Podocyte Number in Children and Adults: Associations with Glomerular Size and Numbers of Other Glomerular Resident Cells.

Increases in glomerular size occur with normal body growth and in many pathologic conditions. In this study, we determined associations between glomerular size and numbers of glomerular resident cells, with a particular focus on podocytes. Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4 children (≤3 years old) to define baseline values of early life and 12 adults (≥18 years old), were collected at autopsy in Jackson, Mississippi.

Glomerular hypertrophy in subjects with low nephron number: contributions of sex, body size and race.

Background: We have shown that low nephron number (Nglom) is a strong determinant of individual glomerular volume (IGV) in male Americans. However, whether the same pattern is present in female Americans remains unclear. The contributions of body surface area (BSA) and race to IGV in the context of Nglom also require further evaluation.

Hypertension, glomerular hypertrophy and nephrosclerosis: the effect of race.

Background: African Americans have more severe hypertensive nephrosclerosis than white Americans, possibly at similar levels of blood pressure. Glomerular volume is increased in African Americans relative to whites, but it is uncertain how this relates to nephrosclerosis and whether it contributes to or compensates for glomerulosclerosis.

Methods: Stereological disector/fractionator estimates of glomerular number (N(glom)) and average glomerular volume (V(glom)) were obtained on autopsy kidneys of 171 African Americans and 131 whites.

Design-based stereological methods for estimating numbers of glomerular podocytes.

The podocyte depletion hypothesis has emerged as a unifying concept in glomerular pathology. According to this hypothesis podocyte depletion may be absolute (decrease in number of healthy mature podocytes), relative (fewer podocytes per unit of glomerular volume) or involve alterations to the specialized podocyte architecture (such as foot process effacement). To study and understand podocyte depletion it is important to be able to accurately and precisely count these cells.

Renal biopsy findings among Indigenous Australians: a nationwide review.

Australia's Indigenous people have high rates of chronic kidney disease and kidney failure. To define renal disease among these people, we reviewed 643 renal biopsies on Indigenous people across Australia, and compared them with 249 biopsies of non-Indigenous patients. The intent was to reach a consensus on pathological findings and terminology, quantify glomerular size, and establish and compare regional biopsy profiles.

Estimating total nephron number in the adult kidney using the physical disector/fractionator combination.

Nephron number has emerged as a useful parameter for assessing the roles of specific genes and feto-maternal environmental factors in kidney development. Nephron number is also of clinical interest due to increasing evidence suggesting that low nephron number is associated with increased risk for developing chronic adult disease, including cardiovascular and renal disease. The physical disector/fractionator combination is considered the gold standard method for estimating total nephron number in kidneys.

Estimating individual glomerular volume in the human kidney: clinical perspectives.

Background: Measurement of individual glomerular volumes (IGV) has allowed the identification of drivers of glomerular hypertrophy in subjects without overt renal pathology. This study aims to highlight the relevance of IGV measurements with possible clinical implications and determine how many profiles must be measured in order to achieve stable size distribution estimates.

Methods: We re-analysed 2250 IGV estimates obtained using the disector/Cavalieri method in 41 African and 34 Caucasian Americans.

Distribution of volumes of individual glomeruli in kidneys at autopsy: association with physical and clinical characteristics and with ethnic group.

We have demonstrated considerable variability in the volumes of different glomeruli in given individuals (individual 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.

Human nephron number: implications for health and disease.

Several studies have shown that total nephron (glomerular) number varies widely in normal human kidneys. Whereas the studies agree that average nephron number is approximately 900,000 to 1 million per kidney, numbers for individual kidneys range from approximately 200,000 to >2.5 million.

Towards a definition of glomerulomegaly: clinical-pathological and methodological considerations.

Background: Glomerulomegaly, the abnormal enlargement of glomeruli, has been related to an increased risk of glomerulosclerosis, but the degree of enlargement that constitutes glomerulomegaly has not been defined.

Methods: The principal stereological methods for estimating glomerular volume are [1] the disector/Cavalieri method that is considered the 'gold standard' for measuring individual glomerular volume (IV(glom)) and [2] the disector/fractionator technique that estimates average glomerular volume (V(glom)) together with total glomerular number (N(glom)) for the entire kidney. The two methods produce different estimates with V(glom) consistently exceeding IV(glom).

Glomerular number and size variability and risk for kidney disease.

Purpose Of Review: This review discusses current understandings of variability in glomerular number and size, and the implications for renal health.

Recent Findings: The quantitative microanatomy of the normal human kidney varies widely. Of greatest significance, total nephron number varies at least 13-fold, and several genes and environmental factors that regulate human nephron endowment have been identified.

CKD in Aboriginal Australians.

Chronic kidney disease (CKD) is one component of a spectrum of chronic disease in Aboriginal Australians. CKD is marked by albuminuria, which predicts renal failure and nonrenal natural death. Rates vary greatly by community and region and are much higher in remote areas.

A comparison of nephron number, glomerular volume and kidney weight in Senegalese Africans and African Americans.

