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IgA nephropathy research

New research progress on prognostic factors of IgA nephropathy IgA nephropathy is one of the most common primary glomerular diseases, with different clinical manifestations, different outcomes and inpidual differences It is difficult to det...

IgA nephropathy research

May 09, 2017 by Kidney Disease Expert

New research progress on prognostic factors of IgA nephropathy

IgA nephropathy is one of the most common primary glomerular diseases, with different clinical manifestations, different outcomes and inpidual differences

It is difficult to determine the progression of disease progression and its prognosis from the onset of disease to end-stage renal failure. This article affects the prognosis of IgA nephropathy

The factors are summarized.

IgA nephropathy (IgAN immunoglobulin A nephropathy, one of the most common primary glomerular disease is one of the world, is leading to end-stage renal failure (end - stage takes diseases, ESRD, the main reasons for the renal biopsy immune pathological examination showed in glomerular mesangial area have given priority to with IgA sample particle deposition, clinically with recurrent gross hematuria or microscopic hematuria as the main performance, may be accompanied by A small amount of proteinuria. But IgAN inpidual difference is big, the clinical symptoms can be any type (only found in donor kidneys, Japan reported healthy crowd kidney donors have [1] 16% of IgAN), severe cases are radical nephritis, the prognosis of disease has larger heterogeneity, some patients can complete response, finally has A 15% 40% of patients for the development of ESRD. Factors affecting the risk of IgAN prognosis timely recognition and intervention, has important significance for delay progression. Now IgAN prognosis factors.

1,Age and gender

The impact of age and gender on the development of the problem remains controversial [2, 3]. Some studies in [4] confirm that men and advanced age are the risk factors for the risk of death. The prevalence of cerebrovascular disease was associated with the elderly, men and patients with the disease. Patients with good kidney function, men and certain [3] vascular disease were independently associated; IgAN patients clinical manifestation, pathological characteristics of the different age groups, along with the age increase, the major clinical prognosis refers to [5] the integral, pathological classification and pathological prognostic indicators are aggravating trend but a multicenter study of statistical data were retrospectively analyzed 711 patients with IgAN found that young strongly suggest kidney disease with 2 2 deposit rate is low, on the contrary, the higher the age of onset prompted to slow disease progression slow [6]. This may be related to the severity of the clinical symptoms and the severity of the disease screening before the diagnosis.

2,Family history 

Now sure can have familial IgAN part, often can occur in first-degree relatives, and sporadic IgAN comparison, both similar clinical manifestations and pathological, familial IgAN prognosis is still poor for [7]. Schena etc. Familial and sporadic IgAN in southern Italy to study, found that after the onset of familial IgAN kidney 20 years survival rate was 41%, significantly lower than the group of 94%, familial IgAN than sporadic IgAN prognosis is poor, 64% of the familial IgAN 15 years [8] progress to ESRD, and sending out group was only 8%. But the prognosis of familial IgAN, such as Izzi, is not poor in the distribution group, and indicates that the distribution group is more susceptible to high blood pressure. The mechanism for familial disease is still not fully understood and may be linked to genetics and the environment, and the progress of the disease remains to be further studied.

3 clinical features

3. 1 hematuria

About half of IgAN clinical manifestation for typical recurrent upper respiratory tract and the digestive tract infection with macroscopic haematuria, after the initial hematuria can disappear, most patients with macroscopic haematuria attack interphase urine test can be normal, but can then be converted to persistent microscopic haematuria, and associated with the degree of proteinuria, half presented with persistent microscopic haematuria. The effect of hematuria on the prognosis is controversial, and the prognosis of macroscopic hematuria is generally better than that of the hematuria in the mirror. But to the naked eye [9] blood urine onset acute renal failure, and interphase for renal hematuria attack to wear to the naked eye, can be found kidney pathological changes such as segmental hard [10] and crescent. Blood in the urine is a sign of acute inflammation, secondary to lining epithelial cell necrosis and collagen, is a sign of kidney tissue damage, the severity of the damage depends on the duration of inflammation and tissue repair capacity and progress. Focal segmental necrosis can be quickly repair the balloon adhesions or crescent widely form and cause hematuria temporary relief, but these pathological changes along with the aggravating and recurrence of blood in the urine is aggravating, lead to gradual progress of the clinical manifestations and renal fibrosis [2] Rauta, etc Also found that if renal glomerular filtration rate (glomerulafiltration rate, GFR) of 85 ml/min or prognosis of patients with the number of red blood cells in urine and independent, prove that hematuria has a certain influence on prognosis.

