Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Article Collections
    • JASN Podcasts
    • Archives
    • Saved Searches
    • ASN Meeting Abstracts
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Subscriptions
  • More
    • About JASN
    • Alerts
    • Advertising
    • Editorial Fellowship Team
    • Feedback
    • Reprints
    • Impact Factor
    • Editorial Fellowship Application Process
  • ASN Kidney News
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • Log out
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • Log out
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Article Collections
    • JASN Podcasts
    • Archives
    • Saved Searches
    • ASN Meeting Abstracts
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Subscriptions
  • More
    • About JASN
    • Alerts
    • Advertising
    • Editorial Fellowship Team
    • Feedback
    • Reprints
    • Impact Factor
    • Editorial Fellowship Application Process
  • ASN Kidney News
  • Follow JASN on Twitter
  • Visit ASN on Facebook
  • Follow JASN on RSS
  • Community Forum
Frontiers in Nephrology: Perinatal Antecedents of Adult Disease
You have accessRestricted Access

Nephron Number, Hypertension, Renal Disease, and Renal Failure

Wendy E. Hoy, Michael D. Hughson, John F. Bertram, Rebecca Douglas-Denton and Kerstin Amann
JASN September 2005, 16 (9) 2557-2564; DOI: https://doi.org/10.1681/ASN.2005020172
Wendy E. Hoy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael D. Hughson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John F. Bertram
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rebecca Douglas-Denton
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kerstin Amann
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

Essential hypertension is one of the most common diseases in the Western world, affecting about 26.4% of the adult population, and it is increasing (1). Its causes are heterogeneous and include genetic and environmental factors (2), but several observations point to an important role of the kidney in its genesis (3). In addition to variations in tubular transport mechanisms that could, for example, affect salt handling, structural characteristics of the kidney might also contribute to hypertension.

The burden of chronic kidney disease is also increasing worldwide, due to population growth, increasing longevity, and changing risk factors. Although single-cause models of disease are still widely promoted, multideterminant or “multihit” models that can accommodate multiple risk factors in an individual or in a population are probably more applicable (4,5). In such a framework, nephron endowment is one potential determinant of disease susceptibility.

Some time ago, Brenner and colleagues (6,7) proposed that lower nephron numbers predispose both to essential hypertension and to renal disease. They also proposed that hypertension and progressive renal insufficiency might be initiated and accelerated by glomerular hypertrophy and intraglomerular hypertension that develops as nephron number is reduced (8). In this review, we summarize data from recent studies that shed more light on these hypotheses. The data supply a new twist to possible mechanisms of the “Barker hypothesis,” which proposes that intrauterine growth retardation predisposes to chronic disease in later life (9).

The review describes how nephron number is estimated and its range and some determinants and morphologic correlates. It then considers possible causes of low nephron numbers. Finally, associations of hypertension and renal disease with reduced nephron numbers are considered, and some potential clinical implications are discussed.

Assessment of Nephron Number in Humans

Nephron numbers are estimated through the surrogate of glomerular number. Direct assessment of glomerular number in living humans is currently not possible, although a combination of magnetic computer tomography and histologic analysis of kidney biopsies has enabled rough estimates of the number of glomeruli per kidney (10). A relatively noninvasive technique to estimate nephron number would be immensely useful.

The only really quantitative information so far has come from studies of whole kidneys at autopsy (11–19). Glomerular number is estimated using either the acid maceration method, which assesses the entire organ and takes into account the different density of glomeruli in the various zones of the renal cortex, or unbiased techniques, e.g., with the disector/fractionator combination, that do not involve assumptions about the size and shape of glomeruli (20,21). Although the laborious nature of these techniques has restricted them to a few specialized centers, such studies are beginning to expose the range and relationships of glomerular number and glomerular size in humans and their possible relationships to hypertension and renal disease.

In a study of 208 adults from Mississippi in the United States and the Northern Territory of Australia, who underwent autopsy for sudden or unexpected death, there was a 10-fold range in glomerular number, a five-fold variation in mean glomerular volume, and an astonishing 13.5-fold range of estimated total glomerular tuft volume (Table 1) (13,14,16)

View this table:
  • View inline
  • View popup
Table 1.

US/Australian autopsy series: Characteristics of the right kidney, in subjects age ≥18 yr, n = 208

Glomerular number was significantly linked to gender (approximately 17% higher in men), age (inversely), race (lower in Australian Aborigines), and birth weight (13,14,16,18,19). The loss of glomeruli with age seemed to operate over a continuum of adult life, with a mean predicted loss of approximately 4500 glomeruli per kidney per year between ages 18 and 70 yr, although in Nyengaard’s Danish autopsy series the phenomenon was mostly discernible after age 60 yr (12).

Two important determinants of mean glomerular volume defined in these autopsy studies were body surface area, directly, and glomerular number, inversely. The relationship with glomerular number has been interpreted as compensatory enlargement of remaining glomeruli in situations of nephron deficiency or loss, a process “targeted” at restoring total filtering surface toward “normal.” It is one of the first responses to nephron loss in animal models. Thus, increased glomerular volume (or area in biopsies), which is described in several populations at high risk for kidney disease and kidney failure (22–27), might be a surrogate marker for nephron deficiency. Nephrons with critically enlarged glomeruli seemed doomed to premature death. Most hypotheses revolve around premature glomerulosclerosis, developing first as segmental lesions, perhaps mediated through injury of podocytes, and reflected in proteinuria (8,28–31). However, contributions from tubular and interstitial injury, possibly mediated through protein toxicity, are probably also important (31). Ongoing nephron loss potentially accelerates development of hypertension and progression of renal injury (32,33).

