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Kidney transplantation in adults: Issues related to lupus nephritis

Kidney transplantation in adults: Issues related to lupus nephritis
Literature review current through: May 2024.
This topic last updated: Dec 14, 2022.

INTRODUCTION — Approximately 10 to 30 percent of patients with lupus nephritis (LN) progress to end-stage kidney disease (ESKD), depending upon the severity of the disease, ancestral and socioeconomic factors, nonadherence to treatment, and the response to initial treatment [1]. Kidney transplantation has been safely performed in patients with ESKD due to LN and is associated with improved patient survival.

Issues related to LN in kidney transplant candidates and recipients, including the diagnosis and treatment of recurrent LN in the kidney allograft, are reviewed here. The diagnosis and treatment of LN in the native kidneys are discussed elsewhere:

(See "Lupus nephritis: Diagnosis and classification".)

(See "Lupus nephritis: Initial and subsequent therapy for focal or diffuse lupus nephritis".)

(See "Lupus nephritis: Therapy of lupus membranous nephropathy".)

(See "Lupus nephritis: Treatment of focal or diffuse lupus nephritis resistant to initial therapy".)

END-STAGE KIDNEY DISEASE DUE TO LUPUS NEPHRITIS

Lupus activity in patients with end-stage kidney disease — The development of end-stage kidney disease (ESKD) is, in many patients, associated with gradual complete or partial resolution of the extrarenal manifestations of systemic lupus erythematosus (SLE) [2-6]. In one literature review, for example, the percentage of patients with active clinical lupus (eg, arthritis/arthralgias, rash, and serositis) fell from 55 percent at the onset of dialysis to 6.5 percent in the 5th year and, in a small number of patients, to 0 percent in the 10th year [2]. During this time span, the incidence of serologic activity (defined as the percentage of patients with two or more abnormal studies for antinuclear antibody [ANA], anti-double-stranded DNA [anti-dsDNA], CH50, or C3) fell from 80 to 22 percent. How these changes occur is not clear but may relate to modifications of the immune system with prolonged ESKD.

In addition, most patients in whom the disease remains active have only mild to moderate symptoms. As an example, in one study, the number of patients with severe extrarenal activity (defined by a Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] >10) declined from 17 to 3 after the initiation of dialysis and to zero after transplantation [4].

However, some investigators contend that the observation that SLE becomes quiescent with the onset of ESKD is exaggerated and that up to one-quarter of patients on dialysis may continue to have extrarenal manifestations including alopecia, arthritis, myositis, pleuritis, pericarditis, fever, thrombocytopenia, leukopenia, and vasculitis [7-9]. These contradictory observations may be due in part to varying patient populations and the clinical specialty of the examining physician (ie, nephrology versus rheumatology versus dermatology).

Kidney transplantation for lupus nephritis — Lupus nephritis (LN) accounts for approximately 2 percent of the United States kidney transplantation population [1,10]. Several studies have shown that patients with SLE and ESKD have a lower rate of preemptive transplantation than those with other forms of glomerular disease such as immunoglobulin A (IgA) nephropathy [11,12]. Patients with SLE who develop ESKD are predominantly female (>80 percent) and African American (approximately 50 percent) and have a mean age of approximately 40 years when they initiate kidney replacement therapy (dialysis or kidney transplantation) [13].

PRETRANSPLANTATION CONSIDERATIONS — Transplantation should be discussed as a treatment option with all patients with systemic lupus erythematosus (SLE) and end-stage kidney disease (ESKD) unless clear contraindications exist. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient", section on 'Timing of referral'.)

Timing and type of transplantation — There are no evidence-based guidelines on how long a patient who has ESKD due to lupus nephritis (LN) should wait prior to kidney transplantation. We suggest not setting an arbitrary waiting time on dialysis before transplantation for most patients with SLE. Patients who have a potential living donor should undergo preemptive transplantation provided their extrarenal manifestations of SLE, if present, are deemed stable for surgery [1,10].

