Pediatric IgA nephropathy

　　The etiology of pediatric IgA nephropathy is not yet fully understood and is related to various factors. Most scholars believe that the disease is caused by the deposition of IgA-containing circulating immune complexes in the kidney. The antigens in the complexes may be related to viruses, bacteria, or certain components in foods that cause infections in the respiratory or gastrointestinal mucosa.

　　In addition to general symptoms, it can also cause other diseases. Some children with pediatric IgA nephropathy may develop renal insufficiency, hypertension, and hypoalbuminemia. A few cases may present with rapidly progressive nephritis. Therefore, once diagnosed, active treatment is required, and preventive measures should also be taken in daily life.

　　Children with IgA nephropathy are more common in older children and adolescents, with a male-to-female ratio of 2:1. The onset is often preceded by a trigger such as upper respiratory tract infection, and there are also reports of onset triggered by diarrhea, urinary tract infection, etc. The clinical manifestations are diverse, ranging from only microscopic hematuria to nephrotic syndrome, which can all be the manifestation at the onset. The various clinical manifestations can also change with the course of the disease. 80% of children with IgA nephropathy have gross hematuria as the initial symptom. The incidence in North America and Europe is higher than in Asia, often associated with upper respiratory tract infection (Berger disease); blooduria may occur within a short interval (24-72h) after upper respiratory tract infection, and occasionally within a few hours. Most patients have tonsillar enlargement, and the cessation of gross hematuria occurs in most patients after tonsillectomy. Some children may present with hematuria and proteinuria, at this time, hematuria can be either episodic gross hematuria or microscopic hematuria, and proteinuria is usually mild to moderate. IgA nephropathy manifested as nephrotic syndrome accounts for about 15% to 30% of the total, with prominent manifestations of 'high proteinuria, high blood pressure, high cholesterol, and low albumin'. It is often rare to have respiratory tract infections before onset, and some cases may present with nephritis syndrome, in addition to hematuria, there are also hypertension, renal insufficiency. Hypertension is more common in older patients, accounting for 20% in adults and only 5% in children. Hypertension is an important sign of disease progression in IgA nephropathy, most of which are accompanied by rapid deterioration of renal function. Less than 5% of patients with IgA nephropathy present with rapid progressive glomerulonephritis.

　　Currently, there is no clear preventive method for children with IgA nephropathy. It is necessary to actively prevent and treat various respiratory and digestive tract infections. IgA nephropathy is an immune reactive disease. Therefore, for the prevention of the occurrence and recurrence of the disease, it is first necessary to avoid the invasion of antigenic substances. Therefore, it is necessary to actively prevent and treat, prevent respiratory tract infections, avoid damage to the gastrointestinal mucosa, and minimize the intake of food that may become antigenic substances. When the onset of the patient is related to recurrent tonsillitis, tonsillectomy can be considered after the control of inflammation. It is advisable to eat less spicy food, avoid smoking and drinking. Adolescents should pay attention to a balanced, light diet while absorbing nutrition, and not eat too much high-protein, high-fat food. In addition, during study and work, attention should be paid to rest and avoid overwork. Moderate physical exercise can enhance physical fitness and reduce infections caused by colds and weakened physique. However, when engaging in sports, attention should be paid to the amount, and avoid excessive and intense exercise that leads to overwork.

　　Children with IgA nephropathy are characterized by gross hematuria or microscopic hematuria, so clinical diagnosis mainly relies on urinalysis, supplemented by other examinations. The main examination methods are as follows:

　　1. Urinalysis

　　1. Hematuria: Clinically, about 40% to 45% of patients show gross or microscopic hematuria, 35% to 40% of patients may show only microscopic hematuria, or microscopic hematuria with small amounts of proteinuria. Gross hematuria can last for several hours to several days and then turn into persistent microscopic hematuria. Some patients may experience the disappearance of hematuria, but it often recurs, and gross hematuria reappears during the attack.

　　2、蛋白尿：为轻度蛋白尿，一般尿蛋白定量

　　二、免疫学检查

　　1、IgA增高：约1/4～l/2病人血IgA增高，主要是多聚体IgA的增多。

　　2、循环免疫复合物：约1/5～2/3患儿血中可检出IgA循环免疫复合物和(或)IgG循环免疫复合物。

　　3、抗“O”升高：少数患者有抗“O”滴度升高。

　　4、补体：C3，C4多正常。

　　5、其他：IgA型类风湿因子以及IgA型ANCA也时常为阳性，有人认为血中升高的IgA-纤维结合蛋白复合物是IgA肾病的特征性改变，有较高诊断价值，必要时做B超，心电图和X线检查，免疫病理检查：肾脏免疫病理是确诊IgA肾病惟一关键的依据，有人进行皮肤免疫病理检查发现，20％～50％病人皮肤毛细血管壁上有IgA，C3，备解素的沉积，Bene等报告皮肤活体组织检查的特异性和敏感性分别为88％和75％。

