Responding to the workforce crisis: consensus recommendations from the Second Workforce Summit of the American Society of Pediatric Nephrology.

IMPORTANCE: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care. OBJECTIVE: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce. EVIDENCE REVIEW: Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions. FINDINGS: A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member's time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology. CONCLUSIONS AND RELEVANCE: The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients.

Smaller circuits for smaller patients: improving renal support therapy with Aquadex™.

BACKGROUND: Providing renal support for small children is very challenging using the machinery currently available in the United States. As the extracorporeal volume (ECV) relative to blood volume increases and the state of critical illness worsens, the chance for instability during continuous renal replacement therapy (CRRT) initiation also increases. CRRT machines with smaller ECV could reduce the risks and improve outcomes. METHODS: We present a case series of small children (n = 12) who received continuous venovenous hemofiltration (CVVH) via an Aquadex™ machine (ECV = 33 ml) with 30 ml/kg/h of prereplacement fluids at Children's of Alabama between December 2013 and April 2015. We assessed in vitro fluid precision using the adapted continuous veno-venous hemofiltration (CVVH) system. RESULTS: We used 101 circuits over 261 days to provide CVVH for 12 children (median age 30 days; median weight 3.4 kg). Median CVVH duration was 14.5 days [interquartile range (IQR) = 10; 22.8 days]. Most circuits were routinely changed after 72 h. Five of 101 (5 %) initiations were associated with mild transient change in vital signs. Complications were infrequent (three transient cases of hypothermia, three puncture-site bleedings, one systemic bleed, and one right atrial thrombus). Most patients (7/12, 58 %) were discharged from the intensive care unit; six of them (50 %) were discharged home. CONCLUSIONS: CRRT machines with low ECV can enable clinicians to provide adequate, timely, safe, and efficient renal support to small, critically ill infants.

Uric Acid and Hypertension: An Update With Recommendations.

The association between increased serum urate and hypertension has been a subject of intense controversy. Extracellular uric acid drives uric acid deposition in gout, kidney stones, and possibly vascular calcification. Mendelian randomization studies, however, indicate that serum urate is likely not the causal factor in hypertension although it does increase the risk for sudden cardiac death and diabetic vascular disease. Nevertheless, experimental evidence strongly suggests that an increase in intracellular urate is a key factor in the pathogenesis of primary hypertension. Pilot clinical trials show beneficial effect of lowering serum urate in hyperuricemic individuals who are young, hypertensive, and have preserved kidney function. Some evidence suggest that activation of the renin-angiotensin system (RAS) occurs in hyperuricemia and blocking the RAS may mimic the effects of xanthine oxidase inhibitors. A reduction in intracellular urate may be achieved by lowering serum urate concentration or by suppressing intracellular urate production with dietary measures that include reducing sugar, fructose, and salt intake. We suggest that these elements in the western diet may play a major role in the pathogenesis of primary hypertension. Studies are necessary to better define the interrelation between uric acid concentrations inside and outside the cell. In addition, large-scale clinical trials are needed to determine if extracellular and intracellular urate reduction can provide benefit hypertension and cardiometabolic disease.

Pathogenesis of essential hypertension: historical paradigms and modern insights.

Since its first identification in the late 1800s, a variety of etiologies for essential hypertension have been proposed. In this paper we review the primary proposed hypotheses in the context of both the time in which they were proposed as well as the subsequent studies performed over the years. From these various insights, we propose a current paradigm to explain the renal mechanisms underlying the hypertension epidemic today. Specifically, we propose that hypertension is initiated by agents that cause systemic and intrarenal vasoconstriction. Over time intrarenal injury develops with microvascular disease, interstitial T cell and macrophage recruitment with the induction of an autoimmune response, with local angiotensin II formation and oxidant generation. These changes maintain intrarenal vasoconstriction and hypoxia with a change in local vasoconstrictor-vasodilator balance favoring sodium retention. Both genetic and congenital (nephron number) mechanisms have profound influence on this pathway. As blood pressure rises, renal ischemia is ameliorated and sodium balance restored completely (in salt-resistant) or partially (in salt-sensitive) hypertension, but at the expense of a rightward shift in the pressure natriuresis curve and persistent hypertension.

Hormonal and cytokine effects of uric acid.

PURPOSE OF REVIEW: Current evidence supports the role of soluble uric acid as a true mediator of injury, exerting its effects through the induction of growth factors, cytokines, hormones and autacoids. In the present review, we summarize recent studies on the mechanisms involved in the uric acid deleterious effects. RECENT FINDINGS: Although uric acid is considered an antioxidant in plasma, recent clinical and epidemiological studies have found that hyperuricemia is associated with mortality and development of hypertension, cardiovascular and chronic renal diseases. Experimental studies suggest that uric acid induce its detrimental effects at the cellular level entering to vascular smooth muscle cells (VSMC) via an organic anion transport system, and followed by the activation of specific MAP kinases, nuclear transcription factors, with stimulation of COX-2, PDGF A and C chain, PDGF alpha receptor, and various inflammatory mediators, including C-reactive protein and monocyte chemoattractant protein-1. Physiologically, these effects translate into a rise of arterial pressure, VSMC hypertrophy, tubulointerstitial infiltration and glomerular hypertension in the setting of renal vasoconstriction. Uric acid also promotes endothelial dysfunction through inactivation of NO and arresting the proliferation of endothelial cells. Thus, arteriosclerosis induced by hyperuricemia may be a novel mechanism for the development of essential hypertension. SUMMARY: Soluble uric acid has important biologic roles. While it acts as an antioxidant, there is also evidence that uric acid has pro-inflammatory and proliferative effects on VSMC, and causes dysfunction of endothelial cells. These cellular mechanisms may translate into why uric acid is associated with renal and cardiovascular disease.

Hiperuricemia como factor de riesgo para el desarrollo de hipertensión, daño renal crónico y síndrome metabólico / Hyperuricemia as a risk factor for developing hypertension, chronic kidney damage and metabolic syndrome

Por mucho tiempo se ha descrito una asociación entre la hiperuricemia y el desarrollo de hipertensión arterial, enfermedades cardiovascular y renal, así como síndrome metabólico: sin embargo el mecanismo de año asociado a la hiperuricemia no ha sido aclarado totalmente, principalmente debido a la fala de un modelo experimental adecuado. actualmente existe un renovado interés por el posible papel patogénico del ácido úrico; estudios clínicos, epidemiológicos y expeirmentales sugieren que la hiperuricemia puede contribuir al desarrollo y permanencia de la hipertension arterial sistémica, las enfermedades cardiovasculares y renales, el síndrome metabólico y posiblemente la diabetes mellitus tipo 2.