Uric acid has a J‐shaped association with cardiovascular and all‐cause mortality in kidney transplant recipients

The association between serum uric acid and kidney graft and recipient survival is uncertain. During 2000–2011, we measured serum uric acid at week 10 after transplantation. Of 2748 transplanted patients, 2200 (80.1%) attended this visit. After a median follow‐up of 7.4 yr, 378 patients had died, 143 from a cardiovascular cause, and 185 patients lost their graft. The third quintile of uric acid levels (357–405 μM) had the lowest mortality risk and was used as reference group. In Cox proportional hazard models adjusting for graft and patient characteristics, the fifth quintile of uric acid levels (>474 μM) was independently associated with cardiovascular mortality (hazard ratio [HR] = 2.87 [1.55–5.32], p = 0.001) and all‐cause mortality (HR = 1.57 [1.09–2.25], p = 0.02). Also, the lowest quintile of uric acid levels (<309 μM) showed a trend toward increased risk of cardiovascular mortality (HR = 1.79 [0.90–3.58], p = 0.10) and all‐cause mortality (HR = 1.31 [0.89–1.93], p = 0.18). The increased risk at low uric acid levels was confined to diabetic recipients. Uric acid was not associated with death‐censored graft loss. In conclusion, uric acid has a J‐shaped association with cardiovascular and all‐cause mortality in kidney transplant recipients.     

Prognostic factors of long-term allograft survival in 632 CyA-treated recipients of a primary renal transplant

A total of 632 cyclosporin (CyA)-treated primary renal allograft recipients with a functioning graft at 6 months were retrospectively evaluated for risk factors correlated with long-term allograft function. Mean follow-up after the 6th month was 68.4 ± 40.6 months. One hundred twenty-one of these patients (19 %) were lost: 29 died (23/29 with a functioning graft), 77 of the remaining 92 (83 %) lost their graft because of chronic allograft dysfunction, 9 due to recurrence of glomerulonephritis, 5 due to renal artery thrombosis, and 1 due to chronic CyA toxicity. At univariate analysis, factors correlated with a better renal (R) and pure renal (PR) allograft survival were: dialysis duration of less than 5 years, fewer than 2 rejections within the 6th post-Tx month, immediate graft function recovery, plasma creatinine below 1.5 mg/dl at the 6th month, age at Tx above 15 years, and receiving a living donor graft. Cox's regression analysis was also performed to obtain relative risks for the same parameters. Long-term dialysis patients had more frequent late recoveries (P = 0.002) and reductions in therapy (P = 0.01) in order to reduce the side effects of steroids. In young patients receiving an initial oral CyA dose of 17 mg/kg per day, steroids were stopped at the 6th month in order to achieve catch-up growth: only one such patient lost his graft. In contrast, 72 % of the young patients who lost their grafts received an initial oral CyA dosage of 13 mg/kg per day. Thus, young patients did worse not because of steroid withdrawal, but because of inadequate initial CyA dosage. These results suggest that although we cannot exclude alloantigen-independent mechanisms as factors that stimulate progression of chronic allograft dysfunction, it would appear that the initial lesions are induced by events mostly mediated by immunological mechanisms. Received: 28 January 1997 Received after revision: 4 April 1997 Accepted: 8 April 1997     

Fatigue in kidney transplant recipients

Fatigue is still present in approximately 40%‐50% of kidney transplant recipients (KTR), rates comparable to that of the hemodialysis population. Correlates of fatigue include inflammation, symptoms of depression, sleep disorders, and obesity. Fatigue in KTR determines a significant severe functional impairment, either when globally considered or when analyzed at the level of the single domains such as sleep and rest, homemaking, mobility, social interaction, ambulation, leisure activities, alertness behavior, and work limitations. In addition, fatigue in KTR is significantly associated with a severe deterioration of quality of life. Fatigue is very common among KTR poorly adherent to immunosuppressive therapy. Unfortunately, there is no evidence of studies about the treatments of this symptom in KTR. Efforts to detect and treat fatigue should be a priority in order to improve quality of life of KTR.     

Influence of kidney function to the impact of acute rejection on long-term kidney transplant survival

In kidney transplantation, timing of an initial acute rejection (AR) is correlated with a variable risk of graft loss. However, it is unknown whether the increased risk for graft loss because of AR is conditioned by impaired graft function. A total of 730 cadaveric kidney transplant recipients were retrospectively evaluated from 1994 to 2001. When AR occurred, the risk ratio (RR) for graft loss was strongly time-dependent and increased, the later the rejection episode occurred. Compared with the reference group (no rejection) having an AR within 0-30, 31-365, or >365 days post-transplant conferred a 3.1-, 9.1- and 49.3-fold risk for subsequent graft loss (P < 0.001). By including serum creatinine as an indicator for graft function at the time of rejection RR decreased to 2.4-, 7.1- and 21.8-fold, but remained still significant (P = 0.023). In conclusion, the higher risk of graft loss after late AR is not fully explained by impaired graft function measured by serum creatinine.     