Background: Low nephron number is determined in utero and is a proposed risk for essential hypertension. Glomerular volume is inversely correlated with nephron number, and genetic and environmental factors that determine nephron number are thought to determine glomerular volume. This study compared total glomerular (nephron) number (N(glom)), mean glomerular volume (V(glom)) and kidney weight in two geographically separated black populations with significant common genetic ancestry.

Nephron number and individual glomerular volumes in male Caucasian and African American subjects.

Background: Glomerular hypertrophy has been described in several populations at high risk of chronic kidney disease. Total nephron (and thereby glomerular) number (N(glom)) varies widely in normal adult human kidneys and is generally inversely correlated with mean glomerular volume (V(glom)). However, little is known about the range of individual glomerular volumes (IV(glom)) within single human kidneys and the association with N(glom).

Indomethacin, ibuprofen and gentamicin administered during late stages of glomerulogenesis do not reduce glomerular number at 14 days of age in the neonatal rat.

Premature neonates are frequently administered indomethacin, ibuprofen and gentamicin during the period of active glomerulogenesis. These drugs are known to have nephrotoxic effects, but the morphological effect of these drugs is unknown. The purpose of this study was to determine whether administration of these drugs during the late stages of glomerulogenesis in the rat has an effect on glomerular endowment.

Associations of glomerular number and birth weight with clinicopathological features of African Americans and whites.

Background: Hypertension and its cardiovascular complications affect African Americans more severely than whites, a disparity variously ascribed to low birth weight, low glomerular number, an exaggerated arteriolonephrosclerotic blood pressure response, and inflammation-induced oxidative stress.

Study Design: Case series.

Setting And Participants: Autopsy kidneys of 107 African Americans and 87 whites aged 18 to 65 years at a single medical center between 1998 and 2005.

Nephron number, glomerular volume, renal disease and hypertension.

Purpose Of Review: To discuss studies evaluating associations of glomerular number (Nglom) and glomerular volume with hypertension and kidney disease.

Important Findings: The association of low Nglom with hypertension and renal insufficiency was described in the 1930s. Many investigators have noted loss of glomeruli with age, with most disappearing entirely, and have proposed that hypertension follows.

Renal pathology, glomerular number and volume in a West African urban community.

Background: Low glomerular number and large glomerular volume are hypothesized to be risk factors for hypertensive renal disease in adult life. Reports of human glomerular number are based on studies from developed nations and have found single kidney mean values of approximately 900 000 per kidney with a roughly 8-fold range matched by a similar range in glomerular volume. Glomerular number and volume have never been investigated in people from a developing country.

Applicability of the glomerular size distribution coefficient in assessing human glomerular volume: the Weibel and Gomez method revisited.

Changes in glomerular volume (V(glom)) play an important role in the initiation and progression of various glomerulopathies. Estimation of V(glom) in the normal kidney provides baseline values for studies of glomerular hypertrophy in disease. The traditional model-based method of Weibel and Gomez is widely applied to estimate V(glom) in clinical biopsy specimens.

Long-term effects of a midgestational asphyxial episode in the ovine fetus.

We and others have shown previously that fetuses at midgestation can survive 30 min of complete umbilical cord occlusion, although hydrops fetalis (or gross fetal edema) results. To investigate whether this hydrops resolves by late gestation and if there are any long-term consequences of the asphyxial insult on the heart and kidneys, eight fetuses were subjected to 30 min of complete umbilical cord occlusion at 0.6 gestation (90 days; term 150 days) and were compared to a sham group (n = 10).

Does nephron number matter in the development of kidney disease?

The total number of nephrons in normal human kidneys varies over a 10-fold range. This variation in total nephron number leads us to question whether low nephron number increases the risk of renal disease in adulthood. This review considers the available evidence in humans linking low nephron number/reduced nephron endowment and the susceptibility to renal disease.

Determinants of glomerular volume in different cortical zones of the human kidney.

Enlarged glomerular size is a feature of focal segmental glomerulosclerosis, obesity-related glomerulopathy, diabetic nephropathy, and hypertension. The distribution of glomerular volumes within different cortical zones and glomerular volume alterations with age and obesity may contribute to understanding the evolution of these diseases. We analyzed the distributions of volumes of individual glomeruli in the superficial, middle, and juxtamedullary cortex of normal human kidneys using the disector/Cavalieri method.

A stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy.

Background: This report describes preliminary results of a study of glomerular number and volume and their associations, in kidneys of people coming to autopsy.

Methods: Both kidneys were weighed at autopsy and the right kidney was perfusion-fixed and sub-sampled for stereological estimation of total glomerular number, and of mean renal corpuscle volume, using the physical disector/fractionator combination.

Results: The 78 kidneys studied so far were from Australian Aborigines, Australian non-Aborigines, US blacks and US whites, ages newborn to 84 years.

Glomerular number and size in autopsy kidneys: the relationship to birth weight.

Background: In the Southeast United States, African Americans have an estimated incidence of hypertension and end-stage renal disease (ESRD) that is five times greater than Caucasians. Higher rates of low birth weight (LBW) among African Americans is suggested to predispose African Americans to the higher risk, possibly by reducing the number of glomeruli that develop in the kidney. This study investigates the relationships between age, race, gender, total glomerular number (Nglom), mean glomerular volume (Vglom), body surface area (BSA), and birth weight.