Improvement in posttransplant management, particularly in immunosuppressive therapy, has led to a dramatic increase in patient survival following solid organ transplantation. Specifically, immunosuppressive therapy with the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus has enhanced survival after orthotopic liver transplantation (OLTX) [1, 2]. Despite their associated improved survival, CNIs are inherently nephrotoxic and often cited as the main cause of chronic renal failure (CRF) following OLTX [3–7]. In the first 6 months following OLTX, CNIs have been associated with nearly a 30 % decline in glomerular filtration rate (GFR) [3]. Moreover, CNIs contribute to the development of CRF in approximately 18 % of OLTX patients after 13 years, including 9.5 % who progress to end-stage renal disease (ESRD) [3]. Because nephrotoxicity may lead to the discontinuation of CNIs, less effective immunosuppressive agents are used, which may result in more frequent liver and renal graft dysfunction. For these reasons, CNI toxicity and the acceleration of underlying liver and renal disease may necessitate subsequent liver and/or kidney retransplantation.

Since the implementation of the model for end-stage liver disease (MELD) by the United Network for Organ Sharing (UNOS) in 2002 as an objective allocation system, priority has shifted to end-stage liver disease (ESLD) patients with renal insufficiency. This shift in priority has led to a rapid albeit unintentional increase in the number of simultaneous liver–kidney transplants (SLKTs). Specifically, since 2001, not only did the number of SLKT increase by more than 300 % but the proportion of SLKT to the overall number of OLTX more than doubled from 2.38 % in 2001 to 5.5 % in 2006 [8]. Although significant renal impairment had previously been considered a contraindication for OLTX, SLKT has become a well-established therapeutic option for end-stage renal and liver disease since the first SLKT performed by Margreiter et al. in 1984 [9]. There is compelling evidence supporting the theory for an immunoprotective role assumed by the transplanted liver in preventing renal allograft rejection in SLKT from the same donor. SLKT recipients span the gamut from well-compensated cirrhotics with end-stage renal disease (ESRD) to severely decompensated chronic liver patients suffering acute kidney injury requiring continuous venovenous hemofiltration in the intensive care unit. At the first extreme, the indication for kidney transplantation is clear but the indication for liver transplantation is less obvious. The liver transplant is usually not urgent, but prevents hepatic decompensation after kidney transplantation. Moreover, the liver may also facilitate kidney transplantation by shortening waiting time. At the second extreme, the issues are exactly reversed. The kidney transplant is not urgent since dialysis can be maintained indefinitely. However, inclusion of the kidney for these critically ill patients may avert early posttransplant complications related to renal failure and reduce the risk of future ESRD. The increasing prevalence of acute and chronic renal dysfunction among liver transplant candidates coupled with the burgeoning kidney transplant waitlist has motivated physicians to define and standardize selection criteria for SLKT [10–12]. The model for end-stage liver disease (MELD) scoring system was implemented in 2002 and has been widely accepted as an objective scale of disease severity and accurate predictor of liver waitlist mortality [13, 14]. Prioritization of liver transplant candidates with renal dysfunction by the MELD system has resulted in a substantial increase in the number of simultaneous liver–kidney transplants. There are currently no standard criteria for the evaluation of patients with acute kidney injury (AKI) or chronic kidney disease (CKD) requiring liver transplantation (LT). The decision to perform SLKT is generally driven by concern over the likelihood of recovery of renal function and the associated increase in mortality in patients with non-recovery of renal function following liver transplantation alone (LTA). Because the persistence of preoperative renal dysfunction following LT has been associated with inferior patient survival [15–20] combined with the fact that kidney waitlist survival is comparatively worse for candidates with a previous LT [21, 22], transplant programs often follow center-specific decision-making oriented toward ensuring adequate posttransplant renal function while considering the appropriateness of SLKT. Currently there are several pitfalls in the existing guidelines that make it difficult to accurately distinguish candidates who will benefit from SLKT from those who will not. These include the definition and duration of AKI, glomerular filtration rate (GFR) determination, and the duration of dialysis. It is well known that in patients with cirrhosis, mild degrees of renal dysfunction may go undiagnosed. The proposed organ procurement and transplantation network (OPTN) policy for SLKT criteria has defined AKI based on a GFR ≤ 25 mL/min for a duration of ≥6 weeks determined by modified diet in renal disease (MDRD) or direct measurements, such as iothalamate. In liver transplant candidates with AKI, duration of dialysis is the main criterion used to determine SLKT candidacy. However, no universally accepted guidelines exist regarding when dialysis should be initiated in patients with cirrhosis; it is largely a subjective decision with a wide spectrum of practice variations. In 2004, in response to the lack of a standard definition for AKI, the Acute Dialysis Quality Initiative (ADQI) Workgroup developed a consensus definition and classification for AKI, the RIFLE (risk, injury, failure, loss, end stage) criteria, which stratified acute renal dysfunction into grades of increasing severity of AKI based on changes in patients’ serum creatinine (Scr) or urine output [23]. Subsequently it was recognized that even smaller increases in SCr (absolute increase in SCr ≥ 0.3 mg/dL) are associated with adverse outcome, and thus, the criteria were modified in 2007 to broaden the definition of AKI [24]. The RIFLE criteria have been validated in more than 500,000 patients with AKI, including critically ill patients with cirrhosis pre- and post-liver transplantation, and have been shown to predict clinical outcomes with a progressive increase in mortality with worsening RIFLE class [25–29]. The summit attendees considered the following criteria as an indication for SLKT in patients who were on the liver transplant waitlist: (A) candidates with persistent AKI for ≥ 4 weeks with one of the following: Stage 3 AKI as defined by modified RIFLE, i.e., a threefold increase in Scr from baseline, Scr ≥ 4.0 mg/dL with an acute increase of ≥ 0.5 mg/dL or on renal replacement therapy, and eGFR ≤ 35 mL/min (MDRD-6 equation) or GFR ≤ 25 mL/min (iothalamate clearance); (B) candidates with chronic kidney disease (CKD), as defined by the National Kidney Foundation [30], for 3 months with one of the following: eGFR ≤ 40 mL/min (MDRD-6 equation) or GFR ≤ 30 mL/min (iothalamate clearance), proteinuria ≥ 2 g a day, kidney biopsy showing > 30 % global glomerulosclerosis or > 30 % interstitial fibrosis, and metabolic disease.

