Improved Outcome after ‘Bottom-Up’ Immunosuppression in Liver Transplant Recipients with Preoperative Renal Impairment

Abstract

Background: Most patients with high MELD scores have impaired renal function prior to transplantation. Patient and Methods: A retrospective case control study was conducted with initial low immunosuppression, which was increased when patients rejected or were clinically stable beyond day 30 (‘bottom-up’). Results: Thirty patients with impaired renal function were included. Fifteen were treated with de novo cyclosporine A (CsA; group A), and 15 had ‘bottom-up’ immunosuppression (group B). Baseline renal function was similar: serum creatinine (SCr) median 1.8 mg/dl (range: 1.5–4.0 mg/dl; group A) versus 2.4 mg/dl (range: 1.5–4.0 mg/dl; group B; p = 0.24). The requirement for renal replacement therapy was significantly lower in group B (p = 0.032). Ten received ‘bottom-up’ immunosuppression [4 CsA/1 sirolimus (Sir) ‘on demand’ after rejection, 5 Sir (stable)] beyond day 30. By months 6 and 12 (1.6 mg/dl vs. 1.2 mg/dl), SCr values were significantly better in group B (p = 0.006). Renal function in group B did not differ between patients receiving CsA or Sir. Overall complication rates, survival and biopsy-proven acute rejection were similar, although BANFF scores were higher in group B (p = 0.004). Conclusion: Successful implementation of ‘bottom-up’ immunosuppression in liver transplant recipients with high lab-MELD scores and renal dysfunction at the time of transplantation has the potential to substantially improve short- and long-term outcomes.

Evidence-Based Medicine in Daily Surgical Decision Making: A Survey-Based Comparison between the UK and Germany

“…laparoscopic cholecystectomy, continuously evolving surgical techniques, and natural orifice transluminal endoscopic surgery, single incision laparoscopic surgery or associating liver partition with portal vein ligation for staged hepatectomy in liver resection [24]); (iii) diseases with a lack of guidelines refer to standard treatments and classifications that exist without sufficient and convincing evidence from clinical trials (e.g. sigmoid diverticulitis, suture or stapling of loop ileostomy closure, clipping or sutures in thyroid surgery, immunosuppression in patients with renal impairment or hepatocellular carcinoma after liver transplantation [25,26,27,28,29,30,31,32,33]), and (iv) complex treatment decisions in interdisciplinary oncologic settings that still reveal clinical insecurity and need clarification with clinical trials (e.g. neoadjuvant and adjuvant therapy strategies in colorectal liver metastases), but also warrant an individualized and tailored therapy.…”

Effect of delayed CNI-based immunosuppression with Advagraf® on liver function after MELD-based liver transplantation [IMUTECT]

“…Almost 85% of patients become afflicted with early infections, which is the most common cause of death soon after LT [15]. …”

“…Early renal dysfunction after transplantation has been reported in up to 50% of patients [19,20]. CNI are well documented as major risk factors for early renal impairment and are believed to be responsible for chronic renal failure after LT [15]. Renal function seems to play a key role in the long-term survival of patients with higher MELD-scores, therefore, new immunosuppression strategies are necessary in order to avoid CNI-related impairment of the kidney function after LT.…”

“…Negative side effects of Calcineurin inhibitors (CNI) are, among others, renal impairment and infectious complications [15]. High-MELD patients often present with a limited renal function as creatinine is one component of the MELD-score [1].…”

“…High-MELD patients often present with a limited renal function as creatinine is one component of the MELD-score [1]. The combination of CNI application and higher MELD-scores increases the risk of renal impairment [15]. Furthermore it has been hypothesized that high-MELD recipients have decreased immune competence [16] and can therefore benefit from the lowest possible doses of immunosuppressant drugs after LT. Low-dose Advagraf® with aimed trough levels of Tacrolimus at the end of the first week after LT should protect patients, especially high-MELD patients, from negative side effects of CNI, especially with regard to renal function and infection rate, while simultaneously promoting no increase in the rate of rejection.…”