Lupus nephritis: causes, symptoms, diagnosis, treatment and prognosis

Pathomorphology

The morphology of lupus nephritis can be different. Membranous changes, interposition of the mesangium, expansion of the mesangium, proliferation of glomerular cells, sclerosis of vascular loops and damage to the tubules and interstitium are recorded. Specific morphological features are:

nuclear pathology (karyopyknosis and karyorrhexis)
fibrinoid necrosis of capillary loops
sharp focal thickening of the basement membranes of the glomerular capillaries in the form of wire loops

In recent years, intravascular thrombi have been associated with APS or the presence of IR, which include cryoglobulins. Class C immunoglobulins are typical.

Lupus nephritis and chronic renal failure

Patients with end-stage renal disease require dialysis therapy and are good candidates for kidney transplantation. Patients with lupus nephritis and chronic renal failure account for 1.5% of all patients on hemodialysis. Five-year survival rate for lupus nephritis and uremia with renal replacement therapy is 60-70%, comparable to that for other patients without SLE.

Studies have shown that hemodialysis is preferable to peritoneal dialysis, documenting higher levels of anti-double-stranded DNA (dsDNA) antibodies, severe thrombocytopenia, and the need for higher doses of corticosteroids in patients with SLE and ESRD receiving peritoneal dialysis. Hemodialysis has also been proven to have an anti-inflammatory effect by reducing the number of T-helper cells in lymphocytes. SLE does not usually progress in hemodialysis patients, and flares are rare and present with rash, arthritis, serositis, fever and leukopenia, requiring specific treatment in each case.

Forecast

Over the past 4 decades, changes in the treatment of lupus nephritis and general medical care have significantly improved overall survival and reduced the risk of progression to kidney failure. During the 1950s, the 5-year survival rate among patients with lupus nephritis was close to 0%. Subsequent addition of immunosuppressive drugs resulted in documented 5- and 10-year survival rates reaching 85% and 73%, respectively.

Author Victoria Mishina

Publication date 04/01/2019

Symptoms

Lupus nephritis consistently presents with proteinuria, which is nonselective. Signs of acute nephritic syndrome always appear in parallel. This explains the rarity of hypovolemic crises and the low severity of proteinuria (detection of protein in the urine). An important criterion for activity is hematuria; gross hematuria is very rarely recorded. Leukocyturia is detected aseptically, mainly with lymphocyturia.

Among the symptoms, renal failure is also described, in which the rate of increase in creatinine plays an important role. Rapid progression of the disease is indicated by a doubling of serum creatinine in 3 months or less. The incidence of acute renal failure is 5-10%.

Lupus nephritis can be (according to the severity of symptoms and course) slowly progressive and rapidly progressive. The first type occurs with severe urinary syndrome and nephrotic syndrome. Inactive lupus nephritis with mild urinary syndrome or subclinical proteinuria is also isolated.

The symptoms of rapidly progressive LN are the same as with classic rapidly progressive glomerulonephritis: renal failure increases very quickly, which is combined with erythrocyturia, nephrotic syndrome and arterial hypertension. DIC syndrome is also noted. Morphologically, this variant mainly corresponds to diffuse proliferative lupus nephritis, often with crescents.

The slowly progressive form occurs with severe proteinuria or nephrotic syndrome in combination with hematuria and hypertension. Typical pathomorphological manifestations are noted.

Separately, they speak of an inactive form of lupus nephritis, when proteinuria is below 0.5 g/day and minimal urinary syndrome, there is no hypertension and erythrocyturia, and kidney function is preserved. Tubulointerstitial nephritis is an independent form and is classified as a tubulointerstitial nephropathy. Kidney damage in SLE can occur in another variant - APS-associated nephropathy.

Classification

The course of this disease, from the point of view of morphology and changes in the structure of kidney tissue, is very diverse. Most often, class G immunoglobulins, fibrin deposition and individual fractions of the complement system (C3) are detected in the renal glomeruli.

Somewhat less frequently, glomeruli absorb immunoglobulins of class A and M, and for pathomorphologists a very important sign that allows one to immediately diagnose lupus nephritis are virus-like inclusions in the capillaries of the glomerulus, localized inside the capillary endothelium.

Such a lesion, first of all, of the glomeruli, makes it possible to clarify that nephritis in lupus, of course, is not pyelonephritis at all, as some may imagine, but a lesion of the tubules. In SLE, first of all, we are talking about such a pathological process as lupus glomerulonephritis.

In almost half of the patients, in addition to damage to the renal glomeruli, or “glomerulonephritis in its pure form,” damage occurs to the distal structures of the nephron - tubules, collecting ducts, interstitial tissue. They occur in the form of epithelial atrophy, tubular dystrophy, development of foci of sclerosis, with the deposition of various immunoglobulins on the structures of the interstitium and basement membrane.

