Physicians' Recognition and Management of Kidney Disease: A Randomized Vignette Study Evaluating the Impact of the KDIGO 2012 CKD Classification System.

RATIONALE & OBJECTIVE: The Kidney Disease Outcome Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) classification systems published in 2002 and 2012, respectively, are recommended worldwide and based on strong epidemiologic data. However, their impact on CKD recognition and management is not well evaluated in clinical practice, and we therefore investigated whether they help physicians recognize and appropriately care for patients with CKD. STUDY DESIGN: Randomized vignette experiment with fractional factorial design based on 6 kidney-related scenarios and 3 laboratory presentation methods reflecting the CKD guidelines. Participants evaluated 1 of 3 subsets of the 18 vignettes (ie, 6 vignettes each with 4 answer alternatives). SETTING & PARTICIPANTS: 249 interns, general practitioners, and residents/fellows attending postgraduate meetings and courses in Norway and the United States. INTERVENTION: Kidney-related results (serum creatinine level and urinary albumin excretion) were presented as the "minimal data" (high/low levels), KDOQI-2002 (estimated glomerular filtration rate [eGFR] reported automatically), or KDIGO-2012 (eGFR + albuminuria categorization + risk for complications) laboratory report. OUTCOME: CKD management choice by physicians. RESULTS: When kidney laboratory data were presented as the KDOQI-2002 report (automatic eGFR calculation), there was a significantly higher odds for correct patient management decisions compared with the minimal data report (OR, 1.57; P < 0.001). Additional significant improvement was obtained with the KDIGO-2012 report (OR, 2.28 for correct answer vs minimal data report [P < 0.001]; OR, 1.45 compared to KDOQI-2002 report [P = 0.005]). The KDIGO classification system improved physician management in 4 of the 6 clinical scenarios covering a wide range of kidney-related topics. Interaction analysis showed that general practitioners and those with 1 to 3 years of internal medicine experience had the greatest improvements with the new presentation techniques. LIMITATIONS: Physicians' management was evaluated by theoretical scenarios rather than direct patient care. CONCLUSIONS: Automatic GFR estimation, albuminuria categorization, and notification of the associated risk for complications improve most physicians` recognition and management of a wide range of CKD clinical scenarios.

Implementing the European Renal Best Practice Guidelines suggests that prediction equations work well to differentiate risk of end-stage renal disease vs. death in older patients with low estimated glomerular filtration rate.

Recent European guidelines suggest using the kidney failure risk equation (KFRE) and mortality risk equation for kidney disease (MREK) to guide decisions on whether elderly patients with chronic kidney disease should be referred early for dialysis preparation. However, the concurrent use of the two risk equations has not been validated. To do so we evaluated 1,188 individuals over five years with estimated glomerular filtration rate (eGFR) under 45ml/min/1.73m2 and age over 65 years from the Norwegian population based HUNT study. Forty-two patients started renal replacement therapy and 462 died as their first clinical event. The KFRE was well calibrated (mean risk estimate 4.9% vs observed 3.5%) with high diagnostic accuracy (C-statistics 0.93). The MREK underestimated death risk in those with lower risk (mean risk estimate 30.1% vs observed 38.9%) and had moderate diagnostic accuracy (C-statistics 0.71). Only 31 individuals had estimated end stage kidney disease (ESRD) risk greater than death risk, and most experienced ESRD before death. Only two of 598 patients over 80 years old, and ten of 1,063 with eGFR 25-45ml/min/1.73m2 at baseline experienced ESRD. Decision curve analysis demonstrated that for risk adverse patients, deferring ESRD preparation may be appropriate until predicted ESRD risk exceeds predicted death risk. For those preferring a more aggressive approach, referral when eGFR is under 25 ml/min/1.73m2 may be beneficial if age remains under 80 years. Thus, the risk of ESRD is low compared to the risk of death in many older patients with chronic kidney disease stage 3b or worse, and combination of predicted ESRD and death risks, eGFR levels, age, and the patient`s valuations of harm and benefit can be helpful for deciding when to start dialysis preparations.

Gene Expression Studies and Targeted Metabolomics Reveal Disturbed Serine, Methionine, and Tyrosine Metabolism in Early Hypertensive Nephrosclerosis.

INTRODUCTION: Hypertensive nephrosclerosis is among the leading causes of end-stage renal disease, but its pathophysiology is poorly understood. We wanted to explore early metabolic changes using gene expression and targeted metabolomics analysis. METHODS: We analyzed gene expression in kidneys biopsied from 20 patients with nephrosclerosis and 31 healthy controls with an Affymetrix array. Thirty-one amino acids were measured by liquid chromatography coupled with mass spectrometry (LC-MS) in urine samples from 62 patients with clinical hypertensive nephrosclerosis and 33 age- and sex-matched healthy controls, and major findings were confirmed in an independent cohort of 45 cases and 15 controls. RESULTS: Amino acid catabolism and synthesis were strongly underexpressed in hypertensive nephrosclerosis (13- and 7-fold, respectively), and these patients also showed gene expression patterns indicating decreased fatty acid oxidation (12-fold) and increased interferon gamma (10-fold) and cellular defense response (8-fold). Metabolomics analysis revealed significant distribution differences in 11 amino acids in hypertensive nephrosclerosis, among them tyrosine, phenylalanine, dopamine, homocysteine, and serine, with 30% to 70% lower urine excretion. These findings were replicated in the independent cohort. Integrated gene-metabolite pathway analysis showed perturbations of renal dopamine biosynthesis. There were also significant differences in homocysteine/methionine homeostasis and the serine pathway, which have strong influence on 1-carbon metabolism. Several of these disturbances could be interconnected through reduced regeneration of tetrahydrofolate and tetrahydrobiopterin. CONCLUSION: Early hypertensive nephrosclerosis showed perturbations of intrarenal biosynthesis of dopamine, which regulates natriuresis and blood pressure. There were also disturbances in serine/glycine and methionine/homocysteine metabolism, which may contribute to endothelial dysfunction, atherosclerosis, and renal fibrosis.