ORCID Profile
0000-0002-6482-0564
Current Organisation
James Cook University
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Publisher: Informa UK Limited
Date: 22-05-2020
Publisher: Springer Science and Business Media LLC
Date: 23-02-2006
DOI: 10.1007/S00125-006-0175-X
Abstract: The aim of this study was to investigate the effects of a secondary renal insult, due to chronic infusion of AGEs on renal function, and on early pathological markers in rats with a developmental nephron deficit. Female Wistar-Kyoto rats were fed a low-protein diet (LPD 8.7% casein) or a normal-protein diet (NPD 20% casein) during pregnancy and lactation. Nephron number was estimated in 4-week-old female offspring. Male offspring were allowed to grow to 20 weeks of age, when AGEs derived from BSA (AGE-BSA) or BSA was infused subcutaneously (20 mg kg(-1) day(-1)) for 4 weeks. At 24 weeks, blood pressure, renal function and circulating and renal AGEs were assessed. Real-time PCR was used to investigate early molecular markers of renal pathology. As expected, maternal protein restriction led to reduced nephron endowment in LPD offspring. This alone did not affect blood pressure or lead to hyperfiltration in adulthood. However, when coupled with the secondary renal insult, the expression of the genes encoding transforming growth factor-beta(1) and procollagen III was significantly upregulated in the kidneys. In addition, there was renal accumulation of AGEs in LPD offspring, and this was exacerbated by AGE infusion. Our results demonstrate that the adult kidney with a reduced nephron endowment is more vulnerable to secondary renal insult from AGE-BSA. Since AGE formation is markedly elevated with hyperglycaemia, our findings suggest that a developmental or acquired deficit may render the kidney susceptible to diabetic renal disease.
Publisher: Elsevier BV
Date: 09-2007
Publisher: Oxford University Press (OUP)
Date: 18-03-2009
DOI: 10.1093/NDT/GFP116
Publisher: Oxford University Press (OUP)
Date: 29-11-2011
DOI: 10.1093/NDT/GFQ688
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2008
Publisher: Springer Science and Business Media LLC
Date: 06-2005
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/136942
Abstract: Epidemiological studies have clearly demonstrated a strong association between low birth weight and long-term renal disease. A potential mediator of this long-term risk is a reduction in nephron endowment in the low birth weight infant at the beginning of life. Importantly, nephrons are only formed early in life during normal gestation, nephrogenesis is complete by about 32–36 weeks, with no new nephrons formed after this time during the lifetime of the in idual. Hence, given that a loss of a critical number of nephrons is the hallmark of renal disease, an increased severity and acceleration of renal disease is likely when the number of nephrons is already reduced prior to disease onset. Low birth weight can result from intrauterine growth restriction (IUGR) or preterm birth a high proportion of babies born prematurely also exhibit IUGR. In this paper, we describe how IUGR and preterm birth adversely impact on nephrogenesis and how a subsequent reduced nephron endowment at the beginning of life may lead to long-term risk of renal disease, but not necessarily hypertension.
Publisher: Wiley
Date: 28-01-2008
DOI: 10.1002/AR.20651
Abstract: We have shown that fetuses whose mothers underwent subtotal nephrectomy (STNx) before pregnancy had high urine flow rates and sodium excretions, but lower hematocrits, plasma chloride, and plasma renin levels compared with controls. To see if these functional differences in utero persist after birth and are the result of altered renal development, we studied 8 lambs born to STNx mothers (STNxL) and 10 controls (ConL) in the second week of life. These lambs were of similar body weights, nose-rump lengths and abdominal girths. Their kidney weights were not different (ConL 36.1 +/- 1.9 vs. STNxL 39.8 +/- 3.3 g), nor were kidney dimensions or glomerular number (ConL 423,520 +/- 22,194 vs. STNxL 429,530 +/- 27,471 glomeruli). However, STNxL had 30% larger glomerular volumes (both mean and total, P < 0.01) and there was a positive relationship between total glomerular volume and urinary protein excretion (P < 0.05) in STNxL. Despite this change in glomerular morphology, glomerular filtration rate, tubular function, urine flow, and sodium excretion rates were not different between STNxL and ConL, nor were plasma electrolytes, osmolality, and plasma renin levels. Thus while many of the functional differences seen in late gestation were not present at 1-2 weeks after birth, the alteration in glomerular size and its relationship to protein excretion suggests that exposure to this altered intrauterine environment may predispose offspring of mothers with renal dysfunction to renal disease in adult life.