3.2 proteinuria

Urine protein 1 g/d or higher are independent risk factors influence the progress of disease, more research will be 1 g/d as the severity of proteinuria [11, 12] [13]. The Jafar study showed a significant increase in the risk of blood pressure in patients with normal high levels of urine protein > 1 g/d. In patients with urinary protein of 1 g/d or more, the detection diagnosis and diagnosis after 6 weeks, 6 months and 1 year of 24 hours urinary protein, follow-up 5. In 76, using Co proportional hazards model analysis, found the urine protein high, 1 in the amount of urine protein, urine protein quantity within 1 year slope and related ESRD, one [14] in the amount of urine protein is the strongest risk factor for prognosis. The patients who had a chance to have a urine protein >, 6g/d and did not receive any treatment for years had better kidney function in [15], which may be related to their pathological type. Multiple regression analysis showed that continuous proteinuria and urinary protein levels were the only independent risk factors for the development of [15] to the end of the kidney. Eiro [16] if found such as renal proteinuria number and the amount of urine protein product value and balls, tubular histopathologic grading, and creatinine values significantly related, therefore, put forward to proteinuria index (proteinuria number and the amount of urine protein product value) said the severity of the disease, prognosis. In addition, the composition of urine protein and prognosis is related to renal tubular protein, low molecular weight increased [15] especially protein a1 microglobulin showed poor prognosis.

3.3 High blood pressure

High blood pressure and IgAN important prognostic factors of renal hypertension when wear is a major independent risk factor, risk ratio is 8. [11] [13] 13 risk coexist and proteinuria. Jafar recommends that patients with the urine protein > 1.0 g/d should be kept under 130/70mmhg. [4]

Comunian make retrospective study on 119 patients with IgAN, 60% of patients with high blood pressure, creatinine at the end of 5 years follow-up or 1. 5 mg/dL, and 13% patients with normal blood pressure. Family history of hypertension [17] also have important reference value, studies have shown in 89. 6% with a family history of hypertension IgAN patients suffering from high blood pressure, no family history of hypertension is only 22. 6%, the former has 45. 2% renal failure, while the latter is only 4. 1%, suggesting the family history of hypertension patients with IgAN prognosis is poor.

3. 4 creatinine

Creatinine is good indicator of the severity of kidney disease, most of the single variable study shows that at the time of diagnosis that is found that higher creatinine, relatively strong [6] to suggest poor prognosis. More than a decade ago DA 'mico reported in IgAN course, such as when the creatinine once more than a certain value, IgAN progress to ESRD is unable to avoid, after that if not treated, the patient's creatinine will rise rapidly, 10 months creatinine doubled, the PNR creatinine value that is not reversible point (point of

[18] no - return, when the creatinine value exceeds the PNR. According to DA 'mico, PNR is 3.0mg/dL, while Kom2 is

[19] atsu, etc., confirms that the PNR of Japan's IgAN patients is 2.0 mg/dL. Through the kidney to wear when creatinine value is 1. 2 mg/dL2. 0 mg/dL of 47 patients with IgAN more than 3 years of follow-up, once found creatinine value > 2. 0 mg/dL, one patient creatinine values can be reduced to 2. 0 mg/dL. The differences in the data may have to do with race and the environment.

