Lupus nephritis

Complicates 25-50% of patients with SLE and is associated with increased mortality.

Proliferative lupus nephritis typically manifests with microscopic hematuria, proteinuria, renal insufficiency, and hypertension, whereas membranous lupus nephropathy manifests with nephrotic syndrome.

Characterized by the deposition in glomeruli of immune complexes formed by IgG, IgM, and the IgA autoantibodies.

Lupus nephritis is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE).



Associated with increased mesangial matrix and mesangial hypercellularity. 




More than 50% of glomeruli are involved. 

Lesions can be segmental or global, and active or chronic, with endocapillary or extracapillary proliferative lesions. 

Under electron microscopy, subendothelial deposits are noted, and some mesangial changes may be present. 


A tubuloreticular inclusion within capillary endothelial cells is also characteristic of lupus nephritis and can be  visualized  under an electron microscope.

Hematuria and proteinuria may be present, frequently with nephrotic syndrome, hypertension, hypocomplementemia, elevated anti-dsDNA titres and elevated serum creatinine.



Class I mild disease is not visible on microscopy,and at this stage urinalysis is normal.



Class II disease has mesangial proliferative glomerulonephritis, that is noted by mesangial hypercellularity and matrix expansion. 



Microscopic hematuria with or without proteinuria may be seen, in Class II lupus nephritis.



Hypertension, nephrotic syndrome, and acute kidney injury are very rare at stage II disease.



Class III disease, referred to as goal glomerulonephritis, is indicated by sclerotic lesions involving less than 50% of the glomeruli.



Glomerulonephritis in stage III disease can be segmental or global, and active or chronic, with endocapillary or extracapillary proliferative lesions. 



With electron microscopy, subendothelial deposits are noted, and some mesangial changes may be present. 



Immunofluorescence reveals positively for IgG, IgA, IgM, C3, and C1q. 



Clinically, hematuria and proteinuria are present in stage III disease with or without nephrotic syndrome, hypertension, and elevated serum creatinine.



Class IV disease, the diffuse proliferative nephritis, is both the most severe, and the most common subtype. 


Class V disease, membranous glomerulonephritis, is characterized by diffuse thickening of the glomerular capillary wall with diffuse membrane thickening, and subepithelial deposits seen under the electron microscope. 

Clinically, stage V presents with signs of nephrotic syndrome. 


Microscopic hematuria and hypertension may also be seen. 

Stage V can also lead to thrombotic complications such as renal vein thromboses or pulmonary emboli.


Class VI, or advanced sclerosing lupus nephritis, is represented by global sclerosis involving more than 90% of glomeruli, and represents healing of prior inflammatory injury. 

In class VI lupus active glomerulonephritis is not usually present, and it is characterised by slowly progressive kidney dysfunction, with relatively bland urine sediment. 

Is considered in a young patient with glomerulonephritis, particularly those with a history of rash.

These autoantibodies are directed to nuclear antigens, particularly double stranded DNA.

The deposition of these immune complexes in the glomeruli can result in renal failure and death.

Management consists of induction therapy to achieve remission and long-term maintenance treatment to prevent disease relapse and progression to end-stage renal disease, and prevent mortality.

Cyclophosphamide superior to corticosteroids in preserving renal function and the combination provides additional benefits and is the standard of care.

Bolus cyclophoshamide as effective as daily doses but less toxic.

Monthly bolus treatment with cyclophosphamide for 6 months associated with a lowered rate of flares if treatment continued every 3 months for three years.

Treatment with intermittent intravenous cyclophosphamide with corticosteroids improves renal survival but not overall survival in patients treated with corticosteroids alone.

Proliferative lupus nephritis treatment involves intensive immunosuppression usually with cyclophosphamide or  mycophenolate mofetil  and high dose glucocorticoids in a 3-6 month induction period, followed by maintenance of less intensive immunosuppression.

Mycophenolate can be used in patients refractory to cyclophosphamide or who cannot tolerate that drug.

Patients given intravenous cyclophosphamide for six months and subsequently given maintenance treatment with azathioprine or mycophenolate mofetil or quarterly intravenous cyclophosphamide revealed those given azathioprine or mycophenolate mofetil had equal or superior disease control with fewer adverse reactions than the cyclophosphamide group.

Aspreva Lupus Management Study (ALMS) compared th efficacy and safety of induction therapy with mycophenolate mofetil compared with intravenous cyclophosphamide for active luspus nephritis class III,IV or V: no significance between the two drugs.

In a 36 month follow-up of maintenance treatment with mycophenolate mofetil or zathioprine after induction: mycophenolate mofetil was superior in respect to preventing relapse (Dooley MA et al).

Most patients have an initial response, but relapse are common and treatment resistant disease occurs often.
End stage renal disease develops in 40% of patients with diffuse proliferative lupus nephritis and up to 20% with those with membranous lupus nephritis.
Belimumab May have a role in augmenting induction treatment with mycophenolate in patients with active lupus  nephritis.

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