Renal Involvement in Connective Tissue Diseases - Part 2: Antiphospholipid Syndrome, Primary Sjögren?s Syndrome, Systemic Sclerosis

Abstract

Renal manifestations in antiphospholipid syndrome (APS), primary Sjögren?s syndrome (pSS) and systemic sclerosis (SSc) differ from each other substantially with respect to pathogenesis, histology, clinical picture, prognosis and therapeutic consequences. The frequency of APS-associated renal affections ranges from 10 to 40%. APS can affect the kidney in the form of renal hypertension, thrombosis or stenosis of the renal artery, renal infarction, thrombosis of the renal vein and intrarenal vasculopathy (APS nephropathy). Especially in the case of secondary APS, the differential diagnosis of lupus nephritis by renal biopsy is important because APS requires anticoagulation, but generally no immunosuppression. In pSS, too, renal affections are relatively common (20-40%). The characteristic and most frequent manifestation is interstitial nephritis with distal tubular acidosis type 1. Distal tubular acidosis is often asymptomatic, but can result in hypokalaemia and osteomalacia. Whereas interstitial nephritis and the less frequent glomerulonephritis generally respond well to immunosuppression, the response of distal tubular acidosis to immunosuppression is insufficient. Decrease of renal function and proteinuria as a sign of renal affection are observed in up to 36% of patients with SSc. This type of nephropathy, often multifactorial in origin, is characterised by sclerosed glomeruli, tubular atrophy and interstitial fibrosis, and has a good prognosis with respect to renal function. Scleroderma renal crisis, which is characterised by obstructive vasculopathy, accelerated arterial hypertension and progressive renal failure, is substantially less frequent (4-11%). Risk factors for renal crisis in SSc involve the presence of diffuse cutaneous SSc, older age, male gender, glucocorticoid use, pericardial effusion and the presence of anti-RNA polymerase III antibodies. Therapy of hypertensive renal crisis aims to reduce the systolic blood pressure by 10% per day to the normal range, preferably with ACE inhibitors, while avoiding prolonged periods of hypotension. In the case of insufficient reduction of blood pressure despite ACE inhibitor therapy, alpha-blockers, calcium channel blockers and/or minoxidil are used in addition. Intravenous administration of prostacycline to improve renal perfusion and the use of the endothelin receptor antagonist bosentan are also useful. The availability of ACE inhibitors has resulted in a significant reduction of mortality due to renal crisis; however, a progression to end-stage renal disease is to be expected in 40-50%.