Overview.
Primary glomerular disease with deposition of IgA-based immune complexes in the glomerular mesangial area, with recurrent episodes of microscopic or microscopic hematuria, proteinuria, hypertension, and renal insufficiency. The cause of the disease is unknown, and may be related to immunity, genetics and infection.
Definition
IgA nephropathy is a primary glomerular disease characterized by deposition of immunoglobulin A (IgA)-based immune complexes in the glomerular mesangial area.
The pathology is characterized by hyperplasia of the glomerular mesangium.
Systemic diseases such as systemic lupus erythematosus, dry syndrome, ankylosing spondylitis, herpes-like dermatitis, alcoholic cirrhosis, and chronic hepatitis can also lead to IgA deposition in the glomerular thylakoid membrane region and are called secondary IgA nephropathy.
Morbidity
There are obvious geographical differences in the incidence of IgA nephropathy, which is the most common primary glomerulonephritis in the Asia-Pacific region (China, Japan, Singapore, and Australia), accounting for 30-40% of primary glomerular diseases in the Asia-Pacific region, 20% of primary glomerulonephritis in Europe, and 10% of primary glomerulonephritis in North America.
IgA nephropathy is the most common primary glomerular disease in China, accounting for 30% to 50% of primary glomerular diseases, and the prevalence is on the rise.
IgA nephropathy is the most common primary glomerular disease in China, accounting for 30% to 50% of primary glomerular diseases, and the prevalence is on the rise. 5% to 25% of patients enter end-stage renal disease (ESRD) within 10 years after diagnosis, and 15% to 40% progress to ESRD within 20 years, and it is the most important disease leading to ESRD in China.
IgA nephropathy can occur at any age, and is more common in males between 20 and 30 years old.
Causes
Causes
The etiology and pathogenesis are still unclear, and may be related to immunity, genetics, infection and other factors.
Immunologic factors
Immunofluorescence examination reveals that the disease is dominated by the deposition of IgA and C3 in the thylakoid membrane area, suggesting that the disease may be due to the deposition of circulating immune complexes in the kidneys, which activate the complement and lead to renal damage.
IgA is divided into two subtypes, IgA1 and IgA2, and only IgA1 can lead to the deposition of immune complexes within the kidney. Among them, abnormal glycosylation of the IgA1 molecule is the key cause of the disease.
Abnormal glycosylation of the O-glycan chain galactose of the IgA1 molecule results in the absence of the O-glycan chain galactose, which cannot be recognized and cleared.
The circulating galactose-deficient IgA1 exists in the form of immune complexes, which are large in size but can smoothly pass through the endothelial window of the glomerular capillaries, and then deposited in the glomerular tunica albuginea region, thus causing glomerular inflammatory reaction.
Genetic factors
In most patients with IgA nephropathy and their immediate family members, IgA molecules with defective galactose in the hinge region are present, suggesting that abnormal IgA1 glycosylation is hereditary.
The onset of IgA nephropathy varies with race and geographic distribution, and some have familial aggregation, suggesting the presence of genetic factors.
Five disease-associated loci have been identified. three are in the major histocompatibility complex (MHC) region, and the other two are CFHR1 and CFHR3 deletions on chromosomes 1q32 and 22q12, respectively.
Infectious factors
Current research suggests that viral and bacterial infections can stimulate the production of autoantibodies, the formation and deposition of immune complexes in the glomerulus to produce an inflammatory response, which in turn stimulates the proliferation of the mesangial cells and the accumulation of extramembranous stroma, ultimately leading to glomerulosclerosis and interstitial fibrosis.
Symptoms
IgA nephropathy has an insidious onset and often manifests as asymptomatic hematuria with or without proteinuria, which is often detected during physical examination.
Some patients have prodromal symptoms such as upper respiratory tract, gastrointestinal tract, skin or urinary tract infections a few hours or days before the onset of the disease.
Main Symptoms
Hematuria
It is transient or recurrent and may last for hours or days.
It can be either hematuria or microscopic hematuria (the urine does not turn red to the naked eye, but there are more red blood cells in the urine under the microscope).
Hematuria is often painless.
Proteinuria
May be accompanied by proteinuria and is most common in children and young adults.
It is characterized by foamy urine, i.e., there is a lot of foam in the urine.
Systemic symptoms
Systemic symptoms vary in severity and may include general malaise, fatigue and muscle pain.
Hypertension
20% to 50% of patients have high blood pressure.
It is uncommon to have hypertension at the onset of the disease, and the incidence of hypertension increases with the progress of the disease.
