| Backgound: Chronic kidney disease is advanced end-stage renalfailure. According to the North American and European reports, 100-150per one million people are suffering from chronic renalfailure.Proteinuria as many common kidney disease symptoms, has beenconsidered as proteinuria glomerular disease most common clinicalmanifestation, only reflect glomerular injury, but in recent years a largenumber of experimental studies show that protein filtrated fromglomerular can cause renal tubular epithelial cell injury, and reflect theoccurrence and development of tubulointerstitial fibrosis (TIF).Glomerulars and tubulars are all in renal interstitial, so renal interstitialdiseases will be extended to the glomerular and tubular. Injury inglomeruli and tubules will be accompanied by interstitial lesions.Whatever primary renal lesions in glomerular,tubular or vessel themajority of progressive renal disease can see TIF. Tubulointerstitialfibrosis renal sclerosis is an important feature, the emergence of TIFdetermines prognosis of the disease and suggest poor prognosis. Animalexperiments showed that if not accompanied by interstitial inflammatoryinfiltration and fibrosis, glomerulosclerosis, and even renal dysfunctionhas seldom occurred. Many showed evidence of glomerular diseaseassociated tubulointerstitial damage is more closely related prognosis.Proteinuria is one of the main factors to damage. Urinary protein directlyinjure tubular epithelial cell, and stimulated the latter as TGF-β1, CTGF,FN, and other important factors and inflammatory cytokines, indirectlymediated interstitial fibrosis and chronic inflammation processultimately leaded to fibrosis. In recent years research has shown that, persistent proteinuria plays an important role in the progress chronic renaldysfunction. Prospective clinical study also confirmed that the level ofproteinuria is closely related to CKD progress in speed. Thereforeproteinuria as a separate factor is not only glomerular injury, but led torenal disease progress.The pathology features of TIF is tubulointerstitial damage andfibrosis, interstitial mononuclear inflammatory cell infiltration, andextracellular matrix deposition. The mechanism of tubulointerstitialfibrosis include stromal fibroblasts and transforming into fiber cells, andthe extracellular matrix (ECM) degradation and increased the reduction,or the progess of apoptosis, and so on. Many of the growth factor,vasoactive substances, such as cytokines involved in the fibroblastproliferation and ECM, with transforming growth factor-β1 (TGF-β1) hasan important role in promoting fibrosis cytokines, with a variety offunctions. TGF-β1 may promote the process interstitial cellproliferation and extracellular matrix synthesis accumulation,therebyincreasing glomerulosclerosis, and interstitial fibrosis, specifi- cally toinfluence by:(1)TGF-β1 can promote ECM synthesis and inhibite thedegradation; (2)Inhibition of MMP synthesis; (3) Raise the ECMreceptor expression; (4)Activation of renal interstitial fibroblasts and theirproliferation. But long-term suppression in anti-inflammatory andanti-proliferative and anti-tumor effect would have a negative impact tothe body. And recently discovered that the connective tissue growth factor(CTGF) is an important neurotransmitter in fibrosis. With the biologicalactivity similar to TGF-β1, CTGF can stimulate cell proliferation andextracellular matrix formation, and play an important role in thepromotion of renal fibrosis. In 1991 Bradham first time found CTGF inhuman umbilical vein endothelial cells.It is a cysteine-rich peptide existsin a variety of human tissues and organs, may be TGF-promoting activity of the downstream signal fiber medium, mainly mediated TGF-β1 inpromoting value-added and promote cell extracellular matrix secretion.Ito[10] observed in chronic tubulointerstitial damage site, CTGF mRNAexpression of the molecular cells markedly increased, and with interstitialdisease proportional but these cells in the same timea-SMA expression inmyofibroblasts mainly. Some scholars have also confirmed in vitro CTGFinvolve the process of fibroblasts differentiateing to MyoF.We know tubulointerstitial fibrosis is a common pathological featuresin various end-stage renal disease.Tubulointerstitial fibrosis can affectsome of the major functions such as glomerular filtration function. Themechanism of tubulointerstitial fibrosis including:small capillary tubewas narrow and vascular resistance increases, the decline in glomerularblood flow; and the proximal tubular atrophy inevitable injury tubularfunction, through the feedback mechanism effecting glomerular filtrationrate and other functions; In addition tubulointerstitial fibrosis can causedirectly glomerulosclerosis and crescentic lesions, eventually decreaseglomerular filtration rate, renal disease worsened Foreignscholars Clinical and Experimental Research found glomerul- onephritisglomerular damage occurred laterly the tubulointerstitial lesions, andtubular function is recognized as the renal function indicators. It reflectsnot only the tubular interstitial lesion, and the progress of renal pathologyworsened in clinical. Some experimental also support this view, thesestudy found that renal function is integral unani- mously with renaltubulointerstitial pathological. Clinical indicators reflect tubulo-interstitial damaged such as the small molecular weight proteinabsorption experiment, urinary amino acids experiment, glucose largesttubular reabsorption experiment (TmG), lithium clearance rate, and so on.Urinary enzyme and uromicroprotein are the sensitive index in diagnosticdetection of renal tubulointerstitial injury. NAG is located in the proximal tubule cells of lysosomal acid hydrolase.The molecular weightis about 140,000. NAG presented in all tissues and urinary NAG comesmainly