Screening for an Underlying Tubulopathy in Children With Growth Failure, Simply Maths?

Background: Involving pediatric nephrological input in the clinical diagnostic work-up of children with short stature, gave rise to the hypothesis that the presence of an underlying renal tubular disorder in children with short stature is possibly underestimated. This study focussed on the added value of calculated urinary fractional excretion (FE) in the early detection of tubular disorders in children with growth failure. Methods: This trial was designed as an observational study analyzing the medical files of children between 5 and 16 years who had been referred for short stature to the pediatric endocrinology outpatient clinic at the University Hospital Antwerp between 25/01/2015 and 01/03/2019. Based on the laboratory results of the simultaneously taken blood and urine sample, the fractional excretions of Sodium, Chloride, Potassium, Calcium, Phosphate, and Magnesium were calculated. Results: Of the 299 patients, 54 patients had at least one deviating fractional excretion value, requiring further investigation (control sample of blood and urine, kidney ultrasound or 24 h urine collection). Genetic screening for tubulopathies was performed in 19 patients. In 5 patients (1.7% of the total population) a tubulopathy was confirmed based on genetic analysis. Conclusion: This study explored the possibility of using fractional excretions as a screening test to obtain an earlier diagnosis of tubular disorders in children with short stature. Of the 299 patients, 5 patients were diagnosed with a genetically confirmed tubulopathy. Based on these results, we propose a flowchart for an additional work-up in all children with a deviating fractional excretion.

Efficacy and safety of calcium carbonate in normophosphataemic patients with chronic kidney disease Stages 3 and 4.

BACKGROUND: Disordered bone and mineral metabolism are a common complication of chronic kidney disease (CKD). Phosphate binders are often prescribed in advanced CKD, when hyperphosphataemia develops. Little is known about the role of these drugs in earlier stages, when serum phosphorus levels are kept in the normal range by increased urinary excretion. METHODS: A retrospective, controlled observational study was conducted on a cohort of 78 pre-dialysis patients. Subjects had CKD Stage 3 or 4, normal serum phosphorus levels and increased urinary fractional excretion of phosphate. Thirty-eight patients receiving calcium carbonate for 24 months were compared with 40 patients under no phosphate binders, regarding mineral metabolism parameters and vascular calcification scores. RESULTS: Calcium carbonate decreased mean urinary fractional excretion of phosphate and median 24-h urine phosphorus, whereas no significant change was seen in the control group. Mean serum phosphorus and median serum intact parathyroid hormone (iPTH) remained stable in treated patients but increased in the control group. Vascular calcification, assessed by Kauppila and Adragão scores, worsened under calcium carbonate with no significant change in the control group. CONCLUSIONS: Calcium carbonate reduced urinary phosphate excretion and prevented the rise in phosphorus and iPTH serum levels in a cohort of normophosphataemic pre-dialysis patients. However, treatment was associated with increased vascular calcification, suggesting that calcium-based phosphate binders are not a safe option for CKD patients.

Monocyte chemoattractant protein-1, macrophage colony stimulating factor, survivin, and tissue inhibitor of matrix metalloproteinases-2 in analysis of damage and repair related to pediatric chronic kidney injury.

BACKGROUND: Kidney injury in the course of chronic kidney disease (CKD) is a consequence of aggravated cell migration, inflammation, apoptosis, and fibrosis. However, the sequence of these phenomena, as well as of the reparatory mechanisms, are not fully known. Monocyte chemoattractant protein 1 (MCP-1) and macrophage colony-stimulating factor (MCSF) trigger monocyte migration to the sites of inflammation and their transition into macrophages. Tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) plays a protective role against excessive matrix remodeling, whereas survivin is known for its anti-apoptotic activity. OBJECTIVES: To analyze the serum, urine and fractional excretion (FE) values of MCP1, MCSF, TIMP-2, and survivin in children at subsequent stages of CKD being treated conservatively, and to analyze the potential applicability of these markers in the evaluation of CKD-related renal damage and protective mechanisms against it. MATERIAL AND METHODS: The study group consisted of 70 children with conservatively treated CKD, stages 1-5, and 12 controls. The serum and urine concentrations of MCP1, MCSF, TIMP-2, and survivin were assessed using enzyme-linked immunosorbent assay (ELISA). The FE of these parameters in the urine was also assessed. RESULTS: The serum values of all parameters were significantly elevated at CKD stage 1 compared to the controls. The urinary concentrations of MCP-1 and MCSF (stages 1-2) rose earlier than TIMP-2 and survivin (stage 4) concentrations. The FE values started increasing at CKD stage 3 (MCP-1) or stage 4 (other parameters). CONCLUSIONS: The complex analysis of serum/urinary/FE values of the selected parameters revealed a sequence of multifaceted CKD-related phenomena, when the migration of cells and inflammation were followed by delayed and insufficient anti-fibrotic and anti-apoptotic activity.

