Kidney damage in periarteritis nodosa

Nodular polyarteritis is a necrotizing vasculitis with predominant involvement of medium-sized arteries in the pathological process, clinically manifested by rapidly progressing inflammatory and ischemic damage to soft tissues and internal organs.

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Causes periarteritis nodosa

Polyarteritis nodosa was first described in 1866 by A. Kussmaul and R. Maier in a 27-year-old man as a fatal systemic disease with fever, abdominal pain syndrome, muscle weakness, polyneuropathy, and kidney damage. Polyarteritis nodosa develops in men 3-5 times more often than in women, usually between the ages of 30 and 50, although the disease is also observed in children and the elderly. The average incidence is 0.7 cases (0.2 to 1.0) per 100,000 population. Kidney damage develops in 64-80% of patients with polyarteritis nodosa.

Kidney damage develops in many systemic vasculitides, but its frequency, nature and severity vary depending on the level of damage to the renal vascular bed.

• Vasculitides of large vessels, such as temporal arteritis or Takayasu's disease, rarely cause significant renal pathology. In these diseases, renovascular arterial hypertension develops due to damage to the aorta in the area of the renal artery orifices or their main trunks, which leads to narrowing of the vascular lumen and renal ischemia.
• Vasculitis of medium-sized vessels (polyarteritis nodosa and Kawasaki disease) is characterized by necrotizing inflammation of the main visceral arteries (mesenteric, hepatic, coronary, renal). Unlike polyarteritis nodosa, in which kidney damage is considered the main symptom, the development of kidney pathology is not typical for Kawasaki disease. In polyarteritis nodosa, as a rule, small intrarenal arteries can be affected, but smaller-caliber vessels (arterioles, capillaries, venules) remain intact. Therefore, the development of glomerulonephritis is not typical for this systemic vasculitis.
• The development of glomerulonephritis is typical of small vessel vasculitis (Wegener's granulomatosis, microscopic polyangiitis, Henoch-Schonlein purpura, cryoglobulinemic vasculitis). In this type of vasculitis, the distal sections of arteries that pass into arterioles (for example, branches of the arcuate and interlobular arteries), arterioles, capillaries, and venules are affected. Vasculitis of small and large vessels can spread to medium-sized arteries, but in vasculitis of large and medium arteries, vessels of a smaller caliber than the arteries are not affected.

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Pathogenesis

Polyarteritis nodosa is characterized by the development of segmental necrotizing vasculitis of medium and small caliber arteries. The features of vascular damage are considered to be frequent involvement of all three layers of the vessel wall (panvasculitis), which leads to the formation of aneurysms due to transmural necrosis, and a combination of acute inflammatory changes with chronic ones (fibrinoid necrosis and inflammatory infiltration of the vascular wall, proliferation of myointimal cells, fibrosis, sometimes with vascular occlusion), reflecting the wave-like course of the process.

In the overwhelming majority of cases, renal pathology is represented by primary vascular damage - vasculitis of the intrarenal arteries of medium caliber (arc and their branches, interlobar) with the development of ischemia and renal infarctions. Damage to the glomeruli with the development of glomerulonephritis, including necrotizing, is not typical and is observed only in a small proportion of patients.

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Symptoms periarteritis nodosa

Kidney damage is the most common and prognostically important symptom of polyarteritis nodosa. It develops in 60-80% of patients, and according to some authors, in all patients with polyarteritis nodosa without exception.

As a rule, symptoms of kidney damage are combined with clinical signs of damage to other organs, however, variants of nodular polyarteritis with isolated kidney damage have been described.

The symptoms of polyarteritis nodosa are characterized by significant polymorphism. The disease usually begins gradually. Acute onset is typical for drug-induced polyarteritis nodosa. Nodular periarteritis debuts with nonspecific symptoms: fever, myalgia, arthralgia, weight loss. Fever is of an irregular type, is not relieved by treatment with antibacterial drugs and can last from several weeks to 3-4 months. Myalgia, which is a symptom of ischemic muscle damage, most often appears in the calf muscles. Articular syndrome develops in more than half of patients with polyarteritis nodosa, usually combined with myalgia. Most often, patients are bothered by arthralgia of large joints of the lower extremities; transient arthritis is described in a small number of patients. Weight loss, observed in most patients and reaching the degree of cachexia in some cases, not only serves as an important diagnostic sign of the disease, but also indicates its high activity.

Diagnostics periarteritis nodosa

Diagnosis of polyarteritis nodosa does not cause difficulties at the height of the disease, when there is a combination of kidney damage with high arterial hypertension with disorders of the gastrointestinal tract, heart, and peripheral nervous system. Difficulties in diagnosis are possible at early stages before the development of damage to internal organs and in the case of a monosyndromic course of the disease.

In the case of a polysyndromic nature of the disease in patients with fever, myalgia and significant weight loss, it is necessary to exclude nodular polyarteritis, the diagnosis of which can be confirmed morphologically by biopsy of the skin-muscle flap by detecting signs of necrotizing panvasculitis of medium and small vessels; however, due to the focal nature of the process, a positive result is noted in no more than 50% of patients.

The choice of therapeutic regimen and drug doses is determined by clinical and laboratory signs of disease activity (fever, weight loss, dysproteinemia, increased ESR), the severity and rate of progression of damage to internal organs (kidneys, nervous system, gastrointestinal tract), the severity of arterial hypertension, and the presence of active HBV replication.

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Treatment periarteritis nodosa

For the treatment of patients with polyarteritis nodosa, a combination of glucocorticoids and cytostatics is optimal.

• In the acute period of the disease, before the development of visceral lesions, prednisolone is prescribed at a dose of 30-40 mg/day. Treatment of patients with severe damage to internal organs should begin with pulse therapy with methylprednisolone: 1000 mg intravenously once a day for 3 days. Then prednisolone is prescribed orally at a dose of 1 mg/kg of body weight per day.
• After achieving the clinical effect: normalization of body temperature, reduction of myalgia, cessation of weight loss, reduction of ESR (on average within 4 weeks) - the dose of prednisolone is gradually reduced (5 mg every 2 weeks) to a maintenance dose of 5-10 mg/day, which must be taken for 12 months.
• In the presence of arterial hypertension, especially malignant, it is necessary to reduce the initial dose of prednisolone to 15-20 mg/day and reduce it rapidly.

Forecast

The prognosis depends on the nature of the damage to internal organs, the time of onset and the nature of therapy. Before the use of immunosuppressants, the average life expectancy of patients was 3 months, 5-year survival was 10%. The course of the disease was fulminant in most cases. After the use of monotherapy with glucocorticoids, the 5-year survival increased to 55%, and after adding cytostatics (azathioprine and cyclophosphamide) to the treatment - to 80%. The average life expectancy of patients with nodular polyarteritis currently exceeds 12 years.

The prognosis of the disease worsens in the presence of HBV infection, the onset of the disease at the age over 50 years, with an untimely diagnosis. Unfavorable prognostic factors associated with high mortality include proteinuria exceeding 1 g/day, renal failure with a creatinine level in the blood of more than 140 μmol/l, damage to the heart, gastrointestinal tract and central nervous system.

The highest mortality is observed in the first year of the disease, when there is high activity of vasculitis. The main causes of death in this period are progressive renal failure, complications of malignant arterial hypertension (acute left ventricular failure, stroke), myocardial infarction as a consequence of coronary arteritis, gastrointestinal bleeding. At a later stage, mortality is associated with progressive chronic renal failure, circulatory failure due to heart damage and severe arterial hypertension, myocardial infarction.

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