3.5 metabolic factors

There are studies suggest metabolic factors, especially the high uric acid hematic disease, high blood triglycerides, and family history, high body mass index,3,20 [2] (BM I) indicate the progress of IgAN. Blood uric acid, cholesterol, triglycerides, amount of urine protein, blood pressure, BM I, smoking and IgAN histopathologic changes related to the uric acid is the strongest risk factor for damage of tubulointerstitium, tubular atrophy and interstitial fibrosis and inflammation is the independent risk factors [20], serum triglycerides, BMI and tubular interstitial lesions, vascular lesions, result in IgAN patients with cardiovascular and cerebrovascular disease incidence rate is higher than the general population. In the clinical course of the patients with the disease, the influence of these factors on the prognosis is mixed. MagistroniR using semi-quantitative count, such as clinical prognostic index was proposed for the CPI (clinicalprognostic index) judge IgAN after pre [21], define creatinine > 1. 4 mg/dL to 2 points, proteinuria > 1 g / 24 hours for 1 minute, with high blood pressure for 1 minute, age > 30 to 1 minute, define 02 pided into low CPI group, 35 pided into high CPI group, compared two groups, found that 10 years of survival rate obviously different: low CPI group 91. 7%, the high CPI group was 35%.

4 the pathological

Pathologic changes have a large effect on prognosis. Severe hyperplasia, glomerular sclerosis, crescent formation, capillary wall damage, small tube damage, interstitial fibrosis, and vascular damage are signs of prognosis. The formation of the new moon is characterized by an acute inflammation of the disease, and is more severe than the normal one, which is larger than the normal one. [12] Lee on h. s. Lee 'S pathology classification was improved, the histopathological manifestation of IgAN is pided into five, grade I: normal or local mesangial cell proliferation; Class II: diffuse membrane cell proliferation, or less than < 25% of the glomerular crescent formation (Cr), segmental sclerosis (SS), ball hardening (GS); Level III: 25-49% of the ball Cr/SS/GS; Level IV: 50% 75% of the ball r/SS/GS; V: > 75% of the ball Cr/SS/GS. Combined with clinical data, found the ball grading and renal wear was significantly related with high blood pressure, creatinine, proteinuria, follow-up of 187 patients with IgAN 6. 5 years, both univariate and multivariate analysis found that ball was significantly related classification and disease progression, can be used as one of the evaluation index of prognosis. However, it is important to note that some of the histology that has only minor changes in the histology or the only ones that have been altered only for the focal point of the focal point of the focal area are also progressing

ESRD, for now, is unclear. It is important to note that many IgAN damage of tubulointerstitium and smaller [23] ball damage can prompt the progress of the disease, patients with severe damage of tubulointerstitium often progress to ESRD with the quickest speed, but few IgA was observed in renal interstitial sedimentation, it is not clear how mesangial deposition of IgA lead to damage of tubulointerstitium. Some of the dielectric agents, such as local cytokines and complement, which can be released by membrane cells after IgA deposition, cause proximal tubule epithelial cells and interstitial damage. The expression, such as tnf-alpha, is related to the expression of the small tubule lesion of the disease after IgA deposition. In determining the prognosis of the disease, the natural course of the disease should be taken into account, even if the patient of the same period can have different disease progression

The rate of the show and the outcome of adult disease were heterogeneity, especially in cases of mild proteinuria and slight tissue change. The prognosis is to classify patients at different stages. But the above factors to judge the disease prognosis in patients with a single is sometimes inaccurate, it may be because the prognosis of the disease heterogeneity and intermittent of disease activity. In addition, the patient's response to treatment is also a more important reference factor because of the clinical treatment. The hormone can significantly reduce proteinuria, delay kidney function, and the sensitivity of the hormone and early urinary protein reduction suggest a better prognosis.

