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.     

Increasing access to kidney transplantation in countries with limited resources: The Indian experience with Kidney Paired Donation

According to the Indian chronic kidney disease registry, in 2010 only 2% of end stage kidney disease patients were managed with kidney transplantation, 37% were managed with dialysis and 61% were treated conservatively without renal replacement therapy. In countries like India, where a well‐organized deceased donor kidney transplantation program is not available, living donor kidney transplantation is the major source of organs for kidney transplantation. The most common reason to decline a donor for directed living donation is ABO incompatibility, which eliminates up to one third of the potential living donor pool. Because access to transplantation with human leukocyte antigen (HLA)‐desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end stage kidney disease patients. KPD is a rapidly growing and cost‐effective living donor kidney transplantation strategy for patients who are incompatible with their healthy, willing living donor. In principle, KPD is feasible for any centre that performs living donor kidney transplantation. In transplant centres with a large living donor kidney transplantation program KPD does not require extra infrastructure, decreases waiting time, avoids transplant tourism and prevents commercial trafficking. Although KPD is still underutilized in India, it has been performed more frequently in recent times. To substantially increase donor pool and transplant rates, transplant centres should work together towards a national KPD program and frame a uniform acceptable allocation policy.     

Hepatic ischemia reperfusion injury is associated with acute kidney injury following donation after brain death liver transplantation

Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury (AKI). This suggests that hepatic ischemia‐reperfusion injury may play a critical role in the pathogenesis of AKI after liver transplantation. The aim of this single‐center study was to determine if hepatic ischemia‐reperfusion injury, estimated by peak peri‐operative serum amino‐transferase (AST), is associated with AKI following donation after brain death (DBD) liver transplantation. A total of 296 patients received 298 DBD liver transplants from January 2007 to June 2011. The incidence of AKI was 35.9%. AKI was a risk factor for chronic kidney disease (P = 0.037) and mortality (P = 0.002). On univariate analysis, peak AST correlated with peak creatinine (P < 0.001) and peak change in creatinine from baseline (P < 0.001). Peak AST was higher in AKI patients (P < 0.001). The incidence of AKI in patients with a peak AST of <1500, 1500–2999 and ≥3000 U/l was 26.1%, 39.8% and 71.2%, respectively (P < 0.001). On multiple logistic regression analysis, peak AST was independently associated with the development of AKI (P < 0.001). In conclusion, hepatic ischemia‐reperfusion injury demonstrates a strong relationship with peri‐operative AKI in DBD liver transplant recipients.     

Limited health literacy and adverse outcomes among kidney transplant candidates

More than one‐third of US adults have limited health literacy, putting them at risk of adverse clinical outcomes. We evaluated the prevalence of limited health literacy among 1578 adult kidney transplant (KT) candidates (May 2014‐November 2017) and examined its association with listing for transplant and waitlist mortality in this pilot study. Limited health literacy was assessed at KT evaluation by using a standard cutoff score ≤5 on the Brief Health Literacy Screen (score range 0‐12, lower scores indicate worse health literacy). We used logistic regression and adjusted Cox proportional hazards models to identify risk factors for limited health literacy and to quantify its association with listing and waitlist mortality. We found that 8.9% of candidates had limited health literacy; risk factors included less than college education (adjusted odds ratio [aOR] = 2.87, 95% confidence interval [CI]:1.86‐4.43), frailty (aOR = 1.85, 95% CI:1.22‐2.80), comorbidity (Charlson comorbidity index [1‐point increase] aOR = 1.12, 95% CI: 1.04‐1.20), and cognitive impairment (aOR = 3.45, 95% CI: 2.20‐5.41) after adjusting for age, sex, race, and income. Candidates with limited health literacy had a 30% (adjusted hazard ratio = 0.70, 95% CI: 0.54‐0.91) decreased likelihood of listing and a 2.42‐fold (95% CI: 1.16‐ to 5.05‐fold) increased risk of waitlist mortality. Limited health literacy may be a salient mechanism in access to KT; programs to aid candidates with limited health literacy may improve outcomes and reduce disparities.     

Barriers to access by Indigenous Australians to kidney transplantation: The IMPAKT study

SUMMARY:   Although Indigenous Australians represent less than 2% of the national population, they account for 8–10% of new patients commencing treatment for end-stage renal disease (ESRD). Almost half come from remote regions lacking renal disease treatment services. In those regions, their incidence of ESRD is up to 30 times the incidence for all Australians.
Kidney transplantation is the optimal treatment for ESRD. Compared with long-term dialysis, it results in better quality of life, longer life expectancy and lower costs of health care. Indigenous Australians with ESRD receive transplants at approximately one-third the rate of non-Indigenous patients. There are similar disparities in access to kidney transplants for Native Americans, Aboriginal Canadians and New Zealander Maori. The reasons for such disparities have not been studied in any detail.
IMPAKT (Improving Patient Access to Kidney Transplantation) is an NHMRC-funded study, involving eight major renal units. It aims to identify the reasons for Indigenous Australians' poor access to transplantation. It will systematically examine each of the steps a new dialysis patient must negotiate in order to receive a transplant. Each of these steps can become a barrier.     

