Assessment of fluid status in neonatal dialysis: the need for new tools.

BACKGROUND: Assessment of fluid status in neonatal dialysis has largely focused on traditional tools including clinical assessment, serial weights, and blood pressure (BP) measurements. However, in infants on kidney replacement therapy, the assessment of fluid overload is problematic due to errors in weight assessment, subtlety of physical exam findings, and inaccuracy of non-invasive BP measurements. In this presentation of a neonate with bilateral renal agenesis requiring kidney replacement therapy, the treating team assessed a number of variables in determining the ultrafiltration prescription for dialysis across 2 modalities (hemodialysis and continuous kidney replacement therapy). COMPLICATIONS: Fluid overload, cardiomegaly, and worsened respiratory status occurred when attempting to assess the neonate's fluid status by traditional markers (weights, blood pressures, physical exam findings). B-type natriuretic peptide (BNP) was obtained and was noted to correlate with the degree of fluid overload. KEY MANAGEMENT POINTS: Compared to traditional tools for assessment of fluid status in pediatric dialysis, BNP assisted the medical team in optimizing the volume status of the subject and determining optimal daily ultrafiltration goals. Due to the rapid release in response to myocardial stretch and the lack of kidney clearance of the peptide, BNP may represent an objective, timely, and reliable index of volume status in the pediatric dialysis patient.

Outcomes and risk factors for death among hospitalized children and adolescents with kidney diseases and COVID-19: an analysis of a nationwide database.

BACKGROUND: Patients with kidney diseases (KD) appear to be at particularly high risk for severe COVID-19. This study aimed to characterize the clinical outcomes and risk factors for COVID-19-related death in a large cohort of hospitalized pediatric patients with KD. METHODS: We performed an analysis of all pediatric patients with KD and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 16, 2020, and May 29, 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using cumulative incidence function. RESULTS: Among 21,591 hospitalized patients with COVID-19, 290 cases (1.3%) had KD. Of these, 59 (20.8%) had a fatal outcome compared with 7.5% of the non-KD cohort (P < 0.001). Pediatric patients with KD had an increased hazard of death compared with the non-KD cohort (Hazard ratio [HR] = 2.85, 95% CI 2.21-3.68, P < 0.0001). After adjustment, the factors associated with the death among KD patients were living in Northeast (HR 2.16, 95% CI 1.13-4.31) or North regions (HR 3.50, 95% CI 1.57-7.80), oxygen saturation < 95% at presentation (HR 2.31, 95% CI 1.30-4.10), and presence of two or more associated comorbidities (HR 2.10, 95% CI 1.08-4.04). CONCLUSIONS: Children and adolescents with KD had a higher risk of death compared with the non-KD cohort. The higher risk was associated with low oxygen saturation at admission, living in socioeconomically disadvantaged regions, and presence of other pre-existing comorbidities. A higher resolution version of the Graphical abstract is available as Supplementary information.

Evolution of altered tubular metabolism and mitochondrial function in sepsis-associated acute kidney injury.

Sepsis-associated acute kidney injury (s-AKI) has a staggering impact in patients and lacks any treatment. Incomplete understanding of the pathogenesis of s-AKI is a major barrier to the development of effective therapies. We address the gaps in knowledge regarding renal oxygenation, tubular metabolism, and mitochondrial function in the pathogenesis of s-AKI using the cecal ligation and puncture (CLP) model in mice. At 24 h after CLP, renal oxygen delivery was reduced; however, fractional oxygen extraction was unchanged, suggesting inefficient renal oxygen utilization despite decreased glomerular filtration rate and filtered load. To investigate the underlying mechanisms, we examined temporal changes in mitochondrial function and metabolism at 4 and 24 h after CLP. At 4 h after CLP, markers of mitochondrial content and biogenesis were increased in CLP kidneys, but mitochondrial oxygen consumption rates were suppressed in proximal tubules. Interestingly, at 24 h, proximal tubular mitochondria displayed high respiratory capacity, but with decreased mitochondrial content, biogenesis, fusion, and ATP levels in CLP kidneys, suggesting decreased ATP synthesis efficiency. We further investigated metabolic reprogramming after CLP and observed reduced expression of fatty acid oxidation enzymes but increased expression of glycolytic enzymes at 24 h. However, assessment of functional glycolysis revealed lower glycolytic capacity, glycolytic reserve, and compensatory glycolysis in CLP proximal tubules, which may explain their susceptibility to injury. In conclusion, we demonstrated significant alterations in renal oxygenation, tubular mitochondrial function, and metabolic reprogramming in s-AKI, which may play an important role in the progression of injury and recovery from AKI in sepsis.

