Robust survival benefit seen in lupus nephritis patients receiving renal transplant

1. For patients with Lupus nephritis end stage renal disease (LN ESRD), renal transplant reduced the risk of death by about 70%.

2. The risk reduction was driven primarily by decreased risk of death from cardiovascular disease and infection.

Evidence Rating Level: 2 (Good)

Study Rundown: Lupus nephritis (LN) is a common consequence of systemic lupus erythematous (SLE), and frequently progresses to end stage renal disease (LN-ESRD).  However, previous studies have raised the concern that kidney transplant and immunosuppression may increase the risk of serious infection and allograft failure in this population.  This cohort study included almost all US patients with LN-ESRD who were waitlisted for a transplant between 1995 and 2014.  When comparing patients who received a transplant to those that did not, the authors found a substantial reduction in all-cause mortality in transplant patient.  Upon closer analysis, this was largely attributable to reductions in deaths due to cardiovascular disease, which included stroke and coronary artery disease, and infection, particularly sepsis.  The reduction was complemented in a subset analysis of Medicare patients, which allowed for closer matching for time-varying comorbid conditions.  Importantly, the same decrease in mortality was seen in African American, Asian, Hispanic, and white patients. This study also addressed complex confounders present in previous studies such as geographic variability.

Strengths of this study include its generalizability and robustness of the analysis. One of the major limitations of the study was that SLE activity prior to transplantation was not accounted for. The study presents important data regarding the survival benefits of renal transplantation for patients with LN and should help inform policy regarding improvements in access to renal transplants.

Click to read the study in Annals of Internal Medicine

Click to read an accompanying editorial in Annals of Internal Medicine

Relevant Reading: Outcome of renal transplantation in ninety‐seven cyclosporine‐era patients with systemic lupus erythematosus and matched controls

In-Depth [retrospective cohort]: This study evaluated the risk of death for general and specific causes in two cohorts of patients with LN-ESRD who were waitlisted for transplant.  The larger cohort included nearly all American patients with LN-ESRD who were listed during a two-decade period, for a total of 9659 patients.  Of the 59% who received a transplant, the overall risk of death was reduced 70% (adjusted hazard ratio = 0.30).  This was largely attributed to a 74% reduction in risk of death due to cardiovascular disease (HR = 0.26) and a substantially decreased risk of death due to infection (HR = 0.41).  In the subset Medicare cohort, sequential stratification matching was used to compare 2963 patients who received a transplant to 2963 patients who did not.  While the primary analysis controlled only for confounders present at time of waitlisting, the secondary sample also included variable factors like time since initiation of dialysis and time since entry onto the waitlist.  The Medicare patient subset corroborated the earlier results and demonstrated that both deceased-donor and living-donor transplants provide a substantial survival benefit (HR = 0.32 and 0.24, respectively).  The authors also performed a sensitivity analysis that showed that an unrecognized confounder would have to have a hazard ratio of at least 6.1 to explain these data, which strongly supports the observed mortality benefit of renal transplant.

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