Renal outcomes of simultaneous liver–kidney transplantation compared to liver transplant alone for candidates with renal dysfunction

It is unclear whether a concomitant kidney transplant grants survival benefit to liver transplant (LT) candidates with renal dysfunction (RD). We retrospectively studied LT candidates without RD (n = 714) and LT candidates with RD who underwent either liver transplant alone (RD‐LTA; n = 103) or simultaneous liver–kidney transplant (RD‐SLKT; n = 68). RD was defined as renal replacement therapy (RRT) requirement or modification of diet in renal disease (MDRD)–glomerular filtration rate (GFR) <25 mL/min/1.73 m². RD‐LTAs had worse one‐yr post‐transplant survival compared to RD‐SLKTs (79.6% vs. 91.2%, p = 0.05). However, RD‐LTA recipients more often had hepatitis C (60.2% vs. 41.2%, p = 0.004) and more severe liver disease (MELD 37.9 ± 8.1 vs. 32.7 ± 9.1, p = 0.0001). Twenty RD‐LTA recipients died in the first post‐transplant year. Evaluation of the cause and timing of death relative to native renal recovery revealed that only four RD‐LTA recipients might have derived survival benefit from RD‐SLKT. Overall, 87% of RD‐LTA patients recovered renal function within one month of transplant. One yr after RD‐LTA or RD‐SLKT, serum creatinine (1.5 ± 1.2 mg/dL vs. 1.4 ± 0.5 mg/dL, p = 0.63) and prevalence of stage 4 or 5 chronic kidney disease (CKD; 5.9% vs. 6.8%, p = 0.11) were comparable. Our series provides little evidence that RD‐SLKT would have yielded substantial short‐term survival benefit to RD‐LTA recipients.     

Evaluation of MDRD4, CKD‐EPI,BIS‐1, and modified Cockcroft–Gault equations to estimate glomerular filtration rate in the elderly renal‐transplanted recipients

Equations to estimate glomerular filtration rate (eGFR) were developed in patients using the variables age, body weight, and serum creatinine, which may be different in the elderly. Elderly renal transplant patients (EG; n=70; mean age 65 ± 4 y) who measured plasma ⁵¹Cr‐EDTA‐Clearance (mGFR) had mGFR compared to eGFR obtained by the Cockcroft–Gault corrected by body surface area (CG‐BSA), the modification of diet in renal disease (MDRD‐4), the Berlin Initiative Study (BIS‐1), and the chronic kidney disease epidemiology collaboration (CKD‐EPI). Results were validated using a cohort of 43, of the 70 elderly recipients, who performed a second ⁵¹Cr‐EDTA‐Clearance. Mean mGFR was 47 ± 16 mL/min/1.73 m² and statistically lower than eGFR by MDRD (52 ± 19, P=.001) and BIS‐1 (51 ± 13, P=.007) but not different from the CG‐BSA (47 ± 15) and CKD‐EPI (49 ± 18). The CKD‐EPI and CG‐BSA presented the lowest bias but only CKD‐EPI also showed the highest 30% and 10% accuracy. The same findings were repeated in the validation set. For a cohort of elderly recipients ≥65 years (n=35, 68 ± 3y), the CKD‐EPI performed better with the lowest bias (0 ± 12 mL/min/1.73 m²) and best 30% and 10% accuracy. The CKD‐EPI equation is a valuable tool to monitor GFR in the elderly RTx recipients.     

Simultaneous liver-kidney versus liver transplantation alone in patients with end-stage liver disease and kidney dysfunction not on dialysis

Background

Since implementation of the Model for End-stage Liver Disease (MELD), the number of simultaneous liver-kidney transplantations (SLKT) has increased in the United States. However, predictors and survival benefit of SLKT compared to liver transplantation alone (LTA) are not well defined.