In the past, a period of quiescent clinical and serologic activity was required before transplantation in patients with SLE and ESKD. Some advised dialyzing patients for at least three to six months and up to one to two years to allow their disease activity to "burn out" [3,5,14]. However, studies have shown that increased waiting time, particularly while on dialysis, is associated with worse graft outcomes after transplantation. As an example, an analysis of 4743 patients with ESKD due to LN found that among White patients, those who were transplanted later, compared with those who received a transplant within fewer than three months of dialysis, trended toward an increased risk of graft failure (adjusted hazard ratio [HR] 1.23, 95% CI 0.93-1.63); however, no such association was seen among African-American recipients [15]. In addition, a study of over 8000 patients with ESKD due to LN showed improved graft (HR 0.69, 95% CI 0.55-0.86) and patient (HR 0.55, 95% CI 0.36-0.84) survival among those who underwent preemptive kidney transplantation compared with those who were on dialysis before transplantation [16].

The presence of serologic disease activity at the time of transplantation has not been shown to correlate with transplant outcome. A systematic literature review and analysis of the Toronto lupus cohort found that the persistence of serologic abnormalities at the time of transplantation was not associated with graft failure [17].

Immunosuppressive therapy for antirejection — Induction and maintenance immunosuppressive regimens to prevent rejection are the same among patients with ESKD from LN as among patients with other forms of kidney disease, although the use of glucocorticoid-free regimens among patients with ESKD due to LN is not standard practice. Moreover, prior therapies used for LN (eg, prior cyclophosphamide and other immunosuppressive agents) may influence the risk of transplant marrow suppression and infections such as progressive multifocal leukoencephalopathy (PML). (See "Kidney transplantation in adults: Induction immunosuppressive therapy" and "Kidney transplantation in adults: Maintenance immunosuppressive therapy".)

Presence of antiphospholipid antibodies — Antiphospholipid antibodies (aPL) are detected in up to 40 percent of patients with SLE [18]; however, the development of antiphospholipid syndrome (APS) is much less common. Nonetheless, patients with SLE who also have aPL are at increased risk for thrombotic events, including the development of thrombotic microangiopathy in the allograft [5,19-21]. All patients should be tested for the presence of aPL prior to transplantation. Patients who develop APS should be treated with anticoagulation. (See "Diagnosis of antiphospholipid syndrome", section on 'Antiphospholipid antibody testing' and "Management of antiphospholipid syndrome", section on 'Long-term anticoagulation' and "Management of antiphospholipid syndrome", section on 'Secondary thrombosis prevention'.)

The optimal therapy of patients with aPL but without a history of a thrombotic event is not well defined, and practice varies among different transplant centers. Some centers routinely start all such patients on low-dose aspirin (81 mg daily). In addition, several studies have shown that the use of oral vitamin K antagonists prevents allograft thrombosis in patients who are aPL positive [19,20]. The benefits of anticoagulation must be weighed against the risks of bleeding, and therapy should be individualized. It is unclear if the use of sirolimus provides added benefit against recurrent coagulation or graft loss in this lupus population [22]. (See "Antiphospholipid syndrome and the kidney" and "Management of antiphospholipid syndrome", section on 'Primary thrombosis prevention'.)

OUTCOMES AFTER TRANSPLANTATION

Patient and allograft survival — Kidney transplantation has been associated with improved survival among patients with end-stage kidney disease (ESKD) due to lupus nephritis (LN) [23-26]. In an analysis of 20,974 patients diagnosed with ESKD due to LN, of whom 9659 were waitlisted for kidney transplantation and 5738 received a transplant, kidney transplantation, compared with no transplantation, was associated with a 70 percent reduction in all-cause mortality (hazard ratio [HR] 0.30, 95% CI 0.27-0.33) [25,26]. This difference was largely explained by a lower risk of cardiovascular death (HR 0.26, 95% CI 0.23-0.30) and death from infection (HR 0.41, 95% CI 0.32-0.52). Similar mortality benefits were observed among African American, Asian, Hispanic, and White patients.