Protein-energy wasting and uremic failure to thrive in children with chronic kidney disease: they are not small adults.

Protein-energy wasting (PEW), a condition of decreased body protein and fat mass, is highly prevalent in patients with chronic kidney disease (CKD) and a potent predictor of mortality in this population. In adults with CKD, PEW has typically been defined on the basis of (1) deranged biochemical parameters, (2) reduced body mass, (3) reduced muscle mass, and (4) decreased dietary protein intake. Emerging data suggest that PEW may also commonly afflict children with CKD and have a negative impact on growth and development ("uremic failure to thrive"), yet it remains comparatively understudied and less well characterized in these patients. Given the challenges of applying adult-defined PEW criteria to the pediatric population, the authors of a recent study entitled "Protein energy wasting in children with chronic kidney disease" [Abraham et al. (2014) Pediatr Nephrol 29:1231-1238] have sought to develop a scoring system and three alterative definitions for this condition using a combination of biochemical markers, clinical measurements, and subjective reporting in children in the CKiD cohort: (1) minimal PEW definition (≥2 adult-defined PEW criteria); (2) standard PEW definition (≥3 adult-defined PEW criteria); (3) modified PEW definition (≥3 adult-defined PEW criteria, plus short stature or poor growth). These authors observed that meeting the modified PEW definition was associated with a significantly increased risk of hospitalization in unadjusted analyses, i.e., a 2.2-fold higher risk, and trended towards increased risk in multivariable adjusted analyses, i.e., 2.0-fold higher risk. At the present time, future studies validating these findings and developing further refined definitions and/or scoring systems for the detection and management of PEW in children and uremic failure to thrive are urgently needed.

Role of renal oxygenation and mitochondrial function in the pathophysiology of acute kidney injury.

There are unique features of renal oxygenation that render the kidney susceptible to oxygen demand-supply mismatch and hypoxia. Renal oxygen consumption by oxidative metabolism is closely coupled to and driven by tubular transport, which is linked to the filtered solute load and glomerular filtration rate (GFR). In turn, filtered solute load and GFR are dependent on the renal blood flow. Hence, changes in renal blood flow increase oxygen delivery but also increase oxygen demand (consumption) simultaneously by increasing the tubular workload of solute transport. The renal blood flow to different regions of kidney is also inhomogeneous, increasing the oxygen demand-supply mismatch in particular areas such as the outer medulla which become more susceptible to injury. Thus, tubular transport and oxidative metabolism by miochondria are closely coupled in the kidney and are the principal determinants of intrarenal oxygenation. Here we review the published literature characterizing renal oxygenation and mitochondrial function in ischemic and sepsis-associated acute kidney injury (AKI). However, the coupling of transport and metabolism in AKI has not been examined. This is a potentially fruitful area of research that should become increasingly active given the emerging data linking renal oxygenation and hypoxia to acute and chronic dysfunction in the kidney.

Steroid-resistant nephrotic syndrome: past and current perspectives.

Patients with steroid-resistant nephrotic syndrome (SRNS) represent a challenging subset of patients with nephrotic syndrome who often fail standard immunosuppression and have a higher likelihood of progressing to end-stage renal disease. Appropriate treatment of SRNS requires an adequate understanding of the historical treatment, renal histopathology, and genetics associated with the disease. The aim of this review is to present a comprehensive appraisal of the history, role of renal biopsy, genetics, and treatment of SRNS.