Transplantul hepatic ortotopic

Transplantul hepatic ortotopic (orthotopic liver transplantation, OLT) ofera, a la long,  cel mai bun rezultat la pacientii cu boala hepatica cronica in stadiu final. Selectarea pcientilor pentru translpant este ghidata de un sistem de scoring care face predictia supravietuirii fara transplant. Unul dintre sistemele de scoring este MELD care are in formula ca variabila de luat in calcul, creatinina.

Scorul MELD definire si calculare

Valorile variabilelor se dau in micromoli

MELD Score = (0.957 * ln(Serum Cr) + 0.378 * ln(Serum Bilirubin) + 1.120 * ln(INR) + 0.643 ) * 10

daca pacientul este hemodializat, valoarea creatininei este considerata 4

Prin folosirea acestei formule care utilizeaza creatinina se induc probleme legate de corectitudinea evaluarii functiei renale la hepatic prin creatinina si anume

1. prognosticul functiei hepatice insasi  este partial afectat de introducerea acestei variabile

2. folosirea creatininei subestimeaza prognosticul real al evolutiei renala si il supraestimeaza pe cel hepatic.

Pentru a depasi aceste inconveniente scorul MELD ar trebui sa includa o masurare mai corecta a filtratului glomerular folosind „gold standardul” cystain C. Pentru  a se depasi inconvenientul indus de creatinina serica din formula MELD, respectiva formula a fost modificata la UKELD care include si concentratia serica de Na  [51].Aceasta modificare a facut in Marea Bitanie (UK) supravietuirea dupa includerea in lista de asteptare pentru transplantul hepatic se fie mai buna.

Incidenta bolii renale cronice printre primitorii de transplant hepatic este mare, circa 27% si mai mult de 10% sint in stadiu final, necesitind epurare extrarenal

The incidence of chronic kidney disease among liver recipients is high, around 27%, and up to 10% reach end-stage, requiring renal replacement therapy within 10 years [51]. There are a number of independent risk factors in the pre-transplant period that are associated with chronic kidney disease post-transplantation. These include chronic kidney disease stage, age, gender, ethnicity, and the presence of hypertension, diabetes and hepatitis C prior to transplantation [52]. Importantly, chronic kidney disease post-liver transplantation is associated with a four-fold increase in mortality [53]. Strategies have focused on tailoring immunosuppression regimens to improve long-term renal outcome, in particular, reducing the nephrotoxic calcineurin inhibitor burden, which is often possible due to the immunotolerant properties of the liver. The ReSpECT study compared standard tacrolimus dosing and steroids; low-dose tacrolimus plus steroids; and delayed introduction and low-dose tacrolimus plus steroids plus mycophenolate moefitil. The authors demonstrated reduced nephrotoxicity in the delayed, low dose tacrolimus group [54]. Daclizumab, a monoclonal antibody, was used to provide immunosuppressive cover during the delayed period before the introduction of tacrolimus. The study had a few limitations, however, namely the use of estimated GFR calculated with the Cockcroft-Gault formula, and the fact that a significant number of patients were withdrawn from the high dose group. However, it importantly demonstrated that the tailoring of an immunosuppressive regimen can have a significant impact on nephrotoxicity without detrimental effects on graft function or patient survival [54].

There has also been an increasing trend toward combined liver-kidney transplant if patients have AKI or chronic kidney disease prior to transplantation. However, appropriate allocation of these organs to patients that are most suitable for either OLT alone or combined liver-kidney transplant has created a major dilemma as no single reliable factor has been shown to be predictive of renal recovery or progression of chronic kidney disease after successful OLT.

Pre-emptive kidney transplantation for patients with isolated kidney disease is considered if dialysis is predicted to start within 6 months, which is typically associated with a GFR less than 15 ml/min. Combined liver-kidney transplant is currently indicated for those with combined kidney and liver disease on hemodialysis with viral, polycystic, or primary oxaluria as etiologies. In this scenario, there is a drive to transplant these patients earlier when their liver disease is not so advanced, e.g., Child Pugh score A or B, because of worse outcomes associated with Child Pugh C cirrhosis. Extensive polycystic liver and kidney disease where the mass of cysts exceeds 20 kg causing malnutrition and cachexia is seen as an indication for transplantation, even though liver synthetic function is often well preserved. Primary oxaluria type 1 is an enzymatic defect resulting in renal calculi and extensive extrarenal oxalate deposits. Combined liver-kidney transplant is recommended early in the course of this disease to prevent extra renal manifestations, in a similar way to familial amyloidosis polyneuropathy [55].

End-stage liver and kidney disease is a recognized indication for combined liver-kidney transplant and was first performed in 1983. Retrospective studies have, however, evaluated factors that may help predict the reversibility of kidney dysfunction in patients with end-stage liver disease. There is some evidence that chronic kidney disease (defined as renal dysfunction for more than 12 weeks), pre-transplant serum creatinine > 160 umol/l, and diabetes, are predictors of poor post-transplant kidney function with estimated GFR of less than 20 ml/min/1.73 m2 [52]. There is a paucity of research in this field. The implementation and use of improved measures of residual kidney function and the incorporation of these into MELD would help to more precisely prioritize patients and ensure organ allocation is appropriate for liver, kidney, and combined transplant procedures.

Conclusion

Chronic liver disease is associated with primary and secondary kidney disease and impacts markedly on survival. The evaluation of kidney function and injury relies on the measurement of the concentration of serum creatinine, which is affected by the degree of liver disease and the analytical method employed. The integral role of creatinine concentration in the different classifications of AKI, chronic kidney disease and the survival predictive score, MELD, for chronic liver disease, confers large inaccuracies across this population, but currently offers the most cost-effective measure available. Hepatologists should perhaps use exogenous measures of kidney function and biomarkers, like cystatin C and the cystatin C-based equation for estimated GFR, more frequently, as these have been shown to be superior to creatinine. Improved assessment of the degree of residual kidney function may assist clinical decisions regarding risk of AKI, drug therapy in chronic liver disease, the tailoring of post-liver transplant immunosuppression regimens, and the allocation of organs for combined liver and kidney transplantation. Kidney injury biomarkers need further evaluation in the chronic liver disease population, but they seem likely to continue to perform well. Earlier diagnosis and implementation of currently established beneficial therapies seems to be pivotal in potentially reducing the severity of kidney injury and increasing survival outcomes; whether this will be realized remains to be seen.

Anunțuri