Initial steroid sensitivity in children with steroid-resistant nephrotic syndrome predicts post-transplant recurrence

Abstract

Of children with idiopathic nephrotic syndrome, 10%-20% fail to respond to steroids or develop secondary steroid resistance (termed initial steroid sensitivity) and the majority progress to transplantation. Although 30%-50% of these patients suffer disease recurrence after transplantation, with poor long-term outcome, no reliable indicator of recurrence has yet been identified. Notably, the incidence of recurrence after transplantation appears reduced in patients with steroid-resistant nephrotic syndrome (SRNS) due to monogenic disorders. We reviewed 150 transplanted patients with SRNS to identify biomarkers that consistently predict outcome of SRNS after transplantation. In all, 25 children had genetic or familial SRNS and did not experience post-transplant recurrence. We reviewed phenotypic factors, including initial steroid sensitivity, donor type, age, ethnicity, time to ESRD, and time on dialysis, in the remaining 125 children. Of these patients, 57 (45.6%) developed post-transplant recurrence; 26 of 28 (92.9%) patients with initial steroid sensitivity recurred after transplantation, whereas only 26 of 86 (30.2%) patients resistant from the outset recurred (odds ratio, 30; 95% confidence interval, 6.62 to 135.86; P<0.001). We were unable to determine recurrence in two patients (one with initial steroid sensitivity), and nine patients did not receive initial steroids. Our data show that initial steroid sensitivity is highly predictive of post-transplant disease recurrence in this pediatric patient population. Because a pathogenic circulating permeability factor in nephrotic syndrome remains to be confirmed, we propose initial steroid sensitivity as a surrogate marker for post-transplant recurrence.

Figure 1.

Forest plot of ORs for recurrence in nongenetic/nonfamilial cases. Clinical risk was calculated for each factor listed in the left column. Calculated significance is given in Results.

Figure 2.

A suggested clinical paradigm for idiopathic nephrotic syndrome. Idiopathic nephrotic syndrome is stratified (where possible) according to clinical parameters into “circulating factor disease” and “genetic disease.” This segregates into high and low risk factors for post-transplant disease recurrence.

Figure 3.

Stratifying patient risk according to initial steroid resistance/sensitivity. Groups are divided into genetic, steroid-resistant, and steroid-sensitive groups to give the recurrence risk of each group from this study.