Studies comparing transplant outcomes between patients with ESKD due to LN and those with ESKD due to other kidney diseases have reported mixed results. Some studies have found higher mortality among patients with LN compared with those with other diseases [11,27,28]. Most [2,4,5,27,29-36], but not all [37,38], studies have found that overall 5- and 10-year graft survival rates are similar among patients with LN compared with those in patients with other glomerular diseases. As an example, in a long-term study of 77 adults with LN and 154 matched non-LN glomerulonephritis control patients, the 1-, 5-, and 10-year death-censored graft survival were similar among the groups (88, 81, and 71 percent in LN patients and 91, 83, and 74 percent in control patients, respectively).

Malignancy risk — Solid organ transplant recipients have a higher risk of malignancy compared with the general population (see "Malignancy after solid organ transplantation"), and this risk appears to be higher among patients who have received immunosuppressive medications prior to transplantation, such as those with systemic lupus erythematosus (SLE) [39,40]. Nontransplant patients with SLE have been shown to have an increased risk of overall cancers [41]. However, among kidney transplant recipients, the risk of most malignant tumors (except melanoma) appears to be similar between patients with SLE and those without SLE [42]. At present, surveillance for malignancies should be similar to that for other transplant recipients.

Cardiovascular risk — Patients with SLE have a higher risk of cardiovascular disease (including myocardial infarction, cerebrovascular disease, and peripheral vascular disease) compared with the general population. (See "Coronary artery disease in systemic lupus erythematosus", section on 'Epidemiology'.)

Patients with ESKD due to LN have an increased risk of cardiovascular events (myocardial infarction, ischemic stroke, or cardiovascular or cerebrovascular death) compared with patients with other causes of ESKD, with the exception of diabetic kidney disease [43]. Kidney transplantation has been associated with a reduction in risk of cardiovascular events in such patients. In a cohort study of 5963 patients with ESKD due to LN, of whom 3209 (54 percent) received a kidney transplant, kidney transplantation was associated with a lower risk of myocardial infarction (adjusted HR 0.13, 95% CI 0.08-0.34) and stroke (adjusted HR 0.30, 95% CI 0.16-0.54) compared with maintenance dialysis.  

RECURRENT LUPUS NEPHRITIS POSTTRANSPLANTATION — An important concern among patients with lupus nephritis (LN) who undergo kidney transplantation is the development of recurrent disease in the allograft.

Incidence and risk factors — Reported rates of clinically apparent recurrent LN in the kidney transplant range from 2 to 11 percent [1,2,36,44-48]. The rate of recurrent symptoms of systemic lupus erythematosus (SLE) is also low, at approximately 6 percent [2]. These low rates are thought to reflect diminished immunologic activity in the setting of continuous immunosuppression.

In the largest reported series, the frequency and outcome of recurrence were analyzed using data from the United Network for Organ Sharing (UNOS) files [36]. Among 6850 patients with end-stage kidney disease (ESKD) due to LN who received a transplant between 1987 and 2006, 167 (2.4 percent) had recurrent LN. Rejection was much more common, occurring in 1770 patients (26 percent). Non-Hispanic Black individuals, females, and younger recipients (33 years or younger) were at increased risk for recurrence (odds ratio [OR] 1.88, 1.70, and 1.69, respectively). Similar risk factors have been noted in other studies [48].

Higher rates of recurrence (ranging from 30 to 54 percent) have been reported in some studies [49,50]. This is due at least in part to the increased use of allograft biopsies and, in particular, the detection of subclinical recurrence by protocol biopsies.

Clinical presentation and pathology — Patients with recurrent LN posttransplantation generally present with an increased serum creatinine above their usual baseline, new-onset or worsening proteinuria of a variable degree, and new-onset hematuria on routine screening [1]. Serologic markers such as low complement and high anti-double-stranded DNA (anti-dsDNA) antibody titer have not been found to be reliable predictors of recurrence [1]. (See "Overview of care of the adult kidney transplant recipient", section on 'Routine follow-up and laboratory monitoring'.)

