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BACKGROUND AND AIMS Acute kidney injury (AKI) and acute kidney disease (AKD), a typical inpatient disease spectrum, pose an exceptional burden on the current healthcare system worldwide. By contrast, developing operative diagnostic criteria for AKD in the outpatient setting (AKDOPT) remains an unattained goal due to the data silos built around the disconnected healthcare systems. In 2017, Taiwan launched the National Cloud-based Health Information Exchange Platform and established the interoperability standard that makes the automated monitoring of change of serum creatinine (S-Cre) in the outpatient setting a possible practice. This study aims to verify our previously proposed AKDOPT diagnostic algorithms using both the conventional neutrophil gelatinase-associated lipocalin (NGAL) and DNlite-IVD103 tests, detecting a novel biomarker, a post-translational modified (PTM) fragment of Fetuin-A [1, 2]. METHOD The Big Data Center of China Medical University Hospital (CMUH) has launched the Acute Kidney Injury Detection System (AKIDS) in the outpatient setting since December 2017 based on our AKDOPT diagnostic algorithms (Fig. 1). In November 2020, we conducted a pragmatic randomized trial to evaluate the clinical effectiveness of AKIDS in reducing the risk of AKDOPT progression to dialysis. Among patients who participated in this trial, both urine and blood were obtained at the enrollment and the urine samples were sent for the quantification of NGAL and the unique PTM-Fetuin-A fragment, an ELISA test developed by Bio Preventive Medicine (BPM). The risk of S-Cre doubling was estimated by Firth's logistic regression. RESULTS A total of 56 patients who were captured by the AKIDS and with the last estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m2 recruited in this trial with a median age of 73 years (IQR: 66.2–82.5) and a baseline eGFR of 36.4 (IQR: 21.0–46.3) mL/min/1.7 3 m2. During the follow-up, there were six participants reached the S-Cre double status. The median levels of NGAL and IVD103 were 1360 (IQR: 299–1827) ng/mg and 74.7 (IQR: 37.3–236) ng/mg, respectively, among patients experiencing the endpoint, and they were 187 (81.4–1152) ng/mg and 15.9 (6.16–67.3) ng/mg for patients free of the primary outcome. The odds ratios of the S-Cre doubling for each log unit increase in NGAL and IVD103 were 2.26 (95% confidence interval 0.73–6.98; p-value .16) and 3.48 (0.78–15.6; p-value .10), respectively. In the dose-response plot, we found only IVD103 showed a positive linear relationship with the risk of S-Cre doubling despite the two biomarkers showed comparable area under the receiver operating characteristic curve for predicting poor kidney outcome (NGAL 0.697 versus IVD103 0.723). CONCLUSION This is the first study to phenotypically validate the previously unrecognized phenotype, AKDOPT, by the AKIDS developed under the National Health Insurance (NHI) information technology infrastructure and molecularly validate its prognostic role using kidney injury biomarkers, NGAL and a novel eGFR decline prediction biomarker, a unique PTM-fragment of Fetuin-A (IVD103). The linear association between IVD103 and the risk of S-Cre doubling supports its prognostic value in the risk assessment of AKDOPT.

