Lipid lowering in dialysis patients with cardiovascular disease who are awaiting kidney transplantation

Dyslipidemias are highly prevalent in chronic kidney disease, end‐stage renal disease, and kidney transplant patients. These dyslipidemias are associated with high cardiovascular risk and mortality. Many clinical trials have shown that statin therapy can significantly reduce adverse cardiovascular events in chronic kidney disease patients and kidney transplant recipients. However, three major trials did not show a benefit of statin therapy in end‐stage renal disease patients on dialysis. Major guidelines either recommend against the use of statins in patients on dialysis or provide no recommendations about statin use for this complex patient population. As a result, we suspect many patients on dialysis are not on statins, even if they have known atherosclerotic cardiovascular disease. When these patients receive kidney transplants, the risk of adverse cardiovascular events increases in the peri‐operative period. Although there are no randomized clinical trials looking at statin use in these patients, we suggest that statin use be considered in patients with a history of atherosclerotic cardiovascular disease, to potentially minimize peri‐operative cardiovascular complications. We also recommend further research to determine whether statin therapy in dialysis patients awaiting kidney transplant is associated with better survival.     

Hematopoietic stem cell transplantation in patients with chronic kidney disease

Patients with significant medical comorbidities such as chronic kidney disease (CKD) traditionally have been excluded from hematopoietic stem cell transplantation (HSCT) because of unacceptably high transplant-related morbidity and mortality, an exclusion that can have enormous consequences for patients with CKD from myeloma in particular. Much of the excess HSCT-related morbidity among CKD patients relates to the toxic effects of conditioning regimens, which have a narrow therapeutic index even in patients with normal renal function. Common posttransplant complications are more challenging to prevent and manage in patients with CKD. In selected centers, autologous HSCT is performed with some frequency in patients with advanced CKD and even dialysis-dependent end-stage renal disease (ESRD), with acceptable outcomes, but cure from malignancy rarely is obtained. Allogeneic transplants using reduced-intensity conditioning regimens are being used with increasing frequency in patients with CKD, for both nonmalignant and malignant conditions, relying in the latter case on a graft-versus-malignancy effect to eliminate residual malignancy. In patients with ESRD from myeloma who have suitable donors, simultaneous allogeneic HSCT and kidney transplantation from a human leukocyte antigen-identical sibling provides the opportunity to treat both the malignant condition and the ESRD, avoiding the risks of posttransplant care in a dialysis-dependent patient and freeing the patient of the subsequent burdens of both ongoing dialysis and immunosuppression.     

Flow-PRA evaluation for antibody screening in patients awaiting kidney transplantation

Flow-PRA is a flow cytometric method for both anti-HLA class I and class II antibody (Ab) detection. We evaluated this technique for Ab screening in patients awaiting kidney transplantation. After having established a rigorous threshold for positivity, a three-dilution difference in sensitivity between Flow-PRA and complement-dependent cytotoxicity (CDC) persisted. The sensitivity of the method was satisfactory since all CDC-positive sera were also found to be positive with the Flow-PRA method. Discrimination between anti-HLA class I and class II Abs was excellent. Furthermore, all sera responsible for a positive flow cytometry crossmatch (FCXM) and a negative CDC-crossmatch (CDCXM) at the time of a putative transplant were found to be positive with Flow-PRA beads. The specificity was excellent for anti-class I Ab detection since no false positive serum was found. On the other hand, the specificity was lower for anti-class II detection, since 8.3% (2/24) false positive results were detected among all the negative sera tested. Overall, our results suggested that Flow-PRA should be of value for anti-HLA Ab screening prior to kidney transplantation.     

