Page created on May 24, 2021. Last updated on December 18, 2024 at 16:58

Lupus nephritis

Definition and epidemiology

Lupus nephritis (LN) or lupus nephropathy refers to the renal affection in SLE and is the most dangerous organ complication and a major cause of death in SLE. It’s important to detect and diagnose lupus nephritis because it changes the treatment and prognosis for the SLE patients.

Lupus nephritis is a chronic, aggressive disease. The diagnosis of lupus nephritis means a worse prognosis for the patients. Patients may be free of extrarenal manifestations of lupus but still have progressively worsening kidney function due to LN.

Most patients with SLE will develop lupus nephritis at some point.

Classification

There are six histopathological types of lupus nephritis. It’s important to note that these aren’t stages which every patient progressively goes through, but rather any patient with lupus nephropathy has one of these types. A single patient may change from one type to another, but this is not usual. Each type has an associated prognosis.

Class	Name	Prognosis
I.	Minimal mesangial LN	Very good
II.	Mesangial proliferative LN	Good
III.	Focal proliferative LN	Variable
IV.	Diffuse proliferative LN	Very bad
V.	Membranous LN	Variable
VI.	Sclerotizing LN	Bad

Class IV is the most common pattern, and unfortunately also the most severe type.

In sclerotizing LN the glomeruli are sclerotic and fibrotic and no treatment helps.

Clinical features

Like SLE is the wildcard in rheumatology, lupus nephritis is the wildcard in nephrology, and as such may manifest as any kidney syndrome, i.e. nephritic syndrome, nephrotic syndrome, nephroso-nephritic syndrome, RPGN, chronic kidney injury, or it can be oligosymptomatic (presenting with only proteinuria or only haematuria).

Lupus nephritis is rarely the first manifestation of SLE, and so it’s usually diagnosed in those who already have the SLE diagnosis.

Diagnosis and evaluation

All newly diagnosed patients with SLE must be screened for lupus nephritis, by the use of urine analysis and eGFR. This should be repeated regularly (3 – 6 months) if negative. Almost all persons with lupus nephritis have proteinuria, and so screening for proteinuria is important.

Suspicion of lupus nephritis is an indication for renal biopsy, and so renal biopsy is performed in all suspected cases.

Typical for lupus nephritis is that the kidney biopsy is positive for all four commonly tested markers on immunofluorescence, IgG, IgA, C3, and fibrinogen. This is called “full house” immune complex deposition.

Treatment

The specific treatment depends on the subtype. For severe lupus nephritis (type III – IV), high-dose steroids and either cyclophosphamide or mycophenolate mofetil are used to induce remission, after which low-dose steroids together with an immunosuppressant is used for maintenance of remission.

Non-specific kidney protective treatment against hypertension and proteinuria may be necessary. This is usually accomplished by RAAS inhibitors.

Complications

Approximately 10 – 30% of patients with severe LN (type III, IV) progress to end-stage renal disease.

Nephropathy associated with vasculitis

Definition

Vasculitis is characterised by inflammation of vessels. We categorize vasculitides based on whether they primarily affect large, medium, or small vessels. Large vessel vasculitis can contribute to renovascular hypertension, and medium vessel vasculitis can predispose to renal infarction and haemorrhage. However, the most important vasculitides in nephrology are the small vessel vasculitides, which affect the glomeruli and arterioles.

Etiology

• Small vessel vasculitis
  • ANCA-associated vasculitis
    • Microscopic polyangiitis (MPA)
    • Granulomatosis with polyangiitis (GPA)
    • Eosinophilic granulomatosis with polyangiitis (EGPA)
  • Immunocomplexes in the vessel wall
    • Cryoglobulinaemic vasculitis
    • IgA vasculitis (Henoch-Schönlein purpura)
    • Anti-GBM disease/Goodpasture syndrome
    • SLE vasculitis
• Medium vessel vasculitis
• Large vessel vasculitis

Of these, the ANCA-associated vasculitides are the most important.

Clinical features

Vasculitides which have renal involvement also have systemic involvement, and as such they also cause extrarenal symptoms. They usually have non-specific symptoms like fever, weight loss, malaise, and joint pain. Other extrarenal symptoms include haemoptysis, purpuras, and involvement of the eyes and CNS.

GPA is especially associated with diseases of the upper respiratory tract, like sinusitis, otitis, and perforation of the nasal septum.

EGPA is especially associated with bronchial asthma.

The renal symptoms of small vessel vasculitides include decreased kidney function, proteinuria, and haematuria. They may manifest as glomerulonephritis, often as rapidly progressing glomerulonephritis.

Diagnosis and evaluation

Screening for p-ANCA and c-ANCA is essential. GPA is associated with c-ANCA, while EGPA and MPA are associated with p-ANCA, although this is completely specific or sensitive.

Renal biopsy is performed if ANCA-vasculitis is suspected. The findings (same as in RPGN) include crescents in the glomeruli and pauci-immunity on immunofluorescence.

Treatment

ANCA-vasculitides have very poor prognosis if untreated, so immunosuppressive treatment is important. The treatment is described in the RPGN topic.

Ischaemic nephropathy

Definition and epidemiology

Ischaemic nephropathy can be difficult to define, but it most frequently refers to progressive kidney function loss due to atherosclerosis of the renal artery, called renal artery stenosis.

Narrowing of the renal artery decreases the renal perfusion pressure and renal blood flow, decreasing the GFR. If the narrowing becomes significant (~70%), cortical hypoxia occurs as well, causing loss of glomeruli and progressive loss of kidney function.

Clinical features

Ischaemic nephropathy can present in multiple different ways:

• Chronic kidney disease (progressive reduction of GFR)
• Acute kidney injury in people starting RAAS inhibitors
• Renovascular hypertension

Atherosclerosis occurs everyone simultaneously, so patients with ischaemic nephropathy usually already have symptoms of atherosclerosis elsewhere, like CAD, CVD, or PAD.

Diagnosis and evaluation

Doppler ultrasound reveals narrowing of the renal artery.

Treatment

General anti-atherosclerotic and renoprotective treatment, like statin, RAAS inhibitors, antihypertensives, etc. Renal revascularization is an option.

Haemolytic uraemic syndrome and thrombotic thrombocytopaenic purpura

HUS and TTP are described in topic 23.