Pain affects health-related quality of life in kidney transplant recipients

BACKGROUND: Chronic pain is prevalent in end-stage renal disease patients undergoing chronic hemodialysis. We do not fully know the intensity of chronic pain experienced by kidney recipients in comparison to those on chronic hemodialysis and healthy controls. Moreover, the effect of chronic pain on kidney recipients' health-related quality of life (HRQoL) is yet to be comprehensively addressed. We designed this study to find an answer to these questions. METHODS: In this case control study, we studied 205 kidney recipients, 69 hemodialysis patients, and 100 healthy controls, who were matched for age, sex, monthly family income, and educational level. The patients were evaluated for the intensity of chronic pain by Visual Analogue Scale (VAS). HRQoL was measured with Short Form 36 (SF-36) in the kidney recipients. Chronic pain intensity was compared in the study groups, and in the kidney recipients the correlation between SF-36 subscores and severity of pain was assessed. RESULTS: Severity of pain in the kidney recipients was lower than the hemodialysis patients, but more than the healthy controls (P=.001). The VAS pain score negatively correlated with the scores of SF- 36 total (r=-.329, P=01), mental health (r=-.190, P=07), physical health (r=-.275, P=.001), physical function (r=-.339, P=.001), role limitation due to physical problems (r=-.478, P=.001), role limitation due to emotional problems (r=-.326, P=.001), and bodily pain (r=-.894, P=.001). DISCUSSION: The intensity of chronic pain experienced by the kidney recipients is less than that experienced by patients under chronic hemodialysis, but higher than healthy subjects. Focusing on chronic pain as a cause of post-renal transplantation morbidity is expected to improve post-renal transplantation quality of life.     

Treatment of anemia with darbepoetin alfa administered de novo once every other week in chronic kidney disease

BACKGROUND/AIMS: Darbepoetin alfa is an erythropoiesis-stimulating protein that works via the same mechanism and has a threefold longer serum half-life than recombinant human erythropoietin (rHuEPO). The objective of this study was to evaluate extending the dosing interval of darbepoetin alfa to once every other week administration for the treatment of anemia in patients with chronic kidney disease (CKD) not requiring dialysis who were naive to rHuEPO therapy. METHODS: This was a multi-center, open-label study. Seventy-six rHuEPO-naive patients were enrolled to receive darbepoetin alfa (0.75 microg/kg) once every other week for up to 24 weeks. Doses were titrated to achieve and maintain a hemoglobin target of 11.0 to 13.0 g/dl. RESULTS: Ninety-seven percent (95% CI: 0.92, 1.00) of patients completing 24 weeks of treatment achieved a hemoglobin response. The median time to response was 5 weeks (range 1-25 weeks). The median darbepoetin alfa dose at the time of response was 60 microg(range 30-130 microg). Darbepoetin alfa was safe and well tolerated, and no antibodies to darbepoetin alfa were detected. CONCLUSION: These results demonstrate the utility of darbepoetin alfa administered once every other week in rHuEPO-naive CKD patients. This new treatment paradigm may allow for more widespread management of anemia in patients with CKD.     

A logistic regression model for predicting health-related quality of life in kidney transplant recipients

BACKGROUND: To develop a logistic regression model capable of predicting health-related quality of life (HRQOL) among kidney transplant recipients and determine its accuracy. METHODS: Three groups of patients were selected: 70 healthy controls, 136 kidney transplant patients as a derivation set, and another 110 kidney transplant patients as a validation set. SF-36 score was used for HRQOL measurement. A cutoff point to define poor versus good HRQOL was calculated using the SF-36 scores of healthy controls. A logistic regression model was used to derive predictive parameters from the derivation set. The derived model was then tested among the validation set. HRQOL predictions made by the model for the patients in the validation set and the SF-36 scores were compared. We calculated sensitivity, specificity, positive and negative predictive values, and model accuracy. RESULTS: SF-36 scores below 58.8 were defined as an indication of poor HRQOL. The regression model suggested that poor HRQOL was positively associated with lower education (below high school diploma), being single or widowed, and diabetes/hypertension as etiology. It was negatively associated with younger age (<45 years) at the time of transplantation. Optimal sensitivity and specificity were achieved at a cutoff value of 0.74 for the estimated probability of poor HRQOL. Sensitivity, specificity, positive and negative predictive values, and accuracy of the model were 73%, 70%, 80%, 60%, and 72%, respectively. CONCLUSION: The suggested model can be used to predict poor posttransplant HRQOL among renal graft recipients using simple variables with acceptable accuracy. This modal can be of use in decision making in the recipients for whom achieving good HRQOL is the main aim of transplantation, to select high-risk patients and to start interventional programs to prevent a poor HRQOL.     