Early kidney transplantation improves neurocognitive outcome in patients with severe congenital chronic kidney disease

Renal replacement therapy has become available for the majority of patients suffering from severe congenital chronic kidney disease (CKD). Data on the long‐term neurocognitive outcome and the impact of early kidney transplantation (KTx) in this setting is unclear. Neurocognitive outcomes in 15 patients (11 male) with isolated congenital CKD (stage 3–5) requiring KTx at a mean age of 2.8 ± 1.3 were assessed at a mean age of 8.3 ± 1.4 years. Patients underwent neurological examination and testing for neuromotor and neurocognitive function using three independent tests. Pre‐emptive KTx was performed in six patients, and nine patients were dialyzed prior to KTx for a mean period of 11.1 ± 8.6 months. Neuromotor function was abnormal in 8/15 patients. HAWIK‐III showed a global intelligence quotient (IQ) of 93.5 ± 11.4 (P = 0.05) due to a significantly reduced performance IQ of 89.1 ± 11.3 (P < 0.01). In three patients, the global IQ was clinically significantly reduced by >1 SD to <85. In patients with neuromotor dysfunction, performance IQ was lower than in patients with normal neuromotor function (83.8 ± 10.2 vs. 96.2 ± 9.0, P = 0.04). Time on dialysis was inversely correlated to verbal IQ (r = 0.78, P = 0.02). Pre‐emptive KTx and duration of dialysis treatment <3 months was associated with superior neurocognitive outcome. Early (pre‐emptive) KTx results in superior long‐term neurocognitive outcome in children with severe congenital CKD.     

终末期肺病患者等待肺移植期间的临床分析

目的 总结单中心终末期肺病患者等待肺移植期间的临床结局及其影响因素,探讨等待期患者排序的参考因素.方法 回顾性分析自2003年1月至2013年1月83例等待肺移植的终末期肺病患者的临床资料.结果 22例(26.5％)患者死于等待期,41例(49.4％)接受同种异体肺移植,20例(24.1％)仍在等待供肺.相对于慢性阻塞性肺疾病(COPD)患者,特发性肺纤维化(IPF)患者等待期间死亡率较高,死亡率分别为39.1％和15.6％(P=0.09).存活患者的等待期存活时间为(377.5±527.6)d,死亡患者的等待期存活时间为(181.7±196.9)d(P=0.016).存活的患者的平均肺动脉压力为(38.8±14.1)mm Hg(1 mm Hg=0.133 kPa),死亡患者的平均肺动脉压力为(54.3±25.9)mm Hg(P=0.08).死亡病例中,IPF患者的存活时间为(137.8±199.6)d,其他疾病患者为(212.1±196.9)d(P=0.397).等待期需要常规氧疗和无创正压通气的患者的死亡率为23.9％,接受机械通气患者的死亡率为41.7％(P=0.287).结论 原发疾病的类型、肺动脉高压和机械通气可能是影响终末期肺病患者等待期预后的主要因素,拟定肺移植等待排序时应综合考虑上述因素.     

南方汉族等候肾移植终末期肾功能衰竭患者HLA基因多态性分析

目的对我国南方地区3911例等候肾脏移植的患者进行HLA-A，B，DRB1基因表达的回顾性研究，以探讨在因肾脏疾病导致患者最终并发终末期肾功能衰竭（EsRD）进程中的HLA免疫遗传易感性及其相对风险作用。方法采用聚合酶链反应-序列特异性引物扩增（PcR-SSP）技术进行HLA-A，B，DR基因分型，应用SPPS13．0软件包统计分析ESRD患者中HLA抗原频率、基因频率、HLA—A，B，DR三个位点的单倍型频率（HF）、连锁不平衡参数、相对危险度（RR）及优势比（OR）。结果ESRD患者中表达出HLA-A抗原19个，HLA-B抗原40个，HLA-DR抗原14个；其中呈现抗原频率显著增高（Pc〈O．0001，Pc值即P值乘以所检测的某一位点的抗原数）的是HLA-B75（RR=1．222，OR=1．479）、DR4（RR=1．146，OR=1．294），DR17（RR=1．541，OR=2．639）；呈现出抗原频率显著降低（Pc〈0．0001）的是HLA-DR8（RR=0．812，DR=0．697）、DR9（RR=0．878，OR=0．793）；ESRD患者中具有显著连锁不平衡单倍型（HF〉0．5％）10条，分别为A1-B37．DR10，A2-B7-DR17，A29-B7-DR10，A30-B13-DR7，A33-B13-DR17，A33-B44-DR17，A33-B46-DR17，A33-B58-DR17，A33-B60-DR17和A33-B75-DR17，其中A33-B75-DR17、A33-B58-DR17频率高达7．93％和11．74％。结论研究发现HLA-B75、DR4和DR17可能对南方地区肾脏疾病患者最终并发ESRD具有独立易感关联，而表达HLA-DR8、DR9的肾脏病患者将可能不易并发ESRD；单倍型A33-B75-DR17高频率出现说明HLA-B75，DR17不仅具有独立易感作用还可能对肾脏病患者最终并发ESRD具有集合易感作用。这个发现对于等候肾脏移植患者选择合适供体以提高移植后患者生存时间和远期移植效果具有临床指导意义。     