　　小儿IgA肾病患儿在饮食上要保证主食、钠盐的摄入。同时注意保证优质蛋白摄入。饮食的建议如下：

　　常用可食蔬菜：豆腐，大白菜，大葱(调味)，甘蓝，蕨菜，榆钱，方瓜，佛手瓜，绿豆芽，红心甘薯，芸豆，葫芦，四季豆，丝瓜，茄子，卷心菜，洋葱，冬瓜，南瓜，西葫芦，黄瓜，小白菜，萝卜，苦菜，豆角，辣椒(调味)，芋头，扁豆，胡萝卜，茼蒿，蒜黄，蒜苔，芹菜，韭菜，莴苣，菜花，西红柿，甜柿椒，豆芽，生菜，油菜，藕，榨菜，大蒜(调味)，姜，苜蓿，苦瓜，菠菜，雪里红，干木耳，银耳，荠菜，土豆。

　　Avoid: fishy and spicy foods, fried and crispy foods, seafood such as sea fish, sea crab, chili, garlic, green onions, coriander, and dog meat.

　　In the past, it was believed that there was no specific treatment for pediatric IgA nephropathy, and the prognosis was relatively good, so the treatment measures were not very active. However, in recent years, with the deepening of our understanding of this disease, many studies have shown that active treatment can significantly improve the prognosis. IgA nephropathy has great differences from pathological changes to clinical manifestations, and the prognosis also varies greatly. Therefore, individualized treatment measures must be implemented.

　　1. General treatment

　　The most common clinical type of children is recurrent gross hematuria, and most of them have triggering factors, such as acute upper respiratory tract infection, etc. Therefore, it is necessary to actively control infection, clear the focus of infection, pay attention to rest, and short-term antibiotic treatment also has a certain effect on controlling the symptoms during the acute stage. For children with edema and hypertension, appropriate diuretic and antihypertensive drugs should be administered, and a low-salt, low-protein diet should be adopted.

　　2. Adrenal cortical hormones and immunosuppressive agents

　　For children with nephrotic syndrome or rapidly progressive glomerulonephritis syndrome, corticosteroids and immunosuppressive agents should be administered. Japan has conducted a nationwide multicenter controlled study, in which children treated with prednisone and immunosuppressive therapy for IgA nephropathy had a significantly lower proportion of renal insufficiency in the long term compared to those receiving general treatment. Kabayashi conducted a retrospective study on two groups of patients, one group consisting of 29 cases with proteinuria >2g/d, treated with prednisone for 1 to 3 years, followed up for 2 to 4 years, the results showed that early hormone treatment (when Ccr was above 70ml/min) was beneficial for stabilizing renal function and delaying disease progression. For another group of 18 cases with proteinuria of 1 to 2g/d, corticosteroid treatment was also used for IgA nephropathy, and 42 cases of IgA patients treated with dipyridamole (Persantin) and indomethacin (Anaprox) were used as controls. The treatment group was significantly better than the control group in stabilizing renal function, lowering blood pressure, and reducing proteinuria. Lai et al. reported the results of a prospective randomized controlled trial, in which 17 patients took prednisone for 4 months daily, compared with 17 control group patients, with an average follow-up of 38 months, there was no significant difference in the endogenous creatinine clearance rate between the two groups. Prednisone treatment can significantly improve the remission rate in patients with minimal change nephrotic syndrome, but there are certain adverse reactions. This study suggests that prednisone treatment is beneficial for IgA nephropathy. Some reported a controlled study on adult IgA nephropathy to investigate the efficacy of azathioprine and prednisone, in which 66 patients were treated with azathioprine and prednisone. The results showed that it was beneficial in slowing the progression of IgA nephropathy compared to 48 cases in the control group that did not receive this treatment. Recently, Nagaoka et al. reported the use of a new immunosuppressant, mizoribine, for the treatment of childhood IgA nephropathy. This drug is safe, well-tolerated, can be taken long-term, and can significantly reduce the degree of proteinuria and hematuria. Repeated renal biopsy confirmed that the degree of renal tissue lesions was reduced. There are fewer reports on the use of cyclosporin. Lai et al. conducted a randomized, single-blind controlled trial using cyclosporin, with 12 cases in the treatment group and 12 in the control group. The patients had proteinuria greater than 1.5g/d and a reduction in creatinine clearance rate (Ccr 77±6ml/min), and were treated with cyclosporin for 12 weeks, with plasma concentration levels controlled at 50 to 100ng/ml. The results showed a significant reduction in protein excretion, accompanied by an increase in plasma creatinine clearance rate, but these changes disappeared after treatment was terminated. In summary, the efficacy of immunosuppressants in the treatment of IgA nephropathy still needs to be evaluated. Woo and Walker separately observed the combined therapeutic effects of cyclophosphamide, warfarin, dipyridamole (Persantin), and hormones, and the results showed that compared with the control group, proteinuria could be reduced and renal function stabilized during the treatment period, but there was no significant difference in renal function protection compared with the control group after 2 to 5 years of follow-up.

