SLE is a type of autoimmune disease that involves multiple systems and organs. 60% to 80% of patients can have kidney involvement, i.e. lupus nephritis, which mainly manifests clinically as proteinuria and hematuria with or without renal function abnormalities.
Kidney damage in SLE Kidney damage in SLE is called lupus nephritis, and the incidence rate is 50 cases/100,000 people in foreign countries and 70 cases/100,000 people in China. From pathological examination, it is found that kidney damage in SLE patients is about 90%. Its clinical manifestations are complex. In addition to the common rash, arthralgia, fever, photophobia, alopecia and multi-organ or systemic damage, renal damage is more prominent, manifested as hematuria, proteinuria, edema, hypertension and renal function damage.
Pathological typing of lupus nephritis The unification of pathological typing is of great importance in guiding clinical individualized treatment and judging prognosis
WHO typing.
1. Normal glomerular type (WHO type I) This type is extremely rare
There is no abnormal glomerular structure and no immune complex deposition.
2. Thylakoid glomerulonephritis (WHO type II) lesions are confined to the thylakoid region
Light microscopy may show no structural abnormalities (type IIa) or may show mononuclear cells or thylakoid hyperplasia in the thylakoid region (type IIb). Immunofluorescence shows IgG, C3, C4, C1q in the thylakoid region, with a few granular deposits of IgA and IgM and occasional linear deposits of IgG. Electron-dense deposits in the thylakoid region and segmental loss of glomerular epithelial cell pedicles were seen on electron microscopy. This type often has no tubular, interstitial or vascular abnormalities.
Focal segmental proliferative glomerulonephritis (WHO type III) is common in this type.
It accounts for about 30% of cases. On light microscopy, more than half of the glomeruli are normal on the basis of thylakoid lesions, and the glomeruli with lesions show segmental cell proliferation, which may be accompanied by cell necrosis. Immunofluorescence examination showed small amounts of IgG, IgM, IgA, C1q, C3, C4, and granular deposits of preparedin in the thylakoid region and capillary wall. Electron microscopy showed deposition of electron dense material in the subendothelial and thylakoid areas.
4, Diffuse proliferative glomerulonephritis type (WHO type IV) is the most serious and common
It accounts for about half of the cases. On light microscopy, almost all glomeruli are severely altered, showing proliferation of thylakoid and endothelial cells, aggregation of leukocytes, degenerative changes in many cells, and insertion of thylakoid cells between the basement membrane and endothelial cells, and formation of crescent bodies. The presence of “wire loop-like lesions and hematoxylin vesicles often suggests the diagnosis of lupus nephritis. In addition, hyaline thrombi may be present. Immunofluorescence examination reveals IgG, IgM, IgA, C1q, C3, C4, C5-9, and rarely IgE in granular deposits in all regions of the glomerulus, especially in the subendothelium. Significant electron-dense deposits were seen on electron microscopy, mainly in the subendothelial and thylakoid regions.
5. Membranous lupus nephritis (WHOV type) is less common
The light microscopic appearance may be similar to idiopathic membranous glomerulonephritis (Va) or diffuse thylakoid lesions (Vb) or with focal cellular hyperplasia and sclerosis (Vc) or with diffuse proliferative nephritis changes (Vd). Immunofluorescence showed granular deposition of IgGIgM, IgA, C1q, C4, C3, C5-9 along the capillary wall, with IgG and C1q being the most common and also seen in the thylakoid region. Electron microscopy reveals electron-dense deposits in the thylakoid region, subendothelium, and tubular interstitium, which all suggest the diagnosis of lupus nephritis.
6. Glomerulosclerotic type (WHO type VI) is dominated by glomerulosclerosis and lacks other lesions.
7. Vascular abnormalities and tubulointerstitial inflammation Vascular abnormalities are diverse
The typical hypertensive arterial and small arterial changes are the most common, with small arteries and small arteries into the bulb predominantly showing plasma protein aggregation in the vessel wall, endothelial cell swelling, destruction, luminal narrowing and blockage, and necrotizing arteritis is rare. Interstitial inflammatory cell infiltration is common, often accompanied by tubular atrophy and necrosis, tubular basement membrane thickening and deposition in the interstitium, tubular basement membrane, and peritubular capillaries, etc. These extra-glomerular deposits often correlate with the activity of the glomerular lesion and the severity of glomerular cell proliferation.
The 2003 ISN/RPS classification criteria for lupus nephritis classify lupus nephritis into six types.
Type I is mildly lesioned lupus nephritis of the thylakoid membrane: the light microscopic presentation is essentially normal, and immune complex deposition in the thylakoid region is visible by immunofluorescence.