Birth weights, available from the state registry for many of the Mississippi participants, were strongly correlated with glomerular number (13,14,16), with an additional 232,217 nephrons predicted in each kidney for each 1-kg increase in birth weight after adjustment for other factors (P < 0.001). Birth weight was also significantly and inversely correlated with mean glomerular volume, an effect that was mediated through variation in nephron number (Table 2). This compensatory hypertrophy resulted in a mean total glomerular mass that did not differ by birth weight groupings. Finally, Australian Aborigines had, on average 250,000 (or approximately 30%) fewer glomeruli per kidney than their non-Aboriginal Australian counterparts, with a mean glomerular volume increased by the same proportion (18,19).

View this table:
  • View inline
  • View popup
Table 2.

US/Australian autopsy series: Characteristics of the right kidney, in subjects age ≥18 yr, by birth weight tertiles, adjusted mean (95% CI), n = 87a

It is likely that people with lower glomerular numbers are more susceptible to hypertension and renal disease, which are initiated and propagated through the cascade of events that follows compensatory nephron hypertrophy. Determination of the causes of low nephron numbers will help us understand how exacerbated risk for these conditions is established.

Causes of Low Nephron Number

Studies in rats and sheep show that an experimentally induced loss of a critical nephron mass during fetal development or shortly after birth favors the development of hypertension and kidney damage (34,35). In humans, loss of substantial kidney mass (accidents, resections, cancers, obstructions, vascular occlusions, cortical necrosis, etc.) can have similar results, whereas transplantation of small kidney donor organs into large recipients increases the risk for hypertension and graft failure (36,37).

A potentially more broadly relevant model, however, is that of developmental nephron underdosing, or reduced nephron endowment. Influences on nephron development, in turn, can be grouped broadly as genetic or related to the early environment.

Genetics

Little is yet known about genetic influences in nephron endowment in humans (32,33). Congenital oligomeganephronia, in which glomeruli are few, very large, and prone to sclerosis (38,39), is one blatant model of nephron underendowment. Although most cases are sporadic, it sometimes occurs in family clusters, suggesting a genetic background (40), and an association with PAX2 gene mutations has been described (41). More modest deficiencies of nephron endowment might be part of the same spectrum (31). Mice that are heterozygous for glial-derived neurotrophic factor (GDNF), a critical factor for renal development, are born with approximately 30% fewer nephrons and develop hypertension in adulthood in the absence of renal disease (42). Transgenic mice expressing wild-type P53 have defective nephron development, small kidneys, approximately 50% fewer nephrons, and compensatory enlargement of nephrons that remain and they ultimately develop renal failure (43).

Early Life Influences

Nephron development in humans begins in the ninth week of gestation. Proliferation of nephrons is particularly rapid in the last trimester, continuing up through the 36th week, then it ceases (32–44). The final complement of nephrons, which is reflected in kidney volume estimates by ultrasound, as well as in kidney mass and nephron number, is critically dependent on two factors: gestational age and a favorable intrauterine environment.

In the stressed intrauterine environment, development and growth of the brain and the heart are preserved at the expense of the kidney and other organs and general somatic growth (45). In both animals and humans, nephron number is strongly correlated with fetal weight and is disproportionately reduced by factors that restrict intrauterine growth (44–54). Such factors include protein and micronutrient deficiencies, hypoxia, infections, toxins, certain drugs, metabolic perturbations, and probably psychosocial as well as physical stress (47–51). Their effects are often reflected in various degrees of intrauterine growth retardation (IUGR), with infants that are small for gestational age and sometimes thin relative to their length. These infants have smaller kidneys, whose circumferential dimensions are often more compromised than their length (52,53), and fewer nephrons, with glomeruli enlarged in proportion to their reduced numbers (54). Internationally, most low birth weight in humans is associated with small maternal stature, particularly in mothers with low weight for height, which is a consequence of generations of suboptimal nutrition (55). However, overt malnutrition and specific protein deficiency are also regionally important. The global impact of maternal smoking on fetal growth and potentially nephron number is, apparently, enormous (55,56). Other factors that might not be reflected in measures of fetal growth can also impair nephrogenesis, such as selective vitamin deficiencies, certain antibiotics (including β lactams, penicillin, amoxicillin, ampicillin, and cephalosporins), maternal infections, steroid administration, and hyperglycemia (47–51). A recent report also suggests that maternal alcohol ingestion impairs kidney development (57).

Mechanisms through which adverse intrauterine environments restrict nephrogenesis are still under investigation. They could operate at any of the key steps in kidney development: branching of the ureteric duct in the metanephric mesenchyme (driven strongly by GDNF), condensation of the mesenchymal cells at the tips of the ureteric branches, and conversion of the mesenchymal condensates into epithelium (58). Retinoic acid, derived from dietary vitamin A, regulates the c-Ret receptor for GDNF so powerfully that much of the variation in nephron number in the general population might be regulated through this nutritional marker (48–51,59). This has important implications for disadvantaged populations, where subtle and overt deficiencies of vitamin A and related micronutrients can be widespread. Iron deficiency might also be important. Adequate iron is critical for the rapidly developing fetal organ system, and, in the rat, maternal iron restriction leads to reduced birth weight and elevated BP in the offspring (60).

Factors that restrict fetal growth might impair nephrogenesis through less direct mechanisms as well. In one animal model, maternal protein deprivation was associated with suppression of the renin-angiotensin system in the growth-impaired fetus, which had impaired nephrogenesis and later developed hypertension (61). Another important system is the renal cortisol/cortisone shuttle (62). The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) regulates the inactivation of mineralocorticoid-active cortisol to inactive cortisone. Newborn and adult rats with IUGR have increased renal expression of the mineralocorticoid receptor and a significant reduction of the 11β-HSD2 gene (63). Approximately 20% of children with former IUGR have an increased cortisol/cortisone ratio, suggesting decreased activity of 11β-HSD2. In humans, mutations of the 11β-HSD2 gene cause low birth weight and placental 11β-HSD activity correlates directly with fetal weight. In addition, in rats and sheep, glucocorticoid administration during pregnancy, which inhibits 11 β-HSD, reduces birth weight of offspring, which develop permanent hypertension, hyperglycemia, and increased hypothalamic-pituitary-adrenal (HPA) axis activity as adults. Higher plasma cortisol levels have been documented in humans with former IUGR, indicating HPA axis programming (63,64).

