Pape Lars, Henne Thomas, Offner Gisela, Strehlau Juergen, Ehrich Jochen H H, Mengel Michael, Grimm Paul C
Department of Pediatric Nephrology, Medical School of Hannover, Hannover, Germany.
Transplantation. 2003 Sep 27;76(6):955-8. doi: 10.1097/01.TP.0000078899.62040.E5.
Chronic allograft nephropathy (CAN) has become the predominant limiting factor for long-term transplant survival. A cardinal histomorphologic correlate for CAN is interstitial fibrosis. Currently, no method has been established in routine use that reliably quantifies the extent of interstitial fibrosis in renal grafts. We have used staining with picrosirius red followed by computerized image analysis to study the correlation between graft fibrosis and future development of glomerular filtration rate (GFR) in a group of children with advanced CAN.
Renal biopsies were performed in 56 children (mean age, 13.7+/-3.6 years) after a mean period of 4.6+/-3.1 years after transplantation because of significant increases in serum creatinine. All biopsy specimens were stained with picrosirius red. The magnitude of fibrotic tissue was calculated by computerized image analysis. Linear regression analysis was performed correlating the intensity of graft fibrosis and the changes in the GFR at the time points of renal biopsy and 2 years later.
There was a significant positive correlation (r=0.62, P<0.001) between the picrosirius red-stained cortical fractional interstitial fibrosis volume (V(intFib)) and the decrease of GFR within 2 years postrenal biopsy. When V(intFib) was below 5%, 82% of the patients had an increase in GFR within 2 years. Ninety-three percent of the patients with greater than 10% of fibrosis experienced a worsening renal function after 2 years. When comparing patients with stable GFR with patients having a decrease in GFR, a highly significant difference in V(intFib) was found (P=0.008).
The quantitative measurement of fibrosis by picrosirius red staining appears to be a useful prognostic indicator for estimating long-term graft function in CAN and may provide an easy, fast, and inexpensive tool helpful for treatment decisions in patients developing CAN.
慢性移植肾肾病（CAN）已成为长期移植肾存活的主要限制因素。CAN的一个主要组织形态学相关指标是间质纤维化。目前，尚未建立常规使用的可靠方法来量化肾移植中间质纤维化的程度。我们采用苦味酸天狼星红染色并结合计算机图像分析，研究了一组晚期CAN患儿移植肾纤维化与未来肾小球滤过率（GFR）变化之间的相关性。
对56例儿童（平均年龄13.7±3.6岁）在移植后平均4.6±3.1年因血清肌酐显著升高进行肾活检。所有活检标本均用苦味酸天狼星红染色。通过计算机图像分析计算纤维化组织的量。进行线性回归分析，以关联移植肾纤维化程度与肾活检时及2年后GFR的变化。
苦味酸天狼星红染色的皮质部分间质纤维化体积（V(intFib)）与肾活检后2年内GFR的下降之间存在显著正相关（r = 0.62，P < 0.001）。当V(intFib)低于5%时，82%的患者在2年内GFR升高。纤维化超过10%的患者中，93%在2年后肾功能恶化。比较GFR稳定的患者与GFR下降的患者，发现V(intFib)存在高度显著差异（P = 0.008）。
苦味酸天狼星红染色定量测定纤维化似乎是评估CAN中移植肾长期功能的有用预后指标，可能为CAN患者的治疗决策提供一种简单、快速且廉价的工具。
