Fontan-associated nephropathy: Predictors and outcomes

Fontan-associated nephropathy: Predictors and outcomes.

Khuong JN, Wilson TG, Grigg LE, Bullock A, Celermajer D, Disney P, Wijesekera VA, Hornung T, Zannino D, Iyengar AJ, d’Udekem Y.

Int J Cardiol. 2020 Jan 10. pii: S0167-5273(19)34728-X. doi: 10.1016/j.ijcard.2020.01.014. [Epub ahead of print]

PMID: 31955974


Take Home Points:

  • 20% of patients with Fontan circuits have mild to moderate renal dysfunction as per eGFR.
  • Atrio-pulmonary Fontan and the absence of a prior bidirectional were the only predictors of renal dysfunction
  • In this cohort, renal dysfunction did not impact the outcomes of death, cardiac transplantation or Fontan failure.

Commentary from Dr. Blanche Cupido (Cape Town, South Africa), section editor of ACHD Journal Watch: Although nephropathy is a known complication of a Fontan circuit, not much data is available in contemporary literature on this topic. This study from the Australia and New Zealand Fontan Registry aimed to ascertain the prevalence of nephropathy, identify its predictors and characterize their long term outcomes in young adults with Fontan circuits.

Patients >age 16 with Fontan circuits were included if they had a serum creatinine measurement when between the ages of 16 and 25. Those with primary renal diagnoses, those who underwent Fontan take-downs, received heart transplantation or died before age 16, were excluded. Baseline renal function was assessed by glomerular filtration rate (GFR) as per the Modification of Diet in Renal Disease (MDRD) equation. Renal dysfunction was defined as a GFR < 90ml/kg/min/1.73m2.

The primary end-point for Fontan failure was death, heart transplantation, plastic bronchitis, protein losing enteropathy, Fontan take-down and NYHA III-IV. The secondary outcome was chronic kidney disease – GFR < 90ml/kg/min/1.73m2.

A total of 328 patients were included. Fifty-two percent were male and the mean age was 26 years. The prevalence of renal dysfunction was 20% (n=67). Most had mild renal dysfunction, though 1% (3 patients) had moderate renal dysfunction with a GFR < 60ml/kg/min/1.73m2.

The following factors were associated with increased renal dysfunction on univariate analysis:

  • Atrio-pulmonary Fontan (AP Fontan) – OR 2.22 (95% CI 1.11-4.30, p=0.024)
  • Absence of prior bidirectional cavo-pulmonary shunt – OR 2.23 (95% CI 1.28-3.98, p=0.005)

This did not hold for multi-variate analysis though.

Two patients in the renal dysfunction group (2%) and 19 (7%) of the non-renal dysfunction group died during follow-up. From Figure 1 below, it is evident that fewer deaths occurred in the renal dysfunction group (2/67 deaths vs 9/261 deaths)

Ten year survival for the renal dysfunction group was 96% compared to 89% in the non-renal dysfunction group. (p=0.1) No independent risk factors for mortality were identified.

Figure 2 below shows that the 10-year freedom from death and transplant for the renal dysfunction and no renal dysfunction groups were 96% and 87% respectively (p=0.05)

Fig 2

Fontan failure occurred in 12% of patients (n=38) over a 7 year follow-up period. There was no difference in the prevalence of Fontan failure between those with and without renal dysfunction.

Ten year freedom from Fontan failure was 82.5% in the renal dysfunction group and 81% in the no renal dysfunction group (p=0.84) – see figure 3 below. Independent risk factors for Fontan failure were right atrial isomerism and developing >moderate ventricular systolic dysfunction.

Fig 3

Over an 8 year follow-up period, no significant differences in mean eGFR were found in the group who had renal dysfunction at the outset (eGFR 78 vs 80ml/kg/min/1.73m2, p=0.4). The group with normal renal function initially, did show a decline in eGFR (120 to 108ml/kg/min/1.73m2, p<0.001).