Pharmacoepidemiology of anemia in kidney transplant recipients

ABSTRACT. Anemia has long been known to be a complication of end-stage renal disease (ESRD), and it has been linked to cardiovascular morbidity and mortality. Although kidney transplant recipients (KTR) are prone to experiencing cardiovascular outcomes, little is known about the epidemiology of anemia in this population. With few exceptions, studies to date have not fully evaluated the associations between posttransplant anemia (PTA) and medications commonly used in KTR, particularly immunosuppressant drugs, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB). The authors aimed to specifically investigate possible associations between these drugs and PTA. Detailed medical information was retrospectively collected on 374 consecutive KTR from our transplant clinic. Univariate/multivariate linear regression models were used to test for associations between hematocrit (HCT) and other covariates, and logistic regression models were used to detect independent predictors of PTA, defined as HCT <33%. The mean time since transplantation was 7.7 yr, and mean creatinine was 2.2 mg/dl. The prevalence of PTA was 28.6%. Ten percent of all patients were on erythropoietin therapy, but only 41.6% of patients whose HCT was <30 received this treatment. From multivariate analyses, the authors found that female gender and lower renal function were associated with lower HCT (both P < 0.001). Patients on ACEI had significantly lower HCT (P = 0.005) compared with patients without such treatment. In addition, a significant curvilinear dose-response relationship was found between ACEI dose and HCT. Among the immunosuppressant drugs, mycophenolate mofetil (P = 0.05) and tacrolimus (P = 0.02) were associated with a lower HCT. The authors conclude that PTA is prevalent and undertreated in KTR. Several medications that are possibly modifiable correlates of PTR deserve further study.     

就业状况对肾移植受者生活质量和社会支持的影响

目的探讨就业状况对肾移植受者生活质量和社会支持的影响。方法使用简明健康状况调查表(SF-36)和领悟社会支持量表(PSSS)测量65例就业和71例非就业的门诊肾移植受者的术后生活质量和社会支持程度,并对资料进行统计分析。结果就业组性别、年龄、移植术后时间和移植肾来源与非就业组比较,差异有统计学意义(P0.05,P0.01);就业组SF-36生理领域总分、生理功能、生理职能、躯体疼痛、精力和情感职能5个维度得分显著高于非就业组(P0.05,P0.01);就业组领悟社会支持总分及各分量表得分显著高于非就业组(均P0.01)。结论肾移植受者术后就业状况与其性别、年龄、移植术后时间和移植肾来源相关,术后就业的肾移植受者生活质量和社会支持均高于未就业的肾移植受者。     

Assessment of health-related quality of life in renal transplant recipients and dialysis patients

Health-related quality of life (HRQoL) is becoming an important outcome measure in evaluation of various forms of renal replacement therapy (RRT). The Short Form-36 (SF-36), Giessen Subjective Complaints List (GBB-24), and Zerssen's Mood Scale (Bf-S) are internationally validated questionnaires for the assessment of HRQoL. The goal of the current study was to evaluate the HRQoL of renal transplant recipients and compare it with that of patients on different forms of RRT. The study population consisted of: (1) 120 patients on hemodialysis (HD); (2) 43 patients on peritoneal dialysis (PD); (3) nine recipients who lost their grafts and went back to dialysis; (4) 120 age- and sex-matched healthy individuals (controls); and (5) 48 renal transplant recipients. The mean SF-36 scores were not significantly different between control group and transplant recipients as well as HD and PD patients including previously transplanted patients. The dialysis patients scored significantly worse in all eight SF-36 domains compared with transplant recipients and healthy subjects. In all GBB-24 components, the transplant recipients scored significantly higher than HD and PD patients. In the “fatigue tendency,” “limb pain,” and “cardiac complaints” components, recipients scored significantly higher than control group subjects. The mood analysis (Bf-S) showed that the scores of transplant recipients and controls did not differ, being significantly higher than those of dialysis patients. The HRQoL of patients on HD and PD were similar and lower than that of the general population. Renal transplantation significantly improved HRQoL at least to the level of healthy individuals. Graft loss was associated with significant worsening of HRQoL.     

Efficacy and safety of darbepoetin alfa for anemia in children with chronic kidney disease: a multicenter prospective study in Japan

Background

We evaluated the safety and efficacy of darbepoetin alfa (DA), an attractive alternative to recombinant human erythropoietin (rHuEPO) in managing renal anemia, in Japanese children with chronic kidney disease (CKD) on peritoneal dialysis (PD) and hemodialysis (HD), and not on dialysis (ND).

Methods

A total of 31 pediatric CKD patients (13 PD, 2 HD, and 16 ND) were enrolled. DA was administered bi-weekly intravenously (IV) or subcutaneously (SC) for PD or ND patients, and weekly IV for HD patients for 24 weeks. The target Hb was defined as 11.0 to ≤13.0 g/dl. In patients receiving rHuEPO, the initial DA dose was calculated at 1 μg DA for 200 IU rHuEPO. The initial DA dose for naïve patients was determined by body weight, and intended not to exceed 0.5 μg/kg per administration. For some PD or ND patients, the dosing frequency was subsequently changed to once every 4 weeks.