Recurrent LN can occur as early as the first week to as late as 16 years after transplantation (median 4.3 years in the large study cited above), with most episodes occurring during the first 10 years [36].

On kidney biopsy, the histologic lesion may be different and is often less severe from that observed in the native kidney, as is illustrated by the following observations:

A study of 177 patients with LN and a kidney transplant followed over a 30-year interval included 20 patients (11 percent) with recurrent nephritis [48]. In the native kidneys, the predominant lesion was either a proliferative glomerulonephritis (class III or class IV, n = 10) or membranous nephropathy (class V, n = 6). By contrast, in the transplanted kidneys, the nephritis was most often only a mesangial lesion (class II, n = 12), with just three patients having proliferative lesions. (See "Lupus nephritis: Diagnosis and classification", section on 'Histopathologic classification of LN'.)

Mild disease is particularly likely when the recurrence is detected on protocol biopsy. In a report cited above, most of the patients had subclinical disease that was pathologically classified as class I (minimal mesangial) or class II (mesangial proliferative) nephritis [49], which in the native kidney would not require kidney-targeted immunosuppression and in the allograft does not require a modification of maintenance immunosuppression. (See 'Modification of immunosuppression' below.)

The presence of milder histologic lesions is likely related to ongoing immunosuppression from the time of transplantation and is consistent with the generally good long-term kidney prognosis in patients with recurrent LN. There is no evidence that a given immunosuppressive regimen influences the risk of recurrence [51]. (See 'Prognosis' below.)

Evaluation and diagnosis — Among patients with LN as the cause of ESKD in the native kidneys, the diagnosis of recurrent LN should be suspected in any patient who develops increased proteinuria, hematuria, or an increased serum creatinine after transplantation.

Patients suspected of having recurrent LN should be evaluated using a similar approach to that used to evaluate kidney allograft dysfunction in other transplant recipients. In such patients, it is important to exclude other potential causes of an increased serum creatinine, proteinuria, or hematuria, such as hypovolemia, calcineurin inhibitor toxicity, renal artery stenosis, pyelonephritis, or acute rejection. Patients who do not have an identifiable potential cause for allograft dysfunction frequently require a kidney allograft biopsy to establish a diagnosis. A kidney allograft biopsy with analysis of tissue by light, immunofluorescence, and electron microscopy is generally needed to make the diagnosis of recurrent LN. (See "Kidney transplantation in adults: Evaluation and diagnosis of acute kidney allograft dysfunction", section on 'Patients presenting with an elevated serum creatinine' and "Kidney transplantation in adults: Evaluation and diagnosis of acute kidney allograft dysfunction", section on 'Patients presenting with proteinuria'.)

We do not routinely measure serologic parameters, such as complement levels or titers of anti-dsDNA antibodies, as these are generally not useful in establishing the diagnosis of recurrent LN. Serologic parameters and infrequent extrarenal symptoms of SLE may not accurately assess disease activity and do not help in predicting disease recurrence in the allograft [44,45]. However, some clinicians may choose to monitor these parameters (C3, C4, anti-dsDNA) in transplant recipients as they monitor for relapse in nontransplant patients with LN. (See "Lupus nephritis: Treatment of relapsing focal or diffuse lupus nephritis", section on 'Monitoring for relapse'.)

Treatment — The treatment of recurrent LN depends upon the clinical presentation and findings on the kidney biopsy.

Renin-angiotensin system inhibition — For all patients with recurrent LN who have proteinuria >500 mg/day, even in the absence of hypertension, we suggest treating with renin-angiotensin system (RAS) inhibition (either an angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor blocker [ARB]) to reduce proteinuria and slow the progression of kidney disease.