Methods

Organ Procurement and Transplantation Network data of patients with end-stage liver disease (ESLD) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² who had not been on dialysis while on the waiting list and underwent liver transplantation between 2002 and 2008 were analyzed. To identify predictors of undergoing SLKT versus LTA, multiple logistic regression analysis was performed. Cox proportional hazards regression analysis was used to assess the association between SLKT and post–liver transplant patient and graft survival.

Results

The study cohort comprised 5443 patients; 262 (5%) underwent SLKT and 5181 (95%) underwent LTA. Adjusting for potential confounders, patients who underwent SLKT were 34% less likely to die after liver transplantation than those who underwent LTA (hazard ratio [HR] = 0.66, P = .012) and 33% less likely to have liver graft failure than those who underwent LTA (HR = 0.67, P = .010). Among those who underwent SLKT, 1-, 3-, and 5-year kidney graft survival probabilities were 88%, 80%, and 77%, respectively. Black race and diabetes were associated with a higher likelihood of SLKT versus LTA; female sex, a higher eGFR, and higher MELD score reduced the likelihood of SLKT.

Conclusions

Among those with ESLD and kidney dysfunction not on dialysis, post–liver transplant patient and liver graft survivals of patients who underwent SLKT were superior to those of patients who underwent LTA. Whether this reflects differences in the two groups that could not be adjusted in survival models or a specific effect of kidney dysfunction cannot be established.     

Impact of early conversion from cyclosporin to everolimus on left ventricular mass index: A randomized controlled trial

This is an 18‐month prospective, randomized controlled trial (RCT) designed to compare the effect of early conversion from cyclosporin to everolimus/mycophenolic acid (E‐MPA) between 3 and 4 months post‐transplant to cyclosporin/mycophenolic acid (CsA‐MPA) on left ventricular mass index (LVMI) at 3 and 18 months post‐transplant (primary outcome). Secondary outcomes included estimated glomerular filtration rate (eGFR), viral infection, and adverse events. Twenty‐four patients were randomized in a 1:1 ratio to E‐MPA or CsA‐MPA groups. There were no significant differences in mean (SD) LVMI at 3 (51.6±18.5 vs 53.7±15.7 g/m^2.7) and 18 months (52.7±16.3 vs 51.7±16.8 g/m^2.7) between CsA‐MPA and E‐MPA groups. The incidence of viral infections was reduced in E‐MPA compared to CsA‐MPA treatment groups (8% vs 50%, P=.02), but the incidences of acute rejection, adverse events, and drug discontinuation were similar between groups. There was an overall increase in eGFR with time (0.04 log‐ mL/min/1.73 m² per 6 months, P=.012) but no significant difference between the two groups across time (0.11 log‐ mL/min/1.73 m², P=.311). Immunosuppressive regimen comprising early conversion from cyclosporine to everolimus was not associated with a regression of LVMI, but a lower risk of viral infections was observed.     

Excessive immunosuppression as a potential cause of poor survival in simultaneous liver/kidney transplantation for hepatitis C

Appropriate recipient selection of simultaneous liver/kidney transplantation (SLKT) remains controversial. In particular, data on liver graft survival in hepatitis C virus‐infected (HCV+) SLKT recipients are lacking. We conducted a single‐center, retrospective study of HCV+ SLKT recipients (N = 25) in comparison with HCV? SLKT (N = 26) and HCV+ liver transplantation alone (LTA, N = 296). Despite backgrounds of HCV+ and HCV? SLKT being similar, HCV+ SLKT demonstrated significantly impaired 5‐year liver graft survival of 35% (HCV? SLKT, 79%, P = 0.004). Compared with HCV+ LTA, induction immunosuppression was more frequently used in HCV+ SLKT. Five‐year liver graft survival rate for HCV+ SLKT was significantly lower than that for LTA (35% vs. 74%, respectively, P < 0.001). Adjusted hazard ratio of liver graft loss in HCV+ SLKT was 4.9 (95% confidence interval 2.0–12.1, P = 0.001). HCV+ SLKT recipients were more likely to succumb to recurrent HCV and sepsis compared with LTA (32% vs. 8.8%, P < 0.001 and 24% vs. 8.8%, P = 0.030, respectively). Ten HCV+ SLKT recipients underwent anti‐HCV therapy for recurrent HCV; only 1 achieved sustained virological response. HCV+ SLKT is associated with significantly decreased long‐term prognosis compared with HCV? SLKT and HCV+ LTA.     

