IgA nephropathy (IgAN), also known as Berger’s disease, is a primary glomerulopathy in which IgA or IgA deposits predominate in the glomerular thylakoid region with or without other immunoglobulins deposited in the glomerular thylakoid region. The clinical manifestations are: recurrent episodes of hematuria or microscopic hematuria.
Disease classification
1.Primary IgA nephropathy: caused by the kidney disease itself, mostly seen.
2, secondary IgA nephropathy: caused by diseases other than the kidney, such as: purpura nephritis, HIV infection, seronegative spondyloarthritis, tumor, leprosy, liver disease, familial IgA nephropathy, etc.
Causes of pathogenesis
The exact pathogenesis of IgA nephropathy is not fully understood, and a variety of factors are associated with its development. The current consensus is that IgAN is a glomerular disease caused by immune complexes.
The relationship with the immune system: IgA nephropathy is mainly characterized by the deposition of multimeric IgA (PIgA) in the glomerulus, indicating that the IgA immune system causes the appearance of PIgA molecules in the circulatory system and the deposition in the glomerular thylakoid region.
The relationship with bone marrow: IgA1 deposited in the glomerular thylakoid region and the presence of abnormal glycosylation in the hinge region similar to that of IgA1 in blood suggest that IgA deposited in the glomerular thylakoid region in patients with IgA nephropathy is bone marrow-derived IgA.
3. Relationship with cytokines: IgA1 deposited in the thylakoid region of patients with IgA nephropathy causes thylakoid cells to secrete inflammatory factors.
Clinical manifestations
1. Recurrent episodes of sarcoid hematuria (30-40%)
1) occurring hours to 1-2 days after an upper respiratory tract infection (gastrointestinal or urinary tract infection).
2) mostly without accompanying symptoms, a few with discomfort in urination and diagnosed as acute cystitis
3) carnal hematuria is more common in children and adolescents (80-90 %) than in adults (30-40 %)
4) independent of disease severity.
5) renal pathology is usually Lee’s grade II-III.
2. Occult nephritis type (20-30%)
1) microscopic hematuria, with intermittent episodes of carnituria in 25%.
2) with or without proteinuria (+).
3) a few with hypertension.
4) renal pathology is usually Lee’s grade II-III.
3.Chronic nephritis type
1) microscopic hematuria with or without proteinuria (+-++).
2) often with hypertension.
3) possible decrease in renal function.
4) renal pathology is usually Lee’s grade II to IV.
4, massive proteinuria or nephrotic syndrome type
1) nephrotic syndrome with or without microscopic hematuria.
2) Mostly with hypertension.
3) some patients present with nephrotic syndrome, and renal light microscopy can be: microscopic lesions and mild diffuse proliferative glomerulonephritis.
4) renal pathology is usually Lee’s grade I to IV.
5, malignant hypertensive type
1) malignant hypertension.
2) proteinuria (+-++) with or without microscopic hematuria.
3) often combined with renal insufficiency.
4) renal pathology is usually Lee’s grade III to IV.
6.Acute nephritis syndrome type
1) progressive deterioration of renal function with progressive oliguria.
2) proteinuria (+-++), with or without carnituria.
3) hypertension and anemia.
4) renal pathology is usually crescentic nephritis, Lee’s grade IV to V
Auxiliary tests
1, immunological examination: 50% of patients have elevated serum IgA levels. 37-75% of patients have specific circulating immune complexes containing IgA measured.
2. Proteinuria: proteinuria quantification and typing are important in determining the condition of IgA nephropathy and estimating the prognosis. Proteinuria <1g/24 h is often mild and focal thylakoid hyperplasia is predominant. Moderate to severe proteinuria is mostly diffuse thylakoid hyperplasia, often accompanied by crescent and glomerulosclerosis.
3.Renal function: blood creatinine rises to 1.5mg/dl (132.6umol/L) mostly for the progression of the disease. when GFR<20ml/min, pathological changes are above grade III.
4, hematuria: urinary RBC morphology is polymorphic, suggesting that the source of hematuria is of glomerular origin.
Disease diagnosis
The diagnosis of IgA nephropathy must be supported by renal biopsy pathology and must be supported by immunofluorescence or immunohistochemistry results. The diagnostic features are: diffuse thylakoid hyperplasia or focal segmental hyperplastic glomerulonephritis is common on light microscopy; immunofluorescence reveals IgA or IgA-dominated immune complex deposits in the thylakoid region, which is the diagnostic hallmark of IgA nephropathy.
Differential diagnosis
This disease should be differentiated from the following diseases.
1. Glomerulonephritis after acute streptococcal infection: 1 to 3 weeks before the onset of the disease, there is a history of prodromal streptococcal infection, with hematuria, swelling and hypertension as the three main symptoms. The duration of persistent carnal hematuria is long and can range from days to weeks, which is different from the episodic hematuria of IgA nephropathy. Laboratory tests include decreased complement C3 and increased ASO and sedimentation.
2, benign familial hematuria: this disease mostly has a family history, 90% of the clinical manifestation of persistent microscopic hematuria, only a few with intermittent episodes of hematuria. It is usually asymptomatic and is mostly found during physical examination or routine urinalysis. Electron microscopy confirms that some of them have a thin basement membrane base (basement membrane thickness is about 1/3 to 2/3 of the normal number). The prognosis is good.
3, familial hereditary nephritis: mostly persistent microscopic hematuria, male more than female, showing progressive hyperalgesia, 50% with neurological high frequency area deafness, 15% with eye abnormalities, high mortality in males.
4, left renal vein pressure near syndrome: a non-renal hematuria, no clinical manifestations of glomerulonephritis.
5. Idiopathic hypercalciuria: manifested as persistent microscopic hematuria, or with episodes of carnitic hematuria, non-glomerular hematuria, urinary Ca> 0.1mmol/kg (4mg/kg/d), urinary Uca/Ucr ratio if >0.21 can be the initial diagnosis of the disease
6., Purpura nephritis: it often presents as microscopic hematuria. But the patient has skin bleeding spots, appearing in the distal extremities, buttocks and lower abdomen, mostly symmetrical distribution, slightly above the skin surface, may have an itchy sensation, gradually fading after 1 to 2 weeks, often in batches.