Welham et al. (65) showed recently that maternal diet programs the embryonic kidney, altering cell turnover and gene expression when nephrons and glomeruli have yet to form. They also showed that nephron deficit in fetuses with maternal low-protein diets was associated with increased apoptosis in the metanephros (66), indicating accelerated cell turnover and death. It is not known whether the nephron deficit represents direct deletion of nephron precursors or an indirect effect from loss of supportive interstitial precursors.

A recent study by serial ultrasounds has shown that human infants with IUGR have, not only smaller kidneys at birth, but also reduced kidney growth during the first 18 months of life, both in absolute terms and relative to current body size (67,68).

The renal implications of low birth weight associated with prematurity are potentially important, given the large cohorts of very low birth weight premature infants who are now surviving infancy due to advances in neonatal and perinatal care. It is unlikely that even a relatively “stable” extrauterine environment can support development of the kidney and other organs as adequately as continuation of pregnancy to term under favorable circumstances. One histologic study, which confirmed that nephron number in premature infants is dramatically reduced, showed that nephrogenesis could continue after premature birth, but it was suboptimal, was further impaired by renal insults, and did not progress beyond 40 d after delivery (69). Glomerulomegaly and mesangial proliferation were evident in longer-term survivors. Postnatal and catch-up kidney growth in premature infants is even more impaired than in infants with low birth weight caused by IUGR alone (67,68). Finally, a recent study showed lower GFR and disturbed tubular function in children who were survivors of very low birth weight, usually associated with prematurity (70).

Less well explored is the influence of the postnatal environment on renal development. Infant and childhood malnutrition and repeated infections, which are common in disadvantaged populations, might impair appropriate kidney maturation and hypertrophy, with an especially severe impact on children who are survivors of IUGR (71).

BP and Nephron Number

Some animal experiments show a strong link of nephron number at birth to postnatal blood pressure (47,72,73). The findings of many studies in children and adults, which link IUGR or birthweight, inversely, to higher blood pressure in postnatal life, are at least compatible with a role for nephron endowment in blood pressure regulation in humans as well (9).

Two recent autopsy studies support the notion that hypertension in humans is associated with reduced nephron number. In Western Europe, an autopsy study of white victims of accidents compared stereologic findings in the kidneys of 10 adults who had a history of hypertension and left ventricular hypertrophy with those of age-, gender-, and height-matched control subjects (15). The number of glomeruli was diminished by approximately 46% in the hypertensive individuals. In addition, mean glomerular volume was markedly increased, on average by approximately 50% but in some cases was three times the normal size. In the autopsy study of people in Mississippi, among 80 people whose records were examined scrupulously for evidence of hypertension, glomerular number was significantly reduced in those with hypertension, with a significant increase in mean glomerular volume (Table 3), which was independent of body surface area (16). Again, this compensatory hypertrophy seemed to compensate total glomerular mass to “normal.” In both studies, the general paucity of glomerulosclerosis and cortical fibrosis seemed to weigh against recent accelerated nephron loss as the chief cause of the nephron deficiency. Among Aboriginal Australians, whose nephron number, on average, was already reduced, there was a further reduction in nephron number and increase in mean glomerular volume among those with a history of hypertension (18,19).

View this table:
  • View inline
  • View popup
Table 3.

Characteristics of right kidney, by documented presence of hypertension (US participants only)a

Low Nephron Number, Renal Disease, and Renal Failure

In some animal models, congenital nephron deficiency, both genetic and experimental, is associated with development of renal disease and renal failure in postnatal life (43,74).

In humans, the rapid development of proteinuria, hypertension, and renal failure in children with oligomeganephronia (38,39) and the lower number of nephrons in Australian Aborigines (18,19), whose rates of renal failure are excessive, are compatible with a link between low nephron number and renal disease. An influence of congenital nephron underdosing on renal disease susceptibility is otherwise largely inferred through links of low birthweight or IUGR to renal disease or to reduced renal size. This body of research is less well developed than that of IUGR, hypertension, the metabolic syndrome, and cardiovascular disease. Indeed, relationships between low birthweight and renal disease could be mediated in part through their mutual links to these other conditions (75–77), independent of nephron number.

Links of birth weight to renal disease susceptibility can be explored at the levels of asymptomatic albuminuria/proteinuria, overt nephropathy, development or progression of renal impairment in specific sorts of kidney disease, and renal failure and renal death. Exposure to famine in midgestation during the Dutch “Hongerwinter” was associated with microalbuminuria in people who survived to late middle age (78). A study of people without diabetes in the United Kingdom found higher rates of microalbuminuria in people of low birth weight or with IUGR (79,80). In Pima Indians with type 2 diabetes, birth weights at the highest and lowest ends of the range were associated with increased rates of albuminuria (81). In individuals with type 1 diabetes studied thus far, the effect of birth weight on nephropathy has been equivocal (82,83). In one remote Australian Aboriginal community with generally low birth weights, birth weight in young adults was strongly and inversely correlated with the level of albuminuria and with the presence of overt nephropathy (84,85). Low birth weight children in this same population had lower kidney volumes than those of higher birth weights (22). Furthermore, adults with the lowest kidney volumes, examined in the context of current weight, had the highest rates of albuminuria and highest BP (23), tending to support a role of nephron underdosing in these pathologies. Lower birth weights have been associated with higher relapse rates in children with the nephrotic syndrome (86,87) and with progression in children with IgA nephropathy (88). Associations of birth weight with renal deaths are obscured by the competing effects of the higher numbers of cardiovascular and other nonrenal natural deaths that are predicted by renal markers (75–77,89) and by deficient documentation of the contribution of renal disease to natural deaths (90). Evaluation through ESRD treatment registries poses problems of selection, especially in developing countries with restricted access; however, a study in the southeastern United States did show that ESRD patients tended to be of lower birth weights than matched controls (91).

