Renal lesions in periarteritis nodosa

Nodular polyarteritis - necrotizing vasculitis with primary involvement in the pathological process of middle-caliber arteries, clinically manifested by rapidly progressive inflammatory and ischemic lesions of soft tissues and internal organs.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

Causes of the nodular periarteritis

Nodular polyarteritis 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. Nodular polyarteritis in men develops 3-5 times more often than in women, usually at the age of 30 to 50 years, although the disease is also noted in children and the elderly. The incidence on average is 0.7 cases (0.2 to 1.0) per 100 000 population. Renal damage develops in 64-80% of patients with nodular polyarteritis.

Renal damage develops in many systemic vasculitis, but the frequency, nature and severity of it are different depending on the level of damage to the vascular bed of the kidneys.

• Vasculitis of large vessels, such as temporal arteritis or Takayasu's disease, rarely cause a marked renal pathology. With these diseases, renovascular hypertension develops due to aortic lesions in the region of the mouths of the renal arteries or their main trunks, which leads to narrowing of the lumen of the vessels and ischemia of the kidneys.
• Vasculitis of medium caliber vessels (nodular polyarteritis and Kawasaki disease) are characterized by necrotizing inflammation of the main visceral arteries (mesenteric, hepatic, coronary, renal). Unlike nodular polyarteritis, in which kidney damage is considered the main sign, the development of renal pathology is not characteristic of Kawasaki's disease. When nodular polyarteritis, as a rule, small intracellular arteries can be affected, however, vessels of smaller caliber (arterioles, capillaries, venules) remain intact. Therefore, the development of glomerulonephritis is not typical for this systemic vasculitis.
• The development of glomerulonephritis is characteristic of vasculitis of small vessels (Wegener's granulomatosis, microscopic polyangiitis, Schonlein-Henoch purpura, cryoglobulinemic vasculitis). This type of vasculitis affects the distal parts of the arteries, passing into arterioles (for example, branches of arched and interlobular arteries), arterioles, capillaries, venules. Vasculitis of small and large vessels can spread to the arteries of medium caliber, but with vasculitis of large and medium arteries, vessels smaller than arteries are not affected by caliber.

[11], [12], [13], [14], [15], [16], [17], [18], [19]

Pathogenesis

Nodular polyarteritis is characterized by the development of segmental necrotizing vasculitis of middle and small caliber arteries. Vascular injury is characterized by frequent involvement of all three layers of the vessel wall (panvasculitis), which leads to the formation of aneurysms due to transmural necrosis, and the combination of acute inflammatory changes with chronic (fibrinoid necrosis and inflammatory infiltration of the vascular wall, proliferation of myointimal cells, fibrosis, sometimes with occlusion of the vessel ), reflecting the undulating course of the process.

In the overwhelming majority of cases, renal pathology is represented by a primary vascular lesion - vasculitis of the middle-caliber internal arteries (arches and their branches, interlobar) with the development of ischemia and infarction of the kidneys. The defeat of glomeruli with the development of glomerulonephritis, including necrotizing, is not characteristic and is noted only in a small part of patients.

[20], [21], [22], [23], [24]

Symptoms of the nodular periarteritis

Renal damage is the most frequent and prognostically important symptom of nodular polyarteritis. It develops in 60-80% of patients, and according to some authors, in all patients without nodular polyarteritis.

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

Symptoms of nodular polyarteritis are distinguished by significant polymorphism. The disease, as a rule, begins gradually. An acute onset is characteristic of nodular polyarteritis of drug origin. Nodular periarteritis debuts with nonspecific symptoms: fever,  myalgia, arthralgia, weight loss. The fever is of the wrong type, it does not stop when treated with antibacterial drugs and can last from several weeks to 3-4 months. Myalgia, a symptom of ischemic muscle damage, often appears in the calf muscles. Articular syndrome develops in more than half of patients with nodular polyarteritis, combining, as a rule, with myalgia. Most patients are concerned about  arthralgia of  large joints of the lower limbs; a small number of patients described transient arthritis. The loss of body mass observed in the majority of patients and reaching in some cases the degree of cachexia not only serves as an important diagnostic sign of the disease, but also indicates its high activity.

Diagnostics of the nodular periarteritis

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

In the case of polysyndromic disease in patients with fever, myalgia, and severe weight loss, nodular polyarteritis should be excluded, the diagnosis of which can be confirmed morphologically by  biopsy of the  musculocutaneous flap by detecting signs of necrotizing panvasculitis of medium and small vessels, nevertheless, in connection with the focal character of the process, a positive the result is noted in no more than 50% of patients.

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

[25], [26], [27], [28], [29], [30], [31]

Treatment of the nodular periarteritis

For treatment of patients with nodular polyarteritis optimal combination of glucocorticides and cytostatics.

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

Forecast

The prognosis depends on the nature of the damage to the internal organs, the timing of the onset and the nature of the therapy. Prior to the use of immunosuppressants, the average life expectancy of patients was 3 months, 5-year survival rate - 10%. The course of the disease in most cases was fulminant. After the introduction of glucocorticoid monotherapy, the 5-year survival rate increased to 55%, and after the addition of cytostatics (azathioprine and cyclophosphamide) to the treatment, up to 80%. The average life expectancy of patients with nodular polyarteritis is currently more than 12 years.

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

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

[32], [33], [34], [35]