Current Concepts of Pediatric Acute Kidney Injury—Are We Ready to Translate Them into Everyday Practice?

Pediatric acute kidney injury (AKI) is a major cause of morbidity and mortality in children undergoing interventional procedures. The review summarizes current classifications of AKI and acute kidney disease (AKD), as well as systematizes the knowledge on pathophysiology of kidney injury, with a special focus on renal functional reserve and tubuloglomerular feedback. The aim of this review is also to show the state-of-the-art in methods assessing risk and prognosis by discussing the potential role of risk stratification strategies, taking into account both glomerular function and clinical settings conditioned by fluid overload, urine output, or drug nephrotoxicity. The last task is to suggest careful assessment of eGFR as a surrogate marker of renal functional reserve and implementation of point-of-care testing, available in the case of biomarkers like NGAL and [IGFBP-7] × [TIMP-2] product, into everyday practice in patients at risk of AKI due to planned invasive procedures or treatment.

Renal functional reserve: from physiological phenomenon to clinical biomarker and beyond

Glomerular filtration rate (GFR) is acutely increased following a high-protein meal or systemic infusion of amino acids. The mechanisms underlying this renal functional response remain to be fully elucidated. Nevertheless, they appear to culminate in preglomerular vasodilation. Inhibition of the tubuloglomerular feedback signal appears critical. However, nitric oxide, vasodilator prostaglandins, and glucagon also appear important. The increase in GFR during amino acid infusion reveals a “renal reserve,” which can be utilized when the physiological demand for single nephron GFR increases. This has led to the concept that in subclinical renal disease, before basal GFR begins to reduce, renal functional reserve can be recruited in a manner that preserves renal function. The extension of this concept is that once a decline in basal GFR can be detected, renal disease is already well progressed. This concept likely applies both in the contexts of chronic kidney disease and acute kidney injury. Critically, its corollary is that deficits in renal functional reserve have the potential to provide early detection of renal dysfunction before basal GFR is reduced. There is growing evidence that the renal response to infusion of amino acids can be used to identify patients at risk of developing either chronic kidney disease or acute kidney injury and as a treatment target for acute kidney injury. However, large multicenter clinical trials are required to test these propositions. A renewed effort to understand the renal physiology underlying the response to amino acid infusion is also warranted.

A call to action to evaluate renal functional reserve in patients with COVID-19

Coronavirus disease 2019 (COVID-19) poses an unprecedented challenge to world health systems, substantially increasing hospitalization and mortality rates in all affected countries. Being primarily a respiratory disease, COVID-19 is mainly associated with pneumonia or minor upper respiratory tract symptoms; however, different organs can sustain considerable (if not terminal) damage because of coronavirus. Acute kidney injury is the most common complication of COVID-19-related pneumonia, and more than 20% of patients requiring ventilatory support develop renal failure. Additionally, chronic kidney disease is a major risk factor for COVID-19 severity and mortality. All these data demonstrate the relevance of renal function assessment in patients with COVID-19 and the need of early kidney-directed diagnostic and therapeutic approaches. However, the sole assessment of renal function could be not entirely indicative of kidney tissue status. In this viewpoint, we discuss the clinical significance and potential relevance of renal functional reserve evaluation in patients with COVID-19.

Long-term effects of hyperproteic diet on functional renal reserve and natriuresis

Introduction: A hyperproteic diet normally results in acute changes in renal function evidenced by increases of natriuresis and glomerular filtration rate (renal functional reserve).Objectives: To assess the changes in natriuresis and creatinine clearance during 12 weeks on hyperproteic and hypersodic diet. Materials and Methods: Eighteen adults male Holtzman rats were included and the follow-up period was 12 weeks. The rats were initially distributed into three groups; hyperproteic diet (30%) from an animal source (n = 6), hyperproteic diet (30%) from a plant source (n = 6) and normoproteic diet (18%) from an animal source (n = 6). The diets were isocaloric, normosodic (0.25%). From week 8, each group was divided into three rats each and received a high-sodium (1.5%) and normosodic diet (0.25%) respectively. Results: The hyperproteic diet group (animal or plant vegetal source) had higher creatinine clearance than normoproteic diet (P < 0.05). The hyperproteic vegetal diet group had a peak with an increased renal functional reserve in 21% (P = 0.04). The natriuresis increased in the group on the animal-source diet during the first 2 weeks (P = 0.03). The group plant-source diet did not have significant change at the first week (P = 0.50); however, there was a subsequent decrease in the level of natriuresis between weeks 3 to 8. When the groups were exposed to a hypersodic diet, there was not difference in the natriuretic response between the groups (P > 0.05). Conclusion: A hyperproteic vegetal diet increased renal functional reserve but not natriuresis during an acute or long-term period; however, the natriuretic response was not impaired when a hypersodic diet was added, though hyperfiltration was present.