The most frequent indications are virus- or alcohol-related liver cirrhosis, polycystic disease, genetic or metabolic disorders, and cholestatic disease.

The rationale for SLKT is easily justified in patients with ESLD in the setting of ESRD requiring chronic renal replacement therapy (RRT). However, the matter is more complicated in patients with ESLD who develop acute renal failure when the duration or potential reversibility of the renal failure is uncertain as is often the case in hepatorenal syndrome (HRS) type II. HRS is generally not considered an indication for SLKT due to the well-documented reversibility of the renal failure after OLTX [31, 32]. It has also been shown that kidneys transplanted from donors with HRS result in good renal function [33]. However, there is currently no consensus as to the duration of HRS or RRT after which renal dysfunction is not reversible. The lack of this consensus sets the stage for the debate between proceeding with upfront SLKT versus LTA with the potential need for sequential renal transplant. The advantages of SLKT appear to outweigh the disadvantages. One main advantage of SLKT is the enhanced outcomes compared to kidney after liver transplantation (KALT) and liver after kidney transplantation (LAKT) likely due to the apparent immunoprotection afforded to the kidney by the transplanted liver.

Secondly, a well-functioning kidney allows optimal dosing of necessary immunosuppressants. Lastly, several studies have confirmed the presence of immune complex-mediated glomerulonephropathy (GN) in HCV-positive patients undergoing OLTX even in the absence of clinical signs or symptoms [34–37]. In HCV recipients in particular, the underlying renal disease is surely exacerbated following OLTX, which would otherwise be preserved in SLKT. The use of SLKT is an effective and appropriate therapy in patients with ESLD with proven irreversible or chronic ESRD. Although the recent increase in SLKT performed each year effectively decreases the number of potential donor kidneys available to patients with ESRD awaiting kidney transplantation, SLKT in patients with ESLD and ESRD is justified due to the lower risk of graft loss in SLKT compared to liver transplantation alone (LTA) as well as superior recipient and graft survival compared to serial liver–kidney transplantation.

There is a paucity of data regarding the need for organ liver transplantation OLTX in ESRD patients with asymptomatic liver disease including Child’s A cirrhosis. This issue is important because of the incidence of hepatitis C positive (HCV+) in dialysis patients of 10–40 %, coupled with the fact that ESRD patients have a MELD score of 21 with normal bilirubin and international normalized ratio (INR) [38, 39]. However, the question remains whether these patients are best served with kidney transplant alone (KTA) versus SLKT. The determination of SLKT versus KTA must be based on liver histology and signs of portal hypertension with wedge hepatic vein pressure being the gold standard [40]. In addition, long-term survival analysis showed an overall successful outcome [41, 42] with a comparable graft and patient survival rate in SLKT patients when compared with LTx or KTx alone [43]. Moreover, SLKT for polycystic disease is justified when the patient is symptomatic with dyspepsia, upper abdominal pain, and malnutrition; the liver is full of cysts; and the patient needs to have hemodialysis.

The ideal cadaveric heart-beating donor for SLKT is aged < 60 years without history of kidney diseases, hypertension, and/or diabetes in stable pressure condition without or with mild dosage of vasopressor drugs. When a cadaveric donor is aged < 55 years and the body weight is more than 70 kg and the liver function tests are normal, in particular gamma-glutamyl transferases (GGT) without sign of liver steatosis at liver biopsy, part of the liver can also be suitable for SLK transplantation, splitting the liver if the donor is hemodynamically stable. More often, cadaveric heart-beating donors are extended criteria donors (ECD), and liver biopsy is mandatory to assess the liver quality especially in the case of hepatitis B virus antibody core antigen positive, moderate or severe liver steatosis, and age > 60 years; in the latter case, a kidney biopsy is also mandatory to evaluate whether the kidneys are suitable for single kidney transplant or double kidney transplant or not suitable for transplant.