from the kidney, especially proximal convoluted tubule cells, andcannot pass through the glomerular filtration membrance freely.When thetissue damage, in particular the proximal convoluted tubule cells,lysosomes release urine NAG significantly higher, as early as in otherurinary enzyme, Therefore tubular damaged is of great value to the earlydiagnosis. NAG has high specificity to renal lesions.This experiment initiated in different concentrations of albumineffection on renal fibrosis through the difference of renal filtration rate,tubular function and inflame- matory cytokines as index.We choose thepatients whose pathological are focal segmental glomerular sclerosis asour research object in this study. According to different groups ofproteinuria, follow-up 6 months observate proteinuria effection ontubulointerstitial injery, and through the index of internal creatinineclearance rate, NAG and the impact of CTGF.To know the relationshipbetween proteinuria and TIF.Objective: To study the different levels of proteinuria effection ontubulointerstitial fibrosis process,and effection on endogenous creatinineclearance rate, urinary NAG and urinary CTGF.Methods: Case choice.During the 2005--2006 September period,hospitalizated in zhongnan university in Xiangya second hospital withinformation integrity. Kidney biopsy diagnosed as primary focalsegmental glomerulosclerosis (FSGS).We have a total of 78 patient casesand a 15 cases normal control group. Based on the clinical proteinuriadifference, we divided 48 cases into three groups. They are＜1.0g/d groupincluding 26 patients; 1.0-3.5g/d group with 33 cases; 3.5g/d group with30cases.Then a follow-up investigation, eliminate hormone-sensitive anduncontroled of blood pressure, the final choice of which 48 cases studied. Calculated creatinine clearance rate, and standardization correctedaccording to body surface area.The formula of standard endogenous creatinine clearance rate:Ccr (respectively.In)=[urine creatinine x] [24-hour urine creatinine×24×60]Correction ccr(respectively.In)=endogenous creatinine clearancerate×1.73/skin surface area Area (m2)=[height (cm)×0.0061+bodyweight (kg)×0.0128]-0.1529MDRD formula: simplified MDRD equation 7 eGFR(ml/min/1.73m2)=170×[Pcr]-0.999×[age (years)]-0.176×[female×0.762]×[BUN]-0.170×[Alb]0.318.1 Calculating four groups of cases with creatinine clearance rate,using the standard formula formula (according to the standardizationbody surface area and corrected), and the MDRD formula, followed-upsix months repeated measurements corresponding to the endogenouscreatinine clearance rate, analysis statistical, and search the fifferencesbefore and after.2 Collected four group study of urine, tracking six months, repeat it,using ELISA experiment to detect unimary CTGF figure, use statisticalsoftware for analysis.3 Collected four groups urine sent to hospital laboratories to detecturinary NAG, tracking six months, repeat it. Use statistical software foranalysis.Results:We track 48 cases. Results of creatinine clearance rate andurine NAG, CTGF are following:1 Ccr (used of standardized formula based on body surface areacorrected), the four groups results are as follows: Before tracking, normalcontrol group is 96.21±13.82.＜1.0g/d group is 77.84±18.66;1.0-3.5g/dgroup is 69.27±14.15;＞3.5g/d group is 67.48±15.93. After follow-up, the results of the control group is 101.61±17.83,＜1.0g/d group is70.13±20.61;1.0-3.5g/d group is 64.31±14.59;＞3.5g/d group is 56.62±19.62.We can see all proteinuria groups are different with control groupin numerical (P＜0.05) After tracking three proteinuria groups changedcompared with before, But only the results of＞3.5g/d ground changesobviously between before and after(P＜0.05).2 With MDRD formula of the results are as follows: pre-trackingcontrol group is 99.81±16.48.Three groups are 69.39±17.40, 68.99±20.90and 60.72±16.27 respectively;After follow-up results of the control groupis 101.23±17.46.The result of three groups are 65.71±18.46, 61.93±17.18and 49.95±20.32 respectively. We can see all proteinuria groups aredifferent with control group in numerical (P＜0.05) After tracking threeproteinuria groups changed compared with before, But only the results of＞3.5g/d ground changes obviously between before and after (P＜0.05).3 Collecting patients 24-hour urine, Application of enzyme-linkedimmunosorbent assay (ELISA) detect urinary CTGF numerical: Thenormal group is 11.75±1.96, and three groups' result are 116.53±16.29,258.42±43.88 and 365.87±93.85;After followed up the results of controlgroup is 12.52±2.01, and three groups' result are 123.13±20.11,281.63±55.53 and 478.20±119.75. We can see all proteinuria groups aredifferent with control group in numerical(P＜0.05) After tracking threeproteinuria groups changed compared with before, But only the results of＞3.5g/d ground changes obviously between before and after(P＜0.05).4 Collecting four of the study As a urine sample sent to our hospitallaboratory test results of the NAG (u/l), as follows, normal control groupwas 1.54±0.13 and proteinuria results of the three groups were24.97±5.91, 34.59±7.92 and 51.69±12.24, proteinuria groups and thecontrol group were different obviously.After followed-up the four groups are 1.57±0.16, 28.16±6.43, 40.15±9.40 and 72.03±16.97, only>3.5 grouphave a significant difference between before and after (P<0.05).Conclusion:1,Proteinuria played an important role in the process of promptingtubulo-interstitial fibrosis, have a greater impact on internal creatinineclearance rate.2,Proteinuria has effction on reflecting tubulointerstitial injuryindicators such as urinary CTGF and NAG3,Generally, nephrotic proteinuria that is above 3.5g/L could fasterdevelopment of prognostic even greater.More obvious differences betw-een before and after. |
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