Simultaneous Liver–Kidney Transplantation: A Survey of US Transplant Centers

Consensus recommendations have been published to help better define those patients who would benefit from simultaneous liver–kidney transplantation (SLK). We conducted a survey of transplant centers that perform SLK (n = 88, 65% response rate) to determine practice patterns in the United States. The majority of centers (73%) stated that they use dialysis duration whereas only 30% of centers use acute kidney injury duration as a criterion for determining need for SLK. Dialysis duration >4 weeks was used by 32% of centers, >6 weeks by 37% and >8 weeks by 32% of centers. Glomerular filtration rate (GFR) was estimated using the modified diet in renal disease (MDRD)‐4 equation in roughly half of centers whereas the MDRD‐6 equation was used by only 6%. In patients with chronic kidney disease, GFR < 40 mL/min was used by 24% of centers as a criterion for SLK transplants instead of the recommended threshold of < 30 mL/min. Regional differences in practices were also observed. This survey demonstrates significant variation in the criteria used for SLK among transplant centers, with few centers following the current published recommendations, and emphasizes the need for evidence‐based guidelines and uniformity in studying renal dysfunction in liver transplant candidates.     

Outcomes and Native Renal Recovery Following Simultaneous Liver–Kidney Transplantation

With the increase in patients having impaired renal function at liver transplant due to MELD, accurate predictors of posttransplant native renal recovery are needed to select candidates for simultaneous liver–kidney transplantation (SLK). Current UNOS guidelines rely on specific clinical criteria for SLK allocation. To examine these guidelines and other variables predicting nonrecovery, we analyzed 155 SLK recipients, focusing on a subset (n = 78) that had post‐SLK native GFR (nGFR) determined by radionuclide renal scans. The 77 patients not having renal scans received a higher number of extended criteria donor organs and had worse posttransplant survival. Of the 78 renal scan patients, 31 met and 47 did not meet pre‐SLK UNOS criteria. The UNOS criteria were more predictive than our institutional criteria for all nGFR recovery thresholds (20–40 mL/min), although at the most conservative cut‐off (nGFR ≤ 20) it had low sensitivity (55.3%), specificity (75%), PPV (67.6%) and NPV (63.8%) for predicting post‐SLK nonrecovery. On multivariate analysis, the only predictor of native renal nonrecovery (nGFR ≤ 20) was abnormal pre‐SLK renal imaging (OR 3.85, CI 1.22–12.5). Our data support the need to refine SLK selection utilizing more definitive biomarkers and predictors of native renal recovery than current clinical criteria.     

Microvascular Damage in Type 1 Diabetic Patients Is Reversed in the First Year After Simultaneous Pancreas–Kidney Transplantation

Simultaneous pancreas–kidney transplantation (SPK) is an advanced treatment option for type 1 diabetes mellitus (DM) patients with microvascular disease including nephropathy. Sidestreamdarkfield (SDF) imaging has emerged as a noninvasive tool to visualize the human microcirculation. This study assessed the effect of SPK in diabetic nephropathy (DN) patients on microvascular alterations using SDF and correlated this with markers for endothelial dysfunction. Microvascular morphology was visualized using SDF of the oral mucosa in DN (n = 26) and SPK patients (n = 38), healthy controls (n = 20), DM1 patients (n = 15, DM ≥ 40 mL/min) and DN patients with a kidney transplant (KTx, n = 15). Furthermore, 21 DN patients were studied longitudinally up to 12 months after SPK. Circulating levels of angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2) and soluble thrombomodulin (sTM) were measured using ELISA. Capillary tortuosity in the DN (1.83 ± 0.42) and DM ≥ 40 mL/min (1.55 ± 0.1) group was increased and showed reversal after SPK (1.31 ± 0.3, p < 0.001), but not after KTx (1.64 ± 0.1). sTM levels were increased in DN patients and reduced in SPK and KTx recipients (p < 0.05), while the Ang‐2/Ang‐1 ratio was normalized after SPK and not after KTx alone (from 0.16 ± 0.04 to 0.08 ± 0.02, p < 0.05). Interestingly, in the longitudinal study, reversal of capillary tortuosity and decrease in Ang‐2/Ang‐1 ratio and sTM was observed within 12 months after SPK. SPK is effective in reversing the systemic microvascular structural abnormalities in DN patients in the first year after transplantation.     