Recreational marijuana use is not associated with worse outcomes after renal transplantation

As marijuana (MJ) legalization is increasing, kidney transplant programs must develop listing criteria for marijuana users. However, no data exist on the effect of MJ on kidney allograft outcomes, and there is no consensus on whether MJ use should be a contraindication to transplantation. We retrospectively reviewed 1225 kidney recipients from 2008 to 2013. Marijuana use was defined by positive urine toxicology screen and/or self‐reported recent use. The primary outcome was death at 1 year or graft failure (defined as GFR<20 mL/min/1.73 m²). The secondary outcome was graft function at 1 year. Using logistic regression analyses, we compared these outcomes between MJ users and non‐users. Marijuana use was not associated with worse primary outcomes by unadjusted (odds ratio 1.07, 95% CI 0.45–2.57, P=.87) or adjusted (odds ratio 0.79, 95% CI 0.28–2.28, P=.67) analysis. Ninety‐two percent of grafts functioned at 1 year. Among these, the mean creatinine (1.52, 95% CI 1.39–1.69 vs 1.46, 95% CI 1.42–1.49; P=.38) and MDRD GFR (50.7, 95% CI 45.6–56.5 vs 49.5, 95% CI 48.3–50.7; P=.65) were similar between groups. Isolated recreational MJ use is not associated with poorer patient or kidney allograft outcomes at 1 year. Therefore, recreational MJ use should not necessarily be considered a contraindication to kidney transplantation.     

Kidney Allocation to Liver Transplant Candidates with Renal Failure of Undetermined Etiology: Role of Percutaneous Renal Biopsy

The feasibility, value and risk of percutaneous renal biopsy (PRB) in liver transplant candidates with renal failure are unknown. PRB was performed on 44 liver transplant candidates with renal failure of undetermined etiology and glomerular filtration rate (GFR) <40 mL/min/1.73 m² (n = 37) or on renal replacement therapy (RRT) (n = 7). Patients with ≥30% interstitial fibrosis (IF), ≥40% global glomerulosclerosis (gGS) and/or diffuse glomerulonephritis were approved for simultaneous‐liver‐kidney (SLK) transplantation. Prebiopsy GFR, urinary sodium indices, dependency on RRT and kidney size were comparable between 27 liver‐transplant‐alone (LTA) and 17 SLK candidates and did not relate to the biopsy diagnosis. The interobserver agreement for the degree of IF or gGS was moderate‐to‐excellent. After a mean of 78 ± 67 days, 16 and 8 patients received LTA and SLK transplants. All five LTA recipients on RRT recovered kidney function after transplantation and serum creatinine was comparable between LTA and SLK recipients at last follow‐up. Biopsy complications developed in 13, of these, five required intervention. PRB is feasible in liver transplant candidates with renal failure and provides reproducible histological information that does not relate to the pretransplant clinical data. Randomized studies are needed to determine if PRB can direct kidney allocation in this challenging group of liver transplant candidates.     