Vitamin D deficiency is common in kidney transplant recipients,but is not associated with infections after transplantation

The relevance of vitamin D for infections after kidney transplantation is poorly defined. 25-OH vitamin D (25-OHD) levels of 135 kidney transplant recipients, enrolled in the Swiss Transplant Cohort Study, were determined peri-transplant and 6 months post-transplant. Logistic regression was used to address the associations of 25-OHD and overall infections and bacterial infections, respectively. For the first 6 months post-transplant, 25-OHD peri-transplant, and for the second period (after 6 to 30 months post-transplant), 25-OHD at 6 months post-transplant was considered. Vitamin D deficiency was common peri-transplant and remained highly prevalent 6 months after transplantation despite frequent supplementation. Median 25-OHD levels increased from 12.0 ng/mL (IQR 5.3-19.5) peri-transplant to 16.5 ng/mL (IQR 10.6-22.6) 6 months post-transplant (P = .005). We did not detect a significant association between 25-OHD and overall infections (adjusted odds ratio (aOR) 1.05, 95% confidence interval (95%CI) 0.44-2.51; aOR 0.67, 95%CI 0.31-1.43) or bacterial infections (aOR 0.79, 95%CI 0.32-1.96; aOR 0.79, 95%CI 0.35-1.75) for the first and second period. To conclude, at both time points, vitamin D deficiency was observed in more than 50% of kidney recipients, albeit an increase in 25-OHD in the longitudinal course was observed. No significant association between 25-OHD and infections was detected.     

Barriers to access by Indigenous Australians to kidney transplantation: the IMPAKT study

Although Indigenous Australians represent less than 2% of the national population, they account for 8-10% of new patients commencing treatment for end-stage renal disease (ESRD). Almost half come from remote regions lacking renal disease treatment services. In those regions, their incidence of ESRD is up to 30 times the incidence for all Australians. Kidney transplantation is the optimal treatment for ESRD. Compared with long-term dialysis, it results in better quality of life, longer life expectancy and lower costs of health care. Indigenous Australians with ESRD receive transplants at approximately one-third the rate of non-Indigenous patients. There are similar disparities in access to kidney transplants for Native Americans, Aboriginal Canadians and New Zealander Maori. The reasons for such disparities have not been studied in any detail. IMPAKT (Improving Patient Access to Kidney Transplantation) is an NHMRC-funded study, involving eight major renal units. It aims to identify the reasons for Indigenous Australians' poor access to transplantation. It will systematically examine each of the steps a new dialysis patient must negotiate in order to receive a transplant. Each of these steps can become a barrier.     

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.     

Transplant center characteristics associated with living‐donor kidney transplantation: a cohort study with a hierarchical modeling approach

Transplant center organization, that is a modifiable factor, may affect the access to living‐donor kidney transplantation (LDKT). The objective of this study was to identify the center characteristics associated with LDKT using a hierarchical analysis. This was a retrospective multicenter observational study of 8701 patients who received a first renal graft between 2010 and 2014 in 32 transplantation centers of France. Hierarchical modeling was used to estimate the center effect and organization associated with LDKT. Among 8507 patients, 1225 (12%) were transplanted with a LD kidney. There was a transplant center effect on the proportion of LDKT. After adjustment for patient and center characteristics, the random effect variance decreased by 47%. Patients transplanted at a center with more than four nephrologists [1.81 (95% CI: 1.10–2.95)] and more than 1.5 nurse transplant coordinators [1.98 (95% CI: 1.26–3.13)] were more likely to be transplanted with a LD kidney. ABO‐incompatible program was associated with LDKT [2.23 (95% CI: 1.22–4.06)]. There was a transplant center effect on the proportion of LDKT that could be decreased by modifiable center characteristics. Our study suggests the importance of the transplant team organization on the LDKT utilization.     

Dialysis prior to living donor kidney transplantation and rates of acute rejection.

BACKGROUND: The relationship between transplantation prior to chronic dialysis initiation and the pattern of acute rejection of kidneys from living donors (LDKT) has not been fully explored. METHODS: Using data provided by the United States Renal Data System, we performed a retrospective cohort study fitting multivariate proportional hazards models to characterize the association of chronic use of dialysis prior to transplantation [non-pre-emptive LDKT (non-PLDKT)] and acute rejection, and to examine if this association varies throughout the first year. RESULTS: Non-PLDKT was associated with a 2.5-fold higher rate of biopsy-confirmed rejection during the first month [adjusted HR 2.5, 95% confidence interval (1.85-3.33)], compared with no dialysis prior to transplantation. Increasing duration of pre-transplant dialysis was associated with increasing rate of biopsy-confirmed acute rejection during the first month (P = 0.001 for trend). Over the first year, there was a diminishing relationship between non-PLDKT and acute rejection: 2.5-, 2.22-, 2.13- and 1.78-fold elevation in the episodes of biopsy-confirmed acute rejection during the first, second, third through to the sixth and seventh through to the twelfth month post-transplant, respectively (P = 0.05 for trend). CONCLUSIONS: The waning of the association of non-PLDKT with acute rejection over time supports the hypothesis that dialysis exposure prior to transplantation may modulate the immune system to increase the rates of acute rejection.     

