Abstract Background Kidney disease is a frequent but underestimated complication in patients suffering from intestinal failure (IF) treated by long-term home parenteral nutrition (HPN). The evolution in glomerular filtration rate (GFR) over time is poorly characterized. The current equations for estimating GFR have limited precision. No study has specifically investigated the reliability of recent creatinine-based estimated GFR (eGFR) equations in this population. The aim of this study was to evaluate the renal function decline under home parenteral nutrition (HPN) with a gold standard method and compare the performances of routinely used eGFR equations. Methods Forty patients with HPN and two or more GFR measurements were retrospectively studied. The renal function decline was calculated by the slope drawn between the successive measured GFRs (mGFRs). The performances of the Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, full age spectrum and revised Lund–Malmö equations were compared with reference methods (inulin or iohexol clearance). Results The mean mGFR was 78 ± 28 mL/min/1.73 m2. The annual decline of mGFR was −1.9 mL/min/1.73 m2/year. No predisposing factor was identified to predict impairment in renal function. eGFR formulas grossly overestimated mGFR and had a low level of accuracy. Conclusions Patients with IF are at significant risk for impaired renal function. In this population, the tested eGFR equations were inaccurate. However, monitoring kidney function with mGFR remains important in these patients, as their GFR regularly declines and no specific risk factor has yet been identified.