Excreção fracionada urinária de sódio, potássio e cloreto em cordeiros suplementados com cloreto de amônio para prevenção de urolitíase / Urinary fractional excretion of sodium, potassium and chloride in lambs supplemented with ammonium chloride to prevent urolithiasis

A urolitíase é uma doença importante de cordeiros confinados. A acidificação da urina, pela ingestão de cloreto de amônio, é o método preventivo mais frequentemente empregado. Devido à falta de informação específica em ovinos, este estudo foi realizado para avaliar as alterações que ocorrem nos eletrólitos urinários de cordeiros, que receberam cloreto de amônio na dieta. Foram utilizados 100 cordeiros, com 3 meses de idade, que foram mantidos em confinamento durante 56 dias, e distribuídos em 3 grupos: G1 (n=40) que receberam 400mg/kg de peso vivo (PV) de cloreto de amônio/dia, durante 21 dias; G2 (n=40) que receberam 400mg/kg de PV de cloreto de amônio/dia durante 42 dias; e G3 (n=20) que não receberam cloreto de amônio. Os cordeiros foram examinados e as amostras de sangue e urina foram colhidas a cada 7 dias: 0 (antes do início da ingestão de cloreto de amônio), 7, 14, 21, 28, 35, e 42 dias. As concentrações séricas e urinárias de sódio (Na+), potássio (K+), cloreto (Cl-), e de creatinina foram mensuradas em todos os momentos de colheita. A excreção fracionada urinária (EFu) de eletrólitos e a diferença de íons fortes (SID) na urina [(Na+ + K+) - Cl] foram calculadas. A EFu de Na+, K+ e Cl- não variou ao longo do tempo em G3, provando que a dieta de confinamento, por si só, não influenciou a excreção urinária destes eletrólitos. A ingestão de cloreto de amônio, pelo grupo G1 e G2, influenciou a EFu sobre o tempo de confinamento. A SID urinária foi mais precisa do que a EFu de Cl- para demonstrar que a concentração de Cl- aumentou na urina, o que destacou a relevância desta variável.(AU)

Urolithiasis is an important disease of lambs confined. The urine acidification, by ammonium chloride intake, is the preventive method most frequently employed. Due to the lack of specific information in sheep, this study was performed to evaluate the electrolyte changes that occur in the urine of lambs receiving ammonium chloride in the diet. One hundred male lambs, 3 months old, were kept in a feedlot during 56 days, and distributed in 3 groups: G1 (n=40) receiving 400mg/kg BW of ammonium chloride/day during 21 days; G2 (n=40) receiving 400mg/kg BW of ammonium chloride/day during 42 days; and G3 (n=20) that did not receive ammonium chloride. The lambs were examined and blood and urine samples were collected every 7 days: 0 (the beginning of ammonium chloride intake), 7, 14, 21, 28, 35, and 42 days. Serum and urine sodium (Na+), potassium (K+), chloride (Cl-), and creatinine concentrations were measured. The urinary fractional excretion (FE) of electrolytes and the urine strong ion difference [(Na+ + K+) - Cl-] were calculated. FEs of Na+, K+, and Cl- did not vary over time in G3, proving that the feedlot diet, by itself, did not influence the urinary excretion of these electrolytes. The ingestion of ammonium chloride, instead, influenced FEs over the time of feedlot. The urinary SID was more accurate than the FE of Cl- to demonstrate that the concentration of Cl- increased in the urine. It highlights the relevance of this variable.(AU)

Early urinary angiotensinogen excretion in critically ill neonates.

INTRODUCTION: Urinary angiotensinogen is considered a reliable biomarker for intrarenal renin-angiotensin system activity. The aims of this study were to assess the urinary angiotensinogen level during the first day of life and to evaluate its correlation with renal function in critically ill neonates. METHODS: Urinary angiotensinogen concentration during the first 24 hours of life was measured in 98 critically ill neonates. Neonatal renal function was assessed by urinary levels of cystatin-C, albumin and α1-microglobulin and urinary electrolyte excretion. RESULTS: Urinary angiotensinogen level decreased with increasing gestational age and body weight in critically ill neonates (P<0.001). After adjustment for gestational age, urinary angiotensinogen level correlated with urinary fractional excretion of sodium and urinary levels of cystatin-C and α1-microglobulin. Multivariate linear regression identified a significant impact of urinary cystatin-C on urinary angiotensinogen level (P<0.001). Furthermore, urinary angiotensinogen was significantly increased in neonates with a urinary cystatin-C-to-creatinine ratio ⩾2500 ng/mg, which was the optimal cut-off value to predict acute kidney injury in our previous study. CONCLUSIONS: The urinary angiotensinogen level correlates with the overall maturity of renal function during the early postnatal period in critically ill neonates and an increased urinary angiotensinogen level might reflect renal injury in immature neonates.

Relationship between urinary fractional excretion of sodium and life prognosis in liver cirrhosis patients.

AIM: Renal vasoconstriction in generalized vasodilatation with blood pooling and the consequent reduction in effective arterial volume is the pathophysiological basis of liver cirrhosis (LC). Low levels of fractional excretion of sodium (FENa) are an effective marker of hypoperfusion of the renal artery. However, the relationship between levels of FENa, LC severity and life prognosis has not yet been elucidated. METHODS: We examined 57 LC patients (39 men and 18 women; mean age, 70.5 ± 8.8 years; underlying liver disease, type B hepatitis in eight patients, type C hepatitis in 37, alcoholic hepatitis in four and others in eight) with renal dysfunction (estimated glomerular filtration rate (eGFR) <60 mL/min) who were admitted to our hospital. RESULTS: Nine patients died because of uremia, liver failure, gastrointestinal bleeding and infection. No differences were found in patient background and blood pressure. However, in addition to differences in the levels of aspartate aminotransferase (AST), cholinesterase, albumin, prothrombin time (PT), eGFR and Model for End-Stage Liver Disease (MELD) score, the patients who died had significant differences in levels of FENa. The levels of FENa were significantly and inversely correlated with blood urea nitrogen, total bilirubin, AST, Child-Pugh score and MELD score, and were significantly and positively correlated with cholinesterase, albumin and PT. Moreover, the sensitivity (88%) and specificity (93%) of the levels of FENa of less than 0.4% to predict death were remarkably high. CONCLUSION: Levels of FENa may reflect LC severity and may be associated with the life prognosis of LC patients.