26th June 2023

Connective Tissue Disease and the kidney

Vasculitis

Inflammation and necrosis of blood vessel walls occur in many primary vasculitic disorders. Small vessel vasculitis is often associated with kidney disease due to the susceptible microcirculation of the kidneys. On histology, there is a focal inflammatory glomerulonephritis, usually with necrosis. Typically, the patient is unwell with an acute phase response, weight loss and arthralgia. In some patients, pulmonary haemorrhage may occur and can lead to respiratory impairment and/or death.

An important cause of renal impairment to exclude is ANCA-positive vasculitis. Anti-neutrophil cytoplasmic antibodies (ANCA) can attack the kidney tissue and lead to a deterioration in function. Subtypes of ANCA-positive vasculitis include:

• MPA (microscopic polyangiitis) – typically associated with renal dysfunction from glomerulonephritis and occasionally with pulmonary haemorrhage or gastrointestinal involvement.
• Granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis – typically involves the upper respiratory tract, the lower respiratory tract, and the kidneys. Upper respiratory tract involvement typically manifests as granulomas affecting the nasal passages and sinuses, causing nasal stuffiness, crusting, and epistaxis. Lower respiratory tract involvement manifests as granulomatous lung disease causing infiltrates, cavitating lesions, and pulmonary haemorrhage.
• Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is another subtype of ANCA-positive small vessel vasculitis causing fever, sweating, weight loss, fatigue and hypereosinophilia. It is more common in patients with a history of allergic rhinitis and asthma. It can also be a cause of pulmonary haemorrhage.

PR3-ANCA (or cANCA) is most associated with Wegener’s granulomatosis, whereas MPO-ANCA (or pANCA) is most associated with microscopic polyangiitis. However, these are not specific, and biopsies should be obtained. Variation in the ANCA titres can be used in the assessment of disease activity.

The standard treatment of ANCA-positive vasculitis is with high dose steroids, cyclophosphamide, and mycophenolate. Glomerulonephritis secondary to vasculitis can also be seen in other conditions, such as cryoglobulinemia and SLE. Medium to large vessel vasculitis, such as polyarteritis nodosa (PAN), do not cause glomerulonephritis but can cause renal infarction if the renal blood vessels are involved.

Systemic Lupus Erythematosus

Renal disease occurs in at least 1/3rd of patients with systemic lupus erythematosus (SLE), and of these, a quarter reach end stage renal failure within ten years. SLE is a multi-system disorder affecting most body systems. SLE can also cause a clinical picture of glomerulonephritis.

The most common presentation is of a sub-acute nephritic disease with haematuria, hypertension, and renal impairment. Almost any histological pattern of glomerular disease can be seen in SLE on renal biopsy, including stains positive for IgG, IgM, IgA and complement proteins. The clinical presentation ranges from an indolent and slowing progressive nephrotic syndrome to a florid rapidly progressive glomerulonephritis requiring renal replacement therapy. Immunofluorescence staining shows substantial deposits within the glomerulus.

The classification of lupus nephritis (LN) is as follows:

Class I – minimal mesangial deposition (asymptomatic)
Class II – mesangial proliferative LN (mild renal disease)
Class III – focal LN, involving <50% glomeruli (haematuria and proteinuria)
Class IV – diffuse LN, involving >50% glomeruli (most common and severe form of LN)
Class V – membranous LN (good prognosis)
Class VI – advanced sclerosing LN >90% sclerosed glomeruli (progressive CKD)

Treatment is with high dose steroids and intravenous cyclophosphamide. Prognosis is best for patients with type I, II and V.