In some of these studies, the birth weight effect was more pronounced in women (20,83,84,86). Most, too, showed the important effect of higher levels of body fat in postnatal life in educing or exacerbating the adverse effects of lower birth weights, not only on renal disease but also on BP and metabolic profiles. Maintenance of a lean adult weight minimized or effaced the potential adverse effects of low birth weight in all settings in which it was studied.

Further studies might inspect the influence of birth weight in existing population-based surveys of renal markers. Its influence on progression could be studied in longitudinal cohort studies such as the Australian Diabetes, Obesity, and Lifestyle (AusDiab) study, the African-American Study of Kidney Disease and Hypertension (AASK) study, and in existing Aboriginal cohorts.

Conclusions and Clinical Implications

Nephron endowment is probably one determinant of blood pressure levels and renal disease risk in later life. Multideterminant models can incorporate nephron endowment as one risk factor for hypertension or renal disease while retaining other risk factors whose roles are better recognized. The contribution of low or marginal nephron endowment to the burden of disease in different populations could range from trivial to highly significant, depending on the frequency of factors impairing nephron development, such as IUGR, and of postnatal factors that compromise vascular or renal health, such as obesity, diabetes, and infections.

Implications for populations in epidemiologic transition are especially important (92). The burden of chronic disease increases as populations grow, as adults live longer, and as body fat increases, all of which are happening more rapidly in the developing world (71). In that setting, too, reductions in infant deaths associated with social advances and health interventions are resulting in survival of sometimes large cohorts of low birthweight babies to adult life, at exacerbated risk for chronic disease. In affluent groups in westernized countries, the impact of the increased survival of very low birthweight premature babies is yet to be fully ascertained, although rates of IUGR are now quite low. In that setting, the predominant challenge is to moderate the harmful influence of the current epidemic of obesity and inactivity on even adequately formed organs (93).

Currently, with so little known about genetic or other intrinsic modulators of nephron endowment, prevention depends on optimizing intrauterine conditions, and specifically avoiding maternal smoking, micronutrient deficiency, frank malnutrition, and probably drinking. For survivors of low birthweight, surveillance and minimization of exacerbating postnatal factors are central. Avoiding the secular trend towards increasing body mass is important, although some programmed preferential deposition of central fat might not easily be prevented without pharmacologic intervention. Avoidance of infections and potentially harmful drugs is also wise. Finally, for those in whom elevated blood pressure or albuminuria has already appeared, multipronged therapy that includes renal protective drugs promises extension of life by many years (94).

Footnotes

  • Published online ahead of print. Publication date available at www.jasn.org.

