Background: The nephrotoxity of calcineurin inhibitors in lung-transplanted patients is well described, but previous studies have estimated rather than directly measured glomerular filtration rate (GFR). This study describes the decline of measured GFR in a large cohort of lung-transplanted patients from a national centre, and the correlation between measured and calculated GFR.
Methods: All lung-transplanted patients 1992-2004 (n = 390) were included in a longitudinal analysis. Seven patients were excluded due to retransplantation. Pre- and post-transplant parameters included (51)Cr-labelled EDTA clearance (mGFR) and the Cockcroft-Gault calculated clearance (cGFR). Trough cyclosporine levels (C0) and demographic and transplant information were also included in the analysis.
Results: A total of 66959 C0 and serum creatinine and 1945 mGFR measurements pertaining to 383 patients were included in the analysis. Pre-transplant mGFR was significantly lower with respect to recipient age over 60 years; and patients with a referral diagnosis of pulmonary hypertension had a lower mGFR and higher baseline serum creatinine levels than patients with emphysematous disease (P < 0.05). There were linear correlations between log(10) mean interval serum creatinine and log(2) mGFR at all time points pre- and post-transplantation (P < 0.0001, Spearman correlation coefficient = -0.81) and between log(2) cGFR and log(2) mGFR (P < 0.0001, Spearman correlation coefficient = 0.81), however, the agreement between mGFR and cGFR was poor (-2.7 +/- 38.6 ml/min). A simplified repeated measure ANOVA model describing post-transplant GFR over time demonstrated a 54% decline in mGFR within the first 6 months post-transplant. Pre-transplant mGFR was an important determinant of 6 month post-transplantation mGFR. Increasing mean C0, body mass index and early acute renal failure were independent risk factors for a more rapid decline in post-transplant mGFR.
Conclusion: mGFR decreases dramatically during the first 6 months after lung-transplantation. Avoidance of high dose calcineurin inhibition may postpone the onset of post-transplant end-stage renal failure.