It has been estimated that during the course of their disease 60% of patients with systemic lupus erythmatosus (SLE) will present with some level of nephritis.1 Despite the fact that in the last few decades treatment and prognosis of lupus nephritis (LN), has improved, between approximately 10% and 30% of patients develop end-stage renal disease (ESRD),1–3 which requires kidney replacement therapy.

Initially SLE was considered a contraindication for kidney transplant (KT) due to the high probability of recurrence of LN (RLN) and to high morbidity. This opinion changed in 1975 when the Advisory Committee to the Renal Transplantation Registry of the American College of Surgeons (ACS) and the National Institute of Health (NIH) concluded that KT in lupus was successful and with similar outcomes to those obtained with the more common causes of ESRD.4 From then onwards, KT began to be considered a reasonable treatment option.

It is believed that ethnic/racial differences are a determining factor in the outcome of NL. Women with Hispanic and Afro-American origins are at higher risk of progression to ESRD when compared with Caucasians.5 Low socio-economic status, the Afro-American race and people of Hispanic/Latin American origin at greater risk of kidney graft loss.6,7 The Afro-Americans have a lower kidney graft survival rate compared with Hispanics, particularly due to a higher rate of graft rejection from cadaveric donor.7 In people from Latin American countries, observational studies which have compared survival of the graft with other causes of ESRD report a similar graft survival to that of comparison groups,8–10 and in the study in Brazil which included mainly Caucasian individuals (91%) they reported better survival of the graft in the group with SLE.11

In transplant centres the frequency of KT in patients with SLE varies between .01% and 5.5% of all KT.9,12–16 Survival of the graft is a subject of great interest due to the long-term prognosis of the graft and the rate of RLN continuing to be a controversial point.4,17,18 The aim of our study was to compare survival of the kidney graft in patients transplanted by LN with other causes of ESRD.

A retrospective cohort study. Patients who met with the SLE classification from the Americano College of Rheumatology19 were included and who had undergone a KT for LN in 2 third-tier hospitals, during the period between 1st January 1991 and 31st May 2010 in the Centro Médico Nacional (CMN) Siglo XXI (CMN SXXI), and during the period from January 2003 to December 2014 in the CMN “La Raza”. Graft loss was defined by the need for dialysis or creatinine >5mg/dl in 2 tests. Patients with diabetes or who had had transplants due to another autoimmune diseases were excluded. To assess if survival difference from other causes of lo ESRD, 2 controls were selected for each patient with SLE, chosen randomly from the KT patient database, paired by age, gender and date of transplant.

In our study, overall survival of the graft using Kaplan–Meier curve assessment demonstrated that the survival rate was similar to the comparison group. However, after adjusting for possible factors of confusion, the receptors with SLE demonstrated an increase in the risk of 95% of graft loss compared with the control group, but this difference was not statistically significant, which could be due to the low statistical strength of the study and future research is required with a larger number of subjects to rule out this possibility. The importance of adjustment of possible confusing variables comes from the fact that risk may change when they are included in analysis. In the study by Chelamcharla et al.,20 better survival of the graft was found in the subjects with SLE in the Kaplan–Meier analysis but the multivariate analysis demonstrated a worse outcome. In contrast, Ward21 found in the univariate analysis that there was a risk of graft loss which was considerably higher in the SLE patients but the risk was similar in the multivariate analysis.

Most studies which compare survival between SLE patients with other causes of kidney disease report a similar survival rate between the groups,3,10,22–29 although others report a lower survival of the graft and slightly higher rates of graft rejection in subjects with SLE.13,20,30,31 This discordance may be due both to the population included and to different follow-up times, to heterogeneity in comparison group selection (historic controls, inclusion or not of diabetics, different SLE glomerulonephritis or all of the causes of ESRD without SLE), or the year of publication. Survival in 1975 at 2 years was 66%4; in the nineties 5 and 10 year survival rates were 68%–81.7%, 45.9%–80% and 18.5%, respectively,13 and in the last decade this has increased to 89.5%–100%, 67%–93% and 57%–86%,13,18,24 respectively. Survival at 15 and 20 years is now 62%–73%3,24,28 and 33%–52%,20,24 respectively.