  • © 2005 American Society of Nephrology

References

  1. ↵
    Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J: Global burden of hypertension: Analysis of worldwide data. Lancet 365 : 217 –223, 2005
    OpenUrlCrossRefPubMed
  2. ↵
    Luft FC: Present status of genetic mechanisms in hypertension. Med Clin North Am 88 : 1 –18, 2004
    OpenUrlCrossRefPubMed
  3. ↵
    Rettig R, Folberth C, Stauss H, Kopf D, Waldherr R, Unger T: Role of the kidney in primary hypertension: A renal transplantation study in rats. Am J Physiol 258 : F606 –F611, 1990
  4. ↵
    Hoy WE, Mathews JD, Pugsley DJ, Hayhurst BG, Rees M, Kile E, Walker KA, Wang Z: The multidimensional nature of renal disease: Rates and associations of albuminuria in an Australian Aboriginal community. Kidney Int 54 : 1296 –1304, 1998
    OpenUrlCrossRefPubMed
  5. ↵
    Nenov VD, Taal MW, Sakharova OV, Brenner BM: Multi-hit nature of chronic renal disease. Curr Opin Nephrol Hypertens 9 : 85 –97, 2000
    OpenUrlCrossRefPubMed
  6. ↵
    Brenner BM, Garcia DL, Anderson S: Glomeruli and blood pressure: Less of one, more of the other? Am J Hypertens 1 : 335 –347, 1988
    OpenUrlCrossRefPubMed
  7. ↵
    Brenner BM, Mackenzie HS: Nephron mass as a risk factor for progression of renal disease. Kidney Int Suppl 63 : S124 –S127, 1997
    OpenUrlPubMed
  8. ↵
    Brenner BM, Lawler EV, Mackenzie HS: The hyperfiltration theory: A paradigm shift in nephrology. Kidney Int 49 : 1774 –1777, 1996
    OpenUrlCrossRefPubMed
  9. ↵
    Barker DJ: Intrauterine programming of adult disease. Mol Med Today 1 : 418 –423, 1995
    OpenUrlCrossRefPubMed
  10. ↵
    Fulladosa X, Moreso F, Narvaez JA, Grinyo JM, Seron D: Estimation of total glomerular number in stable renal transplants. J Am Soc Nephrol 14 : 2662 –2668, 2003
    OpenUrlAbstract/FREE Full Text
  11. ↵
    McLachlan MSF, Guthrie JC, Anderson CK, Fulker MJ: Vascular and glomerular changes in the ageing kidney. Am J Pathol 121 : 65 –78, 1977
  12. ↵
    Nyengaard JR, Bendtsen TF: Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec 232 : 194 –201, 1992
    OpenUrlCrossRefPubMed
  13. ↵
    Hoy WE, Douglas-Denton RN, Hughson M, Cass A, Johnson K, Bertram JF: A stereological study of glomerular number and volume: Preliminary findings in a multiracial study of kidneys at autopsy. Kidney Int Suppl 83 : S31 –S37, 2003
  14. ↵
    Hughson M, Farris AB 3rd, Douglas-Denton R, Hoy WE, Bertram JF: Glomerular number and size in autopsy kidneys: The relationship to birthweight. Kidney Int 63 : 2113 –2122, 2003
    OpenUrlCrossRefPubMed
  15. ↵
    Keller G, Zimmer G, Mall G, Ritz E, Amann K: Nephron number in patients with primary hypertension. N Engl J Med 348 : 101 –108, 2003
    OpenUrlCrossRefPubMed
  16. ↵
    Samuel T, Hoy WE, Douglas-Denton R, Hughson MD, Bertram J: Determinants of glomerular volume in different cortical zones of the kidney. J Am Soc Nephrol 2005 , in press
  17. Samuel T, Douglas-Denton R, Bertram JF, Hughson MD, Hoy WE: Determinants of individual glomerular volume in the human kidney [Abstract]. J Am Soc Nephrol 15 : 245A , 2004
    OpenUrl
  18. ↵
    Douglas Denton R, Hoy WE, Bertram JF, Hughson MD: Kidney mass, glomerular number, mean glomerular corpuscle volume and total renal corpuscle volume in Aboriginal and nonAboriginal Australians at autopsy [Abstract]. Nephrology 8[Suppl] : A59 , 2003
    OpenUrlCrossRef
  19. ↵
    Hoy WE, Douglas-Denton R. Hughson MD, Bertram JF: Nephron deficit and hypertension in Australian Aboriginal people [Abstract]. Nephrology 2005 , in press
  20. ↵
    Gundersen HJ, Bagger P, Bendtsen TF, Evans SM, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, et al.: The new stereological tools: Disector, three-dimensional stereological method, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS 96 : 857 –881, 1988
    OpenUrlCrossRefPubMed
  21. ↵
    Bertram JF: Counting in the kidney. Kidney Int 59 : 792 –796, 2001
    OpenUrlCrossRefPubMed
  22. ↵
    Spencer JS, Wang Z, Hoy WE: Birthweight and renal volume in Aboriginal children. Is the susceptibility to renal disease associated with low birthweight mediated through impaired nephrogenesis? Am J Kidney Dis 37 : 915 –920, 2001
    OpenUrlPubMed
  23. ↵
    Singh GR, Hoy WE: Kidney volume, blood pressure, and albuminuria: Findings in an Australian aboriginal community. Am J Kidney Dis 43 : 254 –259, 2004
    OpenUrlCrossRefPubMed
  24. Pesce CM, Schmidt C, Fogo A, Okoye MI, Kim R, Striker LJ, Striker GE: Glomerular size and the incidence of renal disease in African Americans and Caucasians. Clin Invest 7 : 355 –358, 1994
    OpenUrl
  25. Samuel T, Douglas-Denton R, Bertram JF, Hughson MD, Hoy WE: Racial difference in glomerular volume in nondiabetic renal disease [Abstract]. J Am Soc Nephrol 15 : 503A , 2004
    OpenUrl
  26. Schmidt K, Pesce C, Liu Q, Nelson RG, Bennett PH, Karnitschnig H, Striker LJ, Striker GE: Large glomerular size in Pima Indians: Lack of change with diabetic nephropathy. J Am Soc Nephrol 3 : 229 –235, 1992
    OpenUrlAbstract
  27. ↵
    Bertram JF, Young RJ, Kincaid Smith P, Seymour AE, Hoy WE: Glomerulomegaly in Australian Aborigines. Nephrology 4[Suppl] : S46 –S53, 1998
    OpenUrl
  28. ↵
    Fogo A, Ichikawa I: Evidence for a pathogenetic link between glomerular hypertrophy and sclerosis. Am J Kidney Dis 17 : 666 –669, 1991
    OpenUrlCrossRefPubMed
  29. Young RJ, Hoy WE, Kincaid Smith P, Seymour AE, Bertram JF: Glomerular size and glomerulosclerosis in Australian Aborigines. Am J Kidney Dis 36 : 481 –489, 2000
    OpenUrlPubMed
  30. Hughson MD, Johnson K, Young RJ, Hoy WE, Bertram JF: Glomerular size and glomerulosclerosis: Relationships to disease categories, glomerular solidification, and ischemic obsolescence. Am J Kidney Dis 39 : 679 –688, 2002
    OpenUrlPubMed
  31. ↵
    Kriz W, Lehir M: Pathways to nephron loss starting from glomerular diseases—Insights from animal models. Kidney Int 67 : 404 –419, 2005
    OpenUrlCrossRefPubMed