Publisher: Oxford University Press (OUP)
Date: 02-05-2014
DOI: 10.1093/NDT/GFU088
Publisher: Wiley
Date: 11-2014
Abstract: Epidemiological studies have shown an association between low birthweight and adult disease development with transmission to subsequent generations. The aim of the present study was to examine the effect of intrauterine growth restriction in rats, induced by uteroplacental insufficiency, on cardiac structure, number, size, nuclearity, and adult blood pressure in first (F1) and second (F2) generation male offspring. Uteroplacental insufficiency or sham surgery was induced in F0 Wistar-Kyoto pregnant rats in late gestation giving rise to F1 restricted and control offspring, respectively. F1 control and restricted females were mated with normal males, resulting in F2 control and restricted offspring, respectively. F1 restricted male offspring were significantly lighter at birth (P < 0.05), but there were no differences in birthweight of F2 offspring. Left ventricular weights and volumes were significantly increased (P < 0.05) in F1 and F2 restricted offspring at day 35. Left ventricular cardiomyocyte number was not different in F1 and F2 restricted offspring. At 6 months-of-age, F1 and F2 restricted offspring had elevated blood pressure (8-15 mmHg, P < 0.05). Our findings demonstrate the emergence of left ventricular hypertrophy and hypertension, with no change in cardiomyocyte number, in F1 restricted male offspring, and this was transmitted to the F2 offspring. The findings support transgenerational programming effects.
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000327044
Abstract: We have demonstrated considerable variability in the volumes of different glomeruli in given in iduals (in idual glomerular volume: IGV) in a stereologic study of kidneys at forensic autopsy performed to investigate sudden or unexpected death in people without manifest kidney disease. We review some important associations of IGV by subject characteristics and by ethnic groups. IGVs were measured by the Cavalieri method in 30 glomeruli in each of 111 adult males who belonged to 4 ethnic groups, i.e. US Whites, African-Americans, Africans from Senegal, and Australian Aborigines. Correlations of pooled IGV values with certain subject characteristics were evaluated in the US Whites. Pooled IGV data were compared in subjects across the 4 ethnic groups. In US Whites, mean IGV and its variance were greater with higher age, lower nephron number, lower birth weight, and with gross obesity, hypertension and cardiovascular death. In comparisons by ethnic group, mean IGV and IGV ranges were higher in African-Americans and Australian Aborigines than in US Whites and African Senegalese subjects. We conclude that glomerular enlargement with volume heterogeneity marks more advanced age, relative nephron deficiency, lower birth weight, obesity, hypertension, and advanced cardiovascular disease. The findings in African-Americans and Australian Aborigines suggest that larger IGVs and volume heterogeneity might mark populations with accentuated susceptibility to hypertension and kidney disease, but the data need to be further examined in the context of the determining characteristics defined in the US Whites.
Publisher: Springer Science and Business Media LLC
Date: 12-2002
DOI: 10.1007/S00467-002-0998-8
Abstract: This study investigated the effects of a high-protein diet during pregnancy on nephron endowment and subsequent levels of blood pressure in the offspring. Female WKY rats were fed either a normal (20%, NPD) or a high (54%, HPD) protein diet during pregnancy. Male offspring were paired at birth. At 4 weeks of age, 1 of the pair was randomly chosen for perfusion fixation, and total glomerular number, and thereby nephron number, was estimated using an unbiased stereological technique. The other rat of the pair was allowed to grow to 30 weeks of age, during which time tail cuff systolic blood pressure was monitored twice weekly. There was no effect of the HPD on birth weight (NPD 4.23+/-0.53 g, HPD 4.26+/-0.45 g, mean+/-SD), kidney weight (NPD 0.372+/-0.049 g, HPD 0.337+/-0.090 g), or total nephron number (NPD 27,191+/-3,512, HPD 26,738+/-4,735). Systolic blood pressure at 30 weeks was 170+/-14 mmHg in NPD and 169+/-14 in HPD offspring. These findings show that a HPD during pregnancy did not lead to an increase in birth weight, kidney weight, or nephron endowment, nor did the HPD affect adult blood pressure.
Publisher: Wiley
Date: 20-01-2010
DOI: 10.1002/AR.21084
Abstract: Maternal protein restriction leads to a reduction in the number of cardiomyocytes in the rat heart at birth. However, in rats, cardiomyocytes continue to proliferate until about 2 weeks after birth. Hence, this study aimed to examine the effect of maternal protein restriction, on the number of cardiomyocytes in the young rat heart at a time point when the cardiomyocytes have ceased proliferating and are terminally differentiated. Female Wistar Kyoto rats were fed either a normal protein diet (NPD 20% casein) or a low protein diet (LPD 8.7% casein) during pregnancy and lactation. Offspring (seven males and seven females per group) were perfusion fixed at 4 weeks of age. Heart volume and total cardiomyocyte number were determined using stereological techniques. At 4 weeks of age, body weights in both male and female LPD offspring were significantly reduced compared with NPD controls whereas relative heart volumes were significantly increased in LPD offspring. Total number of cardiomyocytes was not significantly different between groups. In both groups, there was a significant linear correlation between cardiomyocyte number and heart volume. In conclusion, total cardiomyocyte number in the postproliferative rat heart does not appear to be affected by maternal protein restriction per se but is directly related to heart size.