Management of leukopenia in kidney and pancreas transplant recipients

Abstract: Leukopenia is frequently observed in the setting of solid organ transplantation. The risk factors, natural history, and outcomes associated with leukopenia post‐transplantation have not been well defined. We retrospectively studied 102 adult kidney and/or pancreas transplant recipients over a one‐yr period of time. By defining leukopenia as a white blood cell count ≤3000 cells/mm³ and neutropenia as an absolute neutrophil count ≤2000/mm³, the combined incidence of either leukopenia or neutropenia was 58% (59/102); the first episode occurred at a mean of 91 d post‐transplant. A significant increase in the incidence of leukopenia was found in patients who either received alemtuzumab induction (42% with alemtuzumab vs. 9% with rabbit anti‐thymocyte globulin induction, p < 0.05) and/or had rapid steroid withdrawal in the early post‐transplant period (44% with vs. 16% without steroid withdrawal, p < 0.05). The most common intervention performed for leukopenia was reducing the dose of mycophenolate mofetil and/or valganciclovir. When granulocyte stimulating factors were used, a mean of 3.1 doses were needed to successfully manage the leukopenia. Although leukopenia was a common finding in our study of kidney and/or pancreas transplant recipients, there was no difference in the rates of infection or acute rejection in patients with and without leukopenia.     

Patterns of kidney injury in pediatric nonkidney solid organ transplant recipients

The incidence of acute kidney injury (AKI) and its impact on chronic kidney disease (CKD) following pediatric nonkidney solid organ transplantation is unknown. We aimed to determine the incidence of AKI and CKD and examine their relationship among children who received a heart, lung, liver, or multiorgan transplant at the Hospital for Sick Children between 2002 and 2011. AKI was assessed in the first year posttransplant. Among 303 children, perioperative AKI (within the first week) occurred in 67% of children, and AKI after the first week occurred in 36%, with the highest incidence among lung and multiorgan recipients. Twenty‐three children (8%) developed CKD after a median follow‐up of 3.4 years. Less than 5 children developed end‐stage renal disease, all within 65 days posttransplant. Those with 1 AKI episode by 3 months posttransplant had significantly greater risk for developing CKD after adjusting for age, sex, and estimated glomerular filtration rate at transplant (hazard ratio: 2.77, 95% confidence interval, 1.13‐6.80, P trend = .008). AKI is common in the first year posttransplant and associated with significantly greater risk of developing CKD. Close monitoring for kidney disease may allow for earlier implementation of kidney‐sparing strategies to decrease risk for progression to CKD.     

The beneficial effects of calcium channel blockers on long-term kidney transplant survival are independent of blood-pressure reduction

There is a growing body of evidence suggesting that calcium channel blockers (CCB) exert beneficial effects on kidney transplant survival. However, it is not completely understood if these agents act independently of blood-pressure reduction. In the present study, the 5-yr follow-up of 45 kidney transplant recipients receiving CCB during the 60-month follow-up period was compared to that of recipients with lower blood pressure and an antihypertensive treatment without CCB. During the whole follow-up, systolic (127.4 +/- 2.5 vs. 139.4 +/- 2.1 mmHg, p < 0.05) as well as diastolic blood pressure (78.8 +/- 1.1 vs. 84.8 +/- 1.8 mmHg, p < 0.05) was higher in the group receiving CCB. Moreover, in CCB-treated recipients, a significant (p < 0.05) higher increase in proteinuria was detected (from 759 +/- 120 to 1690 +/- 359 mg/24 h vs. 180 +/- 45 to 340 +/- 45 mg/24 h). Despite higher blood pressure and higher proteinuria, the increase in serum creatinine in the group of CCB-treated recipients was significantly lower (0.01 mg/dL/month) in comparison to that of the controls (0.02 mg/dL/month, p < 0.05). Moreover, the 5-yr transplant survival was significantly higher in CCB-treated recipients (62.3 vs. 31.8%, p < 0.05). The results of the present study further support the beneficial effects of CCB in kidney transplant recipients, which are independent of blood-pressure reduction.     