  32. ↵
    Ingelfinger JR: Is microanatomy destiny? N Engl J Med 348 : 99 –100, 2003
    OpenUrlCrossRefPubMed
  33. ↵
    Ingelfinger JR: Pathogenesis of perinatal programming. Pathogenesis of perinatal programming. Curr Opin Nephrol Hypertens 13 : 459 –464, 2004
    OpenUrlCrossRefPubMed
  34. ↵
    Woods LL: Neonatal uninephrectomy causes hypertension in adult rats. Am J Physiol 276 : R974 –R978, 1999
  35. ↵
    Moritz KM, Wintour EM, Dodic M: Fetal uninephrectomy leads to postnatal hypertension and compromised renal function. Hypertension 39 : 1071 –1076, 2002
    OpenUrlAbstract/FREE Full Text
  36. ↵
    Mei-Zahav M, Korzets Z, Cohen I, Kessler O, Rathaus V, Wolach B, Pomeranz A: Ambulatory blood pressure monitoring in children with a solitary kidney—A comparison between unilateral renal agenesis and uninephrectomy. Blood Press Monit 6 : 263 , 2001
    OpenUrlCrossRefPubMed
  37. ↵
    Brenner BM, Milford EL: Nephron underdosing: A programmed cause of chronic renal allograft failure. Am J Kidney Dis 21[Suppl 2] : 66 –72, 1993
    OpenUrl
  38. ↵
    Drukker A: Oligonephropathy: From a rare childhood disorder to a possible health problem in the adult. Isr Med Assoc J 4 : 191 –195, 2002
    OpenUrlPubMed
  39. ↵
    McGraw M, Poucell S, Sweet J, Baumal R: The significance of focal segmental glomerulosclerosis in oligomeganephronia. Int J Pediatr Nephrol 5 : 67 –72, 1984
    OpenUrlPubMed
  40. ↵
    Kusuyama Y, Tsukino R, Oomori H, Kuribayashi K, Katayama H, Koike M, Saito K: Familial occurrence of oligomeganephronia. Acta Pathol Jpn 35 : 449 –457, 1985
    OpenUrlPubMed
  41. ↵
    Salomon R, Tellier AL, Attie-Bitach T, Amiel J, Vekemans M, Lyonnet S, Dureau P, Niaudet P, Gubler MC, Broyer M: PAX2 mutations in oligomeganephronia. Kidney Int 59 : 457 –462, 2001
    OpenUrlCrossRefPubMed
  42. ↵
    Cullen-McEwen LA, Kett MM, Dowling J, Anderson WP, Bertram JF: Nephron number, renal function, and arterial pressure in aged GDNF heterozygous mice. Hypertension 41 : 335 –340, 2003
    OpenUrlAbstract/FREE Full Text
  43. ↵
    Godley LA, Kopp JB, Eckhaus M, Paglino JJ, Owens J, Varmus HE: Wild-type p53 transgenic mice exhibit altered differentiation of the ureteric bud and possess small kidneys. Genes Dev 10 : 836 –850, 1996
    OpenUrlAbstract/FREE Full Text
  44. ↵
    Hinchliffe SA, Sargent PH, Howard CV, Chan YF, van Velzen D: Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle. Lab Invest 64 : 777 –784, 1991
    OpenUrlPubMed
  45. ↵
    Lumbers E, Yu Z-V, Gibson K: The selfish brain and the Barker hypothesis. Clin Exp Pharmacol Physiol 28 : 942 –947, 2001
    OpenUrlCrossRefPubMed
  46. Hinchliffe SA, Lynch MRJ, Sargent PH, Howard CV, van Velzen D: The effect of intrauterine growth retardation on the development of renal nephrons. Br J Obstet Gynaecol 99 : 296 –301, 1992
    OpenUrlCrossRefPubMed
  47. ↵
    Langely-Evans SC, Welham SJM, Jackson AA: Fetal exposure to maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sci 64 : 965 –974, 1999
    OpenUrlCrossRefPubMed
  48. ↵
    Merlet-Benichou C: Influence of the fetal environment on kidney development. Int J Dev Biol 43 : 453 –456, 1999
    OpenUrlPubMed
  49. Merlet-Benichou C, Vilar J, Lelievre-Pegorier M, Moreau E, Gilbert T: Fetal nephron mass, its control and deficit. Adv Nephrol Necker Hosp 26 : 19 –45, 1997
    OpenUrlPubMed
  50. Lelievre-Pegorier M, Merlet-Benichou C: The number of nephrons in the mammalian kidney: Environmental influences play a determining role. Exp Nephrol 8 : 63 –65, 2000
    OpenUrlCrossRefPubMed
  51. ↵
    Solhaug MJ, Bolger PM, Jose PA: The developing kidney and environmental toxins. Pediatrics 113[Suppl] : 1084 –1091, 2004
    OpenUrlCrossRefPubMed
  52. ↵
    Lampl M, Kuzawa CW, Jeanty P: Infants thinner at birth exhibit smaller kidneys for their size in late gestation in a sample of fetuses with appropriate growth. Am J Hum Biol 14 : 398 –406, 2002
    OpenUrlCrossRefPubMed
  53. ↵
    Konje JC, Okaro CI, Bell SC, de Chazal R, Taylor DJ: A cross-sectional study of changes in fetal renal size with gestation in appropriate- and small-for-gestational-age fetuses. Ultrasound Obstet Gynecol 10 : 22 –26, 1997
    OpenUrlCrossRefPubMed
  54. ↵
    Manalich R, Reyes L, Herrera M, Melendi C, Fundora I: Relationship between weight at birth and the number and size of renal glomeruli in humans: A histomorphometric study. Kidney Int 58 : 770 –773, 2000
    OpenUrlCrossRefPubMed
  55. ↵
    Robinson JS, Moore VM, Owens JA, McMillen IC: Origins of fetal growth restriction. Eur J Obstet Gynecol Reprod Biol 92 : 13 –19, 2000
    OpenUrlCrossRefPubMed
  56. ↵
    Anderson GD, Blidner IN, McClemont S, Sinclair JC: Determinants of size at birth in a Canadian population. Am J Obstet Gynecol 150 : 236 –244, 1984
    OpenUrlCrossRefPubMed
  57. ↵
    Singh GR, Sayers SM, Hoy WE: Maternal alcohol ingestion during pregnancy predisposes to albuminuria and smaller kidneys in Aboriginal children: Findings in an Aboriginal birth cohort. Nephrology 9[Suppl 1] : P75 , 2004
    OpenUrl
  58. ↵
    Clark AT, Bertram JF: Advances in renal development. Curr Opin Nephrol Hypertens 3 : 247 –251, 2000
  59. ↵
    Clark AT, Bertram JF: Molecular regulation of nephron endowment. Am J Physiol 276 : F485 –F497, 1999
  60. ↵
    Lewis RM, Forhead AJ, Petry CJ, Ozanne SE, Hales CN: Long-term programming of blood pressure by maternal dietary iron restriction in the rat. Br J Nutr 88 : 283 –290, 2002
    OpenUrlCrossRefPubMed
  61. ↵
    Woods LL, Ingelfinger JR, Nyengaard JR, Rasch R: Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr Res 49 : 460 –467, 2001
    OpenUrlCrossRefPubMed
  62. ↵
    Amann K, Plank C, Dotsch J: Low nephron number—A new cardiovascular risk factor in children? Pediatr Nephrol 19 : 1319 –1323, 2004
    OpenUrlCrossRefPubMed
  63. ↵
    Bertram C, Trowern AR, Copin N, Jackson AA, Whorwood CB: The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: Potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 142 : 2841 –2853, 2001
