Post-transplant Renal Function Research Articles

Depression and anxiety as potential correlates of post-transplantation renal function and quality of life

The objective of this study was to determine anxiety and depression and its relationship with quality of life (QOL) in renal transplant (RT) recipients. A total of 105 consecutive patients were assessed cross-sectionally at least 3 months after RT. Hospital Anxiety and Depression Scale was applied to assess anxiety and depression. QOL was assessed through the abbreviated version of World Health Organization QOL scale. Patients’ awareness of illness and treatment was assessed through Structured Interview for Renal Transplantation. Nine (8.57%) patients had syndromal anxiety and 9 (8.57%) had syndromal depression. Both these groups had significantly lower scores in almost all domains of QOL compared with their non-anxious and non-depressed counterparts. There were a higher number of hospitalizations and episodes of complication or rejection in post-RT patients with anxiety as compared to those without (P = 0.001). Syndromal depression and anxiety are associated with poor QOL and syndromal anxiety is associated with significantly higher number of hospitalizations, rejections and complications in post-RT patients.

Serum trace elements before and 3 months after renal transplantation in kidney recipients: An Iranian study

BackgroundDecreased serum levels of trace elements seen in long-term hemodialysied patients, suppress immune system. The aim of this study was to find if any changes occur in trace elements after transplantation and assess the correlation between post-transplantation renal function and levels of trace elements. MethodsLong-term hemodialysied patients with underlying ESRD were divided into two groups, who were undergone transplantation (n = 54) and were not (n = 69). Levels of lithium, magnesium, iron, zinc and copper measured 24 h before and three months after transplantation in both groups. The transplanted patients' serum levels of creatinine were assessed at same intervals as an indicator of graft function. Results54 patients, 18 men (33%), 36 women (67%) with mean age of 47.67 ± 14.33 years underwent transplantation between April 2010 and April 2011. While serum iron (p < 0.001) and copper levels (p < 0.001) significantly increased after transplantation, there was a statistically significant reduction in magnesium levels (p < 0.001). No significant differences were noted in zinc (p = 0.17) and lithium (p = 0.080) levels in comparison to control group. A significant relationship was noted between levels of magnesium (p = 0.015) and zinc (p = 0.025) and creatinine within three months after transplantation. ConclusionOur study showed transplantation alters serum levels of trace elements in long-term hemodialysied patients with underlying ESRD and affects immunity and the results of renal function (Cr levels).

Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: Calcineurin-inhibitors conversion or minimization?

BackgroundIn the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i. MethodsIn a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR<60mL/min/1.73m2), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences. ResultsOverall, after a median time of 2years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p=0.07). ConclusionIn terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk.

The impact of gender and NASH on chronic kidney disease before and after liver transplantation

Chronic kidney disease (CKD) after liver transplant (LT) is associated with increased long-term mortality. The impact of gender on CKD before and after LT is unknown. To further define risk factors and analyse gender differences in the incidence and progression of CKD after liver transplant. Four hundred and fifty-five consecutive adult primary solitary LT recipients were included. Iothalamate clearance tests performed over time were analysed. Mean age was 51.4 ± 10.4 years with 63% males. A percentage of 29.1% of females and 21.1% of males had a GFR<60 ml/min/1.73 m(2) and 10.2% of females and 5.9% of males had GFR<30 ml/min/1.73 m(2) prior to transplant. At 1 year, 52.6% of recipients tested (69.6% females, 43.0% males) had GFR<60 ml/min/1.73 m(2) and 7.3% (11.6% females, 4.9% males) had GFR<30 ml/min/1.73 m(2) . Pre-LT GFR<60 ml/min/1.73 m(2) [OR 3.28, (1.76-6.10), P ≤ 0.001], female gender (OR 2.96, (1.72-5.10), P < 0.001) and age [OR 1.09, (1.05-1.12), P < 0.001] were independently predictive of stage ≥3 CKD at 1 year post-LT. Female gender [OR 2.52, (1.25-4.71), P = 0.004], age [OR 1.05, (1.02-1.08), P = 0.003] and NASH [OR 2.95, (1.06-8.21), P = 0.039] were independently predictive of ≥stage 3 CKD at 5 years post-LT. Pre-LT diabetes was associated with stage 4 CKD at 5 years [OR 2.91, (1.33-6.36), P = 0.008] post-LT. In addition to age and pre-LT CKD, female gender and NASH are independent predictors of ≥stage 3 CKD post-LT. Gender-based approaches to optimize modifiable risk factors are needed to improved post-transplant renal function.