Performances of creatinine‐based glomerular filtration rate estimating equations in simultaneous pancreas‐kidney transplant recipients: a single center cohort study

Estimating glomerular filtration rate (GFR) is important for clinical management and research studies in simultaneous pancreas‐kidney transplantation (SPK) recipients. No study has specifically investigated the reliability of recent creatinine–based GFR estimating equations in this singular population. We assessed the performances of CKD‐EPI, MDRD, Schwartz‐2009, Schwartz‐Lyon, Lund‐Malmo and Full Age Spectrum equations for estimating GFR after SPK. 126 patients were included. GFR was measured by a reference method (mGFR) one year after SPK and estimated with the different equations from a standardized measure of serum creatinine. Relative bias, precisions, 10% and 30% accuracies (P30) were used to determine equations reliability. Ages ranged from 29 to 58. Mean mGFR was 56.3 ± 13.3 [23.6–92.5] ml/min/1.73 m². In the whole population, P30 of the CKD‐EPI and MDRD equations were 42% (38.0; 46.0) and 65% (61.5; 69) respectively. As compared to the other equations, the Schwartz‐Lyon equation was significantly more accurate (P30 = 86.0% [83.5–88.0], P < 0.01) and less biased (1.13 [1.06–1.19], P < 0.01). Conclusions were similar whatever the age class (<40 or ≥40) and mGFR level (<60 or ≥60 ml/min/1.73 m²). This study suggests that the CKD‐EPI and MDRD equations have poor performances in SPK recipients and that the Schwartz‐Lyon equation is a reliable alternative.     

Comparing everolimus‐based immunosuppression with reduction or withdrawal of calcineurin inhibitor reduction from 6 months after heart transplantation: The randomized MANDELA study

In the 12‐month, open‐label MANDELA study, patients were randomized at month 6 after heart transplantation to (1) convert to calcineurin inhibitor (CNI)‐free immunosuppression with everolimus (EVR), mycophenolic acid and steroids (CNI‐free, n = 71), or to (2) continue reduced‐exposure CNI, with EVR and steroids (EVR/redCNI, n = 74). Tacrolimus was administered in 48.8% of EVR/redCNI patients and 52.6% of CNI‐free patients at randomization. Both strategies improved and stabilized renal function based on the primary endpoint (estimated GFR at month 18 posttransplant postrandomization) with superiority of the CNI‐free group vs EVR/redCNI: mean 64.1 mL/min/1.73 m² vs 52.9 mL/min/1.73 m²; difference + 11.3 mL/min/1.73 m² (P < .001). By month 18, estimated GFR had increased by ≥ 10 mL/min/1.73 m² in 31.8% and 55.2% of EVR/redCNI and CNI‐free patients, respectively, and by ≥ 25 mL/min/1.73 m² in 4.5% and 20.9%. Rates of biopsy‐proven acute rejection (BPAR) were 6.8% and 21.1%; all cases were without hemodynamic compromise. BPAR was less frequent with EVR/redCNI vs the CNI‐free regimen (P = .015); 6 of 15 episodes in CNI‐free patients occurred with EVR concentration < 5 ng/mL. Rates of adverse events and associated discontinuations were comparable. EVR/redCNI from month 6 achieved stable renal function with infrequent BPAR. One‐year renal function can be improved by early conversion to EVR‐based CNI‐free therapy but requires close EVR monitoring. Clinical trials registry: ClinicalTrials.gov NCT00862979.     

Estimated or Measured GFR in Living Kidney Donors Work‐up?

The value of estimated glomerular filtration rate (eGFR) in living kidney donors screening is unclear. A recently published web‐based application derived from large cohorts, but not living donors, calculates the probability of a measured GFR (mGFR) lower than a determined threshold. Our objectives were to validate the clinical utility of this tool in a cohort of living donors and to test two other strategies based on chronic kidney disease epidemiology collaboration (CKD‐EPI) and on MDRD‐eGFR. GFR was measured using ⁵¹Cr‐ ethylene‐diamine tetraacetic acid urinary clearance in 311 potential living kidney donors (178 women, mean age 50 ± 11.6 years). The web‐based tool was used to predict those with mGFR < 80 mL/min/1.73 m². Inputs to the application were sex, age, ethnicity, and plasma creatinine. In our cohort, a web‐based probability of mGFR <90 mL/min/1.73 m² higher than 2% had 100% sensitivity for detection of actual mGFR <80 mL/min/1.73 m². The positive predictive value was 0.19. A CKD‐EPI‐eGFR threshold of 104 mL/min/1.73 m² and an MDRD‐eGFR threshold of 100 mL/min/1.73 m² had 100% sensitivity to detect donors with actual mGFR <80 mL/min/1.73 m². We obtained similar results in an external cohort of 354 living donors. We confirm the usefulness of the web‐based application to identify potential donors who should benefit from GFR measurement.     

