Effects of early postnatal hypernutrition on nephron number and long-term renal function and structure in rats

2007 ◽  
Vol 293 (6) ◽  
pp. F1944-F1949 ◽  
Author(s):  
Farid Boubred ◽  
Christophe Buffat ◽  
Jean-Marc Feuerstein ◽  
Laurent Daniel ◽  
Michel Tsimaratos ◽  
...  

Various antenatal events impair nephrogenesis in humans as well as in several animal models. The consecutive low nephron endowment may contribute to an increased risk for cardiovascular and renal diseases in adulthood. However, little knowledge is available on the influence of the postnatal environment, especially nutrition, on nephrogenesis. Moreover, the consequences of early postnatal nutrition in late adulthood are not clear. We used a model of early postnatal overfeeding (OF) induced by reduction of litter size (3 pups/litter) in rats. Systolic blood pressure (SBP; plethysmography), glomerular filtration rate (clearance of creatinine), glomerular number and volume, and glomerulosclerosis were evaluated in 22-mo-old aging offspring. Early postnatal OF was associated with increased weight gain during the suckling period (+40%, P < 0.01) and a 20% increase in glomerular number ( P < 0.05). However, an increase in SBP at 12 mo by an average of 18 mmHg and an increase in proteinuria (2.6-fold) and glomerulosclerosis at 22 mo of age were observed in OF male offspring compared with controls. In conclusion, early postnatal OF in the rat enhances postnatal nephrogenesis, but elevated blood pressure and glomerulosclerosis are still observed in male adults. Factors other than glomerular number reduction are likely to contribute to the arterial hypertension induced by early postnatal OF.

2011 ◽  
Vol 300 (6) ◽  
pp. F1448-F1453 ◽  
Author(s):  
Luise A. Cullen-McEwen ◽  
James A. Armitage ◽  
Jens R. Nyengaard ◽  
Karen M. Moritz ◽  
John F. Bertram

Low glomerular (nephron) endowment has been associated with an increased risk of cardiovascular and renal disease in adulthood. Nephron endowment in humans is determined by 36 wk of gestation, while in rats and mice nephrogenesis ends several days after birth. Specific genes and environmental perturbations have been shown to regulate nephron endowment. Until now, design-based method for estimating nephron number in developing kidneys was unavailable. This was due in part to the difficulty associated with unambiguously identifying developing glomeruli in histological sections. Here, we describe a method that uses lectin histochemistry to identify developing glomeruli and the physical disector/fractionator principle to provide unbiased estimates of total glomerular number ( Nglom). We have characterized Nglom throughout development in kidneys from 76 rats and model this development with a 5-parameter logistic equation to predict Nglom from embryonic day 17.25 to adulthood ( r2 = 0.98). This approach represents the first design-based method with which to estimate Nglom in the developing kidney.


2018 ◽  
Vol 10 (02) ◽  
pp. 154-163 ◽  
Author(s):  
A. Ding ◽  
S. L. Walton ◽  
K. M. Moritz ◽  
J. K. Phillips

AbstractMaternal insufficiency during fetal development can have long-lasting effects on the offspring, most notably on nephron endowment. In polycystic kidney disease (PKD), variability in severity of disease is observed and maternal environment may be a modifying factor. In this study, we first established that in a rodent model of PKD, the Lewis polycystic kidney (LPK) rat’s nephron numbers are 25% lower compared with wildtype animals. We then investigated the effects of prenatal and postnatal maternal environment on phenotype and nephron number. LPK pups born from and raised by homozygous LPK dams (control) were compared with LPK pups cross-fostered onto heterozygous LPK dams to improve postnatal environment; with LPK pups born from and raised by heterozygous LPK dams to improve both prenatal and postnatal environment and with LPK pups born from and raised by Wistar Kyoto-LPK heterozygous dams to improve both prenatal and postnatal environment on a different genetic background. Improvement in both prenatal and postnatal environment improved postnatal growth, renal function and reduced blood pressure, most notably in animals with different genetic background. Animals with improved postnatal environment only showed improved growth and blood pressure, but to a lesser extent. All intervention groups showed increased nephron number compared with control LPK. In summary, prenatal and postnatal environment had significant effect in delaying progression and reducing severity of PKD, including nephron endowment.