    OpenUrlCrossRefPubMed
  64. ↵
    Seckl JR, Meaney MJ: Glucocorticoid programming. Ann N Y Acad Sci 1032 : 63 –84, 2004
    OpenUrlCrossRefPubMed
  65. ↵
    Welham SJ, Riley PR, Wade A, Hubank M, Woolf AS: Maternal diet programs embryonic kidney gene expression. Physiol Genomics 22 : 48 –56, 2005
    OpenUrlCrossRefPubMed
  66. ↵
    Welham SJ, Wade A, Woolf AS: Protein restriction in pregnancy is associated with increased apoptosis of mesenchymal cells at the start of rat metanephrogenesis. Kidney Int 61 : 1231 –1242, 2002
    OpenUrlCrossRefPubMed
  67. ↵
    Schmidt IM, Damgaard IN, Boisen KA, Mau C, Chellakooty M, Olgaard K, Main KM: Increased kidney growth in formula-fed versus breast-fed healthy infants. Pediatr Nephrol 19 : 1137 –1144, 2004
    OpenUrlPubMed
  68. ↵
    Schmidt IM, Chellakooty M, Boisen KA, Damgaard IN, Kai CM, Olgaard K, Main KM: Impaired kidney growth in low birthweight children: Distinct effect of maturity and weight for gestational age. Kidney Int 2005 , in press
  69. ↵
    Rodriguez MM, Gomez AH, Abitbol CL, Chandar JJ, Duara S, Zilleruelo GE: Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev Pathol 7 : 17 –25, 2004
    OpenUrlCrossRefPubMed
  70. ↵
    Rodriguez-Soriano J, Aguirre M, Oliveros R, Vallo A: Long-term renal follow-up of extremely low birth weight infants. Pediatr Nephrol 20 : 579 –584, 2005
    OpenUrlCrossRefPubMed
  71. ↵
    Moser K, Shkolnikov V, Leon DA: World mortality 1950–2000: Divergence replaces convergence from the late 1980s. Bull World Health Organ 83 : 202 –209, 2005
    OpenUrlPubMed
  72. ↵
    Hinchliffe 1, Vehaskari MV, Aviles DH, Manning J: Prenatal programming of adult hypertension in the rat. Kidney Int 59 : 238 –245, 2001
    OpenUrlCrossRefPubMed
  73. ↵
    Woods LL, Weeks DA, Rasch R: Programming of adult blood pressure by maternal protein restriction: Role of nephrogenesis. Kidney Int 65 : 1339 –1348, 2004
    OpenUrlCrossRefPubMed
  74. ↵
    Nwagu MO, Cook A, Langely-Evans SC: Evidence of progressive deterioration of renal function in rats exposed to a maternal low-protein diet in utero. Br J Nutr 83 : 79 –85, 2000
    OpenUrlPubMed
  75. ↵
    Weinstock Brown W, Keane WF: Proteinuria and cardiovascular disease. Am J Kidney Dis 38 : S8 –S13, 2001
    OpenUrlPubMed
  76. Henry RM, Kostense PJ, Bos G, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD: Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study. Kidney Int 62 : 1402 –1407, 2002
    OpenUrlCrossRefPubMed
  77. ↵
    Hoy W, McDonald SP: Albuminuria: Marker or target in indigenous populations. Kidney Int Suppl 92 : S25 –S31, 2004
  78. ↵
    Painter RC, Roseboom TJ, van Montfrans GA, Bossuyt PM, Krediet RT, Osmond C, Barker DJ, Bleker OP: Microalbuminuria in adults after prenatal exposure to the dutch famine. J Am Soc Nephrol 16 : 189 –194, 2005
    OpenUrlAbstract/FREE Full Text
  79. ↵
    Yudkin JS, Phillips DI, Stanner S: Proteinuria and progressive renal disease: Birth weight and microalbuminuria. Nephrol Dial Transplant 12[Suppl 2] : 10 –13, 1997
    OpenUrl
  80. ↵
    Yudkin JS, Martyn CN, Phillips DI, Gale CR: Associations of micro-albuminuria with intra-uterine growth retardation. Nephron 89 : 309 –314, 2001
    OpenUrlCrossRefPubMed
  81. ↵
    Nelson RG, Morgenstern H, Bennett PH: Birthweight and renal disease in Pima Indians with type 2 diabetes mellitus. Am J Epidemiol 148 : 650 –656, 1998
    OpenUrlCrossRefPubMed
  82. ↵
    Rossing P, Tarnow L, Nielsen FS, Hansen BV, Brenner BM, Parving HH: Low birthweight: A risk factor for diabetic nephropathy? Diabetes 44 : 1405 –1408, 1995
    OpenUrlAbstract/FREE Full Text
  83. ↵
    Jacobsen P, Rossing P, Tarnow L, Hovind P, Parving HH: Birthweight—A risk factor for progression in diabetic nephropathy? J Intern Med 253 : 343 –350, 2003
    OpenUrlCrossRefPubMed
  84. ↵
    Hoy WE, Kile E, Rees M, Mathews JD: Low birthweight and renal disease in Australian Aborigines. Lancet 352 : 1826 –1827, 1998
    OpenUrlCrossRefPubMed
  85. ↵
    Hoy WE, Rees M, Kile E, Mathews JD, Wang Z: A new dimension to the Barker hypothesis: Low birthweight and susceptibility to renal disease. Kidney Int 56 : 1072 –1077, 1999
    OpenUrlCrossRefPubMed
  86. ↵
    Zidar N, Avgustin CM, Kenda RB, Ferluge D: Unfavorable course of minimal change nephrotic syndrome with intrauterine growth retardation. Kidney Int 54 : 1320 –1323, 1998
    OpenUrlCrossRefPubMed
  87. ↵
    Na YW, Yang HJ, Choi JH, Yoo KH, Hong YS, Lee JW, Kim SK: Effect of intrauterine growth retardation on the progression of the nephrotic syndrome. Am J Nephrol 22 : 463 –467, 2002
    OpenUrlCrossRefPubMed
  88. ↵
    Zidar N, Cavic MA, Kenda RB, Koselj M, Ferluga D: Effect of intrauterine growth retardation on the clinical course and prognosis of IgA glomerulonephritis in children. Nephron 79 : 28 –32, 1998
    OpenUrlCrossRefPubMed
  89. ↵
    White SL, Cass A, Atkins RC, Chadban SJ: Chronic kidney disease in the general population. Adv Chronic Kidney Dis 12 : 5 –13, 2005
    OpenUrlCrossRefPubMed
  90. ↵
    Li SQ, Cunningham J, Cass A: Renal-related deaths in Australia 1997–1999. Intern Med J 34 : 259 –265, 2004
    OpenUrlCrossRefPubMed
  91. ↵
    Lackland DT, Bendall HE, Osmond C, Egan BM, Barker DJ: Low birthweights contribute to high rates of early-onset chronic renal failure in the Southeastern United States. Arch Intern Med 160 : 1472 –1476, 2000
    OpenUrlCrossRefPubMed
  92. ↵
    Caldwell JC: Health transition: The cultural, social and behavioural determinants of health in the Third World. Soc Sci Med 36 : 125 –135, 1993
  93. ↵
    Boutayeb A, Boutayeb S: The burden of noncommunicable disease in developing countries. Int J Equity Health 4 : 2 , 2005
    OpenUrlCrossRefPubMed
  94. ↵
    Brenner BM: Remission of renal disease: Recounting the challenge, acquiring the goal. J Clin Invest 110 : 1753 –1758, 2002
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