Type II is tegumentary hyperplastic lupus nephritis: light microscopy shows tegumentary cell hyperplasia or increased tegumentary stroma with immune complex deposition in the tegumentary area, and immunofluorescence or electron microscopy shows a small amount of isolated subepithelial or subendothelial deposits.
Type III is focal lupus nephritis: less than 50% of all glomeruli are involved and may present as active or inactive lesions, focal, segmental or globular lesions, and intra- or extra-capillary proliferative lesions. Type III(A) is an active lesion that presents as focal hyperplastic lupus nephritis; type III(AC) is an active with chronic lesion that presents as focal hyperplastic sclerosing nephritis; and type III(C) is a chronic lesion that presents as focal sclerosing nephritis.
Type IV is diffuse lupus nephritis: the glomeruli involved account for more than 50% of all glomeruli, and typical cases often have diffuse subendothelial immune complex deposition with or without thylakoid lesions. According to the glomerular lesions, there are diffuse segmental lupus nephritis (the affected glomeruli exhibit segmental lesions) and diffuse globular lupus nephritis (the affected glomeruli exhibit globular lesions).
Type IVS (A) is active segmental hyperplastic lupus nephritis: Type IVG (A) is active spheroplastic lupus nephritis, Type IVS (AC) is active with chronic segmental hyperplastic sclerosing lupus nephritis, Type IVG (AC) is active with chronic spheroplastic sclerosing lupus nephritis, Type IVS (C) is chronic segmental sclerosing lupus nephritis, and Type IVG (C) is chronic spheroplastic sclerosing lupus nephritis.
Type V is membranous lupus nephritis: light microscopy reveals subepithelial immune complex deposits with or without thylakoid lesions. Immunofluorescence or electron microscopy reveals globular or segmental subepithelial continuous immune complex deposits, and type V is often coexisting with type III or IV.
Type VI is progressive sclerosing lupus nephritis: more than 90% of the glomeruli are spherically sclerotic.
Active lesions are the following: intracapillary cell proliferation, nuclear fragmentation, fibrinoid necrosis, glomerular basement membrane disruption, cellular or fibroblastic crescent formation, and platinum ear. Chronic lesions are defined by the presence of segmental or global glomerulosclerosis, fibrous adhesions, and fibrous crescent formation.
Treatment of lupus nephritis
Glucocorticoids and cytotoxic drugs are still the traditional drugs of choice for the treatment of lupus nephritis, but because they have serious side effects that are difficult to overcome, the goal of future treatment is to minimize the use of these two classes of drugs. Treatment of proliferative lupus nephritis includes induction of remission in the acute phase and long-term maintenance in the stable phase.
Glucocorticoids: Oral high-dose glucocorticoid induction therapy [prednisone 1.5-2.0 mg/(kgd)] is mainly indicated for severe active diffuse proliferative nephritis, and the dose is gradually reduced after remission, maintained at the lowest effective amount, or even discontinued. However, monotherapy is poorly effective, prone to relapse, and adverse effects are common. Therefore, the combination of other immunosuppressive drugs is recommended.
Glucocorticoids combined with cyclophosphamide (CTX): Glucocorticoids can be administered orally or intravenously, and CTX can also be administered orally or intravenously. The currently recommended intravenous CTX regimen is 0.5 to 1 g/m2 once a month for 6 months; thereafter, the same dose is given every 3 months for 2 years. If oral CTX is given, the dose is 1.5 to 2.0 mg/(kgd). CTX given intravenously is now widely used because it has fewer side effects than oral administration. This regimen is mainly based on the NIH regimen. However, for lupus nephritis with clinical manifestation of acute nephritis and pathology of massive crescent formation or necrosis, it is recommended to combine glucocorticoid intravenous shock (MPP) with CTX shock. the MPP regimen is intravenous methylprednisolone 0.5~1.0g/d, which is changed to prednisone 1.5~2.0mg/(kgd) after 3 consecutive days.
Methylprednisolone (MMF): The results of a meta-analysis of four randomized controlled trial studies on the comparison of MMF with CTX showed that MMF was effective in controlling lupus nephritis activity in the treatment of proliferative lupus nephritis induced remission with comparable efficacy to CTX, and both had the same rate of complete remission with fewer adverse effects such as infection, leukopenia, and liver function impairment. It suggests that MMF has certain superiority. However, whether MMF has the same effect as CTX in patients with severe lupus nephritis and whether MMF can reduce the dose of prednisone is yet to be confirmed in multicenter, large sample and longer-term clinical trials.
Rituximab (rituxan): a murine human chimeric anti-CD20 monoclonal antibody that blocks the action of CD20-positive B cells, may be one of the important trends for future development. Some studies in small samples have shown that rituximab significantly improves the activity of lupus nephritis and reduces urinary protein in patients. However, further studies are needed regarding the dose and timing of administration, whether it should be combined with other drugs, and the long-term adverse effects.
