Identification of Diabetic Nephropathy in Patients Undergoing Kidney Biopsy through Blood and Urinary Profiles of d-Serine
Yukimasa Iwata, Hiroki Okushima, Atsushi Hesaka, Masataka Kawamura, Ryoichi Imamura, Shiro Takahara, Masaru Horio, Youko Tanaka, Tatsuhiko Ikeda, Maiko Nakane, Masashi Mita, Terumasa Hayashi, Yoshitaka Isaka, Tomonori Kimura
Abstract
Key Points The blood level of d- serine discriminates participants without kidney diseases, whereas the fractional excretion of d- serine is higher in diabetic nephropathy. The combined analysis of d- serine and clinical factors correctly predicted the presence of diabetic nephropathy. Analysis of d- serine in blood and urinary excretion is useful in identifying diabetic nephropathy in patients undergoing kidney biopsy. Background The diagnosis of diabetic nephropathy (DN), the major cause of ESKD, requires kidney biopsy. d -Serine, present only in trace amounts in humans, is a biomarker for kidney diseases and shows potential to distinguish the origin of kidney diseases, whose diagnoses usually require kidney biopsy. We extended this concept and examined the potential of d- serine in the diagnosis of DN. Methods We enrolled patients with biopsy sample–proven DN and primary GN (minimal change disease and IgA nephropathy) and participants without kidney disease. A total of 388 participants were included in this study, and d- serine levels in blood and urine were measured using two-dimensional high-performance liquid chromatography, and urinary fractional excretion (FE) of d -serine was calculated. Using data from 259 participants, we developed prediction models for detecting DN by logistic regression analyses, and the models were validated in 129 participants. Results A d- serine blood level of >2.34 μ M demonstrated a high specificity of 83% (95% CI, 70% to 93%) for excluding participants without kidney diseases. In participants with a d -serine blood level >2.34 μ M, the threshold of 47% in FE of d -serine provided an optimal threshold for the detection of DN (AUC, 0.85 [95% CI, 0.76 to 0.95]; sensitivity, 79% [95% CI, 61% to 91%]; specificity, 83% [95% CI, 67% to 94%]). This plasma-high and FE-high profile of d -serine in combination with clinical factors (age, sex, eGFR, and albuminuria) correctly predicted DN with a sensitivity of 91% (95% CI, 72% to 99%) and a specificity of 79% (95% CI, 63% to 80%), and outperformed the model based on clinical factors alone in the validation dataset ( P <0.02). Conclusions Analysis of d- serine in blood and urinary excretion is useful in identifying DN in patients undergoing kidney biopsy. Profiling of d -serine in patients with kidney diseases supports the suitable treatment through the auxial diagnosis of the origins of kidney diseases.