OVERVIEW
A number of different types of kidney damage are seen in patients with rheumatoid arthritis (RA), either caused by the disease itself or by the medications used to treat it. The most common lesions are membranous nephropathy, secondary amyloidosis, focal thylakoid nephritis, rheumatoid vasculitis, and nephropathy caused by analgesics.
Etiology
It can be caused either by the disease itself or by the drugs used to treat it.
Symptoms
Renal lesions occurring in RA can be broadly categorized into 3 groups: (1) primary, which includes a variety of glomerulonephritis and tubulointerstitial nephritis; (2) renal amyloidosis; and (3) secondary, which is most often caused by drug therapy. Primary and secondary renal damage can coexist in a rheumatoid arthritis case, and the same drug can cause several different kinds of renal damage.
1. Primary renal damage
(1) Tethered glomerulonephritis is the most common type of renal damage in RA. The pathogenesis of this disease is considered to be related to the involvement of immune complexes. Clinical manifestations are usually simple microscopic hematuria and proteinuria, and a few patients may show nephrotic syndrome. Impairment of renal function is usually mild. The nephrotic granules are proliferation of tethered cells and widening of the tethered matrix. Immunofluorescence examination shows: ① IgG, IgM, IgA, C3 deposition in the thylakoid membrane area, with or without fibrin deposition; ② IgM deposition mainly, with C3 deposition; ③ IgA deposition, manifesting IgA nephropathy; ④ no immunoglobulin deposition, and only C3 positivity is seen; ⑤ immunofluorescence is negative in all. All of the above immunodeposits were in the form of granules. Corresponding electron-dense material deposits were seen under electron microscopy.
(2) Necrotizing vasculitis renal damage is a serious complication of RA, and the lesions may involve medium and small arteries, showing mononuclear cell infiltration, necrosis and thrombus. Clinical manifestations include microscopic hematuria, proteinuria, hypertension and rapid onset of renal decompensation. Renal pathology shows: ① proliferation and inflammatory cell exudation in glomerular capillaries; ② fibrinoid deposition; ③ cell nuclei fragmentation; ④ glomerular basement membrane rupture; ⑤ Baumann’s capsule fibrinoid exudation and cell proliferation. Immunofluorescence shows that IgG, IgA and C3 are deposited in the necrotic area. This type of renal damage should be treated with prednisone and cyclophosphamide as early as possible, then it is expected to improve the condition and stop the deterioration. Therefore, timely renal biopsy, clear diagnosis and early treatment are important.
(3) Membranous glomerulonephritis is commonly seen as secondary renal damage in RA, while primary is rare. Clinical manifestations include persistent proteinuria, hematuria, nephrotic syndrome. Renal biopsy reveals fine particles deposited on the surface of the glomerular basement membrane and under the epithelium between the basement membrane and the pedicle where the cells are fused. Immunofluorescence is dominated by IgG deposition.
2.Renal amyloidosis
About 20% of patients with long-term, severe rheumatoid arthritis may develop secondary amyloidosis. amyloidosis in the RA kidneys presents clinically as a nephrotic syndrome, which may eventually lead to chronic renal failure. Renal ultrasound shows increased or normal renal volume in the early stage and shrinkage in the late stage. Nephropathologic changes are mainly amyloid deposition in the basement membrane of glomerular capillaries, as well as in the renal interstitium, tubules, blood vessels, capillary basement membrane, vascular lumen narrowing and closing, glomeruli are replaced by a large amount of amyloid, and renal tubules are atrophied.
3. Secondary renal damage
It is mostly related to the use of drugs used by patients to treat rheumatoid arthritis. Renal pathology is most common in interstitial nephritis and membranous glomerulonephritis, but other pathologic types can occur. The drugs that cause secondary renal damage mainly include: ① gold preparation and penicillamine, which can cause membranous glomerulonephritis, and rarely acute renal failure; ② long-term, large amount of application of non-steroidal anti-inflammatory drugs (e.g., aspirin, diclofenac, inflammation of the pain Xiekang, etc.) can cause acute and chronic interstitial nephritis, decreased glomerular filtration rate, and even renal papillary necrosis.
Examination
1. Laboratory examination
(1) Urine routine examination: proteinuria or hematuria of different degrees.
(2) Renal function test: normal or abnormal to different degrees; chronic interstitial nephritis is mainly characterized by urinary concentration dysfunction.
(3) Blood sedimentation: rapid blood sedimentation, positive rheumatoid factor, decreased serum complement C3 in a few patients.
(4) Renal biopsy can determine the nature and extent of lesions.
2. Blood tests
(1) Serum rheumatoid factor (RF) There are three kinds of RF: IgG, IgM, and IgA. The latex agglutination method currently used is to detect IgM RF, which is 50% to 80% positive in the active stage, and has a low positive rate in the remission stage.
(2) C-reactive protein and blood sedimentation, both of which may increase in the active phase.
(3) Serum ANCA Some RV patients may be positive for P-ANCA, and the target antigen is MPO or other antigens.
(4) Joint fluid examination Cell count 2000～75000/mm3 Neutrophils predominate, low viscosity.
Diagnosis
In patients with rheumatoid arthritis presenting with renal damage, a careful history, such as whether gold agents or penicillamine have been applied and the time of renal onset, is helpful in clarifying the cause of renal damage. Careful urinalysis is also important to differentiate between different types of kidney damage. Membranous nephropathy and secondary amyloidosis are noninflammatory lesions that usually present with moderate to severe proteinuria, whereas hematuria and leukocyturia are unremarkable and blood creatinine is relatively normal, whereas patients with focal glomerulonephritis and rheumatoid vasculitis usually present with more active urinary deposits (erythrocytes, leukocytes, and other cellular granular tubular patterns). Nephropathy caused by analgesics due to renal papillary necrosis may be characterized by cribriform abdominal pain and chronic renal failure. Those with glomerular basement membrane thinning usually present with asymptomatic microscopic hematuria. Renal biopsy is still required in some patients for definitive diagnosis.
Treatment
The main focus is on the treatment of the primary disease. For combined renal damage, such as proteinuria due to therapeutic drugs such as gold or penicillamine, they must be discontinued. In amyloidosis, glucocorticoids are not effective, and control of the inflammatory response may relieve symptoms and reduce proteinuria. Severe renal lesions caused by rheumatoid vasculitis require aggressive treatment with hormones and cyclophosphamide. Chronic renal insufficiency and other severe renal damage should be treated with dialysis if irreversible.