Significant benefits after renal transplantation in patients with chronic heart failure and chronic kidney disease

Background: Chronic heart failure (CHF) and chronic kidney disease (CKD) are serious medical conditions with significant morbidity and mortality and often coexist. Because of perioperative risks in these patients, they may not be considered a candidate for renal transplantation (RTx).

Material and methods: We compare retrospectively RTx outcomes [graft/patient survival, rejection rates and adverse cardiac events] in study group [low left ventricular ejection fraction (LVEF) ≤45% by echocardiogram, n?=?63] and control group [normal LVEF ≥50%, n?=?537] from a developing country.

Results: The mean EF was 35?±?5.6 and 57?±?3% for the study and control groups, respectively (p?Conclusion: RTx may play a role in reversing LV systolic dysfunction. Once thought by many to be a contraindication for renal transplantation, this appears not to be the case. The outcomes between the 2 groups are comparable and transplant is an option for even low EF patients.     

Cardiovascular disease in patients with chronic kidney disease

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with renal failure. Patients with chronic kidney disease have significant CVD, and carry a high cardiovascular burden by the time they commence renal replacement therapy (RRT). The severity of CVD that has been observed in dialysis patients lead to a growing body of research examining the pathogenesis and progression of CVD during the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) (ie, predialysis phase). Multiple factors are involved in the development of CVD in CKD. More importantly, critical and key factors seem to develop early in the course of CKD, and result in preventable worsening of CVD in this patient population. Anemia is common in patients with CKD, and has been shown to have an independent role in the genesis of left ventricular hypertrophy (LVH) and subsequent CVD. Unfortunately, it is underdiagnosed and undertreated in patients with CKD. Early intervention, and better correction of anemia, seems to gain a great momentum in the prevention and management of CVD in CKD. Hypertension is another risk factor that has been targeted by the National Kidney Foundation Task Force on CVD in chronic kidney disease. This article reviews the different factors involved in the pathogenesis of CVD in CKD and the evidence supporting early and aggressive intervention.     

Cardiovascular events and investigation in patients who are awaiting cadaveric kidney transplantation

The optimal strategy for cardiovascular (CV) disease surveillance in kidney transplant candidates is uncertain. In this observational study of 604 wait-listed patients in British Columbia, the risk for CV event in diabetic and nondiabetic candidates was 12.7 and 4.5% per year, respectively. CV event rates were relatively constant during the first 3 yr of wait-listing (5.3 to 6.6 per 100 patient-years; 95% confidence interval [CI], 3.7 to 9.3) but rose dramatically during the peritransplantation period (39.6/100 patient-years; 95% CI, 20.6 to 76.1) and remained high throughout the first posttransplantation year (4.0 per 100 patient-years; 95% CI, 2.2 to 7.5). The results of noninvasive cardiac investigations before wait-listing were not predictive of the time to CV event after wait-listing. The practice of surveillance cardiac investigation in wait-listed patients on the basis of ongoing clinical assessment of cardiac risk resulted in fewer investigations (n = 171) than with the recommended practice of periodic screening on the basis of waiting time alone (n = 530) and was not associated with an increased frequency of CV events (CV event rate in patients with and without the recommended frequency of investigation was 9.9 [95% CI, 7.1 to 13.7] and 6.7 [95% CI, 5.2 to 8.7] per 100 patient-years). It is concluded that transplant candidates are at high risk for CV events particularly during the perioperative period. Initial cardiac investigations have limited value in guiding the timing of patient reevaluation after wait-listing. Periodic surveillance cardiac investigation after wait-listing may be unnecessary and requires further study.     