Other factors affecting the prognosis of the IgAN

5. 1 iga

Part of the blood of patients with IgAN IgA levels, relationship with the prognosis is not clear, but blood IgA/C3 IgAN patients compared with the other class type [24] glomerulonephritis was increased, helps to distinguish between IgAN and IgAN, and is associated with prognosis, Kaplan and Meier analysis shows the average values of IgA/C3 4 or 5 patients with poor prognosis in the value of < 4. 5 patients, the former five years kidney survival rate is 84. 4%, the latter for [25] [24] 100%. Maeda et al., such as Maeda, used four clinical parameters to distinguish the difference between the one and the non-igan and the prognostic properties of the prognosis: 1. Diuretic red cell > 5 / HP; Continuous urine protein, >, 3g/d; Blood IgA level, > 315 mg/dl; 4. Serum IgA/C3 value > 3.01, in line with the above three or four indicators patients diagnosis of IgAN easily, and patients with good prognosis and the prognosis is relatively good comparison between the above level is also a significant difference between the clinical parameters, explain the rise of blood IgA can be meaningful. But the relationship between the IgA/C3 and kidney damage is not fully clear, may be associated with IgA caused by local complement response after sedimentation, interstitial blood vessel walls around C3 deposition of vascular injury in patients with more serious.

IgA, which is washed away from the kidney, is more of a pIgA, a large molecule that IgA may come from a blood circulation. By examining the serum pIgA level of the patient and the healthy group, the pIgA/total IgA ratio was significantly lower, although the serum pIgA was significantly elevated in patients with the disease. Child IgA levels were associated with macroscopic hematuria, which was not evident in adults, and the level of pIgA and the clinical [26] parameters were not significantly correlated. But there is research that supports the use of pIgA1 through the RAS system and the transformation of the growth factor beta, which results in the kidney fibrosis of [27] and kidney failure. So IgA IgAN impact may be related to the physical and chemical properties of IgA, now pay more attention to the prognosis of abnormal glycosylation IgA1 prompt value, sugar chain in patients with IgAN IgA1 hinge area lack of saliva acidification and galactose base function, with exception glycosylation IgA1 circulating immune complex

The proliferation of membrane cells can be affected in vitro, and may play a major role in [28]. The high level of IgA1 has been found to be rapidly progressing to ESRD, which is characterized by "malignant" IgAN.

5.2 the ras system 5.

The RAS system is the main secretory system for regulating blood pressure in the kidney, which affects the prognosis of the organ by regulating blood pressure. There are more studies on the RAS system, which have been linked to certain markers and prognoses of the gene level. The subgroup C (-20) of the T235 allele of angiotensin (T235) was associated with the development of the disease, which could affect the efficacy of the RAS system to block the drug. The angiotensin conversion enzyme D allele suggests a poor prognosis. The factors associated with high blood pressure can indirectly lead to the development of the IgAN. Insulin resistance is not the direct causes of decline in renal function, but independent of hypertension related and IgAN patients, so the insulin resistance may be [29] indirect risk factors, is the new treatment of IgAN targets; The genetic polymorphism of the gene for primary hypertension may also affect the prognosis of the patients by regulating blood pressure.

5.3 other 

Adhesion molecules, such as icam-i, can be used in small tubes and interstitial expressions as a sign of the small tubule and interstitial damage, which is associated with proteinuria. By the effect of hardening and apoptosis, apoptosis is inhibited and leads to disease progression. Nitric oxide synthase (iNOS) and p53 protein expression in renal cell increases, tumor necrosis factor genotypes TNFA2 / TNFA2, the increase of blood and urine soluble Fas, podocyte Bcl - 2 genes may be related to progress in IgAN. In terms of inflammatory mediators, participate in the regulation of inflammation uterus globin the present study is more, the protein gene knock out and the genetically modified mice can be used as an animal model with IgAN pathological and clinical characteristics, its [30] GG genotype may signal the rapid progress of the disease. Another IL

The -10 genotype g-1082a, urinary il-6, and the cd14/159 genotype are all linked to disease progression.

In addition, the peroxidase body value-added activated receptor gamma genotype specific proteins FSP1 C161T, fibroblasts, adduction protein and angiotensin converting enzyme gene interactions, fibrinolytic enzyme activation inhibitory factor PAI - 1 genotype 4 g / 5 g and IgAN associated disease progression.

6 conclusion

The prognosis of the disease is influenced by a variety of factors, and the prognosis of the disease should be considered in all aspects. Fully recognize its prognostic factors of disease prognosis is not only beneficial to the accurate judgment, and the optimal timing of treatment for the disease and scheme selection is important. At present, the disease mechanism of the disease is not clear, it is positive to strictly control the development of the disease in all aspects.



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