The influence of a contemporaneous portal and hepatic artery revascularization protocol on biliary complications after liver transplantation

We sought to compare the impact of sequential and contemporaneous revascularizations of portal vein and hepatic artery on biliary complications in patients undergoing liver transplantation. We reviewed 184 patients who underwent liver transplantation in our center, and categorized them into different groups based on the duration of time between the portal venous and hepatic arterial reperfusion: >10 minutes in the sequential portal and hepatic artery revascularization group (SPA; n=56), and within 1 minute in the contemporaneous portal and hepatic artery revascularization group (CPA; n = 121).The other patients with an interval from 1-10 minutes (n = 7) were excluded. This study then compared the outcomes between the SPA and CPA groups. Cold ischemic time (mean ± standard deviation) for the SPA and CPA groups were 561 ± 150 vs 577 ± 187 minutes, respectively (P = .53). The incidence of biliary complications for the SPA and CPA groups were 14/56 and 11/121, respectively (25% vs 9%; P = .005). By the Clavien-Dindo Classification of Surgical Complications, the biliary complications in SPA group tended to be more severe compared with the CPA group (grade I, 0% vs 0%; II, 14% vs 36%; IIIa, 71% vs 64%; IIIb, 7% vs 0%; IV, 7% vs 0%; P = .10). Among biliary complications, the incidence of nonanatomic strictures was greater in the SPA group (9% vs 2%; P = .03), whereas the difference was not significant for anastomotic strictures (P = .054). Except for a lower serum albumin level in the SPA group 1 day after liver transplantation (P < .001), there are no differences in post-transplant liver function or renal function at 1, 7, and 30 days after transplantation. The CPA protocol can decrease the incidence of biliary complications substantially after liver transplantation and should replace the SPA protocol used by some centers in liver transplantation.

Pre-Transplant CDKN2A Expression in Kidney Biopsies Predicts Renal Function and Is a Future Component of Donor Scoring Criteria

CDKN2A is a proven and validated biomarker of ageing which acts as an off switch for cell proliferation. We have demonstrated previously that CDKN2A is the most robust and the strongest pre-transplant predictor of post- transplant serum creatinine when compared to “Gold Standard” clinical factors, such as cold ischaemic time and donor chronological age. This report shows that CDKN2A is better than telomere length, the most celebrated biomarker of ageing, as a predictor of post-transplant renal function. It also shows that CDKN2A is as strong a determinant of post-transplant organ function when compared to extended criteria (ECD) kidneys. A multivariate analysis model was able to predict up to 27.1% of eGFR at one year post-transplant (p = 0.008). Significantly, CDKN2A was also able to strongly predict delayed graft function. A pre-transplant donor risk classification system based on CDKN2A and ECD criteria is shown to be feasible and commendable for implementation in the near future.

Xenon treatment attenuates early renal allograft injury associated with prolonged hypothermic storage in rats

Prolonged hypothermic storage elicits severe ischemia-reperfusion injury (IRI) to renal grafts, contributing to delayed graft function (DGF) and episodes of acute immune rejection and shortened graft survival. Organoprotective strategies are therefore needed for improving long-term transplant outcome. The aim of this study is to investigate the renoprotective effect of xenon on early allograft injury associated with prolonged hypothermic storage. Xenon exposure enhanced the expression of heat-shock protein 70 (HSP-70) and heme oxygenase 1 (HO-1) and promoted cell survival after hypothermia-hypoxia insult in human proximal tubular (HK-2) cells, which was abolished by HSP-70 or HO-1 siRNA. In the brown Norway to Lewis rat renal transplantation, xenon administered to donor or recipient decreased the renal tubular cell death, inflammation, and MHC II expression, while delayed graft function (DGF) was therefore reduced. Pathological changes associated with acute rejection, including T-cell, macrophage, and fibroblast infiltration, were also decreased with xenon treatment. Donors or recipients treated with xenon in combination with cyclosporin A had prolonged renal allograft survival. Xenon protects allografts against delayed graft function, attenuates acute immune rejection, and enhances graft survival after prolonged hypothermic storage. Furthermore, xenon works additively with cyclosporin A to preserve post-transplant renal function.

