Patients with lupus nephritis had a significantly higher risk of mortality if they spent lengthy periods of time on dialysis before undergoing renal transplantation, a retrospective review of a long-term observational registry found.
Among 40 patients seen in two London hospitals from 1975 to 2015 who had kidney transplants because of lupus nephritis, 20% died during a median follow-up of 104 months, according to Eleana Ntatsaki, MBBS, of University College London, and colleagues.
On a univariate analysis, the only factor that predicted patient survival was time on dialysis prior to transplantation, with a hazard ratio of 1.013 (95% CI 1.001 to 1.026, P=0.03) for each additional month of dialysis, the researchers reported in .
Approximately one-third of patients with systemic lupus erythematosus (SLE) develop kidney involvement, and 10% to 25% may progress to end-stage renal disease (ESRD). For those patients, transplantation is now considered the preferred treatment, whereas in the past patients with lupus were not considered favorable candidates because they were assumed to have a risk of recurrent nephritis.
have suggested that patients with other causes for nephritis have worse overall survival if they are on dialysis longer, but that possibility has not been explored for lupus nephritis.
Accordingly, Ntatsaki and colleagues reviewed the records of all patients treated at University College London Hospital and the Royal Free Hospital over a 40-year period, with the primary endpoint being patient death.
The team identified 361 patients with lupus nephritis, 121 of whom developed ESRD. Of the 40 who were transplanted, 34 were women, 15 of whom were white, 15 black, and 10 South Asian. Mean age at diagnosis of systemic lupus erythematosus was 21, mean age at ESRD was 32, and mean age at the time of transplant was 36.
Mean time spent on dialysis was 43 months. Five patients had more than one transplant, and two had pre-emptive transplantation with no time on dialysis.
Eight patients died, and 5-year survival was 95%, with the rates similar across the decades.
The cause of death was sepsis in three patients, uremic complications in two, malignancy in two, and ischemic heart disease in one patient.
On univariate Cox regression analysis, factors that were not predictive of mortality included gender, ethnicity, age at the time of SLE diagnosis, lupus nephritis diagnosis, and transplantation. In addition, there was no association with time between diagnosis of SLE and the development of nephritis or the time between nephritis and dialysis, or with the presence of hypertension or dyslipidemia.
Treatments included mycophenolate mofetil (Cellcept) and tacrolimus in nine patients, and the remaining patients had received azathioprine or cyclosporine. Those who had received the mycophenolate/tacrolimus combination had an overall mortality of 11%, whereas the others had a 23% mortality; this difference did not reach statistical significance. There also was no mortality difference according to whether the patient had received hemodialysis or peritoneal dialysis.
The researchers then used a receiver operating characteristic curve to determine the maximal time patients spent on dialysis before having an adverse effect on survival. This calculation found that more than 24 months on dialysis was associated with poor survival, with an area under the curve of 0.795 and a sensitivity and specificity for death of 0.875 and 0.500, respectively.
Given this value, the authors determined that the risk of mortality was 2.8-fold higher for patients whose dialysis was longer than 24 months. "This supports the results from the Cox regression, which showed that mortality was increased by 1.3% for every additional month on dialysis (or 15.6% for every additional year on dialysis) and that most likely if transplantation could be undertaken by 24 months on dialysis or even earlier, it could be of benefit to patients."
Further supporting the potential benefits of early transplantation was the fact that the two patients who received pre-emptive transplants were still alive 22 and 12 years later, respectively.
The findings of this study "should be validated in larger multicenter studies and help identify the optimal timing of transplantation in lupus nephritis following ESRD, whether on dialysis or pre-emptively," the authors concluded.
Limitations of the study, the team said, included the small number of patients and the low number of deaths.
Disclosures
The study was funded by LUPUS UK.
The authors reported having no conflicts of interest.
Primary Source
Clinical Rheumatology
Ntatsaki E, et al "Impact of pre-transplant time on dialysis on survival in patients with lupus nephritis" Clin Rheumatol 2018; doi:10.1007/s10067-018-4115-1.