The kidney in rheumatological disorders

Systemic lupus erythematosus (SLE)

Epidemiology and clinical features of renal disease—10 to 20% of patients with SLE have evidence of renal involvement at presentation, with this subsequently developing in about 40 to 50% of cases, typically during the first 5 years after diagnosis. Presentation is with proteinuria (causing nephrotic syndrome in c.50% of cases), microscopic haematuria, hypertension or rapidly deteriorating renal function.

Diagnosis and classification of renal lupus—the diagnosis of SLE is made on the basis of clinical features in combination with appropriate serological tests for autoantibodies (see Chapter 19.11.2), but precise renal diagnosis depends upon renal biopsy, which can reveal a wide range of appearances that are of prognostic significance. Six classes of lupus nephritis are described: (I) minimal mesangial; (II) mesangial proliferative; (III) focal; (IV) diffuse; (V) membranous; (VI) advanced sclerosing.

Class I and II lupus nephritis—typically present with proteinuria and microscopic haematuria, commonly with normal renal function and a low rate of progressive renal failure; often treated with prednisolone.

Class V lupus nephritis—presents with proteinuria, with nephrotic syndrome in 50%; intermediate prognosis; treated with prednisolone with or without other immunosuppressants (mycophenolate mofetil, ciclosporin, azathioprine).

Class III and IV lupus nephritis—present with active urinary sediment (proteinuria, haematuria, red cell casts) and high risk of progressive renal failure; remission induced by treatment with pulsed intravenous cyclophosphamide or oral mycophenolate mofetil and maintained with azathioprine or mycophenolate mofetil; toxicity of current drug regimens along with tendency of disease to relapse responsible for continuing search for better treatments; 90 to 95% 10-year patient survival, but 5 to 15% with endstage renal failure.

Systemic sclerosis

Scleroderma renal crisis develops in 8 to 19% of patients with systemic sclerosis and characterized by the abrupt onset of severe hypertension, usually with retinopathy, together with the rapid deterioration of renal function and heart failure. Renal impairment is usually accompanied by a microangiopathic haemolytic anaemia, with thrombocytopenia and fragmented red blood cells. On renal biopsy smaller arcuate and interlobular arteries are predominantly involved, showing intimal hyperplasia with concentric mucoid intimal degeneration, and there is fibrinoid necrosis of afferent arterioles and glomeruli, also glomerular thrombosis. Hypertension should be treated with an angiotensin converting enzyme inhibitor, use of which has improved survival from less than 10% to 70% at 5 years.

Rheumatoid arthritis

Rheumatoid arthritis can affect the kidneys in many ways, most commonly by causing amyloid A amyloidosis. This presents with proteinuria, often severe enough to cause nephrotic syndrome, with 50% progressing to end stage renal failure after 5 years (90% at 10 years). Renal vasculitis, mesangiocapillary glomerulonephritis, and mesangial IgA proliferative glomerulonephritis are also described.

Patients with rheumatoid arthritis are at high risk of drug nephrotoxicity, including (1) nonsteroidal anti-inflammatory drugs—can cause reversible haemodynamically mediated renal impairment, acute tubular necrosis, and acute interstitial nephritis with or without a nephrotic syndrome; and (2) gold and penicillamine (now rarely used)—can cause proteinuria, sometimes with nephrotic syndrome.