Perioperative Levosimendan Therapy Improves Renal Function in Heart Transplant Recipients

Purpose We evaluated the effects of perioperative levosimendan therapy on renal function in heart failure patients undergoing heart transplantation. Methods and Materials Of 103 transplant recipients, 56 (53%) received perioperative infusion of levosimendan (0.1 microg/kg/min for 24 hours; LS Group), and 47 (47%) received no levosimendan (Controls). Renal function was assessed pre-transplantation and 1 week thereafter. Results At the time of transplantation, the groups did not differ in age (53±11 years in the LS group vs. 49±14 years in Controls; P=0.07), gender (male: 77% vs. 79%; P=0.82), heart failure etiology (ischemic: 28% vs. 27%; P=0.73), or donor age (41±11 years vs. 38±12 years; P=0.2). Similarly, there was no difference in creatinine (134±126 μmol/L in LS Group vs. 115±72 μmol/L in Controls; P=0.53) and creatinine clearance (Ccr) (84±42 mL/min vs. 83±34 mL/min;P=0.91). At 1 week after transplantation, we found a decrease in creatinine and an increase in Ccr in LS Group, but not in Controls despite similar mean arterial pressure in both groups (76±10 mmHg in LS Group vs. 79±20 mmHg in Controls; P=0.39). This led to a significant intergroup difference in creatinine (79±37 μmol/L in LS Group vs. 107±50 μmol/L in Controls; P=0.02) and Ccr (110±48 mL/min vs. 83±40 mL/min; P=0.005). An improvement in creatinine ≥50 μmol/L occurred in 22 % of patients from LS Group; compared with 5 % of Controls (P=0.01). Conclusions In patients undergoing heart transplantation perioperative levosimendan therapy improves post-transplant renal function. Since impaired renal function is a predictor of adverse outcome, perioperative levosimendan use could improve prognosis of heart transplant recipients.

613 Post-transplant renal function is closely correlated with aortic calcification index (ACI) progression rate in renal transplant recipients

613 Post-transplant renal function is closely correlated with aortic calcification index (ACI) progression rate in renal transplant recipients

Native renal function after combined liver-kidney transplant for type 1 hepatorenal syndrome: initial report on the use of postoperative Technetium-99 m-mercaptoacetyltriglycine scans

Type 1 hepatorenal syndrome (HRS) is characterized by rapid deterioration of renal function. We sought to assess native kidney function after combined kidney-liver transplant (CLKTx) performed for type 1 HRS. We performed a retrospective, cross-sectional, single-center study. All patients with Type 1 HRS who received a CLKTx at the University of California, San Francisco from 1997 to 2007 were screened for enrollment. Patients with a baseline estimated glomerular filtration rate (eGFR) ≥30ml/min/1.73m(2) were eligible. Twenty-three patients were identified and consented to receive a Technetium-99 m-mercaptoacetyltriglycine (MAG3) nuclear scan to measure the native kidney contribution to overall renal function. Only 4 of the 23 subjects (17.4%) demonstrated native renal function that consisted of a contribution ≥50% of total renal function. Several factors and comorbidities such as age, gender, race, duration of HRS, need for and duration of renal replacement therapy, need for pressors, urine sodium, proteinuria, and use of octreotide/midodrine were analyzed and not found to be significant in predicting native renal function. The assessment of post-transplant native renal function following CLKTx may allow for improved accuracy in identifying the patients in need of CLKTx, and thus allow for greater optimization of dual-organ allocation strategies in patients with concomitant liver and renal failure.

