ABSTRACT
BACKGROUND AND OBJECTIVES: The neonatal and juvenile human kidney can be exposed to a variety of potentially toxic drugs (e.g., nonsteroidal anti-inflammatory drugs, antibiotics, antivirals, diuretics), many of which are substrates of the kidney organic anion transporters, OAT1 (SLC22A6, originally NKT) and OAT3 (SLC22A8). Despite the immense concern about the consequences of drug toxicity in this vulnerable population, the developmental regulation of OATs in the immature postnatal kidney is poorly understood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Recognizing that today it is difficult to obtain rich data on neonatal kidney handling of OAT probes due to technical, logistic, and ethical considerations, multiple older physiologic studies that used the prototypical organic anion substrate para-aminohippurate (PAH) were reanalyzed in order to provide a quantitative description of OAT-mediated tubular secretion across the pediatric age continuum. Parametric and semiparametric models were evaluated for kidney function outcome variables of interest (maximum tubular secretory capacity of PAH [TmPAH], effective renal plasma flow [ERPF], and GFR). RESULTS: Data from 119 neonates, infants, and children ranging in age from 1 day to 11.8 years were used to fit TmPAH, ERPF, and GFR as functions of postnatal age. TmPAH is low in the immediate postnatal period and increases markedly after birth, reaching 50% of the adult value (80 mg/min) at 8.3 years of age. During the first 2 years of life, TmPAH is lower than that of GFR when viewed as the fraction of the adult value. CONCLUSIONS: During postnatal human kidney development, proximal tubule secretory function-as measured using PAH, a surrogate for OAT-mediated secretion of organic anion drugs, metabolites, and toxins-is low initially but increases rapidly. Despite developmental differences between species, this overall pattern is roughly consistent with animal studies. The human data raise the possibility that the acquisition of tubular secretory function may not closely parallel glomerular filtration.
Subject(s)
Kidney Tubules, Proximal/metabolism , Kidney/growth & development , Organic Anion Transporters/physiology , Child , Child, Preschool , Humans , Infant , Infant, NewbornABSTRACT
Objective To investigate the influence and mechanism of erythropoietin (EPO) in renal blood flow after limb ischemia reperfusion (LIR). Methods Thirty male SD rats were randomly divided into control group, LIR group and EPO+LIR group with ten in each group. The values of renal blood flow, plasma creatinine (Cr), urea nitrogen (BUN) content in plasma, kidney tissue wet to dry ratio (W/D), nitric oxide (NO), nitric oxide synthase (NOS) and endothelin-1 (ET-1) in re-nal tissue were detected in three groups. The immunohistochemistry assay was used to detect the expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) in renal tissue. The morphological changes of renal tissue were observed with light microscope. Results The renal blood flow was significantly decreased, while the val-ues of Cr, BUN, W/D, NO, ET-1, NOS, expressions of ICAM-1 and VCAM-1 was significantly increased in LIR group than those of control group (P<0.05). Broaden interstitial and infiltration of inflammatory cells were observed in the renal tissue under light microscope. In the EPO+LIR group, the renal blood flow increased, the values of Cr, BUN, W/D, NO, ET-1 and NOS, expressions of ICAM-1 and VCAM-1 decreased significantly compared with those of LIR group (P<0.05). The patho-logical changes were alleviated in EPO+LIR group. Conclusion EPO can improve renal function, increase renal blood flow in rats after LIR. The mechanism may be related to the decreased edema, changed renal vasomotor function and decreased in-flammation.
ABSTRACT
El papel del riñón en la génesis de la hipertensión arterial esencial se ha venido investigando desde hace más de 3 décadas. El propósito del presente trabajo fue valorar el comportamiento de algunas variables morfofuncionales renales en pacientes hipertensos. A voluntarios normales (40) y pacientes hipertensos (45), se les estudió el flujo plasmático renal efectivo (FPRE) mediante aclaramiento de paraminohipurato, intensidad de filtración glomerular (IFG) mediante aclaramiento de creatinina; el aclaramiento plasmático de litio (ApLi), la fracción de reabsorción de litio (FRLi), el manejo renal de sodio y potasio; así como la medición ultrasónica de los diámetros renales anteroposteriores, transversal y longitudinal con los cuales se determinó el volumen de los riñones mediante un programa de computación. Los resultados mostraron diferencias significativas en el FPRE, los diámetros renales y el volumen integrado, así como en el manejo renal del sodio. Estos resultados sugieren una retención hidrosalina en los hipertensos, lo que apoya las hipótesis que establecen la participación del riñón en la génesis de la hipertensión arterial.
The role of the kidney in the genesis of essential arterial hypertension, has been investigated since more than three decades. The purposes of this article was to assess the behaviour of some renal morphofunctional variables in hypertensive patients. The effective renal plasma flow (ERPF) was studied in 40 normal volunteers and 45 hypertensive patients, by means of the paraamino-hippurate clearance, glomerular filtration rate (GFR) by means of creatinine clearance, lithium plasma clearance LiPC), lithium reabsorption fraction (LiRF), sodium and potassium renal management, as well as the ultrasonographic measurement of anteroposterior, transverse and longitudinal renal diameters, with which the kidneys volume was determined by a computed program. The results showed significant differences in ERPF, the renal diameters and the integrated volume, as well as in the sodium management. These outcomes suggest a hydrosaline retention in the hypertensive patients, and this advocates the hypothesis that they restore the kidney participation in the genesis of arterial hypertension.