Significance Of Urinary P?NP/Cr In IgA Nephropathy

Objective: In China,IgA nephropathy is the most common chronic glomerulonephritis,the majority of patients with progressive development.The diagnosis of IgA nephropathy relies on renal biopsy for pathological diagnosis,but kidney biopsies is invasive technical operation,so in clinical practice need noninvasive examination of indicators to assess the progress of the disease.Tubulointerstitial fibrosis is a common path for the development of IgA nephropathy and other kidney diseases to end-stage renal disease.The degree of fibrosis is closely related to the long-term prognosis of nephropathy.In the kidney tissue of IgA nephropathy,when the factors such as injury and inflammation persist,stimulate fibroblast proliferation,produce excessive extracellular matrix,namely collagen type I,collagen type ?,fibronectin and proteoglycans deposited in the renal interstitial.Type ? collagen releases the procollagen ? aminoterminal propeptide(P?NP)under the action of endonuclease during its deposition,and the free fragment enters the peripheral circulation and increases with the activity of collagen fibers.P?NP is composed of three identical polypeptide chains with a molecular weight of 42 kD and a short half-life.The cleavage is mainly carried out in the liver.The aim of this study was to investigate the changes of urinary P?NP concentration in IgA nephropathy,to investigate the relationship between P?NP and tubulointerstitial fibrosis,to evaluate the degree of tubulointerstitial fibrosis,thus providing reliable indicators of disease relief or progression for clinical follow-up.Methods: IgA nephropathy group: We collected 69 patients who first time came to the department of nephrology at the second hospital of Hebei University School of Medicine from November 2015 to June 2016,according to renal biopsy and pathological examination were diagnosed as primary IgA nephropathy.Exclusion criteria: 1)Lupus nephritis,anaphylactic purpuranephritis,tumors and other secondary IgA deposition of nephritis.2)Patients with significant impairment of liver function(ALT> 1.5 times more than normal),because hepatic dysfunction interferes with P?NP metabolism.3)Patients with extrarenal fibrotic diseases,such as systemic sclerosis and pulmonary fibrosis.4)combined with other kidney diseases,such as diabetic nephropathy,acute interstitial nephritis,acute tubular necrosis and so on.5)Patients who are using hormones and(or)immunosuppressive agents.6)patients with transplanted kidney.Grouping: According to Oxford classification mesangial hypercellularity,endocapillary proliferation,segmental glomerulosclerosis/adhesion,and tubular atrophy/ interstitial fibrosis divided into(M0/1)groups,(S0/1)groups,(T0/T1/T2)groups.The control group of 20 cases were selected from our hospital health examination center,assessment of our hospital health examination for the control group.Collected IgA nephropathy and normal control group morning urine.The basic data and clinical indexes were collected from IgA nephropathy and normal control group.The urinary P?NP was measured by enzyme-linked immunosorbent assay(ELISA),and urine creatinine value was measured to correct and immunohistochemical method was used to detect the expression of P?NP in renal tissue.The data were analyzed by SPSS13.0 software.Results:1 General SituationThe differences compared the IgA nephropathy with the control group of the urine P?NP/Cr,serum creatinine,eGFR,?2 microglobulin,serum albumin were significant.The correlation analysis showed that the urinary P?NP/Cr was positively correlated with renal tubular atrophy/interstitial fibrosis(r=0.272,P<0.05)and proteinuria(r=0.258,P<0.05),and negatively correlated with serum albumin(r=-0.333,P<0.05)in IgA nephropathy.2 The comparison between IgA nephropathy group and control group2.1 The comparison of urinary P?NP/Cr among M0,M1 and control groupM0 group,M1 group and control group compared with the levels of urinary P?NP/Cr were significantly different(P<0.05).M0 group,M1 groupcompared with control group the levels of serum creatinine,eGFR,?2-microglobulin and serum albumin were significantly different(P<0.05).The differences compared the M0 group with the M1 group of serum creatinine,?2-microglobulin,serum albumin and proteinuria were significantly different(P <0.05).2.2 The comparison of urinary P?NP/Cr among S0,S1 and control groupS0 group,S1 group compared with control group the levels of urine P?NP/Cr were significant different(P<0.05).There was no significant difference between the S1 group and the S2 group the levels of urinary P?NP/Cr(P>0.05).S0 group,S1 group compared with control group the levels of serum creatinine,?2-microglobulin and serum albumin were significant different(P <0.05).2.3 The comparison of urinary P?NP/Cr among T0,T1,T2 and control groupT1 group,T1 group compared with control group the levels of urinaryP?NP/Cr were significantly different(P<0.05).There was a significant difference between the T0 group and the T2 group the levels of urinaryP?NP/Cr(P<0.05).Because of the number of cases(38 cases,24 cases and 7 cases)were significantly different in the T0 group,T1 group and T2 group.According to renal tubular atrophy/interstitial fibrosis degree regrouped,divided into T0 group and T1 + T2 group,respectively,38 cases and 31 cases.There was no significant difference in urinary P?NP/Cr betweent renal T0 group and the control group(P>0.05),There was significant difference in urinary P?NP/Cr between the control group compared with the T1+T2 group and the T0 group compared with the T1+T2 group(P<0.05).There was significant difference among the serum albumin,serum creatinine and ?2microglobulin betweent T0 group and the control group(P<0.05).The differences compared T1+T2 group with control group of the serum albumin,serum creatinine,eGFR,?2 microglobulin were significant.T0 group and T1+T2 group compared with serum albumin,serum creatinine,eGFR,?2microglobulin,proteinuria were significant different.2.4 The comparison of urine P?NP/Cr in the C0,C1,C2 group and the controlgroupC1 group,C2 group compared with control group the levels of urine P?NP/Cr were significant different(P<0.05).There was no significant difference between the C0 group and control group the levels of urinary P?NP/Cr(P>0.05).There was no significant difference among the C0 group,C1 group and C3 group the levels of urinary P?NP/Cr(P>0.05).C0 group compared with C1,C2 group were significantly different proteinuria(P<0.05).3 P?NP expression in renal tissueIn IgA nephropathy,the expression of P?NP in renal tissue was significantly correlated with urinary P?NP concentration(r=0.560,P<0.05).The expression of P?NP in renal tissue of IgA nephropathy was significantly higher than that in control group(P<0.05).With the IgA nephropathy renal tubular atrophy interstitial fibrosis increased,P?NP expression increased significantly(P<0.05).The expression of P?NP in renal tissue was significantly different between the control group and T1,T2 group from IgA nephropathy(P< 0.05)There was no significant difference in the expression of P?NP in renal tissue between the control group and T0 group(P>0.05).The expression of P?NP in renal tissue was significantly different between T0 group and T2 group in IgA nephropathy(P< 0.05).There was no significant difference in the expression of P?NP in T0 and T1,T1 and T2(P> 0.05).There was no significant difference in the expression of P?NP in T0 and T2 group in IgA nephropathy(P <0.05).Conclusions:Urinary P?NP/Cr and the degree of tubulointerstitial fibrosis was positively correlated in IgA nephropathy,so urinary P?NP/Cr is likely to be used as a relevant indicators judging tubulointerstitial fibrosis in IgA nephropathy.