Results

Mean Hb values increased from 10.5 ± 1.1 to 11.1 ± 1.1 g/dl after 4 weeks of DA treatment. The target Hb was achieved in all patients, 64.5 % of whom maintained the value at completion of the study. Hb responses were similar between IV and SC. The dosing frequency was extended to once every 4 weeks in 37.9 % of PD or ND patients. Eighty-seven adverse events were noted in 27 (87.1 %) of 31 patients, none of which were associated with DA.

Conclusion

These results suggest that IV or SC administration of DA is an effective and safe treatment for renal anemia in Japanese children with CKD.     

Epoetin alfa and darbepoetin alfa: effects on ventricular hypertrophy in patients with chronic kidney disease

BACKGROUND: Anemia is very common in chronic kidney disease (CKD) and is commonly treated with recombinant human erythropoietin. The aim of this study was to analyze the efficacy of epoetin alfa and darbepoetin alfa on left ventricular parameters in patients with CKD. METHODS: Patients with CKD not yet dependent on dialysis were randomly assigned to treatment with epoetin alfa at weekly intervals (Epo group; baseline hemoglobin 8.5 +/- 0.8 mg/dL, creatinine clearance 10.0 +/- 2.0 ml/min per 1.73 m2) or darbepoetin alfa every 2 weeks (Dar group; baseline hemoglobin 8.2 +/- 0.8 mg/dL, creatinine clearance 10.8 +/- 2.4 ml/min per 1.73 m2). Patients not receiving erythropoietin served as a control group. Two-dimensional color Doppler echocardiography was performed at baseline and at 24 weeks to measure left ventricular mass index (LVMI) and ejection fraction. RESULTS: Hemoglobin in the 2 treatment arms was corrected to 10.6 +/- 0.6 mg/dL and 10.7 +/- 0.5 mg/dL for Epo and Dar groups, respectively. The LVMI decreased significantly in both the Epo (-5.7 +/- 14.2 g/m2) and the Dar group (-5.6 +/- 15.8 g/m2) but increased in the control group (9.0 +/- 15.1 g/m2; p=0.02, between the Epo and control groups, and between the Dar and control groups). The ejection fraction was increased in both treatment groups (Epo group: 2.45% +/- 2.28%, Dar group: 1.64% +/- 2.95%) and decreased in controls (-1.15% +/- 3.69%) (p=0.004 among groups). The 2 treatment groups showed similar efficacy. The degree and the change of renal function did not differ among the 3 groups at end of study. CONCLUSIONS: The 2 erythropoiesis-stimulating agents epoetin alfa and darbepoetin alfa, when given to patients with CKD in doses aimed at standard anemia correction are associated with a similar degree of LVMI reduction, in the absence of a concomitant enhancement of CKD progression.     

Cardiovascular diseases in kidney transplant recipients: the role of anemia

Cardiovascular diseases are among the leading causes of mortality and death associated graft loss in kidney transplant recipients. Recently, there has been an increased awareness of the potential role of nontraditional risk factors such as anemia in contributing to the increased burden of cardiovascular diseases in kidney transplant recipients. Studies that are primarily based on retrospective data analyses have shown an association between anemia and cardiovascular outcomes. These findings underscore the need for prospective studies to better understand these risks and to implement management strategies that would have a positive impact on patient and graft outcomes. On the basis of the available data, this article reviews the magnitude of cardiovascular diseases and anemia in kidney transplant recipients with a focus on the role of anemia on cardiovascular outcomes in these patients.     

Impact of personality and psychological distress on health‐related quality of life in kidney transplant recipients

Health‐related quality of life (HRQoL) has become an important outcome in the evaluation of kidney transplantation (KT). Although the medical and sociodemographic predictors of HRQoL in patients after KT are well known, there is still a lack of knowledge about the psychological factors involved. This study focuses on the role of personality and actual psychological distress in predicting HRQoL after KT. Sociodemographic (gender, age, education, average income), medical (glomerular filtration, serum albumin, number of co‐morbid diseases) and psychological data (neuroticism, extroversion, psychological distress) were collected from 177 (60.5% male subjects; 48 ± 12.1 years) kidney transplant recipients, and physical and mental HRQoL were measured using the SF‐36. A univariate general linear model analysis was performed. Higher physical HRQoL was associated with younger age, higher education and income, a low number of co‐morbid diseases, lower neuroticism and distress. Higher mental HRQoL was associated with higher education and income, longer time from KT, higher extroversion, lower neuroticism and distress. In both physical and mental HRQoL, actual distress was the best predictor, even when controlled for neuroticism. These results confirm the importance of psychological distress in patients and its impact on their HRQoL after KT and can be applied in intervention programs focused on increasing HRQoL.     