How does the Serum Catecholamine Change and Post Transplant Renal Function

Objective: To keep different levels of blood pressure and to observe the effects on the posttransplant renal function under general anesthesia. Methods: We selected 20 patients with the renal normal function (group N, n=20) who undergoing live donor nephrectomy under general anesthesia; the renal failure group (group F n=20) who undergoing renal transplantation. Blood pressure, ECG, SpO2, PETCO2, BIS were monitored continuously. Levels of norepinephrine, epinephrine, aldosterone in blood plasma were measured before anesthesia, after anesthesia before skin incision, at the time point of kidney exploration and after nephrectomy 10 min,40 min,120 min or at the renal vascular anastomosis opened for 10 min, 40 min, 120 min and even for 1st, 3rd days after kidney transplant. Meanwhile, we detected the volume of urine, serum concentrations of Cr (Creatinine), BUN (Blood urea nitrogen), cystsin C (CysC) and β2 microglobulin (β2-MG) for group F1(using the vasoactive drug to maintain the SBP 160-140 mmHg) and group F2 (SBP was kept at 139-110 mmHg) at different time points during the donor’s kidney was transplanted. Results: 1. Aldosterone was increased significantly at kidney exploration or the renal vascular anastomosis, comparied to pre-induction (P<0.05). But, there were no difference between two groups at each time points. 2. The volume of urine was increased as the time going on after kidney replacement in group F1 and F2. Meanwhile, The serum concentrations of Cr, BUN, CysC and β2-MG were decreased at the T4,T5,1st, 3rd time points, But there were no difference between F2 and F2 groups at each time point. Conclusion: The renin angiotensin aldosterone system was active in renal function normal or failure patients in peri-operation. And the transplanted kidney could work well under the physiologic levels of blood pressure and the higher SBP might not be essential in the renal failure patients.

The Economic Burden of Post-Transplant Events in Renal Transplant Patients in a Single Centre in Germany (The PORTRAIT Study)

Introduction: Little information is available on the prevalence of post-transplant events, and resource utilization associated with such events in renal transplant patients in clinical practice in Germany. The PORTRAIT study aims to describe the health care resources used and to estimate the cost of managing post-transplant patients using observational data from transplant databases and physician questionnaires from transplant centers across Europe. Aggregated study results have been previously communicated; this abstract describes the results from a centre in Germany. Methods: A retrospective observational study was undertaken in which resource usage over a three year period was employed to derive costs, with results stratified by glomerular filtration rate (GFR) status at one-year post transplant. Descriptive statistics were used to detail medical resources used to manage post-transplant events and its costs. Post-transplants events resources use considered were: hospital stays, delayed graft function, outpatient appointments, laboratory tests, anaemia, hypertension, dyslipidaemia and infections. Immunosuppressant drug costs were not considered in this analysis. Results: The total three-year cost of post-transplant care by GFR at one year varies from a minimum of €15,395 per patient to a maximum of €44,540 per patient. The average three-year costs decrease as a result of improved graft functioning status (increased GFR) at one year. The average three-year costs for a patient with a GFR>45mL/ min/1.73 m2 at one year are 50% lower than those with < 30 mL/min/1.73 m2 GFR in the database and questionnaire analysis respectively. This difference is largely driven by hospitalization costs, where patients with a GFR < 15 at year 1 have a mean length of stay of 40.3 days, compared with a mean stay of 19.7 days for those patients with a GFR >60. Figure 1 shows the mean total post-transplant costs per patient and the percentage of patients by GFR at three years in the analysis.[Figure 1]Conclusions: In line with the multinational results, the German results provide evidence that post-transplant resource usage in a real-life treatment setting increases as post-transplant renal function worsens. Therefore management strategies that promote renal function post transplant are likely to provide important resource savings to the healthcare system. Further research is undergoing to confirm these results with another database in Germany.

