Mechanisms of the Rapid Decline in Glomerular Filtration Rate following Lung Transplantation in Patients with Cystic Fibrosis

Abstract

To the Editor:We read with interest the recent article by Hornum et al.on the rapid decline in renal function during the first weekspost lung transplantation (1). We fully agree that strategiesfor renoprotective regimens are required notably in thevulnerable peri- and postoperative period. It is important tohighlighttheadditionalaccelerateddeclineinrenalfunctionpost lung transplant in patients with cystic fibrosis (CF)when compared to non-CF lung transplantation recipients(2).The histopathological lesions differ in the early renal func-tion loss versus late stages post lung transplantation inpatients with CF. Calcineurin toxicity is important in the ac-celerated renal function decline post lung transplantation,however, the contribution of additional CF- associated fac-tors also deserve mention (3). The early accelerated renalfunction loss is thought to be additionally associated withoxalate nephropathy and pigmented tubulopathy; whereasthese factors are less important in late episodes of renalfunction loss (3).The etiology of oxalate nephropathy in CF patients is mul-tifactorial including: (1) Enteric Hyperoxaluria from the de-creaseincolonicOxalobacterformigenescolonizationsec-ondary to recurrent antibiotic usage in the treatment of CFpulmonary infective exacerbations, reduced gastrointesti-nal oxalate binding from dietary calcium deficiency andfatty acid malabsorption as a consequence of CF malab-sorption (2). Increased renal calcium oxalate deposition onthe surface of proximal tubular cells potentiated by periop-erative stressors including hemodynamic factors, hypoxia,antibiotics and other nephrotoxic agents. In this contextstrategies that reduce oxalate nephropathy in the peri- andpostoperative management of CF lung transplantation re-cipients have been suggested (4), including a reduction indietary oxalate, increased oral calcium supplementation,the avoidance of ascorbic acid (a precursor of oxalic acid),improving hydration status, judicious antibiotic use, poten-tial recolonization of the digestive tract with Oxalobacterformigenes and postoperative monitoring for crystalluriaand/or calcium oxalate supersaturation (4).Pigmented tubulopathy is characterized by the intracellularaccumulation of silver stain positive pigmented granuleswiththehistopathologicalcharacteristicsoflipofucsin.Thisoccurrence has been noted to correlate with antiviral ther-apy, aminoglycoside use and glycopeptides antibiotics inthe month preceding the accelerated renal function loss ina cohort of post lung transplant CF patients (3).Understandingthepathogenesisofacceleratedrenalfunc-tion loss specific to CF lung transplant recipients will facil-itate improved tailored strategies for preventing/retardingthe decline in glomerular filtration rates in this subgroup ofyour population.O. J. O’Connell