Analytical Validation of GFRNMR: A Blood-Based Multiple Biomarker Assay for Accurate Estimation of Glomerular Filtration Rate.

Accurate and precise monitoring of kidney function is critical for a timely and reliable diagnosis of chronic kidney disease (CKD). The determination of kidney function usually involves the estimation of the glomerular filtration rate (eGFR). We recently reported the clinical performance of a new eGFR equation (GFRNMR) based on the nuclear magnetic resonance (NMR) measurement of serum myo-inositol, valine, and creatinine, in addition to the immunoturbidometric quantification of serum cystatin C, age and sex. We now describe the analytical performance evaluation of GFRNMR according to the Clinical and Laboratory Standards Institute guidelines. Within-laboratory coefficients of variation (CV%) of the GFRNMR equation did not exceed 4.3%, with a maximum CV% for repeatability of 3.7%. Between-site reproducibility (three sites) demonstrated a maximum CV% of 5.9%. GFRNMR stability was demonstrated for sera stored for up to 8 days at 2-10°C and for NMR samples stored for up to 10 days in the NMR device at 6 ± 2°C. Substance interference was limited to 4/40 (10.0%) of the investigated substances, resulting in an underestimated GFRNMR (for glucose and metformin) or a loss of results (for naproxen and ribavirin) for concentrations twice as high as usual clinical doses. The analytical performances of GFRNMR, combined with its previously reported clinical performance, support the potential integration of this NMR method into clinical practice.

Estimating Glomerular Filtration Rate from Serum Myo-Inositol, Valine, Creatinine and Cystatin C.

Assessment of renal function relies on the estimation of the glomerular filtration rate (eGFR). Existing eGFR equations, usually based on serum levels of creatinine and/or cystatin C, are not uniformly accurate across patient populations. In the present study, we expanded a recent proof-of-concept approach to optimize an eGFR equation targeting the adult population with and without chronic kidney disease (CKD), based on a nuclear magnetic resonance spectroscopy (NMR) derived 'metabolite constellation' (GFRNMR). A total of 1855 serum samples were partitioned into development, internal validation and external validation datasets. The new GFRNMR equation used serum myo-inositol, valine, creatinine and cystatin C plus age and sex. GFRNMR had a lower bias to tracer measured GFR (mGFR) than existing eGFR equations, with a median bias (95% confidence interval [CI]) of 0.0 (-1.0; 1.0) mL/min/1.73 m2 for GFRNMR vs. -6.0 (-7.0; -5.0) mL/min/1.73 m2 for the Chronic Kidney Disease Epidemiology Collaboration equation that combines creatinine and cystatin C (CKD-EPI2012) (p < 0.0001). Accuracy (95% CI) within 15% of mGFR (1-P15) was 38.8% (34.3; 42.5) for GFRNMR vs. 47.3% (43.2; 51.5) for CKD-EPI2012 (p < 0.010). Thus, GFRNMR holds promise as an alternative way to assess eGFR with superior accuracy in adult patients with and without CKD.

The implications of complexity, systems thinking and philosophy for pediatricians.

National service systems in child healthcare are characterized by diversity and complexity. Primary, secondary, tertiary and quaternary healthcare services create complex networks covering pediatric subspecialties, psychology, sociology, economics and politics. Can pediatrics exist without philosophy? Does the absence of integrating philosophical perspectives during conceptualization of pediatric care contribute to deficiencies in the service systems structuring child healthcare? Philosophy offers new ways of complex systems thinking in scientific and clinical pediatrics. Philosophy could improve coping strategies on different levels when dealing with ethics of research projects, individual child healthcare and crises of healthcare service systems. Boundary and ultimate situations experienced by severely sick children require help, hope and resilience. Patients and families as well as pediatricians and other caregivers must act in concert. All of them may benefit from consulting with philosophers. The aim of this article is to point out the risks of a strict separation of scientific insight and sensory experience affecting child healthcare in our modern society, which is dominated by technology, competition and lack of equity and time.

Serum Myo-Inositol, Dimethyl Sulfone, and Valine in Combination with Creatinine Allow Accurate Assessment of Renal Insufficiency-A Proof of Concept.