Metabonomic Analysis of Perfusion Solution with NMR: A Potential Tool to Predict Graft Outcome in Deceased after Cardiac Arrest Donor Conditions

Introduction: Specific biomarker research is an important issue in physiopathologic disorders especially in kidney transplantation where preservation conditions of organ before transplantation play a crucial role on graft outcome. Nuclear Magnetic Resonance (NMR) spectroscopy is an adapted tool for development of prognostic biomarkers of a better function recovery. This non-invasive method allows a direct quantitation of metabolites from graft perfusate in one experiment. We previously described an improvement of early graft function when preservation solution is supplemented with trimetazidine (TMZ). As machine perfusion (MP) is the recommended preservation method for kidneys obtained from deceased after cardiac death (DCD) donors, we measured the benefits of combining technological and pharmacological optimization using classical biochemical tests and NMR metabonomic approach. Methods: We used an auto-transplantation model on Large White pigs mimicking DCD donors. Sixty minutes of warm ischemia were followed by 24 hours of MP at 4°C. We preserved graft in KPS alone or supplemented with 3 doses of TMZ (10, 20 and 40 mg/L) (N=6). Perfusates samples at T= 0, 3, 10 and 24 hours were analyzed with a NMR spectrometer Bruker 500MHz. We measured diuresis, proteinuria and creatininemia until sacrifice, 3 months after transplantation. Results: Post-transplant renal function parameters indicated that the higher dose of TMZ induced a significantly better function recovery with a faster return of diuresis to basal level. NMR metabonomic analysis of perfusates showed that concentrations of numerous metabolites evolved according to time with a profile dependent to TMZ supplementations. Among those metabolites, the level of total glutathione, a redox cellular buffer and a component of the KPS, decreased over time. After 10 hours, we observed a significant difference between the 3 doses of TMZ with a slower decrease in the higher dose group. After 24 hours, total glutathione concentration for the 3 doses was below the quantification limit of the method. Meanwhile, we observed increases in glycine and glutamate concentrations, two amino acid components of glutathione. Studies on stability of glutathione according to pH did not show any degradation or oxidation of the tripeptide. Activities of glutathione S-transferase and g-glutamyl transferase will be measured in the perfusate in order to explain the rapid decline of this metabolite involved in the resistance to oxidative stress. Another interesting point was the release of succinate into the perfusate. Without TMZ, succinate levels increased according to time and in presence of TMZ, it remained stable. These data seem to support a protective effect of TMZ involving a reduction of cell injuries or an effect on succinate pathway. Conclusion: Prognostic biomarkers such as glutathione measured in perfusate at 10h by NMR could potentially be used to predict a better graft function recovery. Although these results need to be confirmed with different preservation conditions, NMR spectroscopy, easily transposable to the clinic, will be an interesting tool to improve the selection of graft with metabonomic perfusate profile in order to increase donor population and counteract the dramatic organ shortage.

A Comparative Study of Renal Function and Vitamin D Levels Between African and Indian Transplant Recipients

Introduction: There is a paucity of information on graft function in native African patients compared to Indian patients. As the Africans have higher BMI and muscle mass, they may have higher BUN and serum creatinine pre-transplantation. This study was undertaken to compare the outcome of transplantation with regard to renal function between the two groups. Materials and methods: Our retrospective study comprises 388 patients of Indian and African origin. Details such as age, gender, diabetic status, renal parameters pre and post-transplant, HLA typing, induction therapy, immunosuppressive medication and rejection rates were collected. Analysis was done using PASW Statistics 18 with chi-square test and one way Anova with post-hoc Tukey. All African patients received grafts from their own close relatives or spouses. Results: Of the 388 patients, 291 were Indian and 97 were of African origin. Details of the analysis are shown in Tables 1 and 2. It can be observed that the pre-transplant and immediate post-transplant renal function shown by blood urea and serum creatinine of the African patients were higher compared to their Indian counterparts (p< .001) However, the 1 month and 1 year post transplant renal functions were insignificantly different reflecting a similar overall outcome. While 38% of patients were diabetic, diabetic status was not significantly different. (p=0.153) A significant number of Indian patients had 1 or less HLA mismatches (44.5%) as compared to the African patients (15.9%) (p< .001). 27 patients died overall (6.9%) and mortality was not significantly different between the two ethnic groups. (p=0.106) Africans have higher levels of 25,OH Vitamin D3 levels (p=0.038)Table: [Demographic and Laboratory Parameters]Table: [Renal parameters]Conclusion: Our study shows that while the African population tended to have higher blood urea and creatinine pre and immediate post-operatively, this becomes insignificant at 1 month and 12 months and, thus, their overall outcome was similar to that of the Indian population despite a higher incidence of HLA mismatch. This may be attributed to achievement of adequate immunosuppression and overall higher Vitamin D levels.

