Variation In Kidney Size Research Articles

Epistatic interaction between common AGT G(− 6)A (rs5051) and AGTR1 A1166C (rs5186) variants contributes to variation in kidney size at birth

Low nephron number has been recognised as an important cardiovascular risk factor and recently a strong correlation between renal mass and nephron number has been demonstrated in newborns. The aim of this study was to investigate individual, as well as combined, effects of common variants of genes which encode for major components of the renin–angiotensin system (REN G10601A, AGT G(−6)A, ACE I/D, AGTR1 A1166C) on kidney size in healthy, full-term newborns. A significant additive main effect of the ACE I/D polymorphism, as well as an additive-by-additive interaction between AGT G(−6)A and AGTR1 A1166C variants, were found. The variance attributed to the epistatic effect was 27.9ml2/m4, which accounted for 73.8% of the interaction variance (37.8ml2/m4), 66.4% of the genetic variance (42.0ml2/m4) and 4.4% to the total phenotypic variance (628ml2/m4). No other statistically significant main or epistatic effects were detected. Our results highlight the importance of considering gene–gene interactions as part of the genetic architecture of congenital nephron number, even when the loci do not show significant single locus effects. Unravelling the genetic determinants of low nephron number, along with early molecular screening, may well help to identify children at risk for cardiovascular disease.

Making the right choice: testing the drivers of asymmetric infections within hosts and their consequences for pathology

Despite the ubiquity of bilateral symmetry among animals, a long‐standing mystery centers on why parasites that infect paired organs often do so non‐randomly. Examples from diverse host and parasite taxa continue to accumulate, yet little is known about their causes or implications for host–parasite fitness. We combined field surveys, experimental infections, and parasite choice assays to evaluate both competing explanations for – and consequences of – asymmetric infections of amphibian kidneys by echinostome trematodes, which are widespread and potentially pathogenic infections of larval amphibians. Samples from 6001 hosts representing 26 species indicated that echinostome infections exhibit a consistent, right‐kidney bias, with ˜ 62% of parasites in the right kidney. This pattern could not be explained by variation in kidney size or total infection. Experimental infections of three anuran species reproduced this pattern, with 64% of infections in the right kidney, and indicated it was not the result of differential host or parasite mortality. Based on sequential infection experiments and parasite choice assays, we further showed that earlier infections did not affect the distribution of subsequently colonizing parasites and that echinostome cercariae followed host‐derived cues rather than exhibiting congenital ‘sidedness’. We advance the hypothesis that variation in the position of the right kidney along the anterior–posterior axis controls cue strength in the right nephric duct and thus determines parasite encystment. Correspondingly, anatomical measurements from a subset of larval amphibian hosts revealed that the relative position of the right kidney explained 83% of the variation in infection bias, with no additional contributions associated with kidney volume or host size. We also show that the degree of right‐kidney bias associated positively with host growth in experiments. Morphological asymmetries could therefore function as a unique form of tolerance to mitigate the consequences of infection, despite the oft‐cited costs of asymmetry for mate selection and enemy vulnerability.

Association of BMPR1A polymorphism, but not BMP4, with kidney size in full-term newborns

BackgroundA correlation between renal mass and nephron number in newborns allows the use of total kidney volume at birth as a surrogate for congenital nephron number. As the bone morphogenetic protein type 4 (BMP4), and its receptor type 1A (BMPR1A, ALK3), play an important role in renal development, we hypothesized that common, functional polymorphisms in their genes might be responsible for variation in kidney size among healthy individuals.MethodsWe recruited 179 healthy full-term newborns born to healthy women. Kidney volume was measured sonographically. Total kidney volume (TKV) was calculated as the sum of left and right kidneys, and normalized for body surface area (TKV/BSA). Genomic DNA was extracted from umbilical cord blood leukocytes, and c.455T > C (rs17563) BMP4 and c.67 + 5659A > T (rs7922846) BMPR1A genotypes were identified by PCR-RFLP.ResultsTKV/BSA in newborns carrying at least one A BMPR1A allele (AA + AT) was significantly reduced by approximately 13 % as compared with TT homozygous newborns (106.7 ± 21.5 ml/m2 vs. 122.7 ± 43.8 ml/m2, p < 0.02). No significant differences in TKV/BSA were found among newborns with different BMP4 genotypes.ConclusionsResults suggest that rs7922846 BMPR1A polymorphism may account for subtle variation in kidney size at birth, reflecting congenital nephron endowment.

An insertion/deletion ACE polymorphism and kidney size in Polish full-term newborns

The number of nephrons is a multifactorial trait controlled by the interaction of environmental factors and genetic variants that influence the extent of branching nephrogenesis during foetal life. A correlation between renal mass and nephron number in newborns allows the use of the total kidney volume at birth as a surrogate for congenital nephron number. Since the renin-angiotensin system plays an important role in renal development we hypothesized that the common, functional insertion/deletion (I/D) polymorphism in the ACE gene might be responsible for the variation in kidney size amongst healthy individuals. We recruited 210 healthy Polish full-term newborns born to healthy women with uncomplicated pregnancies. The kidney volume was measured sonographically. Total kidney volume (TKV) was calculated as the sum of left kidney volume and right kidney volume. TKV was normalized to body surface area (TKV/BSA). The I and D alleles were identified using polymerase chain reaction. TKV/BSA in newborns carrying at least one insertion ACE allele was significantly reduced by approximately 8% as compared with homozygous newborns for the D allele (DD genotype) (105.1±23.6 vs. 114.2±28.2 cm(3)/m(2), p<0.05). The results of this study suggest that I/D ACE polymorphism may account for subtle variation in kidney size at birth, which reflects congenital nephron endowment.