Malignant hypertension may occur, mostly in young adult males, presenting with dizziness, headache, blurred vision, nausea, vomiting, diastolic blood pressure ≥130 mmHg, fundus vasculopathy of grade III or higher, which may be accompanied by acute renal injury and/or cardiac failure, acute pulmonary edema.
Nephrotic syndrome
Some patients present with nephrotic syndrome.
It is characterized by massive proteinuria (foamy urine), hypoproteinemia, edema, and hyperlipidemia.
Renal function impairment
Some patients may present with varying degrees of renal impairment, and a few may have progressive deterioration of renal function.
It may be asymptomatic or present with increased nocturia and polyuria; when renal function is severely impaired, it may manifest as anuria.
Complications
Ten to 20 years after the diagnosis of IgA, 20% to 30% of patients gradually progress to chronic renal failure, with metabolite retention, water-electrolyte disorders, acid-base balance disorders and systemic symptoms, which are more common in adults.
Consultation
Conditions that require medical attention
Routine physical examination, found that the urine routine abnormalities, it is recommended to consult a doctor promptly.
Prompt medical consultation is recommended when there is unexplained hematuria of the naked eye, foamy urine, or edema, general malaise, fatigue, muscle pain, and so on.
Follow-up patients should follow the doctor’s instructions and have regular follow-ups.
Suggested consultation department
Nephrology.
Preparation
Registration
Before the outpatient consultation, you need to register at the hospital site, or through the hospital’s official website, official APP, 114 and other formal channels.
Preparation of information
Prepare your medical documents such as medical card, social security card (medical insurance card).
Bring previous medical information, such as medical records, physical examination reports, urine routine and kidney function test reports.
You can also prepare a list of medications being used in advance.
What questions the doctor may ask
Where is the discomfort? When did it first appear?
Has the discomfort been persistent? Has there been any aggravation or relief?
In addition to these symptoms, is there back pain, bloody or foamy urine? Are there any other symptoms?
What has been the mental, sleep, bowel, and dietary status since the onset of symptoms?
Have you had any upper respiratory tract infection or tonsillitis recently?
Have you been overworked or exercised strenuously recently?
Have you had any relevant examinations?
Have you been treated? What kind of treatment? How did it work?
Does anyone in your family have similar symptoms?
Questions you can ask your doctor
What tests are needed?
What diseases are being considered?
What causes these symptoms?
What treatments are available?
What are the side effects of the medications used for treatment?
Approximately how long will the treatment take?
Is it curable?
Are there any after-effects?
Is there any risk of contagion or heredity? Do family members need to be examined and treated?
Does this disease affect normal pregnancy and labor?
Diagnosis
Diagnostic Basis
Medical history
A history of infectious disease, such as infections of the upper respiratory tract, gastrointestinal tract, skin, and urinary system, may be present for several days or weeks.
Clinical manifestations
Symptoms may be unremarkable, with abnormal urinary routines detected only on physical examination.
There may be macroscopic hematuria and foamy urine, as well as varying degrees of edema, general malaise, malaise, and muscle pain.
Blood pressure measurements may be hypertensive or malignant hypertension.
Laboratory Tests
Routine urinalysis
Abnormal number of red blood cells in the urine may be detected, and red blood cells are predominantly aberrant red blood cells, which helps in the diagnosis of the disease.
Abnormal protein levels in the urine may be detected, which helps in the diagnosis of the disease.
Serum IgA test
Increased level of serum IgA can be found, which helps in the diagnosis of the disease.
Serum Complement C3 Test
Complement C3 level is mostly normal and can be used for differential diagnosis of the disease.
Renal Function Test
Monitoring of renal function is helpful in understanding the progress of the disease.
In case of renal impairment, elevated blood creatinine, urea and uric acid can be seen.
Others
Erythrocyte sedimentation rate (ESR) tests, anti-streptococcal hemolysin “O” test (ASO) and genetic analysis may be considered for differential diagnosis if necessary.
Pathologic tests
Important tests to confirm the diagnosis of IgA nephropathy.
Immunofluorescence examination shows diffuse deposition of IgA or IgA-based immunoglobulin in the glomerular mesangial area, often accompanied by C3 deposition.
Light microscopy shows various types of lesions, mainly diffuse glomerular mesangial hyperplasia, increased mesangial stroma, and the coexistence of multiple lesions.
Electron microscopy can see glomerular mesangial cell proliferation, mesangial matrix increase and with large clumps of electron dense material deposition.
The pathologic manifestations of IgA nephropathy are now widely used in Oxford staging, which includes the following staging.
Mesangial cell hyperplasia (MO/1).
Endothelial cell proliferation (EO/1).
Segmental sclerosis or adhesions (SO/1).
