Scleroderma and kidney damage - Treatment

Treatment of scleroderma currently involves the use of three main groups of drugs: antifibrotic; anti-inflammatory and immunosuppressant; vascular agents.

• Penicillamine is the basis of basic antifibrotic therapy. The main indications for use are: diffuse scleroderma, acute rapidly progressive scleroderma, most often complicated by the development of true scleroderma kidney. The use of penicillamine in these situations can have a preventive effect on the development of scleroderma nephropathy. Penicillamine inhibits the maturation of collagen and, with prolonged use, helps to reduce indurative changes in the skin. The drug should be used for a long time - for 2-5 years. In acute scleroderma, treatment is carried out in increasing doses, gradually increasing them to 750-1000 mg / day, for a period of at least 3 months with a further decrease to a maintenance dose of 250-300 mg / day. Treatment with penicillamine in adequate doses is limited by the frequency of its side effects, the most serious of which are nephrotic syndrome, leukopenia and thrombocytopenia, myasthenia, and intestinal dyspepsia.
• Glucocorticoids and immunosuppressants are prescribed mainly for acute and subacute systemic scleroderma, when signs of immune inflammation prevail and fibrosis progresses rapidly. The dose of prednisolone for systemic scleroderma in most cases should not exceed 20-30 mg/day, since it is believed that higher doses of prednisolone can lead to the development of acute scleroderma nephropathy. Prednisolone treatment should be combined with penicillamine. Glucocorticoids are ineffective in chronic systemic scleroderma. Immunosuppressant drugs (cyclophosphamide, methotrexate, azathioprine) are used to treat systemic scleroderma with visceritis, polymyositis, circulating ANCA. Cyclosporine, which has been shown to be effective in the treatment of diffuse cutaneous systemic sclerosis, should be used with careful monitoring of renal function, as its use increases the risk of developing true scleroderma kidney.
• To influence the microcirculation system in systemic scleroderma, a number of vascular drugs with different mechanisms of action are used. Among vasodilators, calcium antagonists are the drugs of choice, effective not only against Raynaud's syndrome, but also against signs of kidney and lung damage. Nifedipine is most often used, retard forms are preferred.

It is advisable to combine vasodilators with antiplatelet agents: dipyridamole, pentoxifylline, ticlopidine, which affect the platelet component of the hemostasis system. In cases of increased intravascular blood coagulation, the use of anticoagulants (heparin) is indicated.

In generalized Raynaud's syndrome, signs of visceral vascular pathology, the use of prostaglandin E1 preparations (vasoprostan, iloprost) is indicated. Two courses of therapy with intravenous infusions of preparations should be carried out per year, 15-20 per course. Prostaglandin E1 improves not only peripheral microcirculation, reducing the manifestations of Raynaud's syndrome and eliminating ulcerative-necrotic damage, but also helps improve organ microcirculation, which makes it promising for the treatment of scleroderma nephropathy.

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Treatment of scleroderma nephropathy: features

In case of low-symptom kidney damage, observed in most patients with systemic scleroderma, special treatment may not be required in case of normal blood pressure. The development of moderate arterial hypertension serves as an indication for the beginning of antihypertensive therapy. The drugs of choice are ACE inhibitors, which suppress the increased activity of plasma renin in scleroderma nephropathy. It is possible to prescribe any drugs of this group in doses that ensure the normalization of blood pressure. In case of development of side effects (cough, cytopenia) when using ACE inhibitors, beta-blockers, slow calcium channel blockers, mainly in retard forms, alpha-blockers, diuretics in various combinations should be prescribed.

Since the development of acute scleroderma nephropathy cannot be predicted, all patients with diffuse systemic scleroderma should be closely followed with regular renal function testing. They should avoid situations that may worsen renal perfusion (hypohydration, massive diuretic therapy leading to hypovolemia, arterial hypotension due to the use of certain drugs, hypothermia) due to the risk of provoking the development of true scleroderma kidney.

In the event of malignant arterial hypertension or signs of renal failure, treatment of scleroderma should be started immediately, since the natural course of acute scleroderma nephropathy is characterized by rapid progression, leading to the development of oliguric acute renal failure or death.

The basis of treatment for acute scleroderma nephropathy is ACE inhibitors, the introduction of which into clinical practice has changed the prognosis of true scleroderma kidney: before the use of these drugs, the survival rate of patients during the first year was 18%, after the start of use - 76%.

Careful control of blood pressure is a priority in the treatment of acute scleroderma nephropathy, since it helps slow down the progression of renal failure and avoid damage to the heart, central nervous system, and eyes. However, too rapid a reduction in blood pressure should be avoided in order not to provoke further deterioration of renal perfusion with the development of ischemic acute tubular necrosis. It is advisable to combine ACE inhibitors with calcium channel blockers. Doses should be selected in such a way as to achieve a decrease in both systolic and diastolic blood pressure by 10-15 mm Hg per day, the target level of diastolic blood pressure is 90-80 mm Hg.

Recently, for the treatment of acute scleroderma nephropathy, it is recommended to use prostaglandin E1 in the form of intravenous infusions, which helps to eliminate microvascular damage, restore perfusion of the renal parenchyma, without causing arterial hypotension.

If necessary (oliguric acute renal failure, uncontrolled arterial hypertension), hemodialysis treatment is indicated. In patients with systemic scleroderma, hemodialysis is often problematic due to difficulties in forming vascular access during the scleroderma process (spasm of large vessels, skin induration, thrombosis of the arteriovenous fistula). In some cases, spontaneous restoration of renal function is possible in patients who have suffered acute scleroderma nephropathy after several months (up to 1 year) of hemodialysis treatment, which allows for a period of time to be discontinued. For long-term replacement therapy of scleroderma, peritoneal dialysis is better used, which, however, is often complicated by peritoneal fibrosis.

Kidney transplantation is possible for patients with systemic scleroderma. Contraindications include progressive scleroderma with severe damage to the skin, lungs, heart and gastrointestinal tract.