Clinicopathological Features And Outcomes In Immunoglobulin A Nephropathy Patients With Arteriolar Hyalinosis

Background:Immunoglobulin A nephropathy(IgAN),which is known as Berger’s disease,has been widely studied since first reported in 1968 by Berger and Hinglais.A systematic review of biopsy-based studies in multiple countries suggests that the incidence of IgAN is at least 2.5per 100,000 population.Previous research has also confirmed that IgAN was the most mainly cause of chronic kidney disease(CKD)in China.Despite there has made significant advances in the treatment,IgAN has still been reported to reduce life expectancy by more than 10 years and cause kidney failure in 20%-40% of patients within 20 years of diagnosis.IgAN is clinically manifested as one or more asymptomatic hematuria,proteinuria,and hypertension,or acute nephritis syndrome,rapid progressive nephritis,and nephrotic syndrome.At present,the diagnosis and classification of IgAN mainly rely on renal biopsy,that IgA deposition in the glomerular mesangial area is the gold standard of pathological manifestation.Currently,the pathological classifications have gone through three major versions,including Lee’s classification,Haas classification,and the newest Oxford classification.New diagnostic criteria also seek a more comprehensive description of the pathological lesions,but some pathological features,such as vascular lesions,are not included in the classification criteria.The progression of IgAN is affected by a variety of factors.So far,massive proteinuria,hypertension,high uric acid,and a low estimated glomerular filtration rate(eGFR)have been considered the risk factors for the progression of IgAN.Also,renal histological findings,such as mesangial hypercellularity,segmental glomerulosclerosis,tubular atrophy/interstitial fibrosis,and crescent formation have also been associated with kidney failure.In addition,there are still many other factors,such as intrarenal vascular lesions,also can influence the prognosis of IgAN.In recent years,studies on the intrarenal vascular lesions of IgAN have attracted great attention.For instance,intrarenal vascular lesions,involving arterial intimal thickening,arteriolar hyalinosis,and microangiopathy are quite common in IgAN.A previous study indicated that the prevalence of renal arteriole and arteriolar lesions was 54.6% in patients with IgAN.And those vascular lesions are associated with kidney failure.Arteriolar hyalinosis is a kind of intrarenal vascular lesion,which is common in the renal pathological reports in IgAN.However,it is uncertain whether arteriolar hyalinosis is related to progress and prognosis in patients with IgAN.Therefore,the objective of current study is to investigate the clinical and pathological features,as well as renal outcomes in patients with IgAN with or without arteriolar hyalinosis.Contents and methods:This study consecutively enrolled 762 IgAN patients diagnosed by renal biopsy in the department of nephrology,the second affiliated hospital of Army Medical University,from January 2012 to December 2018.Patients were divided into two groups according to whether arteriolar hyalinosis is involved,IgAN patients without arteriolar hyalinosis group,and IgAN patients with arteriolar hyalinosis group.Firstly,the clinical indicators and pathological indicators of the two groups were compared.Kaplan-Meier survival analysis was used to compare the difference in the composite kidney outcomes between the two groups.Univariate and Multivariate Cox regression analysis then was used to determine whether arteriolar hyalinosis was an independent risk factor for composite kidney outcomes.Then,subgroup analysis was performed,and the IgAN patients with arteriolar hyalinosis were divided into two groups according to whether they were diagnosed with hypertension or not.The composite kidney outcomes were defined as eGFR decreased by more than 30 % or end-stage kidney disease(ESKD).Main finding:1.A total of 762 IgAN patients were enrolled in our study.Their average age was 36.21 years old,and the proportion of females was 54.7 %.The median follow-up time was 34(interquartile range:26,45)months.Among them,54.1 % of IgAN patients had arteriolar hyalinosis under renal biopsy,and 32.3 % of the IgAN patients were diagnosed with hypertension.A total of 11.4 % of the patients reached the composite kidney outcomes during the follow-up period.2.Compared with IgAN patients without arteriolar hyalinosis,IgAN patients with arteriolar hyalinosis were older in age,meanwhile having a higher proportion of hypertension.And clinical indicators such as serum complement 4(C4),tumor necrosis factor α(TNF-α),serum urea nitrogen,serum creatinine(Scr),serum uric acid,24-hour urinary protein quantity(24h-UP),total cholesterol,the proportion of using glucocorticoids and immunosuppressive agents were significantly higher in IgAN patients with arteriolar hyalinosis than IgAN patients without arteriolar hyalinosis.In pathological indicators,IgAN patients with arteriolar hyalinosis have a significantly higher proportion of global glomerulosclerosis rate,mesangial cell proliferation,segmental glomerular sclerosis,and tubular atrophy/interstitial fibrosis than IgAN patients without arteriolar hyalinosis;Kaplan-Meier survival analysis showed that the incidence of composite kidney outcomes in IgAN patients with arteriolar hyalinosis was higher than those without arteriolar hyalinosis(p<0.001).Meanwhile,multivariate Cox regression analysis showed that arteriolar hyalinosis was an independent risk factor for the prognosis of IgAN(HR,2.441;95% CI,1.344-4.435;p=0.003).In addition,the severity of arteriolar hyalinosis is significantly associated with composite kidney outcomes.3.In the subgroup of 412 IgAN patients with arteriolar hyalinosis,they were divided into two groups according to whether combined with hypertension or not.Patients combined with hypertension were older and had a higher proportion of men than patients not combined with hypertension.In clinical indicators such as BMI,TNF-α,C-Reactive Protein(CRP),serum complement 3(C3),serum urea nitrogen,Scr,serum uric acid,24h-UP,and total cholesterol were significantly higher in patients combined with hypertension than patients without hypertension.In pathological indicators,patients combined with hypertension have a significantly higher proportion of global glomerulosclerosis rate,and tubular atrophy/interstitial fibrosis than patients without arteriolar hyalinosis;Kaplan-Meier survival analysis showed that the incidence of composite kidney outcome in IgAN patients with arteriolar hyalinosis combined with hypertension was higher than that in IgAN patients with arteriolar hyalinosis not combined with hypertension(p=0.018).Conclusion:1.Patients with IgAN with arteriolar hyalinosis were older and had a higher proportion of hypertension,and indicators such as C4,TNF-α,serum urea nitrogen,Scr,serum uric acid,24h-UP,total cholesterol,the proportion of using glucocorticoids and immunosuppressive agents,the proportion of global glomerulosclerosis rate,mesangial cell proliferation,segmental glomerular sclerosis,and tubular atrophy/interstitial fibrosis were significantly higher in IgAN patients with arteriolar hyalinosis than IgAN patients without arteriolar hyalinosis.2.Arteriolar hyalinosis is an independent risk factor for composite kidney outcomes in IgAN patients.With the increase of the proportion of arteriolar hyalinosis to interstitial vessels,the risk of composite kidney outcomes is higher in IgAN patients.3.Patients combined with hypertension were older and had a higher proportion of males.Indicators such as BMI,TNF-α,CRP,C3,serum urea nitrogen,Scr,serum uric acid,24h-UP,and total cholesterol,the proportion of global glomerulosclerosis rate,and tubular atrophy/interstitial fibrosis were significantly higher in patients combined with hypertension than patients not combined with hypertension.4.In IgAN patients with arteriolar hyalinosis,the prognosis of patients combined with hypertension is worse than patients not combined with hypertension.