Lupus nephritis is diagnosed in about 50% of patients with SLE Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more and typically develops within 1 year of diagnosis. However, the total incidence is probably > 90%, because renal biopsy Renal biopsy Biopsy of the urinary tract requires a trained specialist (nephrologist, urologist, or interventional radiologist). Indications for diagnostic biopsy include unexplained nephritic or nephrotic... read more in patients with suspected SLE without clinical evidence of renal disease shows changes of glomerulonephritis (GN).
Pathophysiology involves immune complex deposition with development of glomerulonephritis. The immune complexes consist of
Nuclear antigens (especially DNA)
High-affinity complement-fixing IgG antinuclear antibodies
Antibodies to DNA
Subendothelial, intramembranous, subepithelial, or mesangial deposits are characteristic. Wherever immune complexes are deposited, immunofluorescence staining is positive for complement and for IgG, IgA, and IgM in varying proportions. Epithelial cells may proliferate, forming crescents.
Antiphospholipid syndrome nephropathy
This syndrome may occur with or without lupus nephritis in up to one third of patients with SLE. The syndrome occurs in the absence of any other autoimmune process in 30 to 50% of affected patients. In antiphospholipid antibody syndrome Antiphospholipid Antibody Syndrome (APS) Antiphospholipid antibody syndrome is an autoimmune disorder in which patients have autoantibodies to phospholipid-bound proteins. Venous or arterial thrombi may occur. The pathophysiology is... read more , circulating lupus anticoagulant causes microthrombi, endothelial damage, and cortical ischemic atrophy. Antiphospholipid syndrome nephropathy increases a patient’s risk of hypertension and renal insufficiency or failure compared with lupus nephritis alone.
Symptoms and Signs
The most prominent symptoms and signs are those of SLE; patients who present with renal disease may have edema, foaming urine, hypertension, or a combination.
Urinalysis and serum creatinine (all patients with SLE)
Diagnosis is suspected in all patients with SLE, particularly in patients who have proteinuria, microscopic hematuria, red blood cell (RBC) casts, or hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more . Diagnosis is also suspected in patients with unexplained hypertension, elevated serum creatinine levels, or abnormalities on urinalysis who have clinical features suggesting SLE.
Urinalysis is done and serum creatinine is measured.
If either is abnormal, renal biopsy is usually done to confirm the diagnosis and classify the disorder histologically. Histologic classification helps determine prognosis and direct treatment.
Some of the histologic subtypes are similar to other glomerulopathies; eg, membranous lupus nephritis is histologically similar to idiopathic membranous nephropathy Membranous Nephropathy Membranous nephropathy is deposition of immune complexes on the glomerular basement membrane (GBM) with GBM thickening. Cause is usually unknown, although secondary causes include drugs, infections... read more and diffuse proliferative lupus nephritis is histologically similar to type I membranoproliferative glomerulonephritis Membranoproliferative glomerulonephritis type I Membranoproliferative glomerulonephritis is a heterogeneous group of disorders that share mixed nephritic and nephrotic features and microscopic findings. They mostly affect children. Cause... read more . Overlap between these categories is substantial, and patients may progress from one class to another.
Renal function and SLE activity should be monitored regularly. A rising serum creatinine level reflects deteriorating renal function, while a falling serum complement level or a rising anti-DNA antibody titer suggests increased disease activity.
Class of nephritis influences renal prognosis (see table Classification of Lupus Nephritis Classification of Lupus Nephritis ), as do other renal histologic features. Renal biopsies are scored with a chronicity index and with a semiquantitative activity score.
Black patients with lupus nephritis are also at higher risk of progression to end-stage renal disease.
Patients with lupus nephritis are at high risk of cancers, primarily B-cell lymphomas Overview of Lymphoma Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems. The major types are Hodgkin lymphoma Non-Hodgkin lymphoma See table Comparison of Hodgkin... read more . Risk of atherosclerotic complications (eg, coronary artery disease Overview of Coronary Artery Disease Coronary artery disease (CAD) involves impairment of blood flow through the coronary arteries, most commonly by atheromas. Clinical presentations include silent ischemia, angina pectoris, acute... read more , ischemic stroke Ischemic Stroke Ischemic stroke is sudden neurologic deficits that result from focal cerebral ischemia associated with permanent brain infarction (eg, positive results on diffusion-weighted MRI). Common causes... read more ) is also high, because of frequent vasculitis Overview of Vasculitis Vasculitis is inflammation of blood vessels, often with ischemia, necrosis, and organ inflammation. Vasculitis can affect any blood vessel—arteries, arterioles, veins, venules, or capillaries... read more , hypertension, dyslipidemia Dyslipidemia Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol level that contributes to the development of atherosclerosis... read more , and use of corticosteroids.