The rationale for treating with RAS inhibition is based upon indirect evidence from studies in nontransplant patients with proteinuric chronic kidney disease (CKD) that have shown that RAS inhibition decreases the progression of kidney disease. Most studies are of ACE inhibitors, but it seems likely that ARBs have a similar renoprotective effect as ACE inhibitors in nondiabetic CKD. These data are discussed elsewhere. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults", section on 'Effect of renin-angiotensin system inhibitors on progression of CKD'.)

It is less clear if RAS inhibition has a protective effect among proteinuric transplant recipients. These data are discussed in more detail elsewhere. (See "Kidney transplantation in adults: Chronic allograft nephropathy", section on 'Other supportive measures' and "Hypertension after kidney transplantation", section on 'Additional agents for uncontrolled hypertension'.)

ACE inhibitors and ARBs may cause hyperkalemia and decreased perfusion among transplant recipients. They may also induce or worsen anemia in transplant recipients (see "Hypertension after kidney transplantation", section on 'Additional agents for uncontrolled hypertension'). However, given that transplant recipients are generally closely followed and such side effects would be readily detected, we believe the potential benefit of RAS inhibitors in delaying the onset of ESKD among proteinuric patients outweighs the potential risk of a reversible decline in estimated glomerular filtration rate (eGFR), hyperkalemia, or anemia.

Modification of immunosuppression — Most patients with recurrent lupus nephritis, particularly those who have mild lesions on allograft biopsy, do not require any change in the immunosuppressive regimen that was used to prevent rejection.

Selected patients, particularly those with more severe disease, may require modification of their antirejection immunosuppression regimen to treat recurrent LN. Our approach to immunosuppression is as follows:

Patients with recurrent LN who have mild lesions (class I or II LN) on allograft biopsy do not require a change in the maintenance immunosuppressive regimen used to prevent rejection. Such patients can generally be managed with a RAS inhibitor to reduce proteinuria and control blood pressure. (See 'Renin-angiotensin system inhibition' above.)

For patients with recurrent LN who have focal or diffuse (class III or IV LN, respectively) lesions on allograft biopsy, we suggest escalating the maintenance immunosuppression regimen to treat LN.

Induction therapy options for LN in the native kidney primarily include mycophenolate mofetil (MMF) and cyclophosphamide. There are no high-quality studies that have examined the efficacy of these agents in transplant recipients with recurrent LN. Most transplant recipients receive MMF or enteric-coated mycophenolate sodium (EC-MPS) and a calcineurin inhibitor (tacrolimus or cyclosporine) as part of their antirejection immunosuppression regimen. Thus, our approach to modifying immunosuppressive therapy is entirely based upon studies of patients with LN involving the native kidney. These studies are discussed elsewhere. (See "Lupus nephritis: Initial and subsequent therapy for focal or diffuse lupus nephritis", section on 'Initial therapy with mycophenolate or cyclophosphamide'.)

Options for immunosuppression modification include the following:

Increase the dose of MMF to 2000 to 3000 mg/day (or 1440 to 2160 mg/day of EC-MPS). If the patient is on azathioprine (rather than MMF/EC-MPS), we discontinue azathioprine and switch to MMF or EC-MPS. This induction dosing of mycophenolate should be continued for six months before being reduced to conventional maintenance dosing.

or

Administer cyclophosphamide and discontinue the current antimetabolite (usually MMF/EC-MPS or azathioprine). The optimal cyclophosphamide dose for the transplant recipient is not known, and no studies have examined this issue. Based upon studies of LN in the native kidney and our clinical experience, we use the same regimen as we use in the native kidney. After approximately three to six months, cyclophosphamide is replaced by the mycophenolate dose used for transplant rejection prophylaxis, which also serves as ongoing therapy for recurrent LN. (See "Lupus nephritis: Initial and subsequent therapy for focal or diffuse lupus nephritis", section on 'Cyclophosphamide-based regimen'.)