Hypertension in kidney transplant recipients

Arterial hypertension is frequently observed in renal transplant recipients. Its pathogenesis is multifactorial in most cases. Calcineurin inhibitors (CNI) can increase peripheral vascular resistance by inducing arteriolar vasoconstriction and can cause extracellular fluid expansion by reducing the glomerular filtration rate (GFR), activating the renin–angiotensin system (RAS), and by inactivating the atrial natriuretic peptide. Glucocorticoids can impair urinary water and salt excretion. Poor graft function can lead to increased extracellular volume and inappropriate production of renin. Native kidneys, older age of the donor and transplant renal artery stenosis (TRAS) may also contribute to the development of hypertension. Arterial hypertension not only can increases the risk for cardiovascular events but can also deteriorate renal allograft function. A number of studies have shown that the higher the levels of blood pressure are, the higher is the risk of graft failure. On the other hand, a good control of blood pressure may prevent many cardiovascular and renal complications. Appropriate lifestyle modification is the first step for treating hypertension. Calcium channel blockers (CCB) and renin–angiotensin system (RAS) inhibitors are the most frequently used antihypertensive agents, but in many cases, a combination of these and other drugs is required to obtain good control of hypertension.     

Conversion to belatacept maintenance immunosuppression in HIV-positive kidney transplant recipients

There are only scattered case reports documenting belatacept use in HIV + kidney transplant recipients. We performed a retrospective review to describe short-term outcomes following conversion to belatacept in a cohort of HIV + patients. Patients were included if they were converted to belatacept between May 2015 and May 2019, had an HIV- donor, and received ≥4 doses of belatacept. All patients were treated with non-depleting induction and triple maintenance immunosuppression. Allograft and HIV-related outcomes were collected from the date of belatacept infusion until May 2020. Ten HIV + kidney transplant recipients were identified, who were converted to belatacept a median of 364 days post-transplant. At last follow-up (median 3.3 years), 8 patients remained on belatacept therapy, and all patients were alive with functioning allografts. Mean estimated glomerular filtration rates (eGFR) improved from 31.6 mL/min at baseline to 42.8 mL/min at 1 year (P = .03). Two patients developed acute rejection, with one necessitating conversion back to tacrolimus. All patients maintained undetectable HIV-1 viral loads at last follow-up. One patient each developed pneumocystis pneumonia and Kaposi sarcoma following conversion, which were responsive to standard medical therapy. In our cohort of stable HIV + kidney transplant recipients, conversion to belatacept was associated with excellent early patient and allograft survival and improved eGFR at 1 year.     

A prospective study of anaemia and long-term outcomes in kidney transplant recipients.

BACKGROUND: Anaemia is prevalent in kidney transplant recipients (KTR), and only few KTR with anaemia receive treatment with erythropoietin. Some have claimed that this undertreatment might contribute to suboptimal outcomes such as mortality and cardiovascular events in these patients. However, no evidence is currently available that anaemia is actually associated with such risks in KTR. METHODS: We merged two cohorts of KTR to study the associations between anaemia and two outcomes: all-cause mortality and kidney allograft loss. Detailed information on the demographic and clinical characteristics of these 825 patients was available at baseline. As recommended by the American Society of Transplantation, anaemia was considered present if the haemoglobin concentration was < or =13 g/dl in men or < or =12 g/dl in women. Patients were followed using the Austrian Dialysis and Transplant Registry. RESULTS: After 8.2 years of follow-up, 251 patients died and 401 allografts were lost. In multivariate analyses, anaemia was not associated with all-cause mortality (HR: 1.08; 95% CI: 0.80-1.45), but it was associated with 25% greater risk of allograft loss (HR = 1.25; 95% CI: 1.02-1.59). This association was even more pronounced in death-censored analyses. Analyses using haemoglobin as a continuous variable or in categories also found no association with mortality. CONCLUSIONS: Anaemia may not be associated with mortality in KTR. In light of the recent findings of increased mortality in chronic kidney disease patients with higher haemoglobin treatment target, further evidence is needed to guide clinicians in the treatment of anaemia in these patients.     

Preemptive deceased donor kidney transplant not associated with patient survival benefit in minority kidney transplant recipients

Previous studies have shown an inverse association between pre-transplant dialysis exposure and post-kidney transplant outcomes. Socioeconomic and allocation factors, in contrast to medical factors, play a greater role in dialysis exposure among minorities, and medical causes for delay may impact post-transplant outcomes. This study sought to test whether minorities behaved similarly to Caucasians with regard to the effect of duration of dialysis on post-transplant outcomes. All primary deceased donor kidney transplants between 1997 and 2004 (n = 54,162) were analyzed from the Organ Procurement and Transplant Network database and were categorized as either Caucasian or minority. Adjusted patient and graft survivals were determined in each subgroup based on the duration of pre-transplant dialysis. Caucasians recipients show a clear stepwise increase in risk of graft failure and death with increasing duration of dialysis. The risk of graft failure among minorities increased less without a clear stepwise pattern. The risk of death, however, showed a U-shaped risk profile with the highest risk of death among preemptive transplants and recipients with more than five yr of dialysis. The disparate effect of dialysis on minorities suggests that a selection bias and not a biologic effect may explain the association between dialysis duration and outcomes after kidney transplantation previously reported.     

