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      Extra uterine development of preterm kidneys

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          Abstract

          Objective

          We carried out a study to determine the impact of prematurity on renal development. The primary outcomes measured were nephrinuria and albuminuria; renal volume and glomerular filtration rate were the secondary outcomes.

          Methods

          Preterm neonates born at less than 28 weeks of gestation, with birth weight between 10th and 90th centile (appropriate for gestational age), were recruited and underwent assessments at 28, 32 and 37 weeks postmenstrual age (PMA).

          Results

          Fifty-three premature neonates and 31 term neonates (control) were recruited. The median gestational age of the premature neonates was 26.4 [24.7–27.4] weeks, with a mean birth weight of 886 (179) g. The mean gestational age of term neonates was 39.1 (1.2) weeks and the mean birth weight was 3406 (406) g. The median age of the term neonates was 6.5 [3.0–12.5] days. The total kidney volume (TKV) almost doubled from 10.3 (2.9) cm 3 at 28 weeks PMA to 19.2 (3.7) cm 3 at 37 weeks PMA ( P = 0.0001). TKV at 37 weeks PMA was significantly smaller compared to term neonates (19.2 (3.7) vs 26.3 (7.0) cm 3; P = 0.0001). However, there was no significant difference in estimated glomerular filtration rate (eGFR) between premature neonates (at 37 weeks PMA) and term neonates (control) (43.5 [39.7–48.9] vs. 42.0 [38.2–50.0] mL/min/1.73 m 2; P = 0.75). There was a statistically significant decline in nephrin-creatinine ratio and albumin-creatinine ratio from 32 to 37 weeks PMA.

          Conclusions

          Despite having a smaller renal volume (and fewer nephrons), extremely premature neonates achieve similar eGFRs at corrected term as term-born neonates, likely through single nephron hyperfiltration. Extremely premature neonates also show evidence of glomerular injury.

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          Most cited references24

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          The hyperfiltration theory: a paradigm shift in nephrology.

          Experimental studies incriminate glomerular hypertension in mediating progressive renal damage after any of a variety of initiating injuries. Prevention of glomerular hypertension by dietary protein restriction or antihypertensive therapy lessens progressive glomerular damage in several experimental models of chronic renal disease. Glomerular hypertension and hyperfiltration also occur in humans with diabetes mellitus, solitary or remnant kidneys, and various forms of acquired renal disease. Clinical studies indicate that dietary protein restriction and antihypertensive therapy also slow progression in many of these disorders. Large multicenter trials confirm the beneficial effects of these therapeutic maneuvers on the rate of progression of chronic renal disease.
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            Glomerular number and size in relation to age, kidney weight, and body surface in normal man.

            The number and size of glomeruli in normal, mature human kidneys were estimated by a direct and unbiased stereological method, the fractionator. The number was 617,000 on average, and the mean size 6.0 M microns3. Both glomerular number and size showed significant negative correlation to age and significant positive correlation to kidney weight. Apparently, humans loose glomeruli with age. Body surface area correlated positively to kidney weight and total glomerular volume but not to number of glomeruli. Body surface area correlates significantly with metabolic rate (Robertson and Reid, Lancet, 1: 940-943, 1952). Thus, intraspecies adaptation of kidney filtration capacity to the metabolic demand is performed by changing the size of glomeruli, i.e., the number of glomeruli in individuals of a given species is independent of the metabolic rate.
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              Accelerated maturation and abnormal morphology in the preterm neonatal kidney.

              Nephrogenesis is ongoing at the time of birth for the majority of preterm infants, but whether postnatal renal development follows a similar trajectory to normal in utero growth is unknown. Here, we examined tissue collected at autopsy from 28 kidneys from preterm neonates, whose postnatal survival ranged from 2 to 68 days, including 6 that had restricted intrauterine growth. In addition, we examined kidneys from 32 still-born gestational controls. We assessed the width of the nephrogenic zone, number of glomerular generations, cross-sectional area of the renal corpuscle, and glomerular maturity and morphology. Renal maturation accelerated after preterm birth, with an increased number of glomerular generations and a decreased width of the nephrogenic zone in the kidneys of preterm neonates. Of particular concern, compared with gestational controls, preterm kidneys had a greater percentage of morphologically abnormal glomeruli and a significantly larger cross-sectional area of the renal corpuscle, suggestive of renal hyperfiltration. These observations suggest that the preterm kidney may have fewer functional nephrons, thereby increasing vulnerability to impaired renal function in both the early postnatal period and later in life. Copyright © 2011 by the American Society of Nephrology
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                Author and article information

                Contributors
                +61744332989 , Yogavijayan.Kandasamy@jcu.edu.au
                Journal
                Pediatr Nephrol
                Pediatr. Nephrol
                Pediatric Nephrology (Berlin, Germany)
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0931-041X
                1432-198X
                2 March 2018
                2 March 2018
                2018
                : 33
                : 6
                : 1007-1012
                Affiliations
                [1 ]ISNI 0000 0000 9237 0383, GRID grid.417216.7, Department of Neonatology, , The Townsville Hospital, ; 100 Angus Smith Drive, Douglas, QLD 4814 Australia
                [2 ]ISNI 0000 0000 8831 109X, GRID grid.266842.c, Mothers and Babies Research Centre, Hunter Medical Research Institute, , The University of Newcastle, ; Callaghan, NSW 2308 Australia
                [3 ]ISNI 0000 0004 0474 1797, GRID grid.1011.1, College of Public Health, Medical and Veterinary Sciences, , The James Cook University, ; Douglas, QLD 4814 Australia
                [4 ]ISNI 0000 0000 8831 109X, GRID grid.266842.c, School of Biomedical Sciences and Pharmacy, , University of Newcastle, ; Callaghan, NSW 2308 Australia
                [5 ]ISNI 0000 0004 0486 528X, GRID grid.1007.6, Illawarra Health and Medical Research Institute and Graduate Medicine, Faculty of Science, Medicine and Health, , University of Wollongong, ; Wollongong, NSW 2522 Australia
                Article
                3899
                10.1007/s00467-018-3899-1
                5943378
                29500630
                651ca33d-e776-4065-b614-4ea3b7606238
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 19 November 2017
                : 19 January 2018
                : 19 January 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: APP1066971
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © IPNA 2018

                Nephrology
                premature,preterm,renal volume,estimated glomeruli filtration rate
                Nephrology
                premature, preterm, renal volume, estimated glomeruli filtration rate

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