| Background and AimRenal tubules and interstitium are vulnerable to injury and play a central role in the progression of various CKDs.However,high quality epidemiologic and transcriptome studies on the profiles of biopsy-proven tubulointerstitial lesions(TILs)is extremely limited.This study aims to explore the status of epidemiology among Chinese patients with renal tubular interstitial injury and find related gene thatmay provide clues and ideas for follow-up m edical study of kidney disease.MethodsPart 1:We conducted a retrospective renal biopsy series including 62,569 native biopsies at 1,211 hospitals across China from 2015 to 2017.The TILs,including the shedding of tube epithelial,renal tubular atrophy,renal interstitial fibrosis,edema and inflammatory infiltration,were identified from the pathological report.We analyzed the severity and chronicity of TILs stratified by gender,age groups,biopsy indications,and concurrent glomerular diseases.We also examined the correlation between TIL and glomerulosclerosis.Part 2:We included 197 patients with renal biopsy from Nanfang hospital.Through the whole transcriptome sequencing technology,we found the differentiallyexpressed genes between moderate to severe TIL and non-moderate to severe TIL and target genes to explore the potential pathogenesis.ResultsPart 1:Of 56,880 patients with biopsy-proven glomerular disease,79.5%of the patients had TILs.Renal interstitial inflammatory infiltration was the most common type of TIL(77.7%),followed by renal tubular atrophy(56.0%)and renal interstitial fibrosis(32.8%).Severe and chronic TILs were more common in adults than in children.The three glomerular diseases with the highest proportion of moderate to severe and chronic TIL were diabetic nephropathy,IgA nephropathy and focal segmental glomerulosclerosis.The severity of TILs was moderately correlated with glomerulosclerosis score(r=0.51).Moderate to severe TIL was more common in southern China.After adjusting for age,sex,hospital level,region,biopsy indication and type of concurrent glomerular diseases,adults with renal arteriole injury had a six-fold higher risk of TIL(OR 7.12,95%CI,6.42 to 7.91).Part 2:Between the two groups,325 differentially expressed genes were confirmed in relation to the channel activity,further 11 target genes were filtered by lasso regression.More clinical relevance and possible mechanisms required further studies.ConclusionsPart 1:TILs were common in patients with biopsy-proven glomerular disease.The type and severity of TILs varied with age,region and concurrent glomerular diseases.Renal arteriole injury and glomerulosclerosis was associated with a significantly increased risk of TIL.Part 2:Lots of possible TIL-related genes were screened in a large sample RNA sequencing,it provided clues and ideas for future basic and clinic research of tubulointerstitial lesions. |