To what extent estimated or measured GFR could predict subclinical graft fibrosis: a comparative prospective study with protocol biopsies

Monitoring of allograft function entails methods more accurate than serum creatinine and creatinine‐based GFR equations (eGFR). This prospective trial aimed at investigating the diagnostic accuracy of creatinine‐ and cystatin C‐based eGFR with measured GFR (mGFR) and compared them with graft fibrosis detected by protocol biopsies (PBx). Forty‐four kidney transplant recipients were enrolled. PBx were obtained postengraftment and at 6th and 12th months. GFR was measured by Tc‐99m DTPA at 3th, 6th, and 12th months after transplantation. Significant correlation existed between eGFR and mGFR at 3, 6, and 12 months (P < 0.0001). Cystatin C‐based Hoek and Larsson equations had the lowest bias and highest accuracy. The sum of interstitial fibrosis and tubular atrophy score increased from implantation to 6th and 12th months (0.52 ± 0.79, 0.84 ± 0.88, 1.50 ± 1.35). This was accompanied by reduction of mGFR from 54.1 ± 15.2 to 49.9 ± 15.2 and 46.8 ± 16.5 ml/min/1.73 m², while serum creatinine, cystatin C, and eGFR remained stable. Neither creatinine‐ nor cystatin C‐based GFR equations are reliable for detecting insidious graft fibrosis. In the first year after transplantation, mGFR, with its best proximity to histopathology, can be used to monitor allograft function and insidious graft fibrosis.     

Randomized controlled trial assessing the impact of everolimus and low‐exposure tacrolimus on graft outcomes in kidney transplant recipients

This was a single‐center, randomized controlled trial assessing the impact of a 3‐month (10‐16 weeks) conversion to everolimus with low‐exposure tacrolimus, as compared to remaining on full exposure tacrolimus with mycophenolate (NCT 02096107). Adult kidney transplant recipients with a functioning graft were eligible for participation. Goal troughs in the intervention arm were 2‐5 ng/mL for tacrolimus and 3‐8 ng/mL for everolimus, with tacrolimus maintained at 5‐12 ng/mL in the control arm; 60 were randomized (30 in each arm) and were well matched at baseline; mean age was 51 years and 57% were African‐American. At 12‐months, fibrosis scores (27.8% tacrolimus/mycophenolate vs 22.9% tacrolimus/everolimus, P = .391), acute rejection rates (7% tacrolimus/mycophenolate vs 3% tacrolimus/everolimus, P = .554), and graft function (mean eGFR tacrolimus/mycophenolate 56 ± 15 vs tacrolimus/everolimus 59 ± 14 mL/min/1.73 m², P = .465) were similar between arms. The everolimus arm had significantly lower rates of CMV infection, severe BK infection, and improved BK viral clearance kinetics, as compared to the MPA arm. In this population, including a significant number of African‐Americans, an immunosuppression regimen of everolimus with low‐exposure tacrolimus provided similar efficacy to tacrolimus and mycophenolate, with significantly lower rates of BK and CMV.     