Transplant Friends: an interactive education program for patients awaiting kidney transplantation

BACKGROUND: Organ transplantation is the preferred treatment for end-stage renal disease. Renal transplant recipients are surviving longer with a better quality of life. Although many hospitals have transplant education programs in place, transplant patients indicate that there is a need for additional information. Transplant Friends is a program designed to meet these needs. PATIENTS AND METHODS: At the University of Alberta, 128 patients attended the Transplant Friends program between September 2002 and February 2003. Each patient completed an evaluation form consisting of 15 questions designed to evaluate patient's satisfaction regarding session content, ease of scheduling, and the sessions facilitators. Responses were recorded using 5-point Likert scales. RESULTS: All 128 participants completed the questionnaires. The predominantly male (59.1%) and Caucasian (91.6%) population had a median age of 49.1 years. Of the 128 patients, 110 patients (86%) felt that the content of the program met or exceeded their expectations; 120 patients (94%) felt the program facilitators met or exceeded their expectations; and 113 patients (88%) evaluated the scheduling favorably. CONCLUSION: Patients require complete information prior to renal transplantation to make an informed decision about whether to proceed with transplant as well as to enhance the overall transplant experience. Patients evaluated the Transplant Friends program as successfully meeting these needs through a comprehensive interactive teaching program. We recommend that institutions performing renal transplants incorporate an educational program such as Transplant Friends during the workup process of this unique patient population.     

HLA class I antibodies in patients awaiting kidney transplantation and the association with renal graft survival

The presence of alloantibodies against human leukocyte antigens (HLA) in the circulation of a transplant recipient shows a significant negative impact on the outcome of solid-organ transplantations. The aim of this study was to examine the impact on renal graft survival of various patterns of alloantibodies detected among patients awaiting kidney transplantation. Among more than 2000 patients awaiting kidney transplantations between July 1992 and March 2006, were 683 patients who displayed anti-HLA alloantibodies, 318 of whom were enrolled in this study. Each patient was followed for at least 9 months; the presence of HLA alloantibodies was checked every 3 months by an enzyme-linked immunosorbent assay. Among these 318 patients, 55 patients underwent kidney transplantations. Their median follow-up time was 69 (range, 9-129) months, including 267 (84%) who displayed persistent class I HLA alloantibodies. The intermittent presence of class I HLA alloantibodies was seen in 20 (6.3%) patients. Serum class I HLA antibodies which was positive at first then became undetectable in 4 (1.3%) patients. Three (0.9%) patients were unsensitized at first and then developed class I HLA alloantibodies later; & 24 (7.5%) patients had class I HLA alloantibodies only once during the follow-up period. Among these patients, 55 patients received renal transplantations. The median survival time was shortest in the patients with persistent class I HLA alloantibodies (59.9 months) and longest among patients who were positive at first and then became negative thereafter or in whom class I HLA alloantibodies was detected only once (132 months). There was a significant difference in graft survival times between patients who had persistent HLA alloantibodies and those in whom to have class I HLA alloantibodies were detected only once (P < .05). In this study, the persistent presence of class I HLA alloantibodies among pretransplantation patients was associated with poorer renal graft outcomes. Surveys of various patterns of sensitization to class I HLA antigen may help us to perform risk stratification. High-risk patients may need more aggressive approaches to deplete antibody or complement levels.     

Adynamic bone in patients with chronic kidney disease

Adynamic bone in patients with chronic kidney disease (CKD) is a clinical concern because of its potential increased risk for fracture and cardiovascular disease (CVD). Prevalence rates for adynamic bone are reportedly increased, although the variance for its prevalence and incidence is large. Differences in its prevalence are largely attributed to classification and population differences, the latter of which constitutes divergent groups of elderly patients having diabetes and other comorbidities that are prone to low bone formation. Most patients have vitamin D deficiency and the active form, 1,25-dihydroxyvitamin D, invariably decreases to very low levels during CKD progression. Fortunately, therapy with vitamin D receptor activators (VDRAs) appears to be useful in preventing bone loss, in part, by its effect to stimulate bone formation and in decreasing CVD morbidity, and should be considered as essential therapy regardless of bone turnover status. Future studies will depend on assessing cardiovascular outcomes to determine whether the risk/reward profile for complications related to VDRA and CKD is tolerable.