Yukimasa Iwata1, Hiroki Okushima1, Atsushi Hesaka2,3,4, Masataka Kawamura5, Ryoichi Imamura5, Shiro Takahara6, Masaru Horio7, Youko Tanaka2,3, Tatsuhiko Ikeda8, Maiko Nakane8, Masashi Mita8, Terumasa Hayashi1, Yoshitaka Isaka4, Tomonori Kimura2,3,4. 1. Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka, Japan. 2. KAGAMI Project, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki, Japan. 3. Reverse Translational Research Project, Center for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki, Japan. 4. Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. 5. Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. 6. Department of Renal Transplantation, Kansai Medical Hospital, Toyonaka, Osaka, Japan. 7. Department of Nephrology, Kansai Medical Hospital, Toyonaka, Osaka, Japan. 8. KAGAMI Inc., Ibaraki, Japan.
Abstract
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 μM 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 μM, 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.
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 μM 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 μM, 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.
Authors: Toshiharu Ninomiya; Vlado Perkovic; Bastiaan E de Galan; Sophia Zoungas; Avinesh Pillai; Meg Jardine; Anushka Patel; Alan Cass; Bruce Neal; Neil Poulter; Carl-Erik Mogensen; Mark Cooper; Michel Marre; Bryan Williams; Pavel Hamet; Giuseppe Mancia; Mark Woodward; Stephen Macmahon; John Chalmers Journal: J Am Soc Nephrol Date: 2009-05-14 Impact factor: 10.121