Life situation and quality of life in young adult kidney transplant recipients

Background. Young adults, 18–35 years of age, may be morevulnerable to chronic diseases than other age groups. In thisstudy we describe the life situation and lifestyle of youngadult kidney transplant recipients and compare their health-relatedquality of life (HRQoL) with a general population sample. Methods. Questionnaires, including items on life situation,lifestyle, and the SF-36 HRQoL questionnaire, were mailed toall 280 renal transplant recipients in Norway between 18 to35 years of age at the time of investigation of whom 131 (47%)responded. For comparison, we used 2,360 respondents aged 18to 35 years from a general population survey in one Norwegiancounty. SF-36 scores are presented with unadjusted scores andthe mean difference between groups adjusted for age, sex andeducation using multiple linear regression analysis. Results. The kidney transplant recipients reported high participationrates in cultural and sports activities, and the majority ofthem were satisfied with their work. A larger proportion ofthe transplant recipients had attained university educationthan the general population sample. However, 25% of the totalgroup were not integrated in professional life. The transplantrecipients scored lower than the general population on sevenof the eight SF-36 scales and the two summary scales after adjustingfor age, sex and education. Conclusions. The majority of young adult kidney recipients aged18–35 years were well adapted in their family and professionallife and satisfied with their current life situation. However,in aggregate they reported lower HRQoL on most scales of theSF-36 than a general population sample.     

Safety and usage of darbepoetin alfa in children with chronic kidney disease: prospective registry study

Background

Limited prospective data are available on the long-term safety of darbepoetin alfa (DA) for treating anemia in children with chronic kidney disease (CKD).

Methods

In this prospective, phase IV, observational registry study, children ≤16 years of age with CKD anemia and receiving DA were observed for ≤2 years. Adverse events (AEs), DA dosing, hemoglobin (Hb) concentrations, and transfusions were recorded.

Results

A total of 319 patients were included in the analysis (mean age, 9.1 years), 158 (49.5 %) of whom were on dialysis at study entry. Of 434 serious AEs reported in 162 children, the most common were peritonitis (10.0 %), gastroenteritis (6.0 %), and hypertension (4.1 %). Six patients (1.9 %) died (unrelated to DA). Four patients (1.3 %) experienced six serious adverse drug reactions. The geometric mean DA dose range was 1.4–2.0 μg/kg/month. Mean baseline Hb concentration was 11.1 g/dl; mean values for children receiving and not receiving dialysis at baseline ranged between 10.9 and 11.5 g/dl and 11.2–11.7 g/dl, respectively. Overall, 48 patients (15.0 %) received ≥1 transfusion.

Conclusions

No new safety signals for DA were identified in children receiving DA for CKD anemia for ≤2 years. Based on Hb concentrations and transfusion requirements, DA was effective at managing anemia in these patients.

     

Pharmacokinetics of darbepoetin alfa in pediatric patients with chronic kidney disease

Darbepoetin alfa is a novel erythropoiesis-stimulating protein with a two- to threefold longer half-life than recombinant human erythropoietin (epoetin) in adult patients with chronic kidney disease (CKD). This randomized, open-label, crossover study was conducted to determine the pharmacokinetic profile of darbepoetin alfa in pediatric patients with CKD. Twelve patients 3-16 years of age with CKD were randomized and received a single 0.5 micro g/kg dose of darbepoetin alfa administered intravenously (IV) or subcutaneously (SC). After a 14- to 16-day washout period, patients received an identical dose of darbepoetin alfa by the alternate route. After IV administration, the mean clearance of darbepoetin alfa was 2.3 ml/h per kg, with a mean terminal half-life of 22.1 h. After SC administration, absorption was rate limiting, with a mean terminal half-life of 42.8 h and a mean bioavailability of 54%. Comparison of these results with those from a previous study of darbepoetin alfa in adult patients indicated that the disposition of darbepoetin alfa administered IV or SC is similar in adult and pediatric patients, although absorption may be slightly more rapid in pediatric patients after SC dosing. The mean terminal half-life of darbepoetin alfa in this study was approximately two- to fourfold longer than that previously reported for epoetin in pediatric patients.     

Recurrent anemia in kidney transplant recipients with parvovirus B19 infection

Parvovirus B19 (PV B19) infection is known to cause acute anemia in solid organ transplant recipients. Intravenous immunoglobulin combined with reduction of immunosuppression may be of benefit to clear the infection. However, PV B19-associated anemia can be recurrent. We describe three renal transplant recipients with a PV B19 infection. These patients showed recurrent anemia with episodes separated by as much as several months.