Influence of hypercholesterolemia on patient and graft survival in recipients of kidney transplants

AIM: The aim of this retrospective, single centre study, was to study the effect of pre- and post-transplant serum total cholesterol (TC) on patient and graft survival. We also sought to see whether patients who had very high TC (>8 mmol/L) had a higher incidence of graft failure and patient mortality compared with those whose cholesterol was only moderately elevated. METHODS: Records of 935 cadaver kidney transplants between 1984 and 1998 were examined. Patients were placed into three groups based on TC level: <5.5 mmol/L (group 1), 5.5-8 mmol/L (group 2) and >8 mmol/L (group 3). The mean TC value from the first five post-transplant years was taken to seek a correlation between TC and post-transplant events. RESULTS: The mean graft follow-up was 66.9 +/- 50.1 months, ranging from 0.1 to 191 months, while mean patient follow-up was 83.8 +/- 50.1 months, ranging from 0.5 to 191.6 months. Pre-transplant TC was available in 201 patients (21.5%), and post-transplant data was available (for first 5 yr) in 655 patients (70%). During the study period, 220 patients (23.5%) had died, 285 (30.5%) of the grafts had failed during the follow-up, while 129 (13.8%) of the patients died with a functioning graft. We found significantly longer survival of patients having a pre-transplant TC below 5.5 mmol/L vs. patients whose pre-transplant TC was above 5.6 mmol/L (p = 0.02). We also compared patients who had very high pre-transplant TC (>8 mmol/L) level with those whose TC was moderately elevated (5.5-8 mmol/L) and found that there was no higher incidence of graft failure (p = 0.77) nor patient mortality (p = 0.83). No difference could be found in graft survival based on pre-transplant TC. We also did not find a detrimental influence of post-transplant TC on the patient or graft survival. Diabetes mellitus (p = 0.006) and age over 50 yr (p = 0.007) affected patient survival, while low cyclosporine levels (p = 0.02) and acute rejection episodes (p = 0.009) affected graft survival. The mode of dialysis and time on dialysis prior to transplantation did not affect patient and graft survival. CONCLUSIONS: We found significantly greater survival of patients having a pre-transplant TC below 5.5 mmol/L. No difference could be found in graft survival based on pre-transplant TC. Post-transplant TC did not adversely affect patient or graft survival.     

Impaired kidney transplant survival in patients with antibodies to hepatitis C virus.

BACKGROUND: With a few exceptions, most published studies do not show an influence of antibodies to the hepatitis C virus (HCV) on the success of a kidney transplant. METHODS: We studied all our renal transplant recipients who had received kidneys from cadaver donors (n = 335) and had been treated with quadruple immunosuppression (steroids, azathioprine, and antilymphocyte antibodies, followed by cyclosporin). We had information on the status of the hepatitis C antibodies before and/or after the transplant in 320 cases (95.5%; in 300, pre-transplant). Patients with HCV antibodies before and/or after the transplant were considered to be HCV positive (HCV+). RESULTS: The HCV+ patients had more time in dialysis and a greater number of transfusions, hyperimmunized cases, and re-transplants. The evolution in the first post-transplant year was similar in both groups, but afterwards, the HCV+ patients had proteinuria more often as well as worse kidney function. The survival rate of the graft was significantly less in the HCV+ cases: 90.6, 68.3 and 51.0% at respectively 1, 5 and 10 years, compared with 91.5, 84.7 and 66.5% in HCV-patients (P<0.01). The patient survival rate was: 96.4, 87.0, and 71.9% in the HCV+ patients at 1, 5, and 10 years, compared with 98.2, 96.0 and 90.0% in the HCV- cases respectively (P<0.01). The differences remained the same in stratified studies according to time spent in dialysis or pre/post-transplant evolution of HCV antibodies, even when immunologically high-risk patients were excluded. In multivariant analysis, the presence of HCV antibodies acted as a independent prognostic factor for the survival of the kidney and the patient: 3.0 (1.8-5.0) and 3.1 (1.2-7.8) odds-ratio (95% of the confidence interval), respectively. The main cause of death among HCV+ patients was cardiovascular; there was no apparent increase in mortality rate due to infections or chronic liver disease. The loss of organs was mainly due to chronic nephropathy or death with a functioning kidney. CONCLUSION: The presence of hepatitis C antibodies, before or after transplantation, is associated with a worse long-term survival rate for both the patient and the transplanted kidney in our patients treated with quadruple therapy.     