The Economic Burden of Post-Transplant Events in Renal Transplant Patients in Italy (The PORTRAIT Study)

Objectives: Little information is available on the prevalence of post-transplant events, and resource utilization associated with such events in renal transplant patients in clinical practice in Italy. The PORTRAIT study aims to describe the health care resources used and to estimate the cost of managing post-transplant patients using observational data from transplant databases and physician questionnaires from transplant centers across Europe. Aggregated study results have been previously communicated; this abstract describes the results from the local study in Italy. Methods: A questionnaire specifically designed to assess the resource usage of post-transplant events in renal transplanted patients over a three year period was administered to eleven renal consultants. Local costs were used to quantify the resource use described in the questionnaires, with results stratified by glomerular filtration rate (GFR) status at one-year post transplant. Descriptive statistics were used to detail medical resources used to manage post-transplant events occurred and its costs. Post-transplants events resource use considered were: hospital stays, delayed graft function, outpatient appointments, laboratory tests, anaemia, hypertension, dyslipidaemia and infections. Immunosuppressant drug costs were not considered in this analysis. Results: The total three-year cost of post-transplant care by GFR at one year varies from a minimum of €30,535 per patient to a maximum of €42,883 per patient. The average three-year costs decrease as a result of improved graft functioning status (increased GFR) at one year. The average three-year costs for a patient with a GFR>45mL/min/1.73m2 at one year are 25% lower than those with < 30 mL/min/1.73m2 GFR in the database and questionnaire analysis respectively. Figure 1 shows the mean total post-transplant costs per patient and the percentage of patients by GFR at three years.[Figure 1]Conclusions: In line with the multinational results, the Italian results provide evidence that post-transplant resource usage in a real-life treatment setting increases as post-transplant renal function worsens. Therefore management strategies that promote renal function post transplant are likely to provide important resource savings to the healthcare system.

The Economic Burden of Post-Transplant Events in Renal Transplant Patients in Spain (The PORTRAIT Study)

Objectives: Little information is available on the prevalence of post-transplant events, and resource utilization associated with such events in renal transplant patients in clinical practice in Spain. The PORTRAIT study aims to describe the health care resources used and to estimate the cost of managing post-transplant patients using observational data from transplant databases and physician questionnaires in Europe. Aggregated study results have been previously communicated; this abstract describes the results from the local study in Spain. Methods: Data from renal database of Belvitge Hospital and 6 questionnaires have been analyzed to assess 3-year post-transplant resource use and costs stratified by glomerular filtration rate (GFR) status at one-year post transplant. Descriptive statistics were used to detail medical resources used to manage post-transplant events and its costs. Post-transplants events resource use considered were: hospital stays, delayed graft function, outpatient appointments, laboratory tests, anaemia, hypertension, dyslipidaemia and infections. Immunosuppressant drug costs were not considered in this analysis. Results: The total three-year cost of post-transplant care by GFR at one year varies from a minimum of €17,139 per patient to a maximum of €24,218 per patient in the database analysis and from €17,612 per patient to a maximum of €28,983 per patient in the questionnaire analysis. The average three-year costs decrease as a result of improved graft functioning status (increased GFR) at one year. The average three-year costs for a patient with a GFR>45mL/min/1.73m2 at one year are 22% and 33% lower than those with < 30 mL/min/1.73m2 GFR in the database and questionnaire analysis respectively. Figure 1 shows the mean total post-transplant costs per patient and the percentage of patients by GFR at three years.[Figure 1]Conclusions: In line with the multinational results, the Spanish results provide evidence that post-transplant resource usage in a real-life treatment setting increases as post-transplant renal function worsens. Therefore management strategies that promote renal function post transplant are likely to provide important resource savings to the healthcare system. Further research is being conducted to confirm these results.