Postoperative renal function after partial nephrectomy for renal cell carcinoma in patients with pre‐existing chronic kidney disease: A comparison with radical nephrectomy

We assessed whether adequately functioning parenchyma is preserved in patients with pre‐existing chronic kidney disease (CKD) after partial nephrectomy (PN) compared with those who underwent radical nephrectomy (RN). A total of 95 patients with pre‐existing CKD who underwent curative surgery for pathological T1a‐T2N0M0 renal cell carcinoma with a follow‐up period of 12 months or more were the subject of the present study. Of these, 51 patients underwent RN, and 44 PN. Renal function was assessed by using the estimated glomerular filtration rate (e‐GFR). We classified the subjects into two groups according to the preoperative e‐GFR: preoperative e‐GFR 45–59 mL/min/1.73 m² (68 patients); and 30–44 mL/min/1.73 m² (27 patients). In the former group, the probability of freedom from new onset of e‐GFR <45 mL/min/1.73 m² stemmed from the significant difference between the PN and RN groups (P = 0.006; PN: 2 years 64%; RN: 2 years 22%). In contrast, in the latter group, the probability of freedom from new onset of e‐GFR <30 mL/min/1.73 m² was not associated with a significant difference between PN and RN group (P = 0.80). Overall survival and the number of the patients who went on to develop end‐stage renal disease requiring renal replacement therapy between PN and RN were not significantly different in each group. Death from renal cell carcinoma was not noted in either group. PN could significantly prevent development to late‐stage CKD in patients with preoperative e‐GFR 45–59 mL/min/1.73 m² compared with RN. Patients with preoperative e‐GFR 30–44 mL/min/1.73 m² should be reviewed in a more strict study.     

Outcomes of en bloc simultaneous liver‐kidney transplantation compared to the traditional technique

Simultaneous liver‐kidney transplantation (SLKT) is indicated for patients with end‐stage liver disease (ESLD) and concurrent renal insufficiency. En bloc SLKT is an alternative to traditional separate implantations, but studies comparing the two techniques are limited. The en bloc technique maintains renal outflow via donor infrahepatic vena cava and inflow via anastomosis of donor renal artery to donor splenic artery. Comparison of recipients of en bloc (n = 17) vs traditional (n = 17) SLKT between 2013 and 2017 was performed. Recipient demographics and comorbidities were similar. More recipients of traditional SLKT were dialysis dependent (82.4% vs 41.2%, P = .01) with lower baseline pretransplant eGFR (14 vs 18, P = .01). En bloc SLKT was associated with shorter kidney cold ischemia time (341 vs 533 minutes, P < .01) and operative time (374 vs 511 minutes, P < .01). Two en bloc patients underwent reoperation for kidney allograft inflow issues due to kinking and renal steal. Early kidney allograft dysfunction (23.5% in both groups), 1‐year kidney graft survival (88.2% vs 82.4%, P = 1.0), and posttransplantation eGFR were similar between groups. In our experience, the en bloc SLKT technique is safe and feasible, with comparable outcomes to the traditional method.     

Experience with belatacept rescue therapy in kidney transplant recipients

In kidney transplant recipients with chronic graft dysfunction, long‐term immunosuppression with calcineurin inhibitors (CNIs) or mTOR inhibitors (mTORi) can be challenging due to adverse effects, such as nephrotoxicity and proteinuria. Seventy‐nine kidney transplant recipients treated with CNI‐based or mTORi‐based maintenance immunosuppression who had CNI‐induced nephrotoxicity or severe adverse events were switched to belatacept. Mean time from transplantation to belatacept conversion was 69.0 months. Mean estimated glomerular filtration rate (eGFR) ± standard deviation at baseline was 26.1 ± 15.0 ml/min/1.73 m², increasing to 34.0 ± 15.2 ml/min/1.73 m² at 12 months postconversion (P < 0.0005). Renal function improvements were also seen in patients with low eGFR (<25 ml/min/1.73 m²) or high proteinuria (>500 mg/l) at conversion. The Kaplan–Meier estimates for patient and graft survival at 12 months were 95.0% and 85.6%, respectively. The discontinuation rate due to adverse events was 7.9%. One case of post‐transplant lymphoproliferative disorder occurred at 17 months postconversion. For comparison, a historical control group of 41 patients converted to mTORi‐based immunosuppression because of biopsy‐confirmed CNI‐induced toxicity was examined; eGFR increased from 27.6 ± 7.2 ml/min/1.73 m² at baseline to 31.1 ± 11.9 ml/min/1.73 m² at 12 months (P = 0.018). Belatacept‐based immunosuppression may be an alternative regimen for kidney transplant recipients with CNI‐ or mTORi‐induced toxicity.     

