Rationale & Objective

Tubular secretion plays an important role in the efficient elimination of endogenous solutes and medications, and lower secretory clearance is associated with risk of kidney function decline. We evaluated whether histopathologic quantification of interstitial fibrosis and tubular atrophy (IFTA) is associated with lower tubular secretory clearance in persons undergoing kidney biopsy.

Study Design

Cross-sectional.

Settings & Participants

The Boston Kidney Biopsy Cohort is a study of persons undergoing native kidney biopsies for clinical indications.

Exposures

Semiquantitative score of IFTA reported by 2 trained pathologists.

Outcomes

We measured plasma and urine concentrations of 9 endogenous secretory solutes using a targeted liquid chromatography/mass spectrometry assay. We used linear regression to test associations of urine-to-plasma ratios (UPRs) of these solutes with IFTA score after controlling for estimated glomerular filtration rate (eGFR) and albuminuria.

Results

Among 418 participants, mean age was 53 years, 51% were women, 64% were White, and 18% were Black. Mean eGFR was 50 mL/min/1.73 m², and median urinary albumin-creatinine ratio was 819 mg/g. Compared with individuals with ≤25% IFTA, those with >50% IFTA had 12%-37% lower UPRs for all 9 secretory solutes. Adjusting for age, sex, race, eGFR, and urine albumin and creatinine levels attenuated the associations, yet a trend of lower secretion across groups remained statistically significant (P < 0.05 for trend) for 7 of 9 solutes. A standardized composite secretory score incorporating UPR for all 9 secretory solutes using the min-max method showed similar results (P < 0.05 for trend).

Limitations

Single time point and spot measures of secretory solutes.

Conclusions

Greater IFTA severity is associated with lower clearance of endogenous secretory solutes even after adjusting for eGFR and albuminuria.

中文翻译：

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肾小管间质纤维化和肾小管分泌

理由和目标

肾小管分泌在有效消除内源性溶质和药物方面起着重要作用，分泌清除率降低与肾功能下降的风险相关。我们评估了间质纤维化和肾小管萎缩 (IFTA) 的组织病理学定量是否与接受肾活检的人的肾小管分泌清除率降低有关。

学习规划

横截面。

设置和参与者

波士顿肾脏活检队列是一项针对因临床适应症而接受天然肾脏活检的人的研究。

曝光

由 2 名训练有素的病理学家报告的 IFTA 半定量评分。

结果

我们使用靶向液相色谱/质谱法测定了 9 种内源性分泌溶质的血浆和尿液浓度。在控制估计的肾小球滤过率 (eGFR) 和白蛋白尿后，我们使用线性回归来检验这些溶质的尿液与血浆比 (UPR) 与 IFTA 评分之间的关​​联。

结果

在 418 名参与者中，平均年龄为 53 岁，51% 为女性，64% 为白人，18% 为黑人。平均 eGFR 为 50  mL/min/1.73  m ²，中位尿白蛋白肌酐比值为 819  mg/g。与 IFTA ≤ 25% 的个体相比，IFTA >50% 的个体 对所有 9 种分泌溶质的 UPR 降低 12%-37%。针对年龄、性别、种族、eGFR、尿白蛋白和肌酐水平进行调整后，相关性减弱，但对于 9 种溶质中的 7 种，各组间分泌减少的趋势仍然具有统计学意义（趋势 P < 0.05 ） 。 使用最小-最大方法对所有 9 种分泌溶质进行 UPR 的标准化综合分泌评分显示出相似的结果（趋势P  < 0.05）。 

限制

分泌溶质的单时间点和现场测量。

结论

更严重的 IFTA 与内源性分泌溶质的清除率更低相关，即使在调整 eGFR 和白蛋白尿后也是如此。