Azathioprine (AZA): In recent years, some scholars advocate switching to oral azathioprine maintenance therapy after shock-induced remission with cyclophosphamide. the dose of AZA is 1~2.0mg/(kgd) orally, with the addition of prednisone 0.2~0.3mg/(kgd), which can be reduced to withdrawal after the disease is stabilized.
Cyclosporine A (CsA): CsA can be used for induction of remission and long-term maintenance in proliferative lupus nephritis. Some studies have shown that the overall efficacy of low-dose CsA is comparable to CTX treatment. However, CsA has more adverse effects, including hepatic and renal toxicity, hypertension, hypertrichosis, and gingival hyperplasia, so it is not currently used as a first-line agent for the treatment of lupus nephritis. The CsA blood concentration of patients should be monitored during application and the drug dose should be adjusted in a timely manner.
Radix polyglycoside: 20-40mg, tid, po, with attention to side effects such as liver damage and leukopenia, and menstrual disorders, which can be recovered after stopping the drug.
General treatment: including rest, diet, diuresis, hypotension, anticoagulation and prevention of various complications, etc., should be referred to according to the patient’s condition, the treatment of primary glomerular disease. Chinese herbal medicine with evidence-based treatment can improve the efficacy to reduce symptoms and reduce the side effects of western drugs In conclusion, the prognosis of proliferative lupus nephritis has improved greatly in recent years with the use of a large number of new immunosuppressive drugs. However, more randomized controlled trials are needed in the future to verify the clinical efficacy of the drugs.
Precautions and prevention
1. Pay attention to physical factors
In systemic lupus nephritis, the incidence of close relatives is as high as 5%-12%, and the incidence of identical twins is as high as 69%. The incidence of other autoimmune diseases, such as rheumatoid dermatomyositis, dry scleroderma and psoriasis, is also high among relatives of lupus patients. The prevalence of lupus nephritis in blacks and people of Asian descent is higher than that in Caucasians, suggesting that lupus nephritis is influenced by genetic factors and is more frequent in women, and that the low testosterone level in patients indicates that endocrine factors, especially estrogen, are related to the development of lupus nephritis in lupus patients. Once the disease is developed, autoimmune disease should be thought of. Once autoimmune disease is developed, active treatment should be given to prevent lupus nephritis from occurring and causing kidney damage.
2. Active treatment
Viral infection In recent years, experimental studies have found that viral infection of lupus nephritis may be related to the occurrence of systemic lupus erythematosus. Therefore, we should actively treat various viral infections, especially for upper respiratory tract viral infections, such “minor diseases” should never be taken lightly because “wind is the longest of all diseases” and many major diseases start with cold and flu, thus endangering the population.
3. Pay attention to drug toxicity
The drugs related to lupus nephritis are hydrazinepyridazine procaine, amide isoniazid methyl, dopa chloropromazine and quinidine, especially the first two are common probably related to the hydrazinamine sulfhydryl group in the drug, therefore, for lupus nephritis patients with lupus genetic basis, should pay attention to the possible toxicity of these drugs to patients.
4. Avoid sun exposure
Ultraviolet radiation, which aggravates lupus nephritis, is more common because ultraviolet light can convert DNA into thymidine dimers, which enhances antigenicity and contributes to the occurrence of systemic lupus erythematosus.
5. Diet
Lupus nephritis – Prevention of infection Patients with lupus nephritis should take in enough nutrients, such as protein, vitamins and minerals, with lightness being appropriate. Water and salt should be moderately limited. Avoid heavy smoking, alcohol or stimulating foods. Vitamin D can be used for osteoporosis.
6.Exercise
Exercise can promote blood circulation, improve cardiopulmonary function, and maintain the toughness of muscles and bones, which is beneficial to all people, including patients. (Walking. Qigong) do not overwork. However, inflammation of the joints is not suitable for activities.
7.Prevent infection
Patients due to the impact of the disease or the side effects of steroids or immunosuppressants, the immune system is generally reduced, very vulnerable to bacterial invasion, and caused by the infection of various organs. The common ones are respiratory tract infections, urinary tract infections, gastrointestinal tract infections, and wound infections.
8.Emotional adjustment
Patients are diagnosed with lupus nephritis in a sudden situation, which is a heavy blow to the spirit, often depressed, anxiety, depression, anger, guilt, denial and other situations come one after another. However, emotion and disease are inextricably linked and mutually influential. Patients then face physical and psychological challenges. To win this battle, keeping a happy mood will help the disease improve. Also family and friends should provide love and support.