Lupus Nephritis - Signs and Symptoms

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Signs and Symptoms

General Symptoms of Lupus include: Malar Rash, Discoid rash, photosensitivity, oral ulcers, nonerosive arthritis, pleuropericarditis, renal disease, neurologic manifestaions, and hematologic disorders.

Clinically, SLE is manifested by: Fever, weight loss (100%), Arthralgias, synovitis, arthritis (95%), Pleuritis, pericarditis (80%), Malar facial rash, photodermatosis, alopecia (75%), Anemia, leukopenia, thrombocytopenia, thromboses (50%).

About half of cases of SLE demonstrate signs of Lupus Nephritis at one time or another. Renal specific signs: Proteinuria (100%), Nephrotic Syndrome (55%), Granular casts (30%), Red Cell Casts (10%), Microhematuria (80%), Macrohematuria (2%), Reduced Renal Function (60%), RPGN (30%), ARF (2%), Hypertension (35%), Hyperkalemia (15%), Tubular Abnormalities (70%).

In histology, Class I (Minimal Mesangial) disease looks normal under light microscopy, but mesangial deposits are noted in Electron Microscopy. In this stage urinalysis is typically normal.

Class II disease (Mesangial Proliferative) is noted by mesangial hypercellularity and matrix expansion. Microscopic hematuria with or without proteinuria may be seen. Hypertension, Nephrotic Syndrome, and Acute Renal Insufficiency are rare at this stage.

Class III Disease (Focal Lupus Nephritis) is indicated by Sclerotic lesions of <50% of the glomeruli, which can be segmental or global, and active or chronic, with endocapillary or extracapillary proliferative lesions. In Electron Microscopy, subendothelial deposits are noted, and some mesangial changes may be present. Immunofluorescence reveals the so-called "Full House" stain, staining positively for IgG, IgA, IgM, C3, and C1q." Clinically, Hematuria and Proteinuria is present, with or without Nephrotic Syndrome, Hypertension, and elevated Serum Creatinine.

Class IV Lupus Nephritis (Diffuse Proliferative) is both the most severe, and the most common subtype. In it, >50% of glomeruli are involved which can be segmental or global, and active or chronic, with endocapillary or extracapillary proliferative lesions. In Electron Microscopy, subendothelial deposits are noted, and some mesangial changes may be present. Immunofluorescence reveals the so-called "Full House" stain, staining positively for IgG, IgA, IgM, C3, and C1q." Clinically, Hematuria and Proteinuria is present, frequently with Nephrotic Syndrome, Hypertension, Hypocomplementemia, elevated anti-dsDNA titers and elevate Serum Creatinine.

A wire-loop lesion may be present in Class III and IV. The wire loop lesion is a glomerular capillary loop with subendothelial immune complex deposition that is circumferential around the loop. Class V is denoted by a uniformly thickened, eosinophilic basement membrane. Class III and IV are differentiated only by the number of glomeruli involved (which is subject to inherent sample bias), but clinically the presentation and prognosis are both expected to be more severe in Class IV versus Class III.

Class V (Membranous Lupus Nephritis) is characterized by diffuse thickening of the glomerular capillary wall (segmentally or globally), with diffuse membrane thickening, and supepithelial (note the -epi-) deposits seen in Electron Microscopy. Note that the Class in Lupus Nephritis are not chronological in the traditional sense, meaning they do not imply a progression from Class I - IV. In addition, Class V can occur in combination with other stages, e.g. Class III + V, or Class IV + V, or on its own. Suspect a combination diagnosis when subepithelial and subendothelial deposits are both present on Electron Microscopy. Clinically, Class V presents with signs of Nephrotic Syndrome; microscopic hematuria and hypertension may also been seen. Plasma Creatinine is usually normal or slightly elevated, and stage V may not present with any other clinical/serologic manifestations of SLE (complement levels may be normal; anti-DNA Ab may not be detectable). Class 5 is also predisposed to thrombotic complications (renal vein thrombosis, pulmonary embolus).

A final class is usually included by most practitioners, Class VI, or Advanced Sclerosing Lupus Nephritis. It is represented by Global sclerosis >90% of glomeruli, and represents healing of prior inflammatory injury, as well as chronic Class III, IV, V. Active glomerulonephritis should not be observed. This stage is clinically observed as slowly progressive renal dysfunction, with relatively bland urine sediment and is unlikely to respond to immunosuppressive therapy.

A Tubuloreticular inclusion is also characteristic of Lupus Nephritis, and can be seen by Electron Microscopy in all stages. It is not diagnostic however, as it exists in other conditions. It is thought to be due to chronic Interferon exposure.

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