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Clinical and Experimental Nephrology
https://doi.org/10.1007/s10157-019-01721-w
ORIGINAL ARTICLE
Assessment of treatment efcacy using sur face-enhanced Raman
spectroscopy analysis of urine in rats with kidney transplantation
or kidney disease
Shijian Feng
1,2
· Lan Zhou
1,3
· Duo Lin
4
· Jianhua Zhao
5
· Qiunong Guan
1
· Boyuan Zheng
1
· Kunjie Wang
2
· Hong Li
2
·
Rong Chen
6
· Haishan Zeng
5
· Caigan Du
1
Received: 17 August 2018 / Accepted: 21 February 2019
© Japanese Society of Nephrology 2019
Abstract
Background Individuals who have kidney disease or kidney transplants need routine assessment of their kidney damage
and function, which are largely measured based on histological examination of kidney biopsies, blood test, and urinalysis.
These methods are practically difcult or inconvenient, and expensive. The objective of this study was to develop a model
to estimate the kidney damage and function by surface-enhanced Raman spectroscopy (SERS).
Methods Urine samples were collected from two previous studies: renal allograft recipient Lewis rats receiving anti-TGF-β
antibody or control antibody treatment and obese diabetic ZSF1 rats with kidney disease fed with whole grape powder-
containing chow or control chow. Silver nanoparticle-based SERS spectra of urine were measured. SERS spectra were
analyzed using principal component analysis (PCA) combined with linear discriminant analysis (LDA) and partial least
squires (PLS) analysis.
Results PCA/LDA separated anti-TGF-β antibody-treated group from control group with 90% sensitivity and 70% specifc-
ity in kidney transplants, and grape-fed group from controls with 72.7% sensitivity and 60% specifcity in diabetic kidneys.
The receiver operating characteristic curves showed that the integration area under the curve was 0.850 ± 0.095 (p = 0.008)
in kidney transplant groups and 0.800 ± 0.097 (p = 0.02) in diabetic kidney groups. PLS predicted the biochemical param-
eters of kidney function using the SERS spectra, resulting in R
2
= 0.8246 (p < 0.001,urine protein), R
2
= 0.8438 (p < 0.001,
urine creatinine), R
2
= 0.9265 (p < 0.001, urea), R
2
= 0.8719 (p < 0.001, serum creatinine), and R
2
= 0.6014 (p < 0.001, urine
protein to creatinine ratio).
Conclusion Urine SERS spectral analysis suggesting that it may become a convenient method for rapid assessment of renal
impairment.
Keywords Surface-enhanced Raman spectroscopy · Urine · Kidney transplantation · Kidney disease · Diagnosis
Introduction
Patients living with chronic kidney disease (CKD) or trans-
planted kidneys need routine monitoring of their kidney
health or function in CKD or post-transplantation manage-
ment [1–3]. The most commonly used tools for CKD and
kidney grafts monitoring include serum creatinine con-
centration-based estimated glomerular fltration (eGFR)
[3, 4], and the serial serum creatinine levels or eGFR with
surveillance biopsies [2]. However, in addition to the high
cost and inconvenience of blood sample collection, the poor
accuracy and inter-measurements reliability of these tests are
main concerns. In CKD management, the eGFR formulae
can correctly identify CKD patients at risk for renal failure
Shijian Feng and Lan Zhou contributed equally to this paper, and
considered as co-frst authors.
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10157-019-01721-w) contains
supplementary material, which is available to authorized users.
* Haishan Zeng
hzeng@bccrc.ca
* Caigan Du
caigan.du@ubc.ca
Extended author information available on the last page of the article