Recurrence of LN in the Renal Allograft

The reported rate of clinically apparent recurrent lupus nephritis (RLN) in the renal transplant is 2% to 11%.9

RLN in the allograft should be suspected in any patient who progresses to ESRD due to renal lupus, in light of certain clinical or laboratory findings.9 New onset proteinuria or glomerular hematuria should directly lead to the suspicion of lupus nephritis in the allograft. The clinical presentation of increased serum creatinine is also typical of patients with RLN in the graft. Diagnosis of RLN is made by biopsy and histopathologic evaluation by light microscopy, immunofluorescence and electron microscopy.10

It is essential to distinguish clinically apparent RLN in the allograft from incident histopathological findings attributable to a lupus effect in the graft without any concurrent clinical, renal or extra-renal, symptoms or signs of lupus, and thus with questionable clinical importance.

Treatment of Recurrent LN in Renal Allograft

In patients with biopsy confirmed histologic diagnosis of LN and have rapid deterioration of kidney function not explained by chronic nephropathy, certain regimens including mycophenolate mofetil and cyclophosamide may be used.9


Modifications to Immunosuppressive Therapy in Recurrent LN

Kidney transplant recipients with recurrent lupus usually do not require any change in the immunosuppressive regimen, as they already receive maintenance therapy for the transplant.11 However, newer steroid-free regimens used in other graft recipients have not been studied as extensively as in LN patients and usually are not used.11

There are select patients who require additional immunosuppressive treatment. In terms of renal involvement, these primarily include patients with clinically evident disease and severe histopathologic lesions in the graft.12

Use of Non-Immunosuppressive Therapy

Patients with histopathologic changes of RLN in the graft and high urinary protein excretion could potentially benefit from angiotensin-coverting enzyme inhibition, an approach that is based on prior studies describing the blockade of the renin angiotensin system decreased the progression of renal disease.13

Causes of Morbidity and Mortality after Renal Transplant

Infections have been reported as a cause of morbidity and mortality after renal transplant secondary to LN.14 It is thought that the prolonged exposure to immunosuppressive agents to treat LN initiated prior to ESRD can predispose patients to further infections.

Serum lipid abnormalities, hypertension and accelerated atherosclerosis have been reported in recipients of renal transplants. In addition, lupus is associated with accelerated atherosclerosis independent of renal transplantation.15 Aggressive and early control of cardiovascular risk factors is particularly important in this group of patients.

Renal Allograft Prognosis in LN

The reported incidence of renal allograft loss secondary to recurrent LN is relatively low, between 2-4% over periods of 5-10 years.16

The incidence of graft loss due to recurrent disease is low, being less than 2% to 4% over 5 to 10 years in most studies.16

Recipients receiving living-related kidneys that are haplotype matched appear to have the least risk of experiencing allograft loss.16

References

1.       Ponticelli C, Moroni G. Renal transplantation in lupus nephritis. Lupus. 2005;14(1):95-8.

2.       Fiebiger W, Mitterbauer C, Oberbauer R. Health-related quality of life outcomes after kidney transplantation. Health Qual Life Outcomes. 2004;2:2.

3.       Lech M, Anders HJ. The pathogenesis of lupus nephritis. J Am Soc Nephrol. 2013;24(9):1357-66.

4.       Ponticelli C, Moroni G. Renal transplantation in lupus nephritis. Lupus. 2005;14(1):95-8.

5.       Cheigh JS, Stenzel KH. End-stage renal disease in systemic lupus erythematosus. Am J Kidney Dis. 1993;21(1):2-8.

6.       Ortega LM, Schultz DR, Lenz O, Pardo V, Contreras GN. Review: Lupus nephritis: pathologic features, epidemiology and a guide to therapeutic decisions. Lupus. 2010;19(5):557-74.

7.       Plantinga LC, Patzer RE, Drenkard C, et al. Association of time to kidney transplantation with graft failure among U.S. patients with end-stage renal disease due to lupus nephritis. Arthritis Care Res (Hoboken). 2015;67(4):571-81.

8.       Canaud G, Bienaimé F, Noël LH, et al. Severe vascular lesions and poor functional outcome in kidney transplant recipients with lupus anticoagulant antibodies. Am J Transplant. 2010;10(9):2051-60.

9.       Contreras G, Mattiazzi A, Guerra G, et al. Recurrence of lupus nephritis after kidney transplantation. J Am Soc Nephrol. 2010;21(7):1200-7; doi: 10.1681/ASN.2009101093

10.   Appel GB, Cohen DJ, Pirani CL, Meltzer JI, Estes D. Long-term follow-up of patients with lupus nephritis. A study based on the classification of the World Health Organization. Am J Med. 1987;83(5):877-85.

11.   Ponticelli C, Moroni G. Renal transplantation in lupus nephritis. Lupus. 2005;14(1):95-8.

12.   Houssiau FA, Vasconcelos C, D’cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002;46(8):2121-31.

13.   Ibrahim HN, Jackson S, Connaire J, et al. Angiotensin II blockade in kidney transplant recipients. J Am Soc Nephrol. 2013;24(2):320-7.

14.   Lionaki S, Skalioti C, Boletis JN. Kidney transplantation in patients with systemic lupus erythematosus. World J Transplant. 2014;4(3):176-82; doi: 10.5500/wjt.v4.i3.176

15.   Norby GE, Leivestad T, Mjøen G, et al. Premature cardiovascular disease in patients with systemic lupus erythematosus influences survival after renal transplantation. Arthritis Rheum. 2011;63(3):733-7.

16.   Pham PT, Pham PC. Graft loss due to recurrent lupus nephritis in living-related kidney donation. Clin J Am Soc Nephrol. 2011;6(9):2296-9.