Almost a quarter of all patients have damage to the small vessels of the kidneys. In lupus nephritis, very roughly, six different classes of damage to renal structures with different outcomes can be distinguished:

The first class - or minimal activity of nephritis, is characterized by the absence of changes in the urine, normal kidney function, and during biopsy, against the background of normal glomeruli, only isolated immune complexes are distinguished by immunofluorescence.
The second class of changes (from 8 to 30% of all cases) corresponds to mesangial proliferative glomerulonephritis. There will already be slight proteinuria, or the release of protein in the urine, and with a biopsy more serious changes will be observed. The prognosis is favorable if there is no progression.
The third class (10-25%) of lupus glomerulonephritis is characterized by biopsy by already active damage to glomerular tissue, which can be of a different nature; proteinuria and edema increase in the clinic, the process is progressive in nature with a high risk of renal failure. But even at the stage of such focal glomerulonephritis, the condition can be completely stabilized if treated correctly.
The fourth class is characterized by proliferative glomerulonephritis, when more than half of all glomeruli included in the histological specimen are involved in the pathological autoimmune process. Clinically, there is a high risk of nephrogenic arterial hypertension, and the prognosis is most often unfavorable. It is for this class that we present a sample result of a histological examination.
The fifth class or membranous glomerulonephritis indicates damage to all glomeruli, their membrane is thickened evenly, and filtration capacity is sharply reduced. High concentrations of protein appear in the urine. But, despite this, such patients (and there are 10-20%) rarely develop renal failure, and immune disorders are very moderate. If the level of proteinuria is low, then the prognosis for this class may be favorable provided that it is fully treated. In some cases, some patients may even experience spontaneous remissions.
Grade 6 is the outcome, nephrosclerosis. Histological samples show segmental and diffuse sclerosis of the renal tubules with their atrophy, proliferation of connective tissue, and in the clinic - various symptoms of progressive chronic renal failure with a poor prognosis.

Diagnostics

Diagnosis of lupus nephritis is not difficult if there are typical manifestations of a systemic disease:

livedo reticularis
skin lesions
lymphadenopathy
joint syndrome
serositis
fever
cerebrovasculitis
heart damage

To confirm the diagnosis, it is important to obtain laboratory data:

cytopenia, anemia
increase in ESR
antinuclear factor
AT to native DNA, etc.

The morphological type of lupus nephritis is determined by performing a kidney biopsy.

Etiology

The etiology is still unknown; experts note that the first symptoms of SLE are preceded by signs of a virus-like disease.

• Genetic factors

As with many autoimmune diseases, evidence suggests that genetic susceptibility plays a role in the development of both SLE and lupus nephritis. Genes, many of which have not yet been identified, mediate this genetic predisposition.

SLE is more common in first-degree relatives (mother, father, brothers and sisters), familial prevalence is 10-12%, for monozygotic twins - 24-58%, dizygotic twins - 2-5%. This confirms the influence of genetic factors in the development of SLE, but the fact that not 100% of cases of a monozygotic pair will affect both twins suggests that environmental factors should also be taken into account.

• Immunological factors

The initial autoantibody response is potentially directed against a nucleosome that arises from apoptotic cells. In patients with SLE, the mechanisms for clearing “cellular debris” are impaired, which promotes plasmacytoid dendritic cells to produce interferon-α, a powerful inducer of the immune system and autoimmunity. B lymphocytes are activated in SLE due to failure of homeostatic mechanisms, which leads to a breakdown of tolerance and promotes the production of antibodies. Other autoantibodies have also been found to appear over time, from several months to several years before the onset of clinical manifestations.

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treatment

Cyclophosphamide
Treatment regimens for lupus nephritis include: mycophenolate mofetil (MMF), intravenous cyclophosphamide with corticosteroids, and the immunosuppressant azathioprine with corticosteroids.[14] MMF and cyclophosphamide with corticosteroids are equally effective in achieving disease remission, but a recent systematic review found that immunosuppressants were better than corticosteroids for renal outcomes.[15] MMF is safer than cyclophosphamide with corticosteroids, less likely to cause ovarian failure, immune problems or hair loss. It also works better than azathioprine with corticosteroids for maintenance therapy.[16][17] A 2021 network meta-analysis that included 32 RCTs of lupus nephritis found that tacrolimus and MMF followed by azathioprine maintenance therapy was associated with a lower risk of serious infection compared with other immunosuppressants or glucocorticoids.[18][19] People with lupus nephritis have a high risk of B-cell lymphoma (which starts in cells of the immune system).[2]

Lupus anticoagulant (venous blood) in Salekhard