Perinatal nephrology

While the association between low birth weight (LBW; <2500 g) and development of adult chronic renal disease (CKD) is inconsistently reported, less information is available regarding association of high birth weight (HBW; ≥4000 g) with CKD. We undertook a systematic review and meta-analysis on studies published before 30 September 2015 and report associations between birth weight and renal function. Blood (glomerular filtration rate (GFR)) and urine (microalbuminuria/albumin excreation rate (AER)/urinary albumin creatinine ratio (ACR)) parameters were used to define CKD...

OBJECTIVE: We evaluated whether urinary excretion of tubular injury markers could be useful for early detection of gentamicin (GM)-induced renal damage in neonates. STUDY DESIGN: We conducted a prospective, observational trial in neonates admitted to the neonatal intensive care unit (26 GM treated, 20 control). Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and π- and α-glutathione-S-transferase (GSTP1-1 and GSTA1-1) were measured every 2 hours during admission and compared with serum creatinine (sCr) and urine output...

INTRODUCTION: Acute kidney injury (AKI) is common in neonatal intensive care units (NICU). In recent years, every effort is made for early detection of AKI. Our hypothesis was that serum neutrophil gelatinase-associated lipocalin (sNGAL) may be a reliable screening test for early diagnosis of AKI in premature neonates after perinatal asphyxia. Therefore, our aim was to assess the diagnostic accuracy of sNGAL for AKI in premature asphyxiated neonates. MATERIALS AND METHODS: AKI was defined in the third day of life (DOL 3) as a serum creatinine (sCr) increase ≥26...

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6-1/2-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24-hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH), and elevated 1,25(OH)2D...

The renal phenotype induced by loss-of-function mutations of inwardly rectifying potassium channel (Kir), Kcnj10 (Kir4.1), includes salt wasting, hypomagnesemia, metabolic alkalosis and hypokalemia. However, the mechanism by which Kir.4.1 mutations cause the tubulopathy is not completely understood. Here we demonstrate that Kcnj10 is a main contributor to the basolateral K conductance in the early distal convoluted tubule (DCT1) and determines the expression of the apical Na-Cl cotransporter (NCC) in the DCT...

This case report presents fluoconazole efficacy to reduce hypercalcaemia and increased urinary calcium excretion in a patient with nephrocalcinosis after a long history of recurrent renal stones caused by a loss-of-function mutation of the CYP24A1 gene. The CYP24A1 gene codes for a key enzyme in the vitamin D endocrine system that protects against vitamin D toxicity by degrading the circulating excess of both 1,25-dihydroxyvitamin D, the hormonal form of vitamin D, and its precursor, 25-hydroxyvitamin D. In order to expedite the identification of this rare disorder and improve therapies to avoid its progression to nephrocalcinosis, this editorial updates the current knowledge on the frequency of CYP24A1-inactivating mutations, the features of their early clinical presentation and progression, and the pathophysiology of vitamin D activation in health and in granulomatous disorders that may help improve current treatment...

BACKGROUND: Serum creatinine (s[Cr]) reference ranges for very-low-birth-weight (VLBW) infants must account for physiologic changes in the first months of life. METHODS: We retrospectively identified a sample of 218 appropriate-for-gestational age (GA) VLBW infants without risk factors for renal impairment, and classified into one of three GA groups: 25-27, 28-29, and 30-33 wk. We observed three phases of s[Cr] change (initial, decline, and equilibrium), whose characteristics varied by GA group...

Dent-Wrong disease, an X-linked recessive disorder of the proximal tubules, presents with hypercalciuria, nephrocalcinosis, nephrolithiasis, renal insufficiency, low-molecular-weight proteinuria, rickets and/or osteomalacia. Dent and Friedman initially characterized the disorder in 1964 following studies of two patients with rickets who presented with hypercalciuria, hyperphosphaturia, proteinuria and aminoaciduria. Since then, extensive investigation identified two genetic mutations (CLCN5 and OCRL1) to be associated with Dent-Wrong disease...

The clinical phenotypes of patients with Bartter syndrome type III sometimes closely resemble those of Gitelman syndrome. We report a patient with mild, adult-onset symptoms, such as muscular weakness and fatigue, who showed hypokalemic metabolic alkalosis, elevated renin-aldosterone levels with normal blood pressure, hypocalciuria and hypomagnesemia. She was also suffering from chondrocalcinosis. A diuretic test with furosemide and thiazide showed a good response to furosemide, but little response to thiazide...

UNLABELLED: Extremely immature newborns develop a self-limiting normal anion gap metabolic acidosis in early life. This study examined the natural history of this acidosis in a population of infants of gestation less than 26 weeks in the first 14 days of life. The acidosis was maximal on day 4 with a mean base deficit of 10.6 mmol/l and had resolved in 90 % of infants by day 11. Dopamine usage was the only independent predictor of the acidosis. Its use was associated with a greater degree of acidosis...

BACKGROUND: Neonatal atypical hemolytic uremic syndrome (aHUS) is a rare but severe disease that is mainly due to methylmalonic aciduria or genetic complement abnormalities. Traditional management of aHUS includes plasma infusion/exchange, but in small or unstable infants, plasma exchange can be challenging because of high extracorporeal volume and difficulty to obtain an adequate venous access. The C5 complement blocker eculizumab has become a cornerstone of first-line management of aHUS due to complement deregulation in older patients...

CONTEXT: Neonatal severe hyperparathyroidism (NSHPT) is a severe form of familial hypocalciuric hypercalcemia characterized by severe hypercalcemia and skeletal demineralization. In most cases, NSHPT is due to biallelic loss-of-function mutations in the CASR gene encoding the calcium-sensing receptor (CaSR), but some patients have heterozygous mutations. Conventional treatment consists of iv saline, bisphosphonates, and parathyroidectomy. OBJECTIVE: The aim of this project was to characterize the molecular basis for NSHPT in an affected newborn and to describe the response to monotherapy with cinacalcet...