New insights on glomerular hyperfiltration: a Japanese autopsy study

Kanzaki, Go; Puelles, Victor G.; Cullen‐McEwen, Luise A.; Hoy, Wendy E.; Okabayashi, Yusuke; Tsuboi, Nobuyuki; Shimizu, Akira; Denton, Kate M.; Hughson, Michael D.; Yokoo, Takashi; Bertram, John F.

doi:10.1172/jci.insight.94334

Cited by 61 publications

(64 citation statements)

References 54 publications

(54 reference statements)

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“…Glomerular number correlates with kidney function. 31,32 A recent study using a combination of optical clearing and light sheet microscopy in whole kidneys reported a 32% reduction in total glomerular numbers within the first 2 weeks of crescentic nephritis. 5 Our current study suggests that glomerular loss stems from the formation of atubular glomeruli.…”

Section: Discussionmentioning

confidence: 99%

Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis

Puelles

Fleck

Ortz

et al. 2019

Kidney International

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Recent developments in optical tissue clearing have been difficult to apply for the morphometric analysis of organs with high cellular content and small functional structures, such as the kidney. Here, we establish combinations of genetic and immuno-labelling for single cell identification, tissue clearing and subsequent de-clarification for histoimmunopathology and transmission electron microscopy. Using advanced light microscopy and computational analyses, we investigated a murine model of crescentic nephritis, an inflammatory kidney disease typified by immune-mediated damage to glomeruli leading to the formation of hypercellular lesions and the rapid loss of kidney function induced by nephrotoxic serum. Results show a graded susceptibility of the glomeruli, significant podocyte loss and capillary injury. These effects are associated with activation of parietal epithelial cells and formation of glomerular lesions that may evolve and obstruct the kidney tubule, thereby explaining the loss of kidney function. Thus, our work provides new highthroughput endpoints for the analysis of complex tissues with single-cell resolution.

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Section: Discussionmentioning

confidence: 99%

Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis

Puelles

Fleck

Ortz

et al. 2019

Kidney International

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“…Nephron numbers were not extremely low compared to other populations, and birth weights were not available in this study, therefore the contribution of altered developmental programming to the observations can only be inferred. Subsequently, nephron numbers have also been found to be lower in subjects with higher blood pressures in African American, white American, Aboriginal Australian, and Japanese male cohorts, although the relationship among those of African origin may not be as linear as observed in other populations (Hoy et al, 2006;Hughson et al, 2006;Hoy et al, 2008;Kanzaki et al, 2015;Kanzaki et al, 2017). Consistent with the hypothesis that a kidney with fewer nephrons would have a reduced filtration surface area for excretion of sodium, a birth weight below 3 kg has been found to correlate with salt-sensitivity and reduced kidney size (de Boer et al, 2008;Simonetti et al, 2008;Perala et al, 2011).…”

Section: Nephron Number Blood Pressure and Kidney Function In Humansmentioning

confidence: 98%

“…Chronological examples of landmark studies that have broadened the understanding of developmental programming in the kidney and its potential consequences. Compiled from Zeman (1968), Forsdahl (1977), Barker and Osmond (1986), Brenner et al (1988), Hinchliffe et al (1991), Hinchliffe et al (1992), , Nelson et al (1998b), Amri et al (1999), Manalich et al (2000), Vehaskari et al (2001), Hughson et al (2003), Keller et al (2003), Langley-Evans et al (2003), Rodriguez et al (2004), Wlodek et al (2007) Kanzaki et al (2017). AKI, acute kidney injury; IgAN, immunoglobulin A nephropathy; LBW, low birth weight; LPD, low protein diet; NNx, nephron number; PSGN, post-streptococcal glomerulonephritis; SGA, small birth weight for gestational age; V glom , glomerular volume; !, predisposes to.…”

Section: Human Evidence For Programming Of Nephron Numbermentioning

confidence: 99%

Clinical consequences of developmental programming of low nephron number

Luyckx

Brenner

2019

The Anatomical Record

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Nephron number in humans varies up to 13‐fold, likely reflecting the impact of multiple factors on kidney development, including inherited body size and ethnicity, as well as maternal health and nutrition, fetal exposure to gestational diabetes or preeclampsia and other environmental factors, which may potentially be modifiable. Such conditions predispose to low or high offspring birth weight, growth restriction or preterm birth, which have all been associated with increased risks of higher blood pressures and/or kidney dysfunction in later life. Low birth weight, preterm birth, and intrauterine growth restriction are associated with reduced nephron numbers. Humans with hypertension and chronic kidney disease tend to have fewer nephrons than their counterparts with normal blood pressures or kidney function. A developmentally programmed reduction in nephron number therefore enhances an individual's susceptibility to hypertension and kidney disease in later life. A low nephron number at birth may not lead to kidney dysfunction alone except when severe, but in the face of superimposed acute or chronic kidney injury, a kidney endowed with fewer nephrons may be less able to adapt, and overt kidney disease may develop. Given that millions of babies are born either too small, too big or too soon each year, the population impact of altered renal programming is likely to be significant. Many gestational exposures are modifiable, therefore urgent attention is required to implement public health measures to optimize maternal, fetal, and child health, to prevent or mitigate the consequences of developmental programming, to improve the health future generations.

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“…Hughson, Farris III, Douglas‐Denton, Hoy, & Bertram, 2003; Hughson et al 2006; McNamara et al, 2008; Bertram, Douglas‐Denton, Diouf, Hughson, & Hoy, 2011; Luyckx et al, 2013; Kanzaki et al, 2017). These findings have far‐reaching clinical implications, based on Barry Brenner's early research linking people with kidneys at the lower end of the nephron number distribution with vulnerability to the development of hypertension and renal disease (Brenner & Anderson, 1992; Brenner, Garcia, & Anderson, 1988); Barry Brenner along with his long‐term colleague Valerie Luyckx are authors in this Special Issue (Luyckx & Brenner, 2020).…”

Section: Figurementioning

confidence: 99%

Filtering the good from the bad: A focus on kidney development and disease to celebrate John Bertram's long‐standing career in anatomy and renal research

Black

2020

The Anatomical Record

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New insights on glomerular hyperfiltration: a Japanese autopsy study

Cited by 61 publications

References 54 publications

Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis

Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis

Clinical consequences of developmental programming of low nephron number

Filtering the good from the bad: A focus on kidney development and disease to celebrate John Bertram's long‐standing career in anatomy and renal research

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