Nephropathy in patients after Fontan palliation

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Abstract

As the effect of Fontan circulation on the kidneys has not been defined, the purpose of this study was to determine whether it is associated with nephropathy.

Methods

Patients with single ventricle physiology at least 2 years after Fontan procedure with normal cardiac function by echocardiography, history of normal renal ultrasound, and no co-morbidities known to affect the kidneys were evaluated. Patient's demographics, diagnoses, pre- and post-Fontan catheterization data, and current medications were collected. A current glomerular filtration rate (eGFR) was calculated. Morning urine samples were collected for microalbumin/creatinine ratio (MCR).

Results

Twenty-one subjects (M:F = 13:8, ages 15.2 +/− 8.8 years) were studied. Primary diagnoses included hypoplastic left ventricle in 9, forms of hypoplastic right ventricle in 10, and unbalanced atrio-ventricular canal in 2 patients. Time after Fontan completion was 11.4 +/− 6.5 years. Current medications included aspirin (14 patients), coumadin (4), enalapril (8), lisinopril (10), digoxin (11), diuretics (5), and beta-blockers (5). Four subjects had pacemakers.

All patients had a normal blood pressure and eGFR. Nine patients (43%) had a pathologic MCR (> 20 µg/mg). There were no significant differences between the MCR-normal and MCR-abnormal groups in age, gender, type of single ventricle, type of the procedure, age at or time since Fontan operation. The groups differed in post-Fontan pulmonary vascular resistance (PVR) (p < 0.01) and strong positive correlations were found between the MCR and pre- and post-Fontan PVR (r = 0.51, p < 0.05 and r = 0.61, p = 0.02 respectively). The MCR-normal and MCR-abnormal groups did not differ in pacemaker, digoxin, diuretics, or anticoagulant use. However, the groups were different in using ACE inhibitors with a negative correlation (r =  0.45, p = 0.04) between the MCR and lisinopril-equivalent ACE inhibitor dose. Moreover, no patient receiving a lisinopril-equivalent dose greater than 0.4 mg/kg/day had pathologic microalbuminuria. In conclusion, our study demonstrates that patients with Fontan circulation have high incidence of pathologic microalbuminuria, an indicator of renal injury. The use of ACE inhibitors may be beneficial in preserving their renal function.

Introduction

Fontan palliation is a series of surgical procedures that separate deoxygenated from oxygenated blood in patients with a single ventricle physiology [1]. One effect of this palliation is chronically elevated central venous pressures (CVP). Although the increased CVP in Fontan patients has been associated with protein-losing enteropathy, hepatic dysfunction, and arrhythmias [2], [3], [4], [5], its effect on the kidneys has not been defined. The purpose of this study was to determine whether post-Fontan patients show evidence of renal injury and if this process is associated with elevated CVP.

Section snippets

Methods and materials

The study was approved by the Wayne State University Institutional Review Board. Subjects were recruited from patients followed in the Cardiology Clinic at Children's Hospital of Michigan that were at least 2 years after the Fontan procedure. Each patient underwent a clinical and echocardiographic evaluation. Only those with a normal ventricular function by echocardiography, a history of normal renal ultrasound and no comorbifdities known to affect kidneys (such as diabetes, or sickle cell

Results

Twenty-one subjects were evaluated, including 13 males and 8 females. The age was 15.2 +/− 8.8 years. Primary diagnoses included hypoplastic left ventricle in 9, double inlet left ventricle in 3, tricuspid valve atresia in 5, pulmonary atresia with intact ventricular septum in 2, and unbalanced atrio-ventricular canal in 2 patients. Two subjects were after a classic Fontan procedure, 17 after an intracardiac tunnel, and two after an extracardiac Fontan modification. Current medications included

Discussion

The significant finding of the study is the presence of microalbuminuria in a large proportion of post-Fontan patients, even when ventricular function is normal. Microalbuminuria is an earliest indicator of glomerulopathy and is routinely used for monitoring the onset and progression of renal disease [11]. In diabetic patients the presence of microalbuminuria corresponds to two to fourfold increase in cardiovascular mortality and morbidity [12]. As survival of patients after Fontan palliation

Conclusions

The study demonstrates that a significant proportion of patients with Fontan circulation have pathologic microalbuminuria, an indicator of renal injury. The injury is likely related to the elevated CVP in these patients. The use of ACE-I may be beneficial in preserving their renal function.

Acknowledgments

The authors are grateful to Dr. Thomas L'Ecuyer, Mrs. BaBette Chirunga, Mr. Paul Webster, and Ms. Masha Zilberman for their help in collecting the data and preparing the manuscript.

References (18)

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    Elevation in CVP, caused by a lack of a subpulmonic ventricular pump, reduced venous capacitance, and occasionally, anatomic obstruction in the Fontan pathway, is associated with reduced GFR, independent of the cardiac index (7,21,22). By raising the glomerular filtration pressure, elevated CVP can lead to albuminuria (23,24). In line with this, both post-Fontan pulmonary vascular resistance and superior vena cava pressures correlate with urine albumin-to-creatinine ratio (uACR) (23).

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    Arrhythmia and liver fibrosis have been broadly investigated [1–3], but Fontan-associated nephropathy has barely been explored in the literature [4]. Approximately 10–30% of patients living with a Fontan circulation have evidence of mild to moderate renal dysfunction [1,4–6]. In adults living with congenital heart disease, those who have concomitant kidney disease have been shown to have a mortality rate 3-times higher than those with normal kidney function [7].

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