Use of Renal Biopsy In Predicting Outcome In Lupus Nephritis , Vol. 3, No. 1, SEMJ

Department of Internal Medicine
Shiraz E-Medical Journal

Renal involvement is a major cause of morbidity and mortality in SLE. Some authors suggest that renal biopsy should be performed on all patients with SLE and morphological findings be used as a guide for therapy and prognosis. Recent cumulative evidence indicates that presence of the following conditions at the time of biopsy is associated with increased risk for renal failure: young age (<23 years) increased serum creatinine level, diffuse proliferative lesions (WHO classification class IV) and a high chronicity index on renal histologic analysis. This article also reviews the lupus nephritis

Systemic lupus erythematosus (SLE) is a disease of unknown etiology in which tissues and cells are damaged by pathogenic autoantibodies and immune complexes. Ninety percent of cases are woman usually of child bearing age⁽³⁾. Renal involvement is a major cause of morbidity and mortality in SLE. Some authors suggest that renal biopsy should be performed on all patients with SLE and morphological findings be used as a guide for therapy and prognosis.⁽¹⁾Recent cumulative evidence indicates that presence of the following conditions at the time of biopsy is associated with increased risk for renal failure: young age (<23 years) increased serum creatinine level, diffuse proliferative lesions (WHO classification class IV) and a high chronicity index on renal histologic analysis⁽²⁾.

Lupus nephritis is a frequent and a potentially serious complication of systemic lupus erythematosis that may influence morbidity and mortality, both directly and indirectly. Treatment can change prognosis of this serious complication dramaticly⁽⁴⁾.

Clinical manifestations may be constitutional or they may result from inflammation in various organ systems including skin and mucous membranes, joints, kidney, brain, serous membranes, lung, heart and occasionally GI tract. Organ systems may be involved singly or in any combination. Involvement of vital organs particularly the kidneys and central nervous systems accounts for significant morbidity and mortality⁽¹²⁾.

Females greatly out number males by 13:1. However males with SLE have the same incidence of renal disease as do females. Younger adults out number older individuals with over 85% of patients younger than 55 years of age. SLE is more likely to be associated with severe nephritis in children and less likely to be associated with it in the elderly⁽⁴⁾.

Renal disease in SLE is essentially pleomorphic. There is great variation in the characteristics of renal histology, its clinical expression and clinical course and the pathogenetic mechanism of glomerular damage among different patients. The classification scheme that is currently most widely used is that derived by a committee sponsored by the world health organization (table1).

Class I Normal nephritis

Class II Mesangial nephritis

Class III Focal and segmental proliferative nephritis

Class IV Diffuse proliferative nephritis

Class V Membranous nephritis

Determination of histologic class is of prognostic value regardless of the absence or severity of clinical renal disease. WHO's classification has proven useful in prognostication as a guide to therapy. In a number of studies on lupus nephritis some investigators have found more useful information in grading renal biopsies according to the type of lesion: predominantly treatable reversible, active and irreversible and untreatable chronic lesions.
A composition of scores for these items that reflect disease activity and therefore potentially reversible lesions is called activity index. This includes measures of cellular infiltration-proliferation, fibrinoid necrosis, deposition of nuclear debris, immune, complex, deposition similarly a composition of scores for those items that reflect chronic, irreversible lesions including: sclerosis-atrophy and fibrinosis of Bowman's capsule, the glumerulus, tubules or the interstitium is called chronicity index (table 2)⁽⁵⁾.

Table 2: National institutes of Health version of a renal pathology scoring system for assessing activity and chronicity

Activity index Chronicity index

Giomerular abnormalities

1. Cellular proliferation 1. Glomerular sclerosis

2. Fibrinoid necrosis, karyorrhexis 2. Fibrous crescents

3. Cellular crescents

4. Hyaline thrombi, wire loops

5. Leukocyte infiltration

Tubulointerstitial abnormalities

1. Mononulcear-cell infiltrate

Each variable is scored 0-3+. Fibrinoid necrosis and cellular crescents are weighted by a factor of 2. Maximum score of the activity index is 24, and that of the chronicity index is 12.

Renal involvement often develops concurrently or shortly following the onset of SLE and may have a protracted course with periods of remission and exacerbations. Clinical renal involvement usually correlates well with degree of histology involvement in SLE⁽⁶⁾.
The dominant feature of renal lupus is proteinuria present in almost every patient and commonly leading to nephrotic syndrome. Microscopic hematuria is almost always present. Macroscopic hematuria is rare. Hypertension is not overall more common in those with nephritis than in those without it but as expected those with more severe nephritis are more commonly hypertensive⁽⁷⁾. Hematuria-proteinuria and an active urinary sediment can be intermittent initially. Nocturia due to impaired urinary concentrating ability may be present. Unfortunately there is no clear cut relationship between the clinical presentation and urinalysis finding and prognosis. Edema is common manifestation of lupus nephritis usually due to nephrotic syndrome as well as concomitant hypertension. Azotemia and an active urinary sediment suggests a proliferative lesion⁽⁵⁾. Renal tubular syndromes are unusual in lupus nephritis⁽⁶⁾.

In some patients with lupus nephritis there is no doubt that immunosuppression therapy reduces the risk of renal failure. The benefit of treating promptly and early in the course of nephritis may be equally as important. Early treatment of lupus nephritis with immunosuppressive agent reduces the frequency of relapse of nephritis, the frequency of renal failure and the mortality rate. Renal biopsy reduces uncertainly and acts to galvanize a timely and appropriate treatment desicion⁽⁸⁾. Although there may be some controversy for the prognostic value of the WHO classification it is clear that it omits some information that are highly valuable in determining outcome⁽⁸⁾. A number of studies have demonstrated the enhanced value of the activity and chronicity indices in predicting outcome in lupus nephritis.
Early renal biopsy carry prognostic information that may have significant therapeutic implication⁽⁹⁾. Patients with WHO class IV lupus nephritis were more likely to have lower serum complements, greater proteinuria, hematuria and worse renal function. An elevated NIH activity index correlated with microhematuria-proteinuria and impaired renal function whereas an elevated chronicity index correlated with renal function, hypertension microhematuria but not with proteinuria⁽¹⁰⁾. Although the activity index is a weaker predictor of renal failure it still has some value. For example mild to moderate elevation of the index usually represents reversible disease. Marked elevations on the other hand usually reflect more significant destruction of the glumeruli which leads to scarring and irreversibility. Very high scores on the activity index predict the development of renal insufficiency⁽⁵⁾. There is significant correlation between age greater than 31years and an increased chronicity index. Neither the activity nor the chronicity indices correlate with the duration of clinically evident renal disease before biopsy took place. Serum creatinine levels correlated with the chronicity index. Proteinuria didn't correlate significantly with chronicity index. White blood cell counts didn't correlate with either activity or chronicity index⁽²⁾. A higher level on the chronicity index was associated with a greater likelihood of renal failure⁽¹¹⁾.

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