Nonproliferative Forms of Lupus Nephritis: An Overview

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Key points

  • Class I and class II lupus nephritis do not require immunosuppressive therapy but are prone to class switching to more aggressive lesions. A low threshold for repeat biopsy should be used in these patients.

  • Class V lupus nephritis with preserved renal function and subnephrotic proteinuria usually has a good prognosis and can be treated conservatively with blockade of the renin angiotensin aldosterone system.

  • If immunosuppressive therapy is warranted for class V lupus nephritis, as with

Disease presentation

Most patients with SLE will have laboratory evidence of kidney involvement at some point in their disease. In about one-third of SLE patients, kidney involvement first manifests with proteinuria and/or microhematuria on urinalysis; this eventually progresses to reduction in kidney function. Whereas the proliferative forms of lupus nephritis can sometimes present with renal dysfunction at the time of diagnosis, the nonproliferative forms of disease will most commonly manifest in low-level

Kidney biopsy findings: distinguishing proliferative from nonproliferative lupus nephritis

The 2012 American College of Rheumatology (ACR) Guidelines for Screening, Treatment, and Management of Lupus Nephritis recommended that all patients with clinical evidence of active lupus nephritis, previously untreated, undergo renal biopsy so that glomerular disease can be accurately classified according to the International Society of Nephrology and the Renal Pathology Society (ISN/RPS) classification.4 Neither the ACR guidelines nor the guidelines put out 1 year earlier by the ISN provided

Class I and class II lupus nephritis

Class I and class II lupus nephritis, which represent purely mesangial disease, carry a better prognosis than proliferative forms of lupus nephritis (ie, class III or IV) or the membranous form of lupus nephritis (ie, class V). In general, patients with class I and II lesions require no therapy directed at the kidney. Most patients will have good long-term renal outcomes, and the potential toxicity of any immunosuppressive regimen will negatively alter the risk-benefit ratio of treatment. An

Lupus podocytopathy

In 2002, Dube and colleagues24 and Hertig and colleagues25 described small series of patients with SLE, nephrotic syndrome, and biopsy findings of MCD or FSGS. Eight of 18 patients in these reports had mesangial deposits, including 7 of 11 with MCD and 1 of 7 with FSGS, consistent with concurrent mesangial lupus nephritis (ie, class I or II lesions). The patients with MCD universally showed rapid remission of nephrotic syndrome with steroid therapy; the response to steroids was inconsistent in

Class V lupus nephritis

Class V, or membranous, lupus nephritis is defined by subepithelial immune deposits. The membranous alterations may be present alone or on a background of mesangial hypercellularity and mesangial immune deposits. In the past, reports have varied regarding renal survival rates for different populations with membranous LN. These differences were, in part, due to problems with the World Health Organization (WHO) classification of lupus nephritis, which included proliferative lesions superimposed

Mixed proliferative and nonproliferative lupus nephritis

Some patients with lupus nephritis will have evidence of endocapillary proliferative disease, fulfilling criteria for either class III or class IV lesions, as well as a membranous nephropathy pattern of glomerular basement membrane thickening due to subepithelial deposits, fulfilling criteria for class V disease. These mixed cases should be classified as III + V or IV + V, and the treatment is usually dictated by the proliferative lesion. Therefore, first-line therapy will generally be a

Summary

The approach to patients with class I, II, and V lesions of lupus nephritis requires an understanding of the unique nature of each of these lesions as well as the possibility that, over the course of disease, class switching may occur. Conservative, nonimmunomodulatory therapy is sufficient for all patients with class I and II lesions and for patients with class V lesions, preserved renal function, and nonnephrotic range proteinuria. For patients who require kidney-targeted immunosuppression,

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  • Cited by (10)

    • Lupus Podocytopathy: An Overview

      2019, Advances in Chronic Kidney Disease
      Citation Excerpt :

      In the same way as relapsing forms of steroid-sensitive MCD or primary FSGS, lupus podocytopathy can require multiple rounds of immunosuppression for relapses or as steroid-sparing agents. Steroid-sparing agents used in lupus podocytopathy include mycophenolate mofetil, calcineurin inhibitors (CNIs), cyclophosphamide, and rituximab.14 In patients with LN with severe podocyte effacement, CNIs can have better remission rates and better long-term renal outcomes than those treated with other regimens,35 suggesting that therapies that facilitate podocyte stability might be beneficial in this subgroup of patients22 and could be considered a second-line therapy agent.

    • The clinical significance of plasma CFHR 1–5 in lupus nephropathy

      2019, Immunobiology
      Citation Excerpt :

      Lupus nephritis is among the most common complications of systemic lupus erythematosus (SLE), which is characterized by immunocomplex deposition on the glomerular basement membranes (Bomback, 2018).

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    Disclosure Statement: Nothing to disclose.

    A.S. Bomback was supported by National Institutes of Health/National Institute on Minority Health and Health Disparities grant R01MD009223.

    View full text