Use of renal near-infrared spectroscopy measurements in congenital diaphragmatic hernia patients on ECMO.

INTRODUCTION: This study tests the hypothesis that renal tissue oxygen saturation as measured by Near Infrared Spectroscopy (NIRS) would correlate with urine output in neonates with congenital diaphragmatic hernia (CDH) on extracorporeal membrane oxygenation (ECMO). METHODS: Between 2012 and 2015, neonates with CDH were enrolled as part of a comprehensive study that provided renal/cerebral/abdominal NIRS monitoring for the duration of ECMO support. Continuous NIRS measurements, mean arterial pressure, and urine output were recorded. Periods of anuria (NU), adequate urine output >1ml/kg/h (AU), and low urine output <1ml/kg/h (LU) were noted and analyzed. RESULTS: Over 1500h of continuous renal NIRS were obtained from six neonates. NIRS values were significantly different during periods of AU, LU, and anuria (84±6%, 76±3%, and 67±6%, p<0.01). ROC curves identified NIRS >76% as highly predictive of adequate urine output (AUC=0.96). MAP was significantly lower only in anuric patients, 36.42±10.26, compared to patients with AU and LU - 42.99±5.25 and 42.85±7.4, respectively (p<0.001). CONCLUSION: Renal NIRS measurements correlate with urine production. Lower values are noted as urine output declines and precedes a decline in MAP. Renal NIRS may have promise as a non-invasive means of determining adequacy of renal perfusion and urine output in neonates with complex fluid shifts. LEVEL OF EVIDENCE: IIb.

In-depth phenotyping of a Donnai-Barrow patient helps clarify proximal tubule dysfunction.

BACKGROUND: The megalin/cubilin/amnionless complex is essential for albumin and low molecular weight (LMW) protein reabsorption by renal proximal tubules (PT). Mutations of the LRP2 gene encoding megalin cause autosomal recessive Donnai-Barrow/facio-oculo-acoustico-renal syndrome (DB/FOAR), which is characterized by LMW proteinuria. The pathophysiology of DB/FOAR-associated PT dysfunction remains unclear. CLINICAL CASE: A 3-year-old girl presented with growth retardation and proteinuria. Clinical examination was unremarkable, except for a still-opened anterior fontanel and myopia. Psychomotor development was delayed. At 6, she developed sensorineural hearing loss. Hypertelorism was noted when she turned 12. Blood analyses, including renal function parameters, were normal. Urine sediment was bland. Proteinuria was significant and included albumin and LMW proteins. Immunoblotting analyses detected cubilin and type 3 carbonic anhydrase (CA3) in the urine. Renal ultrasound was unremarkable. Optical examination of a renal biopsy did not disclose any tubular or glomerular abnormality. Electron microscopy revealed that PT apical endocytic apparatus was significantly less developed. Immunostaining for megalin showed a faint signal in PT cytosol contrasting with the distribution of cubilin at the apical membrane. The diagnostic procedure led to identifying two mutations of the LRP2 gene. CONCLUSIONS: The functional loss of megalin in DB/FOAR causes PT dysfunction characterized by increased urinary shedding of CA3 and cubilin.