Scleroderma and kidney damage: treatment

Treatment of scleroderma at the present time consists of using three main groups of drugs: antifibrotic; anti-inflammatory and immunosuppressive drugs; vascular means.

• Penicillamine is the basis of basic antifibrotic therapy. The main indications for use: diffuse scleroderma, acute fast-progressive scleroderma, most often complicated by the development of a 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 the inducing 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 reduction to a maintenance 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, leuko- and thrombocytopenia, myasthenia gravis, intestinal dyspepsia. 
• Glucocorticoids and immunosuppressants are prescribed mainly in acute and subacute systemic scleroderma, when signs of immune inflammation predominate and fast progression of fibrosis is noted. The dose of prednisolone in systemic scleroderma in most cases should not exceed 20-30 mg / day, because it is believed that higher doses of prednisolone can lead to the development of acute scleroderma nephropathy. Treatment with prednisolone should be combined with penicillamine. In chronic course of systemic scleroderma, glucocorticoids are ineffective. Immunosuppressive drugs (cyclophosphamide, methotrexate, azathioprine) are used to treat systemic scleroderma with viscerites, polymyositis, circulating ANCA. Cyclosporine, the efficacy of which has been shown to treat the diffuse cutaneous form of systemic scleroderma, should be used with close monitoring of kidney function, as its use increases the risk of developing a true scleroderma kidney.
• To influence the microcirculation system with systemic scleroderma, a variety of vascular preparations with different mechanisms of action are used. Among the vasodilators, the drugs of choice are calcium antagonists, effective not only for Raynaud's syndrome, but also for the signs of kidney and lung damage. Nifedipine is most often used, retard forms are preferred.

Vasodilators should be combined with disaggregants: dipyridamole, pentoxifylline, ticlopidine, which affect the platelet unit of the hemostasis system. In cases of increased intravascular coagulation, the appointment of anticoagulants (heparin) is indicated.

In the generalized Raynaud's syndrome, the signs of visceral vascular pathology show the use of prostaglandin E1 preparations (vasoprostane, iloprost). In a year should be 2 courses of therapy with intravenous infusions of drugs, 15-20 per course. Prostaglandin E1 improves not only peripheral microcirculation, reducing manifestations of Raynaud's syndrome and eliminating ulcerative necrotic lesions, but also contributes to the improvement of organ microcirculation, which makes it promising for the treatment of scleroderma nephropathy.

[1], [2], [3], [4]

Treatment of scleroderma nephropathy: features

With malosimptomnom lesion of the kidney, noted in the majority of patients with systemic scleroderma, in the case of normal arterial pressure, special treatment can be avoided. The development of moderate arterial hypertension serves as an indication for the onset of antihypertensive therapy. The drugs of choice are ACE inhibitors that suppress the plasma renin activity increased in scleroderma nephropathy. It is possible to prescribe any drugs of this group in doses that ensure normalization of blood pressure. In case of side effects (cough, cytopenia) with the use of ACE inhibitors, beta-blockers, slow calcium channel blockers, mainly in retard forms, alpha-adrenoblockers, diuretics in various combinations should be prescribed.

Since the development of acute scleroderma nephropathy can not be predicted, a thorough dynamic observation with regular investigation of renal function is shown to all patients with a diffuse form of systemic scleroderma. They should avoid situations in which deterioration of renal perfusion is possible (hypohydration, massive diuretic therapy leading to hypovolemia, arterial hypotension due to the use of certain drugs, hypothermia) because of the danger of provoking the development of a true scleroderma kidney.

In the case of malignant arterial hypertension or the appearance of signs of renal insufficiency, the treatment of scleroderma must begin immediately, as the natural course of acute scleroderma nephropathy is characterized by rapid progression leading to the development of oliguric acute renal failure or to death.

The basis for the treatment of acute scleroderma nephropathy - ACE inhibitors, the introduction of which into clinical practice changed the prognosis of a 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 monitoring of blood pressure is a priority for the treatment of acute scleroderma nephropathy, because it allows you to slow the progression of renal failure and avoid damage to the heart, the central nervous system, and the eyes. However, too rapid a reduction in blood pressure should be avoided, so as not to provoke further deterioration of renal perfusion with the development of ischemic acute tubular necrosis. ACE inhibitors should be combined with calcium channel blockers. Doses should be selected in such a way as to achieve a reduction in both systolic and diastolic arterial 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, to restore perfusion of the renal parenchyma without causing arterial hypotension.

If necessary (oliguric acute renal failure, uncontrolled arterial hypertension) treatment with hemodialysis is indicated. In patients with systemic scleroderma, hemodialysis is often problematic due to difficulties in forming vascular access in the scleroderma process (spasm of large vessels, skin induration, thrombosis of arteriovenous fistula). In a number of cases, spontaneous recovery of kidney function in patients who have suffered acute scleroderma nephropathy is possible in a few months (up to 1 year) of hemodialysis treatment, which allows for a certain period of time to stop its procedures. For prolonged replacement of scleroderma, it is better to use peritoneal dialysis, which, however, is often complicated by peritoneal fibrosis.

Patients with systemic scleroderma can have a kidney transplant. Contraindications are a progressive course of scleroderma with severe damage to the skin, lungs, heart and GIT.