Renal tubular atrophy or interstitial fibrosis (TO/1/2).
Cellular or cellular fibrous crescent (CO/1/2).
Differential Diagnosis.
Secondary IgA nephropathy
Similarities: both may have hematuria and IgA deposits in the glomerular mesangial zone.
Differences: Patients with secondary IgA nephropathy have a clear history of diseases, such as systemic lupus erythematosus, dry syndrome, ankylosing spondylitis, herpes-like dermatitis, cirrhosis of the liver, chronic hepatitis. The combination of symptoms, various serologic tests, immunologic tests, and pathologic tests can be differentiated.
Acute post-streptococcal glomerulonephritis
Similarity: hematuria, proteinuria.
Differences: acute post-streptococcal infection glomerulonephritis is characterized as follows.
There is a history of antecedent streptococcal infection 1 to 3 weeks before the onset of the disease.
Patients have obvious symptoms of hematuria and persistent gross hematuria for a long period of time, which can range from several days to several weeks; in addition, edema and hypertension are obvious.
Laboratory tests show a decrease in complement C3, an increase in the anti-streptococcal hemolysin “O” test, and an increase in the erythrocyte sedimentation rate.
Allergic purpura nephritis
Similarity: hematuria.
Differences: In addition to hematuria, allergic purpura nephritis may present with skin purpura, black feces, abdominal pain, arthralgia, and systemic vasculitis. Different renal pathology and immunohistologic features can be used in the differential diagnosis of the two.
Thin basement membrane nephropathy
Similarity: hematuria and proteinuria.
Differences: Thin basement membrane nephropathy may have obvious family history, manifested by persistent microscopic hematuria, and renal function may be normal for a long time. In renal pathology, diffuse thinning of glomerular basement membrane is seen in electron microscopy, and no abnormality is seen in immunofluorescence and light microscopy.
Olport’s syndrome
Similarities: Both may have hematuria.
Differences: Olport’s syndrome is characterized as follows.
Patients may have a significant family history.
It presents with persistent microscopic hematuria, progressive decompensation of renal function, and may be associated with neurodeafness and ocular pathology.
In pathologic examination, irregular changes in the dense layer of the glomerular basement membrane with diffuse irregular thickening, thinning, and tearing are seen in electron microscopy; immunofluorescence and light microscopy show no abnormality.
Genetic analysis reveals the causative gene.
Non-IgA tethered proliferative nephritis
Similarity: both may have painless hematuria and proteinuria.
Differences: mainly by pathologic examination. There is no IgA deposition in glomerular membranes in non-IgA thylakoid nephritis; in renal pathology, the increase of thylakoid cells and stroma can be seen under electron microscopy, and the glomerular basement membrane shows “double track sign” and glomerular lobulation.
Treatment
Principles of treatment
Since the clinical manifestations of IgA nephropathy vary greatly, individualized treatment plans should be formulated according to the clinical manifestations and pathological types of patients.
Strict control of blood pressure
For urinary protein＞1g/d, the target of blood pressure control is 125/75mmHg or less.
For urinary protein <1g/d, the goal of blood pressure control is 130/80mmHg or less.
Aggressively control proteinuria levels, aiming for urine protein <1g/d.
Simple microscopic hematuria
In general, patients do not need special treatment.
Most patients’ renal function can be maintained in the normal range for a long time.
Precautions
Monitor urine protein (urine routine) and renal function regularly.
Avoid excessive exertion, nephrotoxic drugs and infections.
Recurrent Episodes of Necrotizing Hematuria
Antibiotics
For patients who have recurrent episodes of hematuria of the flesh eye after infection, or whose routine urinalysis is abnormal and their condition worsens, the infection should be actively controlled.
Antibiotics without nephrotoxicity, such as penicillin, erythromycin, cephalosporin, etc. need to be used.
Surgical treatment
Tonsillectomy should be considered for patients with recurrent chronic tonsillitis.
With proteinuria
Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (ARB)
Purpose of administration: to control the urine protein level <0.5g/d and to delay the progression of renal insufficiency.
Its dosage can be gradually increased to a tolerable dose.
Glucocorticoid
If after 3 to 6 months of treatment with oral ACEI or ARB and control of blood pressure, urine protein still persists to be strongly positive, then glucocorticoid therapy should be considered.
The total course of treatment with this medication should be at least 6 to 12 months; if the disease is in marked remission, a gradual dose reduction can be initiated at week 8 to 12.
Immunosuppressive drugs
Caution should be exercised in their use.
Commonly used drugs: cyclophosphamide, azathioprine, mertiomacrophenol, etc.