Patients who are treated with an increase in the MMF/EC-MPS dose or the addition of cyclophosphamide should also be treated with an increase in glucocorticoids. We generally give a pulse of intravenous (IV) methylprednisolone, usually 250 to 500 mg for one to several days followed by a tapering oral glucocorticoid regimen that, over three to four months, returns to a previous maintenance glucocorticoid dose (eg, prednisone 5 mg daily).

Response to therapy is monitored similarly to that for LN in the native kidney and includes serial evaluation of serum creatinine, proteinuria, and hematuria (see "Lupus nephritis: Initial and subsequent therapy for focal or diffuse lupus nephritis"). In addition, many centers will perform repeat allograft biopsies after six months to assess histologic responses and confirm that activity of the recurrence has significantly declined after induction therapy.

If treatment with mycophenolate or cyclophosphamide is ineffective, some clinicians give rituximab in addition to mycophenolate dosed at 2 to 3 g/day, with or without an increase in glucocorticoids. There are no published studies that support the use of rituximab for recurrent LN among transplant recipients. Our approach is based on data supporting the use of rituximab in patients with resistant LN in the native kidney. These data are discussed elsewhere. (See "Lupus nephritis: Treatment of focal or diffuse lupus nephritis resistant to initial therapy", section on 'Patients resistant to both cyclophosphamide- and MMF-based regimens'.)

If used, the optimal dose of rituximab for recurrent LN is not known. Both authors (AB and GA) suggest that one should use the same dose as has been studied for LN of the native kidney (which is 1000 mg given on days 1 and 15, the US Food and Drug Administration [FDA]-approved dosing scheme for use in rheumatoid arthritis patients) [52]. Alternatively, some centers use the FDA recommended dose for antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (375 mg/m2 per week for four weeks) [53]. One Section Editor (DB) suggests giving one dose of rituximab 200 mg, based upon the dose used in studies of patients undergoing ABO-incompatible transplantation [54-58]. (See "Kidney transplantation in adults: ABO-incompatible transplantation", section on 'Pretransplant ABO desensitization'.)

For recurrent LN in the allograft there are insufficient data to support the addition of either belimumab or voclosporin, both of which have been approved by the FDA for the treatment of LN [59,60]. (See "Lupus nephritis: Initial and subsequent therapy for focal or diffuse lupus nephritis", section on 'Combination regimens'.)

Prognosis — The incidence of graft loss due to recurrent LN is low, being less than 2 to 4 percent over 5 to 10 years in most studies [50,61]. This finding is consistent with the general decrease in lupus activity in patients who develop ESKD and in the less severe histologic findings than in the original disease. Most patients have minimal mesangial (class I), mesangial proliferative (class II), or focal LN (class III), not diffuse LN (class IV), which is the most severe form of LN and is associated with a worse prognosis [48-50]. In addition, the majority of patients who develop impaired kidney function have one or more other histologic findings that could have contributed to progressive disease, including acute rejection, chronic allograft nephropathy, and calcineurin inhibitor nephrotoxicity [49,50].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Glomerular disease in adults" and "Society guideline links: Systemic lupus erythematosus".)

SUMMARY AND RECOMMENDATIONS

General principles – Approximately 10 to 30 percent of patients with lupus nephritis (LN) progress to end-stage kidney disease (ESKD), depending upon the severity of the disease, ancestral and socioeconomic factors, nonadherence, and the response to initial treatment. The development of ESKD is, in many patients, associated with gradual complete or partial resolution of the extrarenal manifestations of systemic lupus erythematosus (SLE). Kidney transplantation has been safely performed in patients with ESKD due to LN and is associated with improved patient survival. (See 'Introduction' above and 'End-stage kidney disease due to lupus nephritis' above.)

Pretransplantation considerations – Transplantation should be discussed as a treatment option with all patients with SLE and ESKD unless clear contraindications exist. Considerations before transplantation include the following:

We suggest against setting an arbitrary waiting time on dialysis before transplantation for most patients with SLE (Grade 2C). Patients who have a potential living donor should undergo preemptive transplantation provided their extrarenal manifestations of SLE, if present, are deemed stable for surgery. (See 'Timing and type of transplantation' above.)