Journal of the American Society of Nephrology: 16 (9)
Journal of the American Society of Nephrology
Vol. 16, Issue 9
1 Sep 2005
  • Table of Contents
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in JASN.
Enter multiple addresses on separate lines or separate them with commas.
Nephron Number, Hypertension, Renal Disease, and Renal Failure
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Nephron Number, Hypertension, Renal Disease, and Renal Failure
Wendy E. Hoy, Michael D. Hughson, John F. Bertram, Rebecca Douglas-Denton, Kerstin Amann
JASN Sep 2005, 16 (9) 2557-2564; DOI: 10.1681/ASN.2005020172

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Nephron Number, Hypertension, Renal Disease, and Renal Failure
Wendy E. Hoy, Michael D. Hughson, John F. Bertram, Rebecca Douglas-Denton, Kerstin Amann
JASN Sep 2005, 16 (9) 2557-2564; DOI: 10.1681/ASN.2005020172
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Assessment of Nephron Number in Humans
    • Causes of Low Nephron Number
    • BP and Nephron Number
    • Low Nephron Number, Renal Disease, and Renal Failure
    • Conclusions and Clinical Implications
    • Footnotes
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

  • Prenatal Programming of Hypertension: Lessons from Experimental Models
  • Developmental Antecedents of Cardiovascular Disease: A Historical Perspective
Show more Frontiers in Nephrology: Perinatal Antecedents of Adult Disease

Cited By...

  • Bioenergetic Evolution Explains Prevalence of Low Nephron Number at Birth: Risk Factor for CKD
  • Relationship between birth weight and chronic kidney disease: an integrative analysis of observational studies and causal inference through genetic approaches
  • Conserved and Divergent Features of Human and Mouse Kidney Organogenesis
  • Troy/TNFRSF19 marks epithelial progenitor cells during mouse kidney development that continue to contribute to turnover in adult kidney
  • Donor Quality in the Eye of the Beholder: Interactions between Nonimmunologic Recipient and Donor Factors as Determinants of Graft Survival
  • Maternal Smoking during Pregnancy, Household Smoking after the Childs Birth, and Childhood Proteinuria at Age 3 Years
  • The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging
  • Carbamylated Erythropoietin Outperforms Erythropoietin in the Treatment of AKI-on-CKD and Other AKI Models
  • Short-Term Gestation, Long-Term Risk: Prematurity and Chronic Kidney Disease
  • Normal Protein Intake Is Required for Body Weight Loss and Weight Maintenance, and Elevated Protein Intake for Additional Preservation of Resting Energy Expenditure and Fat Free Mass
  • Explaining Socioeconomic Inequalities in Childhood Blood Pressure and Prehypertension: The ABCD Study
  • Developmental Origins of Adult Disease: Part 2: Renal Disease
  • Lack of activation of renal functional reserve predicts the risk of significant renal involvement in systemic sclerosis
  • The GUDMAP database - an online resource for genitourinary research
  • Accelerated Maturation and Abnormal Morphology in the Preterm Neonatal Kidney
  • Serum Creatinine Levels Are Significantly Influenced by Renal Size in the Normal Pediatric Population
  • The Clinical Importance of Nephron Mass
  • GUDMAP: The Genitourinary Developmental Molecular Anatomy Project
  • Low Birth Weight Increases Risk for End-Stage Renal Disease
  • Maternal Nutrition, Low Nephron Number, and Hypertension in Later Life: Pathways of Nutritional Programming
  • Adult Hypertension in Intrauterine Growth-Restricted Offspring of Hyperinsulinemic Rats: Evidence of Subtle Renal Damage
  • Adult Hypertension and Kidney Disease: The Role of Fetal Programming
  • Renal Endowment: Developmental Origins of Adult Disease
  • Google Scholar

Similar Articles

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Annual Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Author Resources
  • Editorial Fellowship Program
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • JASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About JASN
  • JASN Email Alerts
  • JASN Key Impact Information
  • JASN Podcasts
  • JASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe

© 2021 American Society of Nephrology

Print ISSN - 1046-6673 Online ISSN - 1533-3450

Powered by HighWire