Nephrotic syndrome
Diuretics
Thiazide diuretics, labeled diuretics, potassium retention diuretics, osmotic diuretics, such as hydrochlorothiazide, furosemide, etc. can be used.
If necessary, plasma or albumin can be used for intravenous infusion to increase plasma osmolality to help diuresis.
ACEI or ARB
The purpose of medication is to reduce urinary protein and delay further deterioration of renal function.
Glucocorticoid
Glucocorticosteroids are used to control the immune-inflammatory reaction, inhibit the secretion of aldosterone and antidiuretic hormone, and affect the permeability of glomerular basement membrane, so as to play the role of diuresis, reduce urinary protein, and protect renal function.
The principle of medication is to start with sufficient amount, slowly reduce the drug, and maintain it for a long time.
Commonly used drugs: prednisone, methylprednisolone.
Patients with long-term hormone therapy are prone to side effects such as centripetal obesity, hyperglycemia, osteoporosis, hirsutism, acne, edema, gastric ulcers, psychiatric symptoms, and infections, which need to be monitored more closely and handled in a timely manner.
Immunosuppressants
Cytotoxic drugs
These drugs can be used in “hormone-dependent” or “hormone-resistant” patients to synergize hormone therapy.
If there is no contraindication to hormone therapy, they are generally not used as first choice or as stand-alone therapy.
Commonly used drugs: cyclophosphamide.
Calmodulin inhibitors
Often used together with hormones to control refractory nephrotic syndrome.
Commonly used drugs: cyclosporine, tacrolimus.
Matemacrophenol ester
Some reports in recent years indicate that this drug is effective in some refractory nephrotic syndrome, but there is a lack of experimental data, and caution should be exercised when using it.
Hypertension
Control of blood pressure can protect renal function and delay the progression of chronic kidney disease.
ACEI or ARB is often used clinically, and other types of antihypertensive drugs need to be applied simultaneously when necessary to effectively control blood pressure and reduce proteinuria in patients with IgA nephropathy.
Renal Failure
Acute renal failure
Intensive treatment with high-dose glucocorticoids and cytotoxic drugs
Commonly used treatment plan is the same as nephrotic syndrome.
Nutritional support
Nutrition can be provided through gastrointestinal tract as a priority, and water, sodium and potassium intake should be restricted as appropriate.
Those who cannot take oral nutrition should be fed intravenously, and the total amount and composition of nutritional support should be increased or decreased according to the clinical situation.
Hemodialysis
Hemodialysis treatment should be considered when necessary.
Chronic renal failure
Control the range of indicators
Blood pressure, blood glucose, urinary protein, increase in blood creatinine and decrease in glomerular filtration rate (GFR) need to be controlled in the ideal range.
Renal Replacement Therapy
This method can be considered when patients with acute renal failure or chronic renal failure, whose renal function is severely reduced and life-threatening, or when they need to maintain the stability of the body’s internal environment and remove various toxic substances.
It includes peritoneal dialysis, intermittent hemodialysis and continuous renal replacement therapy.
Active prevention and treatment of complications
Common complications include hydroelectrolyte disorders (e.g. hyperkalemia, hypocalcemia, hyperphosphatemia), hypertension, anemia, infections, hyperlipidemia, etc.
Symptomatic treatment should be given according to the condition.
Nutritional support
Limit protein intake.
Patients with chronic kidney disease (CKD) stage 1 to 2, with or without diabetes mellitus, are recommended to have a protein intake of 0.8 to 1g/(kg-d).
From CKD stage 3 to patients who are not on dialysis treatment, the recommended protein intake is 0.6 to 0.8 g/(kg-d).
Protein intake for hemodialysis and peritoneal dialysis patients is 1.0 to 1.2 g/(kg-d).
Supplement appropriate amount of α-keto acid preparation, vitamins and folic acid.
Control potassium and phosphorus intake, generally should be <800mg/d.
Chinese medicine treatment
IgA Nephropathy is similar to “Kidney Wind” in Chinese medicine, which can be categorized as “Blood in urine” and “Edema”.
Chinese medicine treatment of IgA nephropathy is based on the principle of eliminating evils and supporting correctness. During the acute exacerbation period, evils and realities are the mainstay, and medicines are used according to the prevalence of wind-heat, fire-heat, damp-heat and stasis of blood; during the chronic stage of the disease, positive deficiencies are the mainstay, and the deficiencies in qi, blood, yin, yang and the localization of the internal organs should be identified. For those with mixed deficiency and reality, both the symptoms and the root cause should be treated.
Patients need to be identified by TCM doctors according to the characteristics of their own conditions, and different treatments will be given in combination with the types of evidence.