A randomized cross‐over comparison of short‐term exposure of once‐daily extended release tacrolimus and twice‐daily tacrolimus on renal function in healthy volunteers

Calcineurin inhibitor nephrotoxicity remains an issue for transplant recipients. The pharmacokinetic profile (PK) of the once‐daily tacrolimus extended release (Tac‐ER) includes equivalent exposure [AUC_(0–24 h)] but lower C_max versus twice‐daily tacrolimus immediate release (Tac‐IR). We hypothesized that the unique PK profiles would result in pharmacodynamic differences in renal function. Nineteen healthy male subjects were allocated to once‐daily Tac‐ER and twice‐daily Tac‐IR in a prospective, randomized, two period, cross‐over study. Tacrolimus was titrated to achieve trough levels of 8–12 ng/ml. Twenty four hours ERPF and GFR estimated by para‐aminohippurate and sinistrin clearance were performed at baseline and at the end of each 10‐day dosing period. Mean Tac C₀ was 11.0 ± 2.2 and 11.3 ± 1.8 ng/ml for Tac‐ER and Tac‐IR, respectively. The mean Effective 24 h renal plasma flow (ERPF) was significantly higher with Tac‐ER compared with Tac‐IR (658 ± 127 vs. 610 ± 93 ml/min/1.73 m², P = 0.046). There was a trend to a greater mean GFR over 24 h for Tac‐ER at 114.5 ± 13.6 ml/min/1.73 m² compared with 108.9 ± 9.7 ml/min/1.73 m² for Tac‐IR, P = 0.116. Under controlled physiological conditions, ERPF was significantly improved with Tac‐ER compared with Tac‐IR, likely owing to the differing PKs of these tacrolimus preparations (ClinicalTrials.gov Identifier: NCT01681134).     

Histological Features of Acute Tubular Necrosis in Native Kidneys and Long-Term Renal Function

There are few studies on the relationship between the morphology of acute tubular necrosis (ATN) in native kidneys and late functional recovery. Eighteen patients with acute renal failure (ARF) who had undergone renal biopsy were studied. All had the histological diagnosis of ATN and were followed for at least six months. Clinical characteristics of ARF were analyzed, and histological features were semi-quantitatively evaluated (tubular atrophy, interstitial inflammatory infiltrate, interstitial fibrosis, and ATN). According to the maximal GFR achieved during the follow-up, patients were divided into two groups: complete recovery (GFR ≥ 90 mL/min/1.73 m²) and partial recovery (GFR < 90 mL/min/1.73 m²). Only 39% of the patients achieved complete recovery. Patients with partial recovery achieved their maximal GFR (63 ± 9 mL/min/1.73 m²) 37 ± 14 months after ARF, a period of time similar to those patients with complete recovery (i.e., 54 ± 22 months). Patients with partial recovery had more severe ARF: oliguria was more frequent (90 versus 17%, p < 0.01), and they had higher peak creatinine (13.85 ± 1.12 versus 8.95 ± 1.30 mg/dL, p = 0.01), and longer hospitalization (45 ± 7 versus 20 ± 4 days, p = 0.03). No single histological parameter was associated with partial recovery, but the sum of all was when expressed as an injury index [4.00 (2.73–5.45) versus 2.00 (1.25–3.31), p < 0.05]. In conclusion, among patients with atypical ATN course, those with more severe ARF and tubule-interstitial lesions are more prone to partial recovery.     