Living donor liver transplantation for hepatorenal syndrome: To do or not to do? That is the question

Acute kidney injury (AKI) is common in patients with end-stage liver disease with an estimated prevalence of 20% at the time of liver transplantation (LT). The evolution of renal dysfunction in the context of liver failure ranges from insidious to rapid and from mild to severe. For patients who do not undergo LT, AKI is associated with a 90% in-hospital mortality rate. Therefore, the development of AKI adds an element of urgency for the patient and strategic complexity for the transplant program in making appropriate and timely decisions. Unfortunately, the utility of the current evidence is incomplete for defining appropriate management algorithms for this patient population. Studies in the published literature have usually been retrospective and single-center, and they have suffered from small sample sizes, reporting bias, and varying definitions of AKI; this makes study comparisons very difficult. The majority have demonstrated pretransplant AKI to be an independent predictor of post-LT mortality. However, these studies have failed to categorize patients according to the etiology of AKI. In a recent single-center, retrospective study, the etiology of AKI was shown to affect posttransplant outcomes: patients with hepatorenal syndrome (HRS) at the time of transplantation achieved survival outcomes similar to those of patients who had no AKI, regardless of the dialysis duration, the Model for End-Stage Liver Disease (MELD) score, or the Sequential Organ Failure Assessment score. The prognosis of patients with HRS and especially patients who develop type 1 HRS is extremely poor, and HRS is a terminal event for patients with advanced cirrhosis with a median survival of approximately 2 weeks. Therapies such as terlipressin and albumin dialysis provide only a modest survival benefit (if any), and the only chance for survival is LT. However, because of concerns about outcomes and ethical issues related to coercion and donor risk, many transplant centers have been reluctant to offer living donor liver transplantation (LDLT) to patients with high MELD scores, including patients with type 1 HRS. In this issue of Liver Transplantation, Chok et al. report the outcomes of patients with HRS who underwent LDLT or deceased donor liver transplantation (DDLT) at their institution. Seventy-one of 726 adult patients who underwent LT at a single center in Korea were considered to have had HRS at the time of transplantation, and 48 of these patients underwent LDLT. Although overall survival was lower for patients with HRS versus patients without HRS, the survival of LDLT recipients with HRS was better than or at least no worse than the survival of DDLT recipients with HRS. A subgroup analysis of patients with high MELD scores ( 30) and patients with type 1 HRS also demonstrated similar survival

The cost implications of first anniversary renal function after living, standard criteria deceased and expanded criteria deceased donor kidney transplantation

Objectives:To quantify relationships of post-transplant renal function with healthcare costs after kidney transplantation.Methods:Clinical and billing records for Medicare-insured kidney transplant recipients (1995–2003) were drawn from the US Renal Data System. Estimated glomerular filtration rate (eGFR) at 1-year post-transplant was computed with the abbreviated Modification of Diet in Renal Disease equation. Associations of eGFR with total Medicare payments in the second and third post-transplant years were examined by multivariate non-linear regression with spline forms. Adjustment covariates were drawn from the survival prediction model developed by the UNOS Kidney Allocation Review Committee.Results:The sample comprised 7103 living donor (LD), 22,110 standard criteria deceased (SCD), and 2594 expanded criteria deceased (ECD) donor transplant recipients. Regardless of donor type, lower 1-year eGFR was associated with significantly increased expenditures during the second and the third years post-transplant. Marginal costs began to increase as eGFR fell below 45 mL/min/1.73 m2 and rose in an accelerating manner. Compared to a reference eGFR of 75 mL/min/1.73 m2, 1-year eGFR of 20 ml/min/1.73 m2 in SCD recipients was associated with ∼ $17,500 and $18,200 higher adjusted payments in the second and third post-transplant years, respectively. Patterns were similar among recipients of LD and ECD transplants.Limitations:The study sample was limited to Medicare beneficiaries who survived with allograft function to the first transplant anniversary, which may limit generalizability of the findings. eGFR is a surrogate measure of renal function. The design is retrospective and changes in post-transplant management may alter long-term cost implication of renal function.Conclusions:Decreased renal function is significantly associated with higher healthcare expenditures following kidney transplantation. Post-transplant eGFR may be a useful metric for discriminating the economic impact of care strategies that differentially affect renal function.