Other Treatments
Fish oil
Some studies have proved that fish oil rich in omega-3 polyunsaturated fatty acids is beneficial to IgA nephropathy, but its exact efficacy is yet to be confirmed.
Fish oil is less dangerous and has cardiovascular benefits, and is currently considered a safe treatment option.
Kidney transplantation
If the disease has progressed to end-stage renal disease, kidney transplantation may be considered if available.
Birth limitation
Patients with less severe IgA nephropathy can tolerate pregnancy and do not need to restrict childbearing.
If the patient is combined with persistent severe hypertension, glomerular filtration rate <60ml/min, or severe renal vascular or interstitial lesions on renal histopathologic examination, pregnancy is not suitable and birth restriction should be considered.
Dietary restrictions
When the disease is induced by a certain type of food, further intake of this type of food should be avoided.
In complicated nephrotic syndrome, sodium should be restricted.
When acute renal failure is complicating the disease, water, sodium and potassium should be restricted as appropriate.
In complications of chronic renal failure, a protein-restricted diet is required.
Prognosis
Cure
The 10-year survival rate of IgA nephropathy is 80% to 85%, and the 20-year survival rate is about 65%. However, there are great individual differences, and some patients have a good long-term prognosis, while others progress rapidly to renal failure.
Indicators of poor disease prognosis are as follows.
Persistent uncontrollable hypertension and proteinuria (especially proteinuria persisting >1 g/d).
Impaired renal function.
Renal biopsy pathology shows glomerulosclerosis, interstitial fibrosis and tubular atrophy, or with massive crescent formation.
Hazards.
Patients with IgA nephropathy with microscopic hematuria alone generally have a better prognosis and less impact on health and longevity.
Patients with IgA nephropathy accompanied by proteinuria have a poorer prognosis and are prone to develop renal failure if the disease is not effectively controlled for a long time.
Patients with nephrotic syndrome have a better prognosis when the pathological changes are mild; on the contrary, the outcome is poor. If proteinuria is difficult to control, renal damage can develop progressively and the prognosis is poor.
Patients with IgA nephropathy who develop renal failure are usually in a more severe condition, which can be life-threatening in severe cases.
Those who develop symptoms of hypertension can be life-threatening when the condition further develops into malignant hypertension.
Patients with moderate to severe IgA nephropathy may accelerate the progression of their condition if they fail to adhere to the main treatment regimen for a long period of time.
Daily
Daily Management
Dietary management
Diet should be light and easy to digest, avoid spicy, stimulating, cold, hard and hot food.
It is recommended to eat more fresh fruits and vegetables and ensure proper water intake.
Attention should be paid to food variety and nutritional balance, and the intake of sodium, protein, potassium and phosphorus should be adjusted according to one’s condition.
When nephrotic syndrome occurs, a normal amount of high-quality protein diet should be taken, not advocating a high-protein diet, protein intake of 0.8-1.0g/(kg-d), can choose eggs, milk, lean meat, fish, shrimp, soy products and other high-quality proteins; when edema occurs, a low-salt (<3g/d) diet is needed.
When acute renal failure occurs, it is necessary to limit the intake of water, sodium and potassium salt as appropriate, and adjust the intake of nutrients according to the condition.
When chronic renal failure occurs, it is necessary to limit protein intake, the specific intake is related to the staging, low-protein diet conditions preferred high-quality protein, can be supplemented at the same time appropriate amount of α-ketoacid preparations, vitamins and folic acid, etc., and it is necessary to limit potassium and phosphorus.
Exercise management
Choose the type and intensity of exercise that the body can tolerate to help improve the body’s immunity.
There is no need to strictly limit activities, but strenuous exercise should be avoided.
Work and rest management
Make it a habit to go to bed early and not stay up late or go to bed late.
Get enough sleep and avoid over-exertion.
Others
Severe hypertension and edema require bed rest.
Family members should pay attention to the patient’s emotional guidance to avoid excessive negative emotions.
Family members should pay attention to care for the patient, give enough support and encouragement, and have patience and confidence in the patient.
Disease monitoring
Pay attention to the progress of the disease and go to the hospital in time when there is any abnormality.
Follow-up and review
Pay attention to regular review, once every 1 to 2 weeks in the early stage of treatment, and once every 1 to 3 months after the condition is stabilized.
Prevention
Actively eliminate predisposing and susceptible factors, such as infections of the upper respiratory tract, digestive tract, skin and urinary system.
Pay attention to your health, advocate regular medical checkups, and actively treat inflammatory infections or other diseases once they appear.
In daily life, good habits can be developed in terms of diet and living habits to improve the body’s immunity.