1,25 Dihydroxyvitamin D circulating levels,calcitriol administration,and incidence of acute rejection,CMV infection,and polyoma virus infection in renal transplant recipients

Observation that 1,25‐Dihydroxyvitamin‐D3 has an immunomodulatory effect on innate and adaptive immunity raises the possible effect on clinical graft outcome. Aim of this study was to evaluate the correlation of biopsy‐proven acute rejection, CMV infection, BKV infection, with 1,25‐Dihydroxyvitamin‐D3 deficiency and the benefit of calcitriol supplementation before and during the transplantation. Risk factors and kidney graft function were also evaluated. All RTRs received induction therapy with basiliximab, cyclosporine, mycophenolic acid, and steroids. During the first year, the incidence of BPAR (4% vs 11%, P=.04), CMV infection (3% vs 9%, P=.04), and BKV infection (6% vs 19%, P=.04) was significantly lower in users compared to controls. By multivariate Cox regression analysis, 1,25‐Dihydroxyvitamin‐D3 deficiency and no calcitriol exposure were independent risk factors for BPAR (HR=4.30, P<.005 and HR=3.25, P<.05), for CMV infection (HR=2.33, P<.05 and HR=2.31, P=.001), and for BKV infection (HR=2.41, P<.05 and HR=2.45, P=.001). After one year, users had a better renal function: eGFR was 62.5±6.7 mL/min vs 51.4±7.6 mL/min (P<.05). Only one user developed polyomavirus‐associated nephropathy vs 15 controls. Two users lost their graft vs 11 controls. 1,25(OH)2‐D3 deficiency circulating levels increased the risk of BPAR, CMV infection, BKV infection after kidney transplantation. Administration of calcitriol is a way to obtain adequate 1,25(OH)2‐D3 circulating levels.     

Efficacy and safety of everolimus with reduced tacrolimus in living‐donor liver transplant recipients: 12‐month results of a randomized multicenter study

In a multicenter, open‐label, study, 284 living‐donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non‐inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference –0.7% (90% CI ?5.2%, 3.7%); P < .001 for non‐inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non‐inferiority (P < .001 for non‐inferiority), but not superiority and was similar between groups overall (mean ?8.0 vs. ?12.1 mL/min/1.73 m², P = .108), and in patients continuing randomized treatment (?8.0 vs. ?13.3 mL/min/1.73 m², P = .046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC‐treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non‐inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432.     

Combined liver–kidney transplantation versus liver transplant alone based on KDIGO stratification of estimated glomerular filtration rate: data from the United Kingdom Transplant registry – a retrospective cohort study

Patient selection for combined liver–kidney transplantation (CLKT) is a current issue on the background of organ shortage. This study aimed to compare outcomes and post‐transplant renal function for patients receiving CLKT and liver transplantation alone (LTA) based on native renal function using estimated glomerular filtration rate (eGFR) stratification. Using the UK National transplant database (NHSBT) 6035 patients receiving a LTA (N = 5912; 98%) or CLKT (N = 123; 2%) [2001–2013] were analysed, and stratified by KDIGO stages of eGFR at transplant (eGFR group‐strata). There was no difference in patient/graft survival between LTA and CLKT in eGFR group‐strata (P > 0.05). Of 377 patients undergoing renal replacement therapy (RRT) at time of transplantation, 305 (81%) and 72 (19%) patients received LTA and CLKT respectively. A significantly greater proportion of CLKT patients had severe end‐stage renal disease (eGFR < 30 ml/min/1.73 m²) at 1 year post‐transplant compared to LTA (9.5% vs. 5.7%, P = 0.001). Patient and graft survival benefit for patients on RRT at transplantation was favouring CLKT versus LTA (P = 0.038 and P = 0.018, respectively) but the renal function of the long‐term survivors was not superior following CLKT. The data does not support CLKT approach based on eGFR alone, and the advantage of CLKT appear to benefit only those who are on established RRT at the time of transplant.