Kidney is one of the most commonly affected organs in patients with systemic lupus erythematosus (SLE). Patients with kidney involvement usually present with proteinuria, hematuria, hypertension and elevated serum creatinine. Despite intensive cytotoxic therapies, 10-30% of patients with kidney involvement progress to end-stage renal disease (ESRD).

By virtue of recent discoveries on transplant immunobiology, new and strong immunosuppressive agents, and improved surgical techniques, kidney transplantation has become a routine and preferred means of managing patients with ESRD. Currently, graft and patient survival rates after transplantation are excellent, greater than those comparable patients awaiting for a transplant on any form of dialysis treatment (hemodialysis or peritoneal dialysis). Patients with SLE constitute approximately 1.2% of ESRD patients who require renal replacement therapy. Kidney transplantation is a successful treatment modality in this patient population, which offers an improved quality of life, better health and longer survival compared to treatment with maintenance dialysis.

In cyclosporine (CsA)–treated SLE patients, the 1-year graft and patient survival rates have been reported as 71.5-83% and 93%-98%, respectively, whereas 5-year graft and patient survival rates have been reported as 69% and 89%-96%, respectively, similar to results for other glomerular diseases.

A recent study conducted within the United States Renal Data System (USRDS) demonstrated that graft and patient survival after first cadaveric and first living-related adult renal transplants are similar in patients with ESRD caused by lupus nephritis and patients with ESRD from other causes. Similarly, a retrospective analysis of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database showed that the results of renal transplantation in young SLE patients (under 18 years of age) are comparable to those seen in an age-, race- and gender-matched control group. The similar patient and graft survival was seen despite the SLE patients having multiorgan involvement as well as receiving immunosuppression for a long period of time before transplantation. In order to prevent acute rejection and subsequent loss of the allograft, transplant recipients must be on immunosuppressive medications as long as they have a working graft.

Consequently, kidney transplant recipients are at risk for developing infections, especially opportunistic infections, as well as hypertension, cardiovascular diseases, hyperlipidemia, bone diseases including osteoporosis and avascular necrosis, and malignancy. One important complication that is unique to patients with SLE is the thrombotic complications, especially when antiphospholipid antibodies (aPL) are present.

Although a recently published large case series demonstrated high incidence of clinical events such as thrombotic microangiopathy, cerebrovascular accident, deep venous thrombosis, and pulmonary embolism in patients with aPL, in the absence of a prospective, randomized, controlled trial, patients with aPL can be transplanted with careful monitoring and anticoagulation.

Another complication, recurrent disease, which can result in significantly lower allograft survival is also worth mentioning in patients with lupus nephritis. Many diseases can recur in the kidney allograft, the most frequent being focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis (50-80%). Although recurrent lupus nephritis (RLN) is reported to be rare in previous reports, less than 1% to 4%, recent studies suggest a higher incidence most likely due to more aggressive use of allograft biopsies and complete tissue examination. Nyberg et al reported their experience with 16 patients with SLE in whom seven (44%) had biopsy-proven RLN. Six of the seven patients with histopathological signs of SLE also had proteinuria, hematuria, and/or elevated serum creatinine and three had extrarenal manifestations such as arthralgia, fever, skin rash and and leukopenia. Only one graft was lost due to RLN 3 years after transplantation. In a recent study, Grimbert and colleagues reported only one case of RLN in 53 renal transplant recipients with SLE. No patient had clinically active SLE at the time of transplantation. They argued that transplant biopsies were performed for clinical reasons such as increased serum creatinine, hematuria, or heavy proteinuria. Thus, morphological recurrence might be underestimated because of subclinical recurrence.

Renal biopsy with immunofluorescence and electron microscopic studies in addition to light microscopy is certainly the only accurate method for the diagnosis of recurrent lupus disease in the kidney allograft. It has been previously demonstrated that the incidence of serologic activity as well as extrarenal manifestations of SLE usually falls significantly when patients start dialysis. But, serologic markers such as low complement levels and high titers of anti-DNA antibodies do not usually help to predict either disease recurrence in the allograft or outcome after transplantation. Although, complete serologic screening is recommended prior to transplantation only for prospective evaluation and follow-up after transplantation in some centers, patients with clinically active disease in addition to serologic activity is still considered very high-risk. Fortunately, the reported incidence of graft loss due to recurrent lupus nephritis is very low, reported 2-4% in most studies.

Currently, the treatment for recurrent lupus nephritis in renal transplant recipients has not been well established. Among new treatments, mycophenolate mofetil (MMF) has been shown to be effective in animal models as well as small number of human trials of SLE. Studies are needed addressing the issues of short- and long-term survival, and the incidence and treatment of recurrent lupus nephritis with the use of new immunosuppressive agents such as MMF, tacrolimus and rapamycin. In conclusion, renal transplantation is an excellent treatment modality in SLE patients with ESRD. Recognition of the current facts and complications related to renal transplantation in lupus nephritis will help to design future clinical trials and further contribute to improve short-and long-term transplant outcome.