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Diagnosis: Lupus nephritis class IV-G (A), with hyaline thrombi

Immunological test in the patient show: ANAs: 1:320; anti-DNA: 1:160; anti-Ro 1763; ANCAs negative; C3: 72 (80-152); C4: 11 (>14); anticardiolipin antibodies: negative. Several months after renal biopsy, cutaneous and hematologic alterations lead to systemic lupus erithematosus diagnosis.

Lupus nephritis uaually arises within 5 years of the systemic lupus erythematosus (SLE) and it is one of the most serious manifestations of this disease; however, renal failure rarely occurs before American College of Rheumatology classification criteria are met. Histological evidence of lupus nephritis is present in most patients with SLE, even if they do not have clinical manifestations of renal disease. The symptoms are generally related to hypertension, proteinuria, and renal failure. The immunologic mechanisms in the pathogenesis include production of autoantibodies directed against nuclear elements; these autoantibodies form pathogenic immune complexes. In the kidneys, deposition of these immune deposits initiates an inflammatory response by activating the complement cascade and recruiting inflammatory cells that can subsequently be observed on biopsy specimens.

The prevalence of clinical lupus nephritis is probably around 50%. Symptoms related to active nephritis may include peripheral edema secondary to hypertension or hypoalbuminemia. Extreme peripheral edema is more common in persons with diffuse proliferative or membranous lupus nephritis because these renal lesions are commonly associated with heavy proteinuria.

Morbidity is related to the renal disease itself, as well as to treatment-related complications and comorbidities, including cardiovascular disease and thrombotic events. Progressive renal failure leads to anemia, uremia, and electrolyte and acid-based abnormalities. Hypertension may lead to an increased risk of coronary artery disease and stroke. Nephrotic syndrome may lead to edema, ascites, and hyperlipidemia, which add to the risk of coronary artery disease and the potential for thrombosis.

The histologic type of lupus nephritis that develops depends on a number of factors, including the antigen specificity and other properties of the autoantibodies, and the type of inflammatory response that is determined by other host factors. In more severe forms of lupus nephritis, proliferation of endothelial, mesangial, and epithelial cells and the production of matrix proteins lead to fibrosis. The only way to define the histology type of Lupus nephritis is by examining a kidney biopsy. Kidney biopsy is necessary in all patients with Lupus who have abnormal urine and/or reduced renal function. It provides information about prognosis and may influence treatment.

Progress in clinico-pathologic studies lead to formulate the International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2003 classification of lupus nephritis (Weening JJ, et al, J Am Soc Nephrol 15:241, 2004 [PubMed link]) Major features in this classification system include non-ambiguous diagnostic criteria based on quantitative assessment of histological abnormalities and further classification of Class IV lesions with regard to the predominance of segmental or global lesions. The ISN/RPS 2003 classification facilitates accurate communication between pathologists and clinicians. It also provides a clear framework for standardization, upon which the clinical and pathogenetic significance of individual lesions and histological subtypes require further elucidation.

A significant improvement in interobserver reproducibility was demonstrated by the new classification of lupus nephritis. The reproducibility of the assessment of disease activity and chronicity remains suboptimal (kappa = 0.33) and is not extensively used. The new classification tends to produce more diagnoses of class IV lupus nephritis, with fewer diagnoses of classes III and V. The improvement in interobserver reproducibility indicates that an important aim of the new classification has been achieved. Further work is needed to determine whether the increase in diagnosis of class IV nephritis represents an improvement in biopsy interpretation or a divergence from the previous classification, as the latter could undermine attempts to relate results from the new system to treatment strategies based on clinical trials which used the old (Furness PN and Taub N. Am J Surg Pathol. 2006;30:1030-5. [PubMed link])

Hyaline thrombi are large intracapillary immune deposits; this term is actually a misnomer because these are not true thrombi but massive intracapillary immune deposits in continuity with large subendothelial deposits. Fibrin thrombi often have a darkly eosinophilic fibrillar appearance, whereas hyaline thrombi of the immune deposits are more lightly eosinophilic, with a homogeneous, glassy, smooth texture. This feature is associated with III or IV Lupus nephritis class.

Treatment of lupus nephritis is prolonged, complex and potentially toxic. However, prognosis and outcome of the disease can usually be improved dramatically by treatment. the considerations regarding the treatment of renal disease rest on an accurate assessment of the type and severity of renal involvement. patients with mild glomerulonephritis (Type 1 and Type II WHO classification) will generally have a good prognosis, do not require therapy or will usually respond to short courses of treatment. more severe forms of lupus nephritis (Type III, IV and V) require aggressive therapy with cytotoxic (cyclophosphamide, mycophenolate mofetil, azathiaprine, tacrolimus), high (pulse) doses of steroids and in some resistant, difficult and severe cases, plasmapheresis. The question of when to stop treatment of lupus nephritis is often asked; treatment is usually long, but it can be stopped at such time as immunological tests are back to normal, proteinuria disappears and renal function is stable.

See the chapter [Nefritis lúpica y compromiso renal en otras enfermedades reumatológicas] (only in spanish).

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Bibliography

• Brent LH, Viola I. Nephritis, Lupus. In e-medicine: Consulted October 31, 2006.
• Furness PN, Taub N. Interobserver reproducibility and application of the ISN/RPS classification of lupus nephritis-a UK-wide study. Am J Surg Pathol. 2006;30:1030-5. [PubMed link]
• Contreras G, Lenz O, Pardo V, Borja E, Cely C, Iqbal K, Nahar N, de La Cuesta C, Hurtado A, Fornoni A, Beltran-Garcia L, Asif A, Young L, Diego J, Zachariah M, Smith-Norwood B. Outcomes in African Americans and Hispanics with lupus nephritis. Kidney Int. 2006 May;69:1846-51. [PubMed link]
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• Jakez-Ocampo J, Arreola-Zavala R, Richaud-Patin Y, Romero-Diaz J, Llorente L. Lupus nephritis outcome with and without renal biopsy: a 5-year comparative study. J Clin Rheumatol. 2004 Dec;10:289-94. [PubMed link]
  

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