Physiology ◽  
2021 ◽  
Vol 36 (1) ◽  
pp. 21-34 ◽  
Author(s):  
Jessica R. Ivy ◽  
Matthew A. Bailey

Blood pressure follows a daily rhythm, dipping during nocturnal sleep in humans. Attenuation of this dip (nondipping) is associated with increased risk of cardiovascular disease. Renal control of sodium homeostasis is essential for long-term blood pressure control. Sodium reabsorption and excretion have rhythms that rely on predictive/circadian as well as reactive adaptations. We explore how these rhythms might contribute to blood pressure rhythm in health and disease.


2013 ◽  
Vol 5 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Y. Kandasamy ◽  
R. Smith ◽  
I. M. R. Wright ◽  
E. R. Lumbers

Rates of chronic kidney disease (CKD) among Indigenous groups in Australia exceed non-Indigenous rates eight-fold. Using kidney volume as a surrogate for nephron number, we carried out a study to determine if Indigenous neonates have a smaller kidney volume (and thus a reduced nephron number) from birth compared with non-Indigenous neonates. We recruited term and preterm neonates (<32 weeks) at a tertiary care neonatal unit over a 12 months period. Preterm neonates were assessed (renal sonography and renal function measurement) at 32 weeks corrected age (CA) and again at 38 weeks CA when blood pressure was also measured. All term neonates were assessed in the first post-natal week, including renal sonography, renal function and blood pressure measurement. The primary outcome measured was total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) was a secondary outcome. Data was available for 44 preterm (11 Indigenous) and 39 term (13 Indigenous) neonates. TKV of Indigenous neonates was significantly lower at 32 weeks [12.0 (2.0)v.15.4 (5.1) ml;P=0.03] and 38 weeks CA [18.6 (4.0)v.22.6 (5.9) ml;P=0.04] respectively. Term Indigenous neonates also had smaller kidney volumes compared with non-Indigenous neonates. Despite a smaller kidney volume (and reduced nephron number), Indigenous neonates did not have a significantly lower eGFR. Indigenous neonates achieve similar eGFRs to Non-Indigenous neonates, presumably through a higher single nephron filtration rate. This places Indigenous neonates at a greater risk of long-term kidney damage later in life.


Author(s):  
Deanna Gray-Miceli ◽  
William Craelius ◽  
Kang Li

Older adults over age 65 are susceptible to loss of balance for a variety of reasons including drops in blood pressure with standing (orthostatic hypotension [OH]; Gray-Miceli, Ratcliffe, Thomasson, Quigley, Li & Craelius, 2016). OH is a treatable condition, and cause of falls if detected. Nearly 50% of the 1.43 million older adults in long-term care experience falls (National Center for Injury Prevention and Control, 2017). Falls often occur among older adults in long term care during periods of transitioning, where older adults are susceptible to loss of balance and increased risk to fall. As found in our prior work, older adults with OH may not always experience classic dizziness symptoms that may accompany OH (Gray-Miceli, Ratcliffe, Liu, Wantland & Johnson, 2012; Gray). To better understand this phenomenon, our project adapted a cellphone as an inertial measurement unit attached to the person’s center of mass to determine body sway. The objective of this pilot study was to determine if a relationship was observable during the sit to stand maneuver (StS) while older adults wore a Smartphone measuring three dimensions of motion among older adults who had evidenced of symptoms or OH. A sample of four older adults from a rehabilitation facility who were 65 years of age, receiving physical therapy at the time of testing, were cognitively intact, able to perform the StS maneuver and had no active cancer, fractures or serious injuries were recruited and enrolled. Oh determinations, pulse rate and symptoms of dizziness were elicited during a 30 second StS maneuver. In Patient A and Patient B we present the Z-axis and X-axis of front acceleration and patterns of motion side by side for case comparison while highlighting clinical findings. In Patient B, a greater degree of sway at the start of the StS maneuver is noted. Patient B’s blood pressure also dropped 33 mmHg and there were symptoms of dizziness. Drops in mean arterial blood pressure were greater among those with symptomatic OH. Limitations of this pilot include noise, selection of filters and time stamping of the data. Project aims are to help clinicians prevent falls by further assessing symptoms among elders who suffer from LOB and OH.


