Neonatal nephrology and laboratory medicine: an effective interdisciplinary model to improve the outcome in neonatal intensive care unit

Almost 25 years ago now, a small group of neonatologists decided to devote more attention to neonatal kidney development and diseases and formed a study group belonging to the Italian Society of Neonatology. At that time, Prof. Gordon B. Avery, during an International Meeting in Rome, pointed that “neonatologists know everything about brain, heart and lungs, but less about other organs like kidneys”; he strongly encouraged to improve our knowledge on this field. Few years later, the group realized the progressive importance of clinical biochemistry and molecular biology in assessing early stages of neonatal kidney impairment and failure, especially in those conditions characterized by the absence of specific clinical signs and symptoms. It was evident that neonatologists were often frustrated by the limitations in the availability of specific and sensitive biomarkers for managing critically ill newborns in neonatal intensive care units (NICUs) and would benefit from the introduction of new reliable tests in routine, specifically to diagnose severe clinical conditions early in their course: asphyxia, sepsis, acute kidney injury (AKI), etc.

Therefore, we developed the idea of a multidisciplinary management in critically ill newborns: to evaluate emerging biomarkers in specific, severe clinical conditions, to collect data, to promote the debate among participants, to publish results, and finally to spread our shared experience in neonatal and pediatric meetings as well as in laboratory medicine meetings. Our aims were to increase the awareness of neonatologists in introducing new effective biochemical tests in their routine and, simultaneously, to increase laboratorians attention to the biochemical “universe” of neonatal age. Investigation of fetal and neonatal kidney function by measuring amniotic fluid and urine specific biomarkers (enzymes and low-molecular mass proteins) was our first step in searching to improve knowledge and clinical application in kidney diseases. In 1989, we presented our preliminary results on “tubular kidney function in healthy full-term newborns” at the 3rd Italian National Congress of Perinatal Medicine (Palermo, Italy). Between 1992 and 1994, the group presented innovative results on the clinical significance of α₁-microglobulin (protein HC), β₂-microglobulin, N-Acetyl-β-D-Glucosaminidase (NAG) and alanine amino peptidase (AAP) in amniotic fluid, discriminating healthy fetuses from those with kidney impairment [1–2]. These were the first steps of the group. Over time, the study group published a body of papers on plasma and urine biomarkers for prenatal and neonatal kidney diseases. Four books were published by our group, including the first book on Neonatal Nephrology published all over the world [3].

New results and new perspectives in neonatal health care were also presented across various international and national congresses and symposia in the field of neonatology, pediatrics, and laboratory medicine and published in important journals, [4].

At the beginning of the 3rd millennium, the increasing knowledge on molecular and biochemical pathways in human diseases and the development of fully-automated analytical devices and reagents integrated with robotics have progressively led to the commercial availability of new, more sophisticated laboratory tests. These revolutionary changes opened the way to the application of personalized medicine based on “omics” in clinical practice. This new generation of tests would offer better clinical and analytical performances, improving diagnostic accuracy, risk stratification, and ultimately, patient outcome. However, no “added value” can be reached without the correct interpretation of test results with a strict and effective liaison between clinicians and laboratory professionals. At the same time, laboratorians and clinicians have to face the lack of available financial resources for the health care systems both in Europe and in North America. As a result, this issue originates a strong pressure to save costs, particularly by cutting down laboratory tests (numbers and types of tests) and performances. To overcome this limit and apply “mandatory changes”, there is the urgent need to improve the appropriateness of test requests and to suppress obsolete laboratory tests to free up financial resources.

It is obvious that today new, more important aims call for maintaining and re-forcing the liaison between neonatology and laboratory medicine, taking into account the need to move away from the current paradigm of acute/chronic-diseases diagnosis and management to the prevention of diseases, early and tailored treatment, and more effective monitoring. In this context, metabolomics represents an intriguing challenge for clinicians and laboratorians. In fact, we are moving toward the comprehension of the system as a whole (systems biology or systems medicine) with an olistic approach to clinical problems. Aristoteles wrote “the whole is not represented by the sum of these components”. Metabolomics represents the passage from a descriptive science to a predictive science, and it has the potential to translate bench top research to real clinical benefits since it is the best indicator of an organism’s phenotype. In Pediatrics, it is a highly informative technique that can also be used as non-invasively collected samples of urine. The first data are available in neonatology and pediatrics and have been very recently reviewed [5]. Our last data suggest an interesting role of metabolomics in evaluating the long-term effects of perinatal programming, IUGR, renal diseases, chronic kidney injury [6,7]. Finally, we are explorating old areas with new eyes, including embryology, immunochemistry and experimental nephrology [8–10].

Similarly, new biomarkers have been recently and very recently proposed for acute, severe neonatal pathologies, like AKI, sepsis-induced AKI, etc. and other promising tissue-specific biomarkers for the early assessment of injuries caused by hemodynamic changes (e.g., arterial and arteriolar vasodilatation, ischemia/reperfusion, etc.) need to be accurately investigated in order to clarify their potential role for improving critically ill newborns outcome. We are hoping that metabolomics along with biomarkers, like those mentioned in such papers published in this issue (urine Neutrophil gelatinase-associated lipocalin: uNGAL, Netrin-1, soluble CD14 subtype presepsin: sCD14-ST, lipopolysaccharide binding protein: LBP, etc.), can allow a more effective diagnosis, monitoring and risk assessment and can be quickly introduced in clinical routine, demonstrating an acceptable cost/effective ratio.

Today, our idea, developed around 25 years ago, is more than ever alive, and we all together should pursue it in the future. Thinking in the view of JFK, an idea, better whether a good idea, should survive to men, hospitals, and nations, aiming to build a better health care system and, ultimately, a better life for future adults.

A man may die, nations may rise and fall, but an idea lives on.

John F. Kennedy