Developmental abnormalities, blood pressure variability and renal disease in Riley Day syndrome

Abstract

Riley Day syndrome, commonly referred to as familial dysautonomia (FD), is a genetic disease with extremely labile blood pressure owing to baroreflex deafferenation. Chronic renal disease is very frequent in these patients and was attributed to recurrent arterial hypotension and renal hypoperfusion. Aggressive treatment of hypotension, however, has not reduced its prevalence. We evaluated the frequency of kidney malformations as well as the impact of hypertension, hypotension and blood pressure variability on the severity of renal impairment. We also investigated the effect of fludrocortisone treatment on the progression of renal disease. Patients with FD appeared to have an increased incidence of hydronephrosis/reflux and patterning defects. Patients <4 years old had hypertension and normal estimated glomerular filtration rates (eGFR). Patients with more severe hypertension and greater variability in their blood pressure had worse renal function (both, P<0.01). In contrast, there was no relationship between eGFR and the lowest blood pressure recorded during upright tilt. The progression of renal disease was faster in patients receiving fludrocortisone (P<0.02). Hypertension precedes kidney disease in these patients. Moreover, increased blood pressure variability as well as mineralocorticoid treatment accelerate the progression of renal disease. No association was found between hypotension and renal disease in patients with FD.

Figures

Figure 1. Supine hypertension, orthostatic hypotension and renal function

The significant relationship between the severity of hypertension when supine and the degree of renal disease in 55 patients with FD is shown in graph a (y = −0.5181x + 147.68, R2 = 0.1568, p<0.001). The lack of association between the lowest upright blood pressure and renal disease is shown in graph b (p=0.75).

Figure 2. Blood pressure variability and renal disease

Linear regression graph shows an inverse relationship between the coefficient of systolic blood pressure variability assessed over 24 hours and renal function (y = −4.1695x + 156.65, R2 = 0.3664, n = 35). Bar chart b shows that patients with renal insufficiency (serum Cr 1.0±0.1 mg/dL, eGFR 55±4 ml/min, n=10) had higher coefficients of systolic blood pressure variability than age, sex, height and weight matched patients with preserved renal function (Serum Cr 0.6±0.1 mg/dL, eGFR: 122±6 ml/min, mean ± SEM, n=12).

Figure 3. 5-year rate of progression of renal disease in patients treated with fludrocortisone and those not

Black squares show average yearly estimated glomerular filtration rates (eGFR) and mean blood pressures (MBP) in 14 patients who began treatment with 0.2 mg of fludrocortisone per day at age 16 and continued on the same dose until age 21. Grey squares show average GFR and MBP between the ages of 16 to 21 in 13 patients with FD who did not receive fludrocortisone. ** p