliance is most important in order to improve the results of paediatric renal transplantation.     

Long-term fracture risk following renal transplantation: a population-based study

Abnormal bone metabolism is a recognized complication of end-stage renal disease, but fracture risk following renal transplantation has not been well quantified. We followed the 86 Olmsted County, Minnesota, residents who underwent initial renal transplantation in 1965–1995 for 911 person-years (median, 10.6 years per subject) in a retrospective cohort study. Fractures, and possible risk factors, were assessed through review of each subjects complete community medical records. Altogether, 117 fractures were observed during follow-up extending to 33 years. The cumulative incidence of any fracture at 15 years was 60% versus 20% expected (P<0.001). There was a significantly increased risk of fractures generally [standardized incidence ratio (SIR), 4.8; 95% CI, 3.6–6.4] and vertebral (SIR, 23.1; 95% CI, 12.3–39.6) and foot fractures (SIR, 8.4; 95% CI, 5.1–12.9) especially. Age at first transplantation, renal failure due to diabetes, pancreas transplantation, peripheral neuropathy, peripheral vascular disease and blindness were all associated with overall fracture risk. In a multivariate analysis, however, only age and diabetic nephropathy were independent predictors of fracture risk generally, while higher activity status was protective. Diabetes was the only independent predictor of lower limb fractures, whereas age and osteoporosis history predicted vertebral fractures. Cumulative corticosteroid dosage was not associated with increased fracture risk in this analysis. Despite the fact that our patients had few risk factors for preexisting bone disease attendant to postmenopausal osteoporosis, prior corticosteroid use or renal osteodystrophy, these data indicate that renal transplantation is associated with a significant increase in fracture risk among unselected patients in the community. Diabetic patients, particularly, experience excess lower limb fractures. Patients and their care providers should be aware of this elevated fracture risk, which continues long-term.Presented at the 24th Annual Meeting of the American Society of Bone and Mineral Research in San Antonio, Tex., USA.