Combined Liver–Kidney Transplantation for Primary Hyperoxaluria Type 2: A Case Report

Combined liver/kidney transplant is the preferred transplant option for most patients with primary hyperoxaluria type 1 (PH1) since orthotopic liver transplantation replaces the deficient liver‐specific AGT enzyme, thus restoring normal metabolic oxalate production. However, primary hyperoxaluria type 2 (PH2) is caused by deficient glyoxylate reductase/hydroxypyruvate reductase (GRHPR), and this enzyme is widely distributed throughout the body. Though the relative abundance and activity of GRHPR in various tissues is not clear, some evidence suggests that the majority of enzyme activity may indeed reside within the liver. Thus the effectiveness of liver transplantation in correcting this metabolic disorder has not been demonstrated. Here we report a case of 44‐year‐old man with PH2, frequent stone events, and end‐stage renal disease; he received a combined liver/kidney transplant. Although requiring confirmation in additional cases, the normalization of plasma oxalate, urine oxalate, and urine glycerate levels observed in this patient within a month of the transplant that remain reduced at the most recent follow‐up at 13 months suggests that correction of the GRHPR deficiency in PH2 can be achieved by liver transplantation.     

Influence of Recipient Race on the Outcome of Simultaneous Pancreas and Kidney Transplantation

Racial differences on the outcome of simultaneous pancreas and kidney (SPK) transplantation have not been well studied. We compared mortality and graft survival of African Americans (AA) recipients to other racial/ethnic groups (non‐AA) using the national data. We studied a total of 6585 adult SPK transplants performed in the United States between January 1, 2000 and December 31, 2007. We performed multivariate logistic regression analyses to determine risk factors associated with early graft failure and immune‐mediated late graft loss. We used conditional Kaplan–Meier survival and multivariate Cox regression analyses to estimate late death‐censored kidney and pancreas graft failure and death between the groups. Although there was no racial disparity in the first 90 days, AA patients had 38% and 47% higher risk for late death‐censored kidney and pancreas graft failure, respectively (p = 0.006 and 0.001). AA patients were twice more likely to lose the kidney and pancreas graft due to rejection (OR 2.31 and 1.86, p = 0.002 and 0.008, respectively). Bladder pancreas drainage was associated with inferior patient survival (HR 1.42, 95% CI 1.15, 1.75, p = 0.001). In the era of modern immunosuppresion, AA SPK transplant patients continue to have inferior graft outcome. Additional studies to explore the mechanisms of such racial disparity are warranted.     

Class II Alloantibody and Mortality in Simultaneous Liver‐Kidney Transplantation

Hyperacute kidney rejection is unusual in crossmatch positive recipients of simultaneous liver–kidney transplants (SLKT). However, recent data suggest that these patients remain at risk for antibody‐mediated kidney rejection. To further investigate the risk associated with donor‐specific alloantibodies (DSA) in SLKT, we studied 86 consecutive SLKT patients with an available pre‐SLKT serum sample. Serum samples were analyzed in a blinded fashion for HLA DSA using single antigen beads (median florescence intensity ≥ 2,000 = positive). Post‐SLKT samples were analyzed when available (76%). Thirty patients had preformed DSA, and nine developed de novo DSA. Preformed class I DSA did not change the risk of rejection, patient or allograft survival. In contrast, preformed class II DSA was associated with a markedly increased risk of renal antibody mediated rejection (AMR) (p = 0.006), liver allograft rejection (p = 0.002), patient death (p = 0.02), liver allograft loss (p = 0.02) and renal allograft loss (p = 0.045). Multivariable modeling showed class II DSA (preformed or de novo) to be an independent predictor of patient death (HR = 2.2; p = 0.043) and liver allograft loss (HR = 2.2; p = 0.044). These data warrant reconsideration of the approach to DSA in SLKT.     

