Tryptophan as a surrogate prognostic marker for diabetic nephropathy

Abstract

Aims/IntroductionDiabetic nephropathy is one of the leading causes of end‐stage renal disease. Unfortunately, reliable surrogate markers for predicting the prognostic outcome of diabetic nephropathy are as yet absent. In order to find new markers in predicting the progression of diabetic nephropathy, we carried out a prospective study by investigating the correlation between serum metabolites and the annual change of estimated glomerular filtration rate (eGFR).Materials and MethodsFrom September 2013 to September 2015, 52 diabetes patients at various stages of chronic kidney disease were enrolled. While serum levels of 175 metabolites were measured by AbsoluteIDQ™ p180 kit, only those with a significant difference in advancing chronic kidney disease stages were selected. After then, serial renal function change of these patients was followed up for 12 months, the outcome of renal function with each selected metabolite was compared according to the occurrence of a rapid decline (sustained annual decrement rate ≥5%) of eGFR.ResultsA total of 26 metabolites were found to be significantly associated with the severity of chronic kidney disease. Tryptophan (Trp) showed a significant association with the event of rapid decline in eGFR (P = 0.036). Serum concentration of Trp <44.20 μmol/L showed the most valuable predictive value with 55.6% sensitivity and 87% specificity.ConclusionsA lower level of Trp, especially <44.20 μmol/L, was related to a rapid decline in eGFR. Accordingly, Trp might be regarded as a potential prognostic marker for diabetic nephropathy.

Effects of Bailing capsule on diabetic nephropathy based on UPLC-MS urine metabolomics

“…Increasing evidence showed that disturbed tryptophan metabolism was associated with the decline in eGFR and tryptophan related metabolites could be potential prognostic markers for DN. [21][22][23] The present investigation added new evidence that tryptophan metabolism is a key metabolic pathway in the progression of DN. As a rate-limiting enzyme in tryptophan catabolism, indoleamine 2,3-dioxygenase was a key player in immunoregulatory of chronic inammation and renal injury.…”

Reprogramming of Metabolism in Kidney Cancer

“…90 In the kidney, during CKD with type 2 diabetes, the blood TRP/KN ratio is decreased. 91,92 The level of TRP was shown to be correlated positively with the estimated glomerular filtration rate whereas levels of KN and quinolinate were correlated negatively. 91…”

Kynurenine/Tryptophan Ratio Predicts Angiotensin Receptor Blocker Responsiveness in Patients with Diabetic Kidney Disease

“…Abbreviation: MAU, macroalbuminuria; mau, microalbuminuria; normo, normoalbuminuria; BMI, body mass index; HbA1c, glycated hemoglobin A1c; DM, diabetes mellitus; SBP, systolic blood pressure; DBP, diastolic blood pressure; UACR, urine albumin-to-creatinine ratio; Cr, creatinine; eGFR, estimated glomerular filtration rate; CKD, chronic kidney disease; OAD, oral antidiabetic drug; DPP4, dipeptidyl-peptidase-4; GLP-1R, glucagon-like peptide-1 receptor; SGLT-2, sodium glucose co-transporters 2; CCB, calcium channel blocker. Since that a correlation between plasma Trp and rapid progression of DKD has been reported [11], we tried to verify whether low Trp and/or high TKR in patients with albuminuria may also predict the progression of DKD and the responsiveness of ARB in a group of patients with similar stages of CKD but various degrees of albuminuria in this study. Thus, UACR were evaluated six months after ARB treatment.…”

“…Previous metabolomics studies have revealed potential pathways and surrogate prognostic markers associated with the development and progression of DKD [10,11]. Nevertheless, little is known about the metabolic change during the progression of albuminuria among DKD patients.…”