Background Scarce evidence associates the first-year estimated glomerular filtration rate (eGFR) variability and longitudinal change scales concomitantly to the risk of developing end-stage renal disease (ESRD), acute coronary syndrome (ACS) and death following pre-ESRD program enrollment in chronic kidney disease (CKD). Methods We conducted a prospective cohort study of 5092 CKD patients receiving multidisciplinary care between 2003 and 2015 with careful ascertainment of ESRD, ACS and death during the follow-up. First-year eGFR variability and longitudinal change scales that were based on all first-year eGFR measurements included coefficient of variation of eGFR (eGFR-CV), percent change (eGFR-PC), absolute difference (eGFR-AD), slope (eGFR-slope) and area under the curve (AUC). Results A total of 786 incident ESRD, 292 ACS and 410 death events occurred during the follow-up. In the multiple Cox regression, the fully adjusted hazard ratios (HRs) of progression to ESRD for each unit change in eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope, eGFR-AUC were 1.03 [95% confidence interval (CI) 1.02–1.04], 1.04 (1.03–1.04), 1.16 (1.14–1.18), 1.16 (1.14–1.17) and 1.04 (1.03–1.04), respectively. The adjusted HRs for incident ESRD comparing the extreme with the reference quartiles of eGFR-CV, eGFR-PC, eGFR-AD, eGFR-slope and eGFR-AUC were 2.67 (95% CI 2.11–3.38), 8.34 (6.33–10.98), 19.08 (11.89–30.62), 13.08 (8.32–20.55) and 6.35 (4.96–8.13), respectively. Similar direction of the effects on the risk of developing ACS and mortality was observed. In the 2 × 2 risk matrices, patients with the highest quartile of eGFR-CV and concomitantly with the most severely declining quartiles of any other longitudinal eGFR change scale had the highest risk of all outcomes. Conclusions The dynamics of eGFR changes, both overall variability and longitudinal changes, over the first year following pre-ESRD program enrollment are crucial prognostic factors for the risk of progression to ESRD, ACS and deaths among patients with CKD. A risk matrix combining the first-year eGFR variability and longitudinal change scales following pre-ESRD enrollment is a novel approach for risk characterization in CKD care. Randomized trials in CKD may be required to ascertain comparable baseline eGFR dynamics.

Background Direct comparisons of the effectiveness of allopurinol with that of other urate-lowering agents in chronic kidney disease (CKD) populations, as well as guideline recommendations for clinical practice, are lacking. Methods We constructed a pharmacoepidemiology cohort study by including patients from Taiwan's long-term integrated CKD care program to compare the effectiveness among allopurinol, febuxostat and benzbromarone in reducing the risk of progression to dialysis. A total of 874 patients with hyperuricemia who were newly treated with allopurinol, febuxostat or benzbromarone were included. The primary and secondary outcomes were incident end-stage renal disease (ESRD) and the serum uric acid (SUA) changes from baseline, respectively. The results were analyzed using multiple Cox proportional models adjusted for multinomial propensity scores. For subgroup analyses, we further stratified patients according to whether their latest SUA level reached the therapeutic target. Results Compared with allopurinol, benzbromarone therapy was associated with a reduced risk of progression to dialysis, the adjusted hazard ratio was 0.50 (95% confidence interval, 0.25-0.99). Patients who received allopurinol or febuxostat exhibited a comparable risk of ESRD [adjusted hazard ratio, 0.99 (0.40-2.44)]. Febuxostat was significantly more potent than allopurinol or benzbromarone in lowering SUA levels in the fully adjusted model. Among patients who reached the therapeutic target, those with febuxostat and benzbromarone initiation had a significantly lower risk of ESRD. Conclusions In conclusion, compared with conventional allopurinol, febuxostat and benzbromarone may be more effective in reducing the risk of progression to dialysis and in lowering SUA levels in CKD populations.

Background. Renal vascular resistance [resistive index (RI)] has been associated with albuminuria in patients with type 2 diabetes. We studied the correlations between renal artery RI and urinary albumin excretion in adolescents and young adults. Methods. From May 2006 through September 2008, we established a cohort of adolescents and young adults based on previous history of elevated blood pressure (EBP) or normal blood pressure in childhood. This cohort was selected from the 1992–2000 nationwide mass urine screening of school children aged 6–18 years in Taiwan. From October through December 2008, we called back these adolescents and young adults living in Taipei to participate in a renal vascular stiffness study. Linear mixed regression models were applied to study the correlation between renal artery RI and urinary albumin excretion after controlling for cardiovascular (CV) risk factors. Results. Of the 147 subjects enrolled in this study, 67 had macroalbuminuria, 36 had microalbuminuria and 44 had normoalbuminuria. Except for high-density lipoprotein cholesterol, most CV risk factors did not differ significantly among these three groups. Mean RI were similar for the three groups. Neither log (urinary albumin concentration) nor log (urinary albumin:creatinine ratio) correlated with RI. Step-wise linear mixed regression models showed that RI was significantly associated only with male gender and diastolic blood pressure, but not with urinary albumin excretion or EBP in childhood. Conclusion. Renal artery RI is not associated with urinary albumin excretion in nondiabetic adolescents and young adults.