Evaluation of renal dysfunction includes estimation of glomerular filtration rate (eGFR) as the initial step and subsequent laboratory testing. We hypothesized that combined analysis of serum creatinine, myo-inositol, dimethyl sulfone, and valine would allow both assessment of renal dysfunction and precise GFR estimation. Bio-banked sera were analyzed using nuclear magnetic resonance spectroscopy (NMR). The metabolites were combined into a metabolite constellation (GFRNMR) using n = 95 training samples and tested in n = 189 independent samples. Tracer-measured GFR (mGFR) served as a reference. GFRNMR was compared to eGFR based on serum creatinine (eGFRCrea and eGFREKFC), cystatin C (eGFRCys-C), and their combination (eGFRCrea-Cys-C) when available. The renal biomarkers provided insights into individual renal and metabolic dysfunction profiles in selected mGFR-matched patients with otherwise homogenous clinical etiology. GFRNMR correlated better with mGFR (Pearson correlation coefficient r = 0.84 vs. 0.79 and 0.80). Overall percentages of eGFR values within 30% of mGFR for GFRNMR matched or exceeded those for eGFRCrea and eGFREKFC (81% vs. 64% and 74%), eGFRCys-C (81% vs. 72%), and eGFRCrea-Cys-C (81% vs. 81%). GFRNMR was independent of patients' age and sex. The metabolite-based NMR approach combined metabolic characterization of renal dysfunction with precise GFR estimation in pediatric and adult patients in a single analytical step.

The European Society for Paediatric Nephrology study of pediatric renal care in Europe: comparative analysis 1998-2017.

BACKGROUND: In 1998, a survey of the European Society for Paediatric Nephrology (ESPN) revealed substantial disparities in pediatric renal care among European countries. Therefore, ESPN aimed at harmonizing renal care in all European countries in the following 20 years. In 2017, we conducted a survey to evaluate the current status of renal health policies for children in Europe. METHODS: A 33-question web-based survey was designed and sent to presidents or representatives of national societies of pediatric nephrology in 44 European countries. RESULTS: Data was reported from 42 (95.5%) countries. The number of pediatric nephrologists per million child population increased from 1998 to 2017 in 70% of countries. Pediatric dialysis facilities for acute kidney injury and end-stage kidney disease were available in 95% of countries. The availability of pediatric kidney transplantation increased from 55 to 93% of countries. Considerable variation was found in the current availability of allied health professionals, including psychosocial and nutritional support, high-tech diagnostic methods, and treatment with expensive drugs for children with kidney diseases between different European countries. CONCLUSIONS: The 20-year follow-up analysis of pediatric renal care services in European countries revealed that pediatric nephrology has become a well-established subspecialty in pediatrics and nephrology in 2017. The ESPN will continue its efforts to further improve pediatric renal care for European children by harmonizing remaining disparities of renal care services.

Worldwide view of nephropathic cystinosis: results from a survey from 30 countries.

BACKGROUND: Nephropathic cystinosis is a rare inherited metabolic disorder leading to progressive renal failure and extra-renal comorbidity. The prognosis relies on early adherence to cysteamine treatment and symptomatic therapies. Developing nations [DiN] experience many challenges for management of cystinosis. The aim of this study was to assess the management characteristics in DiN compared with developed nations [DeN]. METHODS: A questionnaire was sent between April 2010 and May 2011 to 87 members of the International Pediatric Nephrology Association, in 50 countries. RESULTS: A total of 213 patients were included from 41 centres in 30 nations (109 from 17 DiN and 104 from 13 DeN). 7% of DiN patients died at a median age of 5 years whereas no death was observed in DeN. DiN patients were older at the time of diagnosis. In DiN, leukocyte cystine measurement was only available in selected cases for diagnosis but never for continuous monitoring. More patients had reached end-stage renal disease in DiN (53.2 vs. 37.9%, p = 0.03), within a shorter time of evolution (8 vs. 10 yrs., p = 0.0008). The earlier the cysteamine treatment, the better the renal outcome, since the median renal survival increased up to 16.1 [12.5-/] yrs. in patients from DeN treated before the age of 2.5 years of age (p = 0.0001). However, the renal survival was not statistically different between DeN and DiN when patients initiated cysteamine after 2.5 years of age. The number of transplantations and the time from onset of ESRD to transplantation were not different in DeN and DiN. More patients were kept under maintenance dialysis in DiN (26% vs.19%, p = 0.02); 79% of patients from DiN vs. 45% in DeN underwent peritoneal dialysis. CONCLUSIONS: Major discrepancies between DiN and DeN in the management of nephropathic cystinosis remain a current concern for many patients living in countries with limited financial resources.