Sensitivity of USPIO‐enhanced R2 imaging to dynamic blood volume changes in the rat kidney

To determine whether MRI in combination with an intravascular contrast agent is sensitive to pharmacologically induced vasodilation and vasoconstriction in the rat kidney. R(2) imaging was performed in 25 Sprague Dawley rats at 3 Tesla in the presence of ferumoxytol, an ultrasmall superparamagnetic iron oxide (USPIO) agent with a long plasma half-life. R(2) changes were measured following manipulation of blood volume by intravenous administration of adenosine, a short-acting vasodilator, or N(G)-nitro-L-arginine methyl ester (L-NAME), a long-acting nitric oxide synthase inhibitor with known vasoconstrictive effects. As a control, R(2) responses to adenosine and L-NAME were also examined in the absence of ferumoxytol. In the presence of ferumoxytol, adenosine induced a significant increase in R(2), while L-NAME produced a reduction, although the latter was not statistically significant. Control experiments revealed small R(2) changes in the absence of ferumoxytol. An incidental finding was that the cross-sectional area of the kidney also varied dynamically with adenosine and L-NAME. Our results suggest that ferumoxytol-enhanced R(2) imaging is sensitive to adenosine-induced vasodilation. The responses to L-NAME, however, were not statistically significant. The variations in kidney size and the R(2) changes in the absence of ferumoxytol may reflect alterations in the volume of the renal tubules.

Tracking and Determinants of Kidney Size From Fetal Life Until the Age of 2 Years: The Generation R Study

An adverse fetal environment may lead to smaller kidneys and subsequently kidney disease and hypertension in adulthood. The aims of this study are to examine whether kidney size tracks from fetal life to childhood and whether maternal and fetal characteristics are associated with kidney size at the age of 2 years. Prospective cohort study from fetal life onward. The study was conducted in a group of 688 infants in Rotterdam, The Netherlands. Entry criteria were singleton, noncomplicated pregnancies, and Dutch ethnicity. The maternal characteristics age, height, and prepregnancy weight were measured in early pregnancy. Fetal growth, head circumference, abdominal circumference, femur length and estimated fetal weight, and placental characteristics were assessed in the second and third trimesters. Kidney size, defined as length, width, depth, and volume, was measured in the third trimester of pregnancy and at postnatal ages 6 and 24 months. Overall median gestational age was 40.3 weeks (95% range, 36.0 to 42.3 weeks), and mean birth weight was 3,536 +/- 524 (SD) g. Children tended to remain in the lowest and highest quartiles of kidney volume from the third trimester to the age of 2 years (odds ratio, 2.05; 95% confidence interval, 1.38 to 3.06; odds ratio, 3.29; 95% confidence interval, 2.22 to 4.87, respectively). Maternal height and prepregnancy weight were associated positively with kidney volume at the age of 2 years. Third-trimester fetal head circumference, abdominal circumference, and estimated weight and postnatal length were associated positively with kidney volume at the age of 2 years. Preferential fetal blood flow to the brain was associated with smaller kidneys. Kidney measurements successfully performed in only 86% of children. Small kidney size in fetal life tends to persist in early childhood. Maternal anthropometrics and fetal biometrics and blood flow patterns are associated with kidney size in childhood. Follow-up studies are needed to examine whether these variations in kidney size are related to kidney function and blood pressure in later life.

Evaluation of Pediatric Renal Size by Sonography

Ultrasonography has been shown to be a reliable technique for measurement of kidney length in pediatric patients. Ultrasound was used in this study to evaluate normal variation in kidney size in healthy pediatric patients. The data also were used for comparison of kidney size in solitary kidneys to evaluate compensatory hypertrophy in pediatric patients. The authors also compared renal size in pediatric patients with chronic liver disease against those with healthy kidneys. A correlation was found in younger pediatric patients.

Percutaneous nephrolithotomy in the dog. An experimental study.

Percutaneous nephrostomies (PN) were created with teflon fascial dilators under fluoroscopic guidance, to implant stones bilaterally into the renal pelves of five dogs weighing 7 to 35 kg. Between one and seven stones of 0.25 to 1.00 cm diameter were implanted into each renal pelvis. Two to 4 weeks later, PN tracts were recreated, and the implanted renal stones were successfully removed under fluoroscopic and endoscopic visualization. Results of gross and histopathologic evaluation of the kidneys 2, 7, 14, 30, and 90 days after stone removal showed minimal, localized renal parenchymal trauma. Complications, although infrequent, included proximal ureteral tears and hemorrhage. Difficulty was encountered in maneuvering equipment around large or numerous stones. Canine percutaneous nephrolithotomy was successful despite great variation in kidney size, as well as variations in the number, size, and shape of stones in the upper urinary tract.