Parainfluenza 3 Infections Early After Kidney or Simultaneous Pancreas–Kidney Transplantation

Parainfluenza virus (PIV) can cause serious infections after hematopoietic stem cell or lung transplantation. Limited data exist about PIV infections after kidney transplantation. We describe an outbreak of PIV‐3 in a transplant unit. During the outbreak, 45 patients were treated on the ward for postoperative care after kidney or simultaneous pancreas–kidney (SPK) transplantation. Overall, 29 patients were tested for respiratory viruses (12 patients with respiratory symptoms, 17 asymptomatic exposed patients) from nasopharyngeal swabs using polymerase chain reaction. PIV‐3 infection was confirmed in 12 patients. One patient remained asymptomatic. In others, symptoms were mostly mild upper respiratory tract symptoms and subsided within a few days with symptomatic treatment. Two patients suffered from lower respiratory tract symptoms (dyspnea, hypoxemia, pulmonary infiltrates in chest computed tomography) and required supplemental oxygen. Four of six SPK patients and eight of 39 of kidney transplant patients were infected with PIV (p = 0.04). In patients with follow‐up tests, PIV‐3 shedding was still detected 11–16 days after diagnosis. Despite rapid isolation of symptomatic patients, PIV‐3 findings were diagnosed within 24 days, and the outbreak ceased only after closing the transplant ward temporarily. In conclusion, PIV‐3 infections early after kidney or SPK transplantation were mostly mild. PIV‐3 easily infected immunosuppressed transplant recipients, with prolonged viral shedding.     

Kidney and Pancreas Transplantation in the United States, 1996–2005

Kidney and pancreas transplantation in 2005 improved in quantity and outcome quality, despite the increasing average age of kidney graft recipients, with 56% aged 50 or older. Geography and ABO blood type contribute to the discrepancy in waiting time among the deceased donor (DD) candidates. Allocation policy changes are decreasing the median times to transplant for pediatric recipients. Overall, 6% more DD kidney transplants were performed in 2005 with slight increases in standard criteria donors (SCD) and expanded criteria donors (ECD). The largest increase (39%) was in donation after cardiac death (DCD) from non‐ECD donors. These DCD, non‐ECD kidneys had equivalent outcomes to SCD kidneys. 1‐, 3‐ and 5‐year unadjusted graft survival was 91%, 80% and 70% for non‐ECD‐DD transplants, 82%, 68% and 53% for ECD‐DD grafts, and 95%, 88% and 80% for living donor kidney transplants. In 2005, 27% of patients were discharged without steroids compared to 3% in 1999. Acute rejection decreased to 11% in 2004. There was a slight increase in the number of simultaneous pancreas‐kidney transplants (895), with fewer pancreas after kidney transplants (343 from 419 in 2004), and a stable number of pancreas alone transplants (129). Pancreas underutilization appears to be an ongoing issue.     

The First Simultaneous Kidney–Adrenal Gland–Pancreas Transplantation: Outcome at 1 Year

Adrenal insufficiency is a rare but life‐threatening disease. Replacement therapy sometimes fails to prevent an acute adrenal crisis and most often does not lead to restoration of well‐being. We report here the 1‐year outcome of the first simultaneous kidney–adrenal gland–pancreas transplantation in a 33‐year‐old patient with type 1 diabetes and concomitant autoimmune adrenal insufficiency. En bloc left adrenal gland and kidney grafts were anastomosed on the left iliac vessels in normal vascular conditions and the pancreas graft was anastomosed on the right iliac vessels. The immunosuppressive regimen was not modified by the addition of the adrenal gland. We observed no additional morbidity due to the adrenal gland transplantation, as there were no surgical complications. One‐year kidney and pancreas graft functions were satisfactory (estimated glomerular filtration rate: 55 mL/min/1.73 m² and HbA1c: 4.8%). The adrenal graft functioned well at 12 months with a normalization of cortisol and aldosterone baseline levels. Functional imaging at 3 months showed good uptake of [¹²³I]‐metaiodobenzylguanidine by the adrenal graft. Transplantation of the adrenal gland en bloc with the left kidney appears to be a good therapeutic option in patients with adrenal insufficiency awaiting kidney or kidney–pancreas transplantation.     