Serum phosphate and calcium concentrations are associated with reduced patient survival following kidney transplantation

Moore J, Tomson CRV, Tessa Savage M, Borrows R, Ferro CJ. Serum phosphate and calcium concentrations are associated with reduced patient survival following kidney transplantation.
Clin Transplant 2011: 25: 406–416. © 2010 John Wiley & Sons A/S. Abstract: The impact of disordered mineral and bone metabolism following kidney transplantation is not well defined. We studied the association of serum phosphate and calcium concentrations, and surrogate measures of arterial stiffness (augmentation index: AIx and Timing of the reflected wave: Tr), with long‐term kidney transplant recipient and allograft survival. Prevalent adult renal transplant patients (n = 270) were prospectively studied over a median 88‐month follow‐up. Detailed demographic, clinical and laboratory data, in addition to both peripheral and central non‐invasive blood pressure measurements, were recorded. Higher serum phosphate and calcium levels were associated with increased all‐cause mortality (HR: 1.21; 95% CI 1.09,1.35, p < 0.001 and HR: 1.22; 95% CI 1.01,1.48; p < 0.04, respectively; adjusted Cox model) and death‐uncensored graft loss (p < 0.001 and p = 0.03, respectively). In addition, serum calcium and phosphate were associated with death‐censored graft loss on univariable analysis (p < 0.001 and p = 0.02, respectively), but did not retain significance on multivariable analysis. AIx and Tr were not associated with mortality or graft loss on multivariable analysis. This is the first report to demonstrate that both higher serum phosphate and calcium levels are associated with increased mortality in kidney transplant recipients. It highlights the need for randomized trials assessing current interventions available for improving disordered mineral–bone metabolism post transplantation.     

Persistent cytomegalovirus infection in kidney allografts is associated with inferior graft function and survival

The long-term effects of cytomegalovirus (CMV) infections on kidney allografts are unknown. We examined the impact of persistent intragraft CMV infection on long-term kidney allograft function and survival. CMV was diagnosed in 82/172 renal transplant recipients by antigenemia test and viral cultures. Biopsies from 48 of 82 patients taken after CMV infection and from 15 patients with no previous CMV infection detected were available for the immunohistochemical demonstration of CMV antigens and DNA hybridization in situ. Five-year follow-up data from these 63 patients were analysed. In 17 patients, CMV antigens and/or DNA persisted in the biopsy >2 months after the last positive finding in blood or urine. Patients with persistent intragraft CMV had reduced graft survival (P = 0.041) and Cox regression analysis showed persistent CMV as a risk factor for reduced graft survival (RR: 3.5). Recipients with persistent intragraft CMV had reduced creatinine clearance 1 and 2 years after transplantation (P = 0.007) and in multivariate logistic regression analyses including several potential pre- and posttransplant risk factors, persistent CMV was an independent risk factor for lower clearance at 1 and 2 years (OR: 4.4 and 4.9). Our novel findings show that persistent intragraft CMV infection was associated with reduced kidney allograft function and survival.     

High prevalence of patients with a high risk for obstructive sleep apnoea syndrome after kidney transplantation--association with declining renal function.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) is much more prevalent in patients on dialysis than in the general population. Our aim was to assess for the first time the prevalence of patients with a high risk for OSAS and its clinical correlates in a large sample of kidney transplanted patients. We also wanted to compare the prevalence of the disorder between waitlisted dialysis patients (WL) and kidney transplanted patients (Tx). METHODS: One thousand sixty-seven kidney transplanted patients were asked to participate in a cross-sectional survey ('TransQoL-HU Study'). Socio-demographic data, history of renal disease, medication, comorbidity and laboratory parameters were collected at enrolment. Patients completed a battery of self-administered questionnaires including the Berlin Sleep Apnoea Questionnaire to assess risk status of OSAS. RESULTS: The final analyses included 841 Tx and 175 WL patients. The prevalence of high risk for OSAS was similar in the transplanted group vs WL patients (27% vs 33%). In multivariate logistic regression analysis male gender, older age, lower educational status, worse kidney function, use of hypnotic drugs and comorbidity were independent predictors for high risk of OSAS in kidney transplanted patients. CONCLUSIONS: High risk for sleep apnoea is highly prevalent in the kidney transplanted population. In addition to the well-known risk factors of OSAS (male gender, obesity, use of hypnotic drugs, comorbidity), impaired kidney function was also independently associated with high risk for OSAS.