Effect of Increased Pressure During Pulsatile Pump Perfusion of Deceased Donor Kidneys in Transplantation

IntroductionPulsatile pump perfusion of potential kidneys for transplantation is known to decrease the rate of delayed graft function (DGF) and improve their 1-year survival. Flow and resistance parameters are often used to determine the suitability of kidneys for transplantation. Kidneys with low flow rates are often subjected to higher pressures to improve flow. This study evaluated the effect of higher pump pressures on posttransplant renal function. MethodsWe performed a retrospective analysis of 73 deceased donor kidneys preserved using pump perfusion (LifePort) at our center between May 2006 and September 2009. We calculated the mean pump pressure (MP) for the duration of perfusion of each kidney, using systolic pressure (SP) and diastolic pressure (DP) readings with the following formula: (MP = DP + 1/3 (SP − DP). The kidneys were divided into a low (LP; n = 49) and a high-pressure group (HP; n = 24) based on a MP cutoff value of 23 mm Hg. The two groups were then compared for differences in perfusion dynamics and primary endpoints including DGF and 1-year graft survival. Statistical analysis was performed using paired Student t test and chi-square analysis. ResultsThe two groups were comparable for donor age, extended criteria, sensitization, and cold ischemic times. They differed significantly in higher initial (0.65 ± 0.4 versus 0.4 ± 0.2, P = .01), average (0.25 ± 0.08 versus 0.18 ± 0.06, P = .0006), and terminal resistance (0.21 ± 0.07 versus 0.17 ± 0.06, P = .008) of HP versus LP kidneys. Flow rates were comparable between the two groups. DGF was higher in HP kidneys (75% versus 40%, P = .006) with similar 1-year graft survival (87.5% versus 89%, P = .7). ConclusionsPerfusate flow through a kidney can be improved by increasing pressure settings to overcome elevated resistance. This maneuver was not associated with a lower rate of DGF after transplantation. One-year graft survival remained unaffected.

Pretransplant and Protocol Biopsies May Help in Defining Short and Mid-term Kidney Transplant Outcome

Although many variables may affect long-term graft survival no biomarker is available to identify donor kidney with poor quality and with inadequate short and long-term outcome. While in marginal donors pre-transplant renal biopsies are commonly performed to establish if donor kidneys are suitable for transplantation they are not performed in standard donors. In this study we assessed the relevance of pre-transplant morphological features on post-transplant renal function and evaluated the association between perioperative parameters with posttransplant histological and clinical findings. Kidney transplant recipients undergone pre-transplant and post transplant protocol biopsies at 1, 6, and 12 months were enrolled in the study. Perioperative and posttransplant clinical and biochemical parameters were recorded. Semiquantitative analysis of PAS stained kidney sections was used to determine the degree of lesions. Glomerular volume was measured by computed morphometry. A strong inverse correlation was found between donor age and renal graft function at 1, 6, and 12 months after transplantation. A prompt functional recovery was associated with a better renal function at 6 months and one year. Kidneys with higher glomerular volume demonstrated a lower serum creatinine at 1 month. Higher tubulo-interstitial grading at protocol biopsies was associated with a poor renal function at 1 month.Our findings confirm the importance of donor age in kidney transplant long-term outcome and demonstrate that pretransplant and protocol biopsies are valid options to determine graft outcome and to define therapeutic strategies and tailor immunosuppressive regimen for each patient.