Knowledge, beliefs and attitudes of kidney transplant recipients regarding their risk of cancer

Aim: Despite an increased risk of cancer post transplant, little is known about the knowledge, beliefs of and attitudes to cancer and its prevention among kidney transplant recipients. This study aims to explore these beliefs and attitudes, to better understand patient motives and potential barriers to early detection of cancer. Methods: Semi‐structured interviews were conducted with 14 kidney and eight kidney–pancreas transplant recipients based at a single transplant centre in Sydney, Australia, between October 2009 and February 2010. Results: Thematic data analysis identified four major themes: (1) skin cancer‐focused: participants were generally only aware about their increased risk of skin cancer and available prevention strategies for that cancer alone; (2) limited awareness: participants knew little about their excess risk for non‐skin cancers and possible preventative and screening strategies; (3) fear of cancer: cancer fears were heightened by prior experiences; some felt vulnerable to cancer and perceived that cancer outcomes were worse than kidney disease; and (4) prioritizing present health issues: participants believed cancer was not imminent and had limited capacity to absorb information about long‐term risks, particularly as current health concerns appeared pressing and important. Conclusion: Awareness of increased cancer risk and cancer screening among kidney transplant recipients is focused narrowly on skin cancer, with limited awareness for other cancers. Recipients prioritized current health issues rather than future risks to health such as cancer. Transplant care providers should provide evidence‐based information on cancer risk and screening, being sensitive to the timing and needs of the patient. Improved knowledge may empower patients to minimize their risk of cancer by participating in screening and cancer prevention programmes.     

胰肾联合移植治疗肝移植后糖尿病合并肾功能衰竭二例

目的 总结肝移植后再行胰肾联合移植治疗糖尿病合并肾功能衰竭的临床处理经验.方法 2例肝移植受者术前合并有2型糖尿病,分别于肝移植后7年余和4年余发生肾功能衰竭,遂行胰肾联合移植,2例的移植肝功能均正常.采取腹部器官联合快速切取技术整块切取双肾、全胰及十二指肠节段,先行肾移植,再行胰腺移植,供肾移植于左侧髂窝,供胰移植于右侧髂窝,供者的十二指肠与受者的空肠侧侧吻合,供者的十二指肠内置管,通过受者的空肠引流出体外.例1采用抗白细胞介素受体单克隆抗体诱导的四联免疫抑制方案预防排斥反应;例2术中给予抗胸腺细胞球蛋白和甲泼尼龙,术后继续使用2d,采用他克莫司+吗替麦考酚酯+皮质激素预防排斥反应.结果 2例手术过程顺利,术后移植胰腺功能正常,血糖均于术后10d左右恢复正常,无需胰岛素治疗,移植肾功能1周时恢复正常,第2例1周后血清肌酐渐进性升高,经验性抗排斥反应治疗效果不明显,移植肾活组织检查未见明显排斥反应征象,遂将他克莫司替换为西罗莫司,之后受者的肾功能逐渐恢复正常.目前2例受者已分别随访36个月及9个月,移植肝、肾及胰腺功能均正常.结论 肝移植后合并糖尿病、肾功能衰竭时可考虑行胰肾联合移植,但术后免疫反应复杂,需严密监测移植物功能.     

Difference in quality of life,fatigue and societal participation between living and deceased donor kidney transplant recipients

Purpose of this study was to assess whether living (LD) and deceased donor (DD) kidney transplant recipients differ in health‐related quality of life (HRQoL), fatigue and societal participation, depending on time since transplantation and after adjustment for clinical and demographic variables. A questionnaire study was performed among 309 LD and 226 DD recipients (response rate 74% and 61%) transplanted between 1997 and 2009. After adjustment for age, sex, and education, LD recipients transplanted less than or equal to five yr ago experienced better HRQoL than DD recipients on the domains' role limitations due to physical problems, general health perception, and on the physical component summary score (all p < 0.05) and a better societal participation (all subscales, p < 0.05). No differences were found in the mental health domains. The LD recipients also had better renal clearance than DD recipients (62.1 vs. 55.9 mL/min, p = 0.01). After additional adjustment for renal clearance, the differences in HRQoL and societal participation between LD and DD recipients remained. No differences were found in recipients transplanted more than five yr ago. We conclude that LD recipients on average have better HRQoL and societal participation than DD recipients, in the first years after transplantation.