　　3. Immunoglobulin

　　In a group of open prospective studies, Postoker and others used high-dose human serum gamma globulin intravenous injection, 1 time/d, 2g/kg each time, for 3 months, then changed to 16.5% human serum gamma globulin intramuscular injection, 0.35ml/kg each time, once every two weeks, for 6 months. The results showed that after treatment, the urine protein excretion decreased from 5.2g/d to 2.2g/d, hematuria and leukocyte urine disappeared, and the monthly decreasing rate of glomerular filtration rate slowed from 3.78ml/min to 0.

　　4. Fish Oil (fishoil)

　　Patients with IgA nephropathy lack essential fatty acids, and fish oil can supplement essential fatty acids, thereby preventing early glomerular damage. Fish oil is rich in long-chain ω-3 polyunsaturated fatty acids, EPA (Eicosapentaenoic acid), DHA, which can replace arachidonic acid and act as substrates for lipooxygenase and cyclooxygenase, exerting effects by changing membrane fluidity and reducing platelet aggregation. As early as 1984, Hamazaki collected 20 IgA nephropathy patients for preliminary research. The treatment group received fish oil treatment for 1 year, and the renal function was maintained stable. However, the control group that did not receive fish oil showed a decrease in plasma creatinine clearance rate. In 1994, Donadio conducted a multicenter double-blind randomized controlled trial, collecting a total of 55 patients. The treatment group took 12g fish oil orally daily, while the control group took 51g olive oil. Among the selected cases, 68% had an increased baseline serum creatinine value. The initial observation endpoint was an increase in serum creatinine by >50%. The results showed that during the treatment period (2 years), only 6% of the patients in the fish oil group progressed to the observation endpoint, while 33% in the control group did. The annual increase rate of serum creatinine in the treatment group was 0.03mg/dl, and in the control group was 0.14mg/dl. Four years later, the incidence of end-stage renal disease in the control group was 40%, while in the treatment group it was 10%. The results were statistically significant, and no patients stopped treatment due to adverse reactions, indicating that fish oil can slow down the decline rate of GFR. The author also reported the long-term follow-up results of the above cases in 1999, showing that early and sustained use of fish oil can significantly delay the onset of renal failure in high-risk IgA nephropathy patients.

　　5. Other

　　Copp recently organized a 6-year prospective, multicenter, double-blind, randomized controlled trial to explore the therapeutic efficacy of long-term administration of benazepril [benazepril, 0.2mg/(kg·d)] in children and young adults with moderate proteinuria and good renal function due to IgA nephropathy. The trial was completed in 2004. In the past, some people used phenytoin sodium 5mg/(kg·d) to treat IgA nephropathy and found that it could reduce the levels of IgA and poly IgA in serum and reduce the frequency of hematuria episodes, but the decrease in circulating immune complexes was not reduced, and the long-term efficacy was not certain. In recent years, it has been used less. Traditional Chinese medicine and Chinese herbal medicine treatment of IgA nephropathy also has certain efficacy. For moderate proteinuria, the use of Tripterygium glycosides tablets 1mg/(kg·d) for 3 months can achieve significant efficacy.

　　6. Hemodialysis and renal transplantation are feasible for end-stage renal failure patients.

　　Prognosis

　　After 10 years, about 15% of adult IgA nephropathy progresses to end-stage renal failure, and after 20 years, it rises to 25% to 30%. The prognosis of pediatric IgA nephropathy is better than that of adults. Yoshikawa reported that 10% progressed to end-stage renal failure after 20 years. Many factors affect the prognosis, including severe proteinuria, hypertension, glomerulosclerosis, and severe interstitial tubular lesions, which are indicators of poor prognosis; males are also more prone to progression; the relationship between gross hematuria and prognosis is still controversial. It is reported that the annual reduction rate of GFR in IgA nephropathy patients from normal renal function is 1-3 ml/min, while the reduction rate of GFR in IgA nephropathy patients with nephrotic syndrome is 9 ml/min. When hypertension is combined, the reduction rate of GFR is even higher, reaching 12 ml/min per year. Therefore, controlling blood pressure and proteinuria is crucial in the treatment of IgA nephropathy.