Outcomes of Combined Liver–Kidney Transplantation in Children: Analysis of the Scientific Registry of Transplant Recipients

Combined liver–kidney transplantation (CLKT) in children is uncommon and outcomes have not been well defined. Using the Scientific Registry of Transplant Recipients, data were analyzed on 152 primary pediatric CLKTs performed from October 1987 to February 2011, to determine their outcome in the largest series reported to date. Patient survival was 86.8%, 82.1% and 78.9% at 1, 5 and 10 years, liver graft survival was 81.9%, 76.5% and 72.6%, and kidney graft survival was 83.4%, 76.5% and 66.8%. By way of comparison, the Registry was queried for pediatric patient survival following isolated liver transplantation (LT) during the same time frame: 86.7%, 81.2% and 77.4% and following isolated kidney transplant (KT): 98.2%, 95.4% and 90% at 1, 5 and 10 years. In patients having undergone CLKT, primary hyperoxaluria was associated with reduced patient (p = 0.01), liver graft (p = 0.01) and kidney graft survival (p = 0.01). Furthermore, graft outcome following CLKT improved over the past decade (p = 0.04 for liver, p = 0.02 for kidney), but this did not translate into improved patient outcome (p = 0.2). All in all, our results confirmed that survival following LT was less than following KT, and that CLKT offered similar patient survival to isolated LT.     

Corticosteroid elimination in simultaneous liver–kidney transplantation recipients

Abstract: Background: Simultaneous liver–kidney transplantation (SLK) has more than doubled since 2002. While less common in kidney transplant alone recipients (KTA), corticosteroid discontinuation is performed routinely in liver transplantation, raising the question of optimal immunosuppression for SLK recipients. Methods: A retrospective case series of 16 SLK recipients under a steroid withdrawal protocol was performed to compare short‐term outcomes to a contemporaneous cohort of 32 KTA recipients. Results: In 69% of SLK recipients, corticosteroids were eliminated compared to 3% of KTA recipients, p < 0.0001. When comparing SLK and KTA recipients one yr post‐transplant, there were no significant differences in renal graft rejection (23.1% vs. 6.3%), death‐censored renal graft survival (100% vs. 97%), estimated glomerular filtration rate (74.4 vs. 62.6 mL/min), serum creatinine (1.10 vs. 1.39 mg/dL), or maintenance immunosuppression, respectively. Conclusions: Corticosteroids may be withdrawn safely in SLK recipients with one‐yr renal outcomes comparable to a KTA cohort.     

Kidney and Pancreas Transplantation in the United States, 1996–2005

Kidney and pancreas transplantation in 2005 improved in quantity and outcome quality, despite the increasing average age of kidney graft recipients, with 56% aged 50 or older. Geography and ABO blood type contribute to the discrepancy in waiting time among the deceased donor (DD) candidates. Allocation policy changes are decreasing the median times to transplant for pediatric recipients. Overall, 6% more DD kidney transplants were performed in 2005 with slight increases in standard criteria donors (SCD) and expanded criteria donors (ECD). The largest increase (39%) was in donation after cardiac death (DCD) from non-ECD donors. These DCD, non-ECD kidneys had equivalent outcomes to SCD kidneys. 1-, 3- and 5-year unadjusted graft survival was 91%, 80% and 70% for non-ECD-DD transplants, 82%, 68% and 53% for ECD-DD grafts, and 95%, 88% and 80% for living donor kidney transplants. In 2005, 27% of patients were discharged without steroids compared to 3% in 1999. Acute rejection decreased to 11% in 2004. There was a slight increase in the number of simultaneous pancreas-kidney transplants (895), with fewer pancreas after kidney transplants (343 from 419 in 2004), and a stable number of pancreas alone transplants (129). Pancreas underutilization appears to be an ongoing issue.     

Early Hospital Readmission After Simultaneous Pancreas–Kidney Transplantation: Patient and Center‐Level Factors

Early hospital readmission is associated with increased morbidity, mortality, and cost. Following simultaneous pancreas–kidney transplantation, rates of readmission and risk factors for readmission are unknown. We used United States Renal Data System data to study 3643 adult primary first‐time simultaneous pancreas–kidney recipients from December 1, 1999 to October 31, 2011. Early hospital readmission was any hospitalization within 30 days of discharge. Modified Poisson regression was used to determine the association between readmission and patient‐level factors. Empirical Bayes statistics were used to determine the variation attributable to center‐level factors. The incidence of readmission was 55.5%. Each decade increase in age was associated with an 11% lower risk of readmission to age 40, beyond which there was no association. Donor African‐American race was associated with a 13% higher risk of readmission. Each day increase in length of stay was associated with a 2% higher risk of readmission until 14 days, beyond which each day increase was associated with a 1% reduction in the risk of readmission. Center‐level factors were not associated with readmission. The high incidence of early hospital readmission following simultaneous pancreas–kidney transplant may reflect clinical complexity rather than poor quality of care.