2019 ◽  
Vol 47 (4) ◽  
pp. 299-309
Author(s):  
V. E. Uspenskiy ◽  
E. G. Malev ◽  
N. D. Gavriliuk ◽  
B. K. Salavatov ◽  
S. A. Ermolov ◽  
...  

Background: Ascending aortic (AA) dilatation is common in patients with bicuspid aortic valve (BAV). In BAV replacement, surgery of the AA is indicated in the case if AA diameter exceeds 45 mm. Aortic valve replacement combined with an AA intervention is associated with increased risk of complications. The feasibility of the reduction ascending aortoplasty for correction of the dilated AA remains disputable.Aim: To analyze the results of BAV surgical replacement with simultaneous surgical correction of the borderline AA dilatation (45-50 mm) by the reduction aortoplasty (RAP) or supracoronary AA replacement (SPR).Materials and methods: This single center prospective non-randomized study included 53 patients with significant BAV stenosis and AA dilatation (45-50 mm), divided into 2 groups: BAV surgical replacement combined with RAP AA replacement (group 1, 36 patients) and BAV replacement with SPR (group 2, 17 patients). There were no significant differences between the patients of the two groups in their characteristics of the underlying disease, complications and comorbidities.Results: Hospital mortality was 0%. No between-group differences in the early postoperative course were found. At later term, 44 (81.5%) patients were assessed; median (dispersion) of the follow-up was 36 (25; 50) months. Two patients from the group 2 died during the follow-up. The long-term survival was better in the group 1 (p = 0.028). No differences in the combined adverse event rate were observed between the groups (p = 0.633). The median (dispersion) of the AA absolute increment and the rate of dilatation after RAP were 1.0 (0.0; 3.0) mm and 0.24 (0.00; 0.95) mm/year, respectively. The predictor of AA increment rate ≥ 2 mm/year was the baseline blood pressure level (odds ratio 1.321, 95% confidence interval 1.050-1.662; p=0.017). The threshold preoperative blood pressure value for the increased risk of the long-term AA expansion rate was 138 mmHg.Conclusion: The efficacy and safety of RAP and SRP combined with BAV replacement in AA borderline dilatation are similar. Combined BAV surgery and RAP is effective and safe in patients with systolic blood pressure level ≤ 135 mmHg. Combined BAV replacement with SRP seems reasonable in patients with arterial hypertension.


2019 ◽  
Vol 317 (4) ◽  
pp. F865-F873 ◽  
Author(s):  
Edwin J. Baldelomar ◽  
Jennifer R. Charlton ◽  
Kimberly A. deRonde ◽  
Kevin M. Bennett

