One of the main causes of end-stage renal disease (ESRD) in children is focal segmental glomerulosclerosis (FSGS), the third most common diagnosis among pediatric kidney transplant recipients in the United States. Treatment of children with FSGS post-transplant is complicated by primary disease recurrence in 15% to 64% of patients, and is linked to increased risk for allograft loss. Loss of allograft and the need to return to dialysis therapy is a leading risk factor for mortality in this patient population.
There are limited data on long-term survival of pediatric kidney transplant recipients with ESRD secondary to FSGS. In a recent retrospective cohort study in Atlanta, Georgia, Chia-shi Wang, MD, MSc, and colleagues sought to describe time trends of all-cause mortality in pediatric patients with FSGS-caused ESRD compared with patients with ESRD from other causes (other-caused ESRD) over two decades: 1990 through 1999 and 2000 through 2009. They reported results of the study in the American Journal of Kidney Diseases [2018;71(3):392-398].
The study was designed to test the hypothesis that rates of allograft loss and all-cause mortality for all patients improved during the two decades, and that rates of mortality are higher in patients with ESRD caused by FSGS due in part to higher rates of allograft loss. The researchers also sought to “gain a more complete understanding of the long-term morbidity and mortality of childhood FSGS that results in ESRD and transplantation.”
The study utilized data from the US Renal Data System database on patients who received a first kidney transplant prior to age 18 years from 1990 through 2009; to ensure a minimum follow-up of 5 years, participants were followed up through June 30, 2015.
Outcomes of interest included (1) patient death, from date of first transplantation to death, censored by end of study follow-up on June 30, 2015, and (2) allograft failure censored by death or end of study follow-up, with the premise that death is a noninformative event for allograft failure.
From 1990 through 2009, 12,303 pediatric patients underwent kidney transplantation; of those, 5527 underwent transplantation in the decade 1990 through 1999 and 6776 in the decade 2000 through 2009. In the 1990-1999 decade, 10% (n=558) of patients had FSGS-caused ESRD, and in the 2000-2009 decade, 13% (n=850) had FSGS-caused ESRD.
In both decades, patients with FSGS-caused ESRD who underwent transplantation tended to be significantly older at time of transplant compared with patients with other-caused ESRD (P<.001). Patients were more equal in male to female distribution in both decades as well (P=.005 in the 1990s and P=.009 in the 2000s).
Among patients with FSGS-caused ESRD, a significantly greater proportion were black (31.72% vs 16.10% in the 1990s and 34.35% vs 16.84% in the 2000s), compared with other-caused ESRD patients. In both decades, patients were also significantly less likely to have undergone preemptive transplantation (24.55% vs 38.00% and 10.47% vs 28.10%, respectively) and had longer duration of dialysis therapy prior to transplantation (32.80% vs 29.10% and 48.18% vs 42.12%, respectively, were dialyzed for >1 year).
Median follow-up for patients in the 1990s was 19.04 years and 9.83 for patients in the 2000s. During the two decades, death rates improved for patients with and without FSGS-caused ESRD. Among patients with FSGS-caused ESRD, death rates improved from 12.24 deaths per 1000 patient-years for those who underwent transplantation in the 1990s to 6.72 deaths per patient-years in those who underwent transplantation in the 2000s (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.39-0.78; P<.001). Death rates also improved in patients with other-caused ESRD.
The rate of allograft survival also improved during the two decades for patients with and without FSGS-caused ESRD, although the change was smaller in magnitude, particularly in patients with FSGS-caused ESRD. In patients with FSGS-caused ESRD undergoing transplantation, the allograft failure rate was 89.05 versus 75.91 events per 1000 patient-years in the 1990s and 2000s, respectively (HR, 0.85; 95% CI, 0.74-0.98; P=.02). Allograft failure rates also improved in patients with other-caused ESRD over the two decades.
In the 1990s, there was a 29.7% increase in mortality among transplant recipients with FSGS-caused ESRD compared with transplant recipients with other-caused ESRD in the same period (HR, 1.297; 95% CI, 1.072-1.554; P=.01). Among patients who underwent transplantation in the 2000s, this differential risk was no longer seen (HR, 1.133; 95% CI, 0.843-1.523; P=.4).
Following adjustment for baseline characteristics at time of transplantation, the differential risk for death between patients with FSGS-caused ESRD and all other transplant recipients was eliminated in either decade. The risk for mortality further decreased when allograft failure was entered into the model as a time-varying covariate. In the fully adjusted model, transplant recipients with FSGS-caused ESRD had a statistically significant 30% reduction in mortality compared with other patients who underwent transplantation in the same decade.
Regardless of the time period of transplantation, allograft failure was significantly higher for patients with FSGS-caused ESRD compared with patients with other-caused ESRD. In the 1990s, patients with FSGS-caused ESRD who underwent transplantation had a 37% increase in allograft loss compared with other caused-ESRD (HR, 1.37; 95% CI, 1.24-1.52; P<.001). In the 2000s, the magnitude of difference was even greater, with increased allograft loss of 64% among patients with FSGS-caused ESRD (HR, 1.64; 95% CI, 1.48-1.81; P<.001). Following adjustments for baseline characteristics, the differential risk remained.
There were several limitations to the study cited by the authors, including the inability to assess important risk factors for mortality such as duration of chronic kidney disease and treatments provided, comorbid conditions, body mass index, and income status. Second, data on race and ethnicity were less complete for patients who underwent transplantation in the 1990s. Finally, errors in coding may have led to misclassification of primary disease.
In conclusion, the researchers said, “Notwithstanding the limitations of our study, the present analysis adds crucial information for long-term patient and allograft survival and changes over time using one of the largest cohorts of pediatric patients with FSGS in the United States. Further delineating the underlying risk factors for mortality in patients with FSGS will require prospective studies with clearly defined disease cohorts, more complete descriptors of patient characteristics, and details of disease management.”
- The rates of disease recurrence and allograft failure are high among pediatric kidney transplantation patients with focal segmental glomerulosclerosis (FSGS). There are few data on long-term survival in this patient cohort.
- In a retrospective cohort study comparing outcomes over two decades, there was significant improvement in all-cause mortality for transplant recipients with FSGS-caused ESRD in the 2000s versus the 1990s.
- There were also reductions in allograft loss, although those reductions were less dramatic.