In studies with Latin American patients graft survival is similar to the comparison groups.8,9 In Colombian subjects, reported survival is 92%–96% at one year, 82%–83% at 5 years and 71% at 15 years8,10; for Mexican subjects it is 94% at one year, 74%–79.9% at 5 years and 73% at 10 years32; and in Brazilian subjects it is 93% at one year, 80%–90.9% at 5 years and 68%–85.7% at 10 years.11,17,18 The RLN would vary between 0 and 54% in the studies3,18,33; this wide range may be due to ethnicity and whether the biopsy was performed by protocol or due to medical indication. The clinically significant recurrence in the studies was found to be between 2% and 19%,4,6,22,23,29 and by protocol between 30% and 54%.3,28 In Latin American countries, the RLN according to the country of study was: Mexico 4%–7.4%9,32; Colombia 3%8,10 and Brazil 0%–11%.11,18 Although RLN increases the risk of graft failure, only 2%–7% of graft losses are attributable to this, compared with 43% attributable to rejection.29,31,34 Similarly to our results, acute rejection is a factor significantly associated with graft loss in patients with SLE, although risk of acute rejection is no different from the comparison group risk.8,32 The frequency of acute rejection in patients with SLE varies between studies. Some report a higher rate.28,35 others report a similar frequency to the comparison group3,20,21,30 and, in contrast Yu et al.23 report a lower frequency.

Controversy still exists regarding patients with SLE about what factors are associated with renal graft loss, and the most commonly described are: being a younger recipient. Not receiving induction therapy, having immunosuppressant therapy with 2 drugs, multiple blood transfusions, a higher comorbidity index, higher body weight, donor or recipient of Afro-American race, cadaveric donor, time in dialysis, a lower number of shared haplotypes, tobacco consumption, the presence of acute rejection, lack of treatment adherence, thrombosis of the artery or renal vein and delay in graft function.1,3,13,17,22,24,30,31,34 In contrast, the use of mycophenolic acid, tacrolimus and the absence of APA appear to be related to better survival of renal graft.22 The persistence of serological changes (raised dsDNA and/or hypocomplementemia) during KT is not associated with graft loss.36

As with other aetiologies of ESKD, the main cause of graft loss is chronic nephropathy of the graft (8%–35%).8,23,37,38 In our study, a patient in treatment with cyclosporine after transplant presented with toxicity by cyclosporine, a risk factor of chronic nephropathy of the graft,39 with an improvement in the kidney function after its suspension and no development of chronic nephropathy.

Similarly to that described,9,15,18,32 no association was found between the loss of transplant and the time in dialysis. In clinical practice, the best transplant time is open to controversy. In general, most authors recommend starting dialysis of the transplant and waiting until the SLE is in complete from 6 to 12 months,9,14,23 especially between fast progression to ESKD to verify that no spontaneous recuperation of kidney function had occurred.40 In contrast, other studies have demonstrated a better result in patients with less time in dialysis22,29,41 and without previous dialysis.4,33,39

Because thrombotic events usually result in graft loss, from absence of collateral blood vessels, the presence of APA is a concern due to the risk of thrombosis. In some studies a higher risk of thrombosis has been described in SLE subjects,9,15,27,28,42,43 while in others thrombosis as a cause of graft failure is reported as no different to the control groups.3,20,44 In our study, one patient with SLE with negative APA on 3 occasions and with no obstetric morbidity presented with thrombosis of the renal vein. Diagnosis of APS cannot be ruled out totally for 2 reasons: the possibility of presenting with antibodies aimed against phospholipids or cofactors could exist which are not assessed in clinical practice (prothrombin, phosphatidylethanolamine, annexin v or the vimentin/cardiolipin complex) which could cause the seronegative APS.45 The case has been described of 2 subjects who presented with repeated renal graft loss due to thrombotic complications with negative APA, which were positive prior to the 3 transplant.22 APA may play a role in the early loss of the graft, and it is therefore recommended that their repeated, systematic detection be made during the pre-transplant period.4,18,22

The patient profile with SLE who has undergone KT differs from that of other ESRD causes, and particularly because they are younger, there is a predominance of women and there are fewer comorbidities.3 Despite the previously described controversies, KT may be the best alternative of replacement for kidney function because it offers significantly better survival than peritoneal dialysis or haemodialysis,3,4,46,47 the prognosis at 10 years is comparable with other ESRD aetiologies, it may offer better quality of life in comparison to dialysis, and it is lower in cost in the long term.6

Our results may be interpreted with reserve due to their limitations, which include: a low number of cases, the retrospective design of our analysis and that review of clinical records could not be obtained in all cases of risk factors described. However, we believe it is useful to have the description of the KT outcomes in our population, since our results are consistent with those of previous studies. Notwithstanding, there is a need for future studies where systematic recording of the before-mentioned risk factors should be included to produce a prospective type analysis.

The study was conducted in accordance with the ethical guidelines of research in human beings. It was approved by the local ethical and research committees in both hospital and is registered as: R-2014-3501-4 and R-2011-3601-75.

The authors declare they have not received any financing and there are no conflicts of interests.