Publisher: Springer Science and Business Media LLC
Date: 07-2006
DOI: 10.1203/01.PDR.0000220361.08181.C3
Abstract: This study examines the effect of maternal protein restriction in rats on levels of cardiac fibrosis, myocardial capillarization, and media:lumen ratio of intramyocardial arteries in adult offspring. Female Wistar Kyoto rats were fed either a normal protein diet (NPD 20% casein) or a low-protein diet (LPD 8.7% casein) during pregnancy and lactation. Female offspring (seven per group) were weaned at 4 wk of age and grown to adulthood. At 24 wk of age, the offspring were perfusion fixed. Cardiac fibrosis and media:lumen ratio of intramyocardial arterioles was assessed using image analysis and cardiac capillarization was stereologically investigated. Body weights at 2 and 24 wk of age were significantly reduced (31% and 8%, respectively) in the LPD offspring however, heart size was not different at 24 wk. Importantly by adulthood, there was a significant 15% increase in left ventricular interstitial fibrosis in LPD offspring. There were no differences in levels of perivascular fibrosis, myocardial capillarization, or in the media:lumen ratio of intramyocardial arteries between groups. Because cardiac fibrosis is associated with impaired cardiac contractility and arrhythmia, our results suggest that induction of interstitial fibrosis may contribute to the increased cardiac disease in adult subjects who were exposed to an adverse intrauterine environment.
Publisher: Springer Science and Business Media LLC
Date: 12-09-2007
DOI: 10.1007/S00467-007-0572-5
Abstract: A reduced nephron complement at birth renders the kidney susceptible to renal disease in adulthood. Retinoic acid (RA the active metabolite of vitamin A) is linked to nephrogenesis in vitro and in vivo. The aim of this study was to determine the effect of administration of retinoic acid in midgestation in rats on nephron endowment in offspring exposed to maternal protein restriction. Rats were fed either a normal-protein diet (NPD) or a low-protein diet (LPD) during pregnancy and lactation. Half of the dams in the LPD group were injected intraperitoneally with retinoic acid (20 mg/kg) during gestation at embryonic day 11.5. At 4 weeks of age, the offspring were anesthetized and perfusion-fixed, and nephron number estimated using unbiased stereological techniques. Body weight and kidney volume was significantly reduced in all LPD offspring. There was a significant 29% reduction in nephron number in the LPD group compared with the NPD offspring, whereas the number of nephrons in kidneys from the LPD + RA offspring was not significantly different compared with controls. In conclusion, administration of a single bolus dose of retinoic acid during midgestation restored nephron endowment to normal in offspring exposed to maternal protein restriction.
Publisher: Oxford University Press (OUP)
Date: 09-10-2012
DOI: 10.1093/NDT/GFR539
Publisher: S. Karger AG
Date: 2004
DOI: 10.1159/000079868
Abstract: i Aim: /i This study tested the hypothesis that a nephron deficit predisposes rats to salt-sensitive hypertension in adulthood. i Methods: /i Female Wistar-Kyoto rats were fed a low (9%) or a normal (20%) protein diet during pregnancy and lactation. Male, birth-weight-matched offspring were paired. One rat from each pair was perfusion fixed at 4 weeks of age and the other rat at 40 weeks of age. Kidneys were removed and nephron number and total renal filtration surface area (FSA) determined using unbiased stereological techniques. The rats that were allowed to grow to adulthood had tail-cuff systolic blood pressure and body weight determined twice weekly. Between 30 and 40 weeks of age, a normal or a high-salt diet was fed to the rats. i Results: /i The offspring of rats fed the low-protein diet were significantly smaller at birth, and at 4 weeks of age they had a significant reduction in kidney volume, nephron number, and total renal FSA when compared to controls. Tail-cuff systolic blood pressure in the offspring from 4 to 29 weeks of age did not significantly differ between the two groups. Administration of a high-salt diet from 30 to 40 weeks of age led to a significant increase in blood pressure in both dietary treatment groups however, it was not exacerbated in the rats exposed to the low-protein diet in utero. i Conclusions: /i Maternal protein restriction in rats did not lead to salt-sensitive hypertension. Nephron endowment and FSA did not correlate with blood pressure in adulthood.
No related grants have been discovered for Monika Zimanyi.