The development of chronic kidney disease (CKD) is associated with the loss of functional nephrons. However, there are no methods to directly measure nephron number in living subjects. Thus, there are no methods to track the early stages of progressive CKD before changes in total renal function. In this work, we used cationic ferritin-enhanced magnetic resonance imaging (CFE-MRI) to enable measurements of glomerular number ( Nglom) and apparent glomerular volume (aVglom) in vivo in healthy wild-type (WT) mice ( n = 4) and mice with oligosyndactylism (Os/+; n = 4), a model of congenital renal hypoplasia leading to nephron reduction. We validated in vivo measurements of Nglom and aVglom by high-resolution ex vivo MRI. CFE-MRI measured a mean Nglom of 12,220 ± 2,028 and 6,848 ± 1,676 (means ± SD) for WT and Os/+ mouse kidneys in vivo, respectively. Nglom measured in all mice in vivo using CFE-MRI varied by an average 15% from Nglom measured ex vivo in the same kidney (α = 0.05, P = 0.67). To confirm that CFE-MRI can also be used to track nephron endowment longitudinally, a WT mouse was imaged three times by CFE-MRI over 2 wk. Values of Nglom measured in vivo in the same kidney varied within ~3%. Values of aVglom calculated from CFE-MRI in vivo were significantly different (~15% on average, P < 0.01) from those measured ex vivo, warranting further investigation. This is the first report of direct measurements of Nglom and aVglom in healthy and diseased mice in vivo.


1988 ◽  
Vol 6 (11) ◽  
pp. 1728-1731 ◽  
Author(s):  
S W Hansen ◽  
S Groth ◽  
G Daugaard ◽  
N Rossing ◽  
M Rørth

Long-term effects of cisplatin on renal function were investigated in 34 patients with germ cell cancer observed for a median of 65 months (range, 43 to 97 months). All patients achieved a complete remission after treatment with cisplatin (median dose 583 mg/m2), vinblastine, and bleomycin. None of the patients relapsed during follow-up. During treatment the glomerular filtration rate (GFR) decreased by 18% (P less than .05). During follow-up kidney function recovered in ten patients and partly improved in eight patients. Changes in plasma creatinine did not consistently correspond to alterations in GFR. The mean increase in systolic blood pressure during follow-up did not differ from the increase seen in a group of age-matched healthy men. The mean increase in diastolic pressure, however, was significant (P less than .05), but was entirely due to hypertension observed in six patients. Renography of these patients was normal. We conclude that the decrease in GFR observed during treatment with cisplatin is partly reversible. Cisplatin-treated patients have an increased risk of developing hypertension years after treatment.


2009 ◽  
Vol 297 (4) ◽  
pp. F943-F951 ◽  
Author(s):  
Farid Boubred ◽  
Laurent Daniel ◽  
Christophe Buffat ◽  
Jean-Marc Feuerstein ◽  
Michel Tsimaratos ◽  
...  

Low birth weight is associated with an increased risk of hypertension and renal dysfunction at adulthood. Such an association has been shown to involve a reduction of nephron endowment and to be enhanced by accelerated postnatal growth in humans. However, while low-birth-weight infants often undergo catch-up growth, little is known about the long-term vascular and renal effects of accelerated postnatal growth. We surimposed early postnatal overfeeding (OF; reduction of litter size during the suckling period) to appropriate-birth-weight (NBW+OF) and intrauterine growth restriction (IUGR; IUGR+OF) pups, obtained after a maternal gestational low-protein diet. Blood pressure (systolic blood pressure; SBP) and renal function (glomerular filtration rate; GFR) were measured in young and aging offspring. Glomerulosclerosis and nephron number were determined in aging offspring (22 mo). Nephron number was reduced in both IUGR and IUGR+OF male offspring (by 24 and 26%). GFR was reduced by 40% in 12-mo-old IUGR+OF male offspring, and both NBW+OF and IUGR+OF aging male offspring had sustained hypertension (+25 mmHg) and glomerulosclerosis, while SBP and renal function were unaffected in IUGR aging offspring. Female offspring were unaffected. In conclusion, in this experimental model, early postnatal OF in the neonatal period has major long-lasting effects. Such effects are gender dependent. Reduced nephron number alone, associated with IUGR, may not be sufficient to induce long-lasting physiological alterations, and early postnatal OF acts as a “second hit.” Early postnatal OF is a suitable model with which to study the long-term effects of postnatal growth in the pathogenesis of vascular disorders and renal disease.


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