Induction and maintenance immunosuppressive regimens to prevent rejection are the same among patients with ESKD from LN as among patients with other forms of kidney disease, although the use of glucocorticoid-free regimens among patients with ESKD due to LN is not standard practice. (See 'Immunosuppressive therapy for antirejection' above.)

All patients with SLE should be tested for the presence of antiphospholipid antibodies (aPL) prior to transplantation. Patients with SLE who also have aPL are at increased risk for thrombotic events, including the development of thrombotic microangiopathy in the allograft. (See 'Presence of antiphospholipid antibodies' above.)

Posttransplantation outcomes – Kidney transplantation has been associated with improved patient survival among patients with ESKD due to LN. Overall 5- and 10-year graft survival rates are similar among patients with LN compared with those in patients with other glomerular diseases. Among kidney transplant recipients, the risk of most malignant tumors (except melanoma) appears to be similar between patients with SLE and those without SLE. (See 'Outcomes after transplantation' above.)

Recurrent lupus nephritis posttransplantation – An important concern among patients with LN who undergo kidney transplantation is the development of recurrent disease in the allograft:

Clinical presentation and pathology – Patients with recurrent LN posttransplantation generally present with an increased serum creatinine above their usual baseline, new-onset or worsening proteinuria of a variable degree, and new-onset hematuria on routine screening. Recurrent LN can occur at any time after transplantation, with most episodes occurring during the first 10 years. On kidney biopsy, the histologic lesion may be different and is often less severe from that observed in the native kidney. (See 'Clinical presentation and pathology' above.)

Evaluation and diagnosis – Among patients with LN as the cause of ESKD in the native kidneys, the diagnosis of recurrent LN should be suspected in any patient who develops increased proteinuria, hematuria, or an increased serum creatinine after transplantation. Patients suspected of having recurrent LN should be evaluated using a similar approach to that used to evaluate kidney allograft dysfunction in other transplant recipients. A kidney allograft biopsy with analysis of tissue by light, immunofluorescence, and electron microscopy is required to make the diagnosis of recurrent LN. (See 'Evaluation and diagnosis' above.)

Treatment – The treatment of recurrent LN depends upon the clinical presentation and findings on the kidney biopsy. Most patients with recurrent LN, particularly those who have mild lesions on allograft biopsy, do not require any change in the immunosuppressive regimen that was used to prevent rejection. Our overall approach is as follows:

-For all patients with recurrent LN who have proteinuria >500 mg/day, even in the absence of hypertension, we suggest treating with renin-angiotensin system (RAS) inhibition (either an angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor blocker [ARB]) to reduce proteinuria and slow the progression of kidney disease (Grade 2C). (See 'Renin-angiotensin system inhibition' above.)

-Patients with recurrent LN who have mild lesions (class I or II LN) on allograft biopsy do not require a change in the maintenance immunosuppressive regimen used to prevent rejection. Such patients can generally be managed with a RAS inhibitor to reduce proteinuria and control blood pressure. (See 'Modification of immunosuppression' above.)

-For patients with recurrent LN who have focal or diffuse (class III or IV LN, respectively) lesions on allograft biopsy, we suggest escalating the maintenance immunosuppression regimen to treat LN (Grade 2C). Options for immunosuppression modification include increasing the dose of mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) to doses used for induction therapy of LN or switching from the antimetabolite (MMF/EC-MPS or azathioprine) to cyclophosphamide. Such modifications should also be accompanied by an increase in glucocorticoids. (See 'Modification of immunosuppression' above.)

Prognosis – The incidence of graft loss due to recurrent LN is low, being less than 2 to 4 percent over 5 to 10 years in most studies. (See 'Prognosis' above.)

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Topic 3066 Version 32.0

References

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