Longitudinal Analysis of Renal Function using ZIP GEE on OLT Transplant Patients Undergoing NAC Prophylaxis

Organ dysfunction is associated with oxidative stress following Orthotropic Liver Transplant (OLT) surgery. N-Acetyl Cysteine (NAC) is an acetylated form of the amino acid cysteine. NAC is known to replenish glutathione in the bloodstream which helps relieve cell damage caused by oxidative stress. NAC was used in a placebo controlled study to discover its effects on organ dysfunction caused by oxidative stress following OLT surgery. A standard NAC treatment, as used to treat acetaminophen toxicity, was used as a treatment during surgery. Measures of hepatic and renal dysfunction were recorded at unequally spaced time-points for a follow-up time of one year. The Generalized Estimating Equation (GEE) approach was used to model continuous hepatic responses. Discrete renal dysfunction responses are shown to follow a unique distribution. This unique distribution was accommodated by the GEE procedure proposed by Liang and Zeger to produce consistent and efficient estimates of the treatment effect of NAC. The estimates produced contradictory results for a hypothesized protective effect of NAC against hepatic dysfunction. The public health relevance of this work is that NAC treatment, if shown to be efficacious with respect to renal function, can benefit over six thousand OLT patients each year