Angiotensin inhibition for hypertension or proteinuria
Cyclophosphamide and prednisone for active, potentially reversible nephritis
Kidney transplantation Kidney Transplantation Kidney transplantation is the most common type of solid organ transplantation. (See also Overview of Transplantation.) The primary indication for kidney transplantation is End-stage renal failure... read more for patients with end-stage renal disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more
Angiotensin inhibition with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) is indicated for patients with even mild hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more (eg, blood pressure [BP] > 130/80 mm Hg) or proteinuria. Also, dyslipidemia Dyslipidemia Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol level that contributes to the development of atherosclerosis... read more and risk factors for atherosclerosis Atherosclerosis Atherosclerosis is characterized by patchy intimal plaques (atheromas) that encroach on the lumen of medium-sized and large arteries. The plaques contain lipids, inflammatory cells, smooth muscle... read more should be treated aggressively.
Treatment is toxic and thus is reserved for nephritis that has the following characteristics:
Has the potential for a poor prognosis
Is potentially reversible
Activity is estimated by the activity score as well as clinical criteria (eg, urine sediment, increasing urine protein, increasing serum creatinine). Many experts believe that a mild to moderate chronicity score, because it suggests reversibility, should provoke more aggressive therapy than a more severe chronicity score. Nephritis with the potential for deterioration and for reversibility is usually class III or IV; it is unclear whether class V nephritis warrants aggressive treatment.
The activity score describes the degree of inflammation. The score is based on cellular proliferation, fibrinoid necrosis, cellular crescents, hyaline thrombi, wire loop lesions, glomerular leukocyte infiltration, and interstitial mononuclear cell infiltration. The activity score is less well correlated with disease progression, and is used, rather, to help identify active nephritis.
The chronicity index describes the degree of scarring. It is based on presence of glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis. The chronicity index predicts progression of lupus nephritis to renal failure. A mild to moderate chronicity score suggests at least partially reversible disease, whereas more severe chronicity scores may indicate irreversible disease.
Treatment for proliferative lupus nephritis usually combines cytotoxic drugs, corticosteroids, and sometimes other immunosuppressants.
One induction regimen consists of cyclophosphamide, which is usually given in IV boluses (monthly for up to 6 months) beginning with 0.75 g/m2 in a saline solution over 30 to 60 minutes and, assuming a white blood cell (WBC) count > 3000/microL, increasing to a maximum of 1 g/m2. Oral or IV fluid administration to create rapid urine flow minimizes the bladder toxicity of cyclophosphamide, as does mesna (see table IV Cyclophosphamide Protocols for Systemic Lupus Erythematosus IV Cyclophosphamide Protocols for Systemic Lupus Erythematosus ).
Another induction regimen uses mycophenolate mofetil with a target dose of 3 g/day. Prednisone is also begun at 60 to 80 mg orally once a day and tapered according to response to 20 to 25 mg every other day over 6 to 12 months. The amount of prednisone is determined by the extrarenal manifestations and number of relapses. Relapses are usually treated with increasing doses of prednisone. Both induction regimens are equally efficacious, although systemic toxicity may be less with mycophenolate mofetil than with cyclophosphamide.
Many experts are replacing the more toxic cyclophosphamide maintenance regimens (after induction with 6 or 7 monthly IV cyclophosphamide doses) with protocols using mycophenolate mofetil 500 mg to 1 g orally twice a day or, as a second choice, azathioprine 2 mg/kg orally once a day (maximum 150 to 200 mg/day). Chlorambucil, cyclosporine, and tacrolimus have also been used, but relative efficacies are not clear. Low-dose prednisone 0.05 to 0.2 mg/kg orally once a day is continued and titrated based on disease activity. Duration of maintenance therapy is at least 1 year.
Anticoagulation is of theoretical benefit for patients with antiphospholipid syndrome nephropathy, but the value of such treatment has not been established.
Kidney transplantation Kidney Transplantation Kidney transplantation is the most common type of solid organ transplantation. (See also Overview of Transplantation.) The primary indication for kidney transplantation is End-stage renal failure... read more is an option for patients with end-stage renal disease due to lupus nephritis. Recurrent disease in the graft is uncommon (< 5%), but risk may be increased in blacks, females, and younger patients.
Nephritis, although clinically evident in only 50%, occurs in probably > 90% of patients with SLE.
Do urinalysis and measure serum creatinine in all patients with lupus and do renal biopsy if an unexplained abnormality is found in either.
Initiate angiotensin inhibition for even mild hypertension and treat atherosclerotic risk factors aggressively.
Treat active, potentially reversible nephritis with corticosteroids plus cyclophosphamide and/or mycophenolate mofetil.