Association of Increasing GFR with Change in Albuminuria in the General Population

Melsom, Toralf; Stefansson, Vidar Tor Nyborg; Schei, Jørgen; Solbu, Marit Dahl; Jenssen, Trond; Wilsgaard, Tom; Eriksen, Bjørn Odvar

doi:10.2215/cjn.04940516

Cited by 40 publications

(31 citation statements)

References 51 publications

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“…In line with previous findings on the possible biologic link between albuminuria and cardiovascular events, it is likely that an increase in UACR is a manifestation of worsened generalized vascular dysfunction, particularly endothelial dysfunction, as proposed in the Steno hypothesis (36). Increasing UACR might also reflect increased single-nephron hyperfiltration accompanied by the decrease in the number of functional nephrons (i.e., compensatory hyperfiltration of the remaining nephrons) as well as glycocalyx dysfunction in the glomerular endothelium, both of which are risk factors for subsequent glomerulosclerosis (37)(38)(39). Recent evidence also suggests that increased glomerular albumin leakage increases the exposure and uptake of excessive albumin in proximal tubular cells, which in turn, trigger the activation of intracellular signaling pathways that induces the release of inflammatory, vasoactive, and fibrotic substances (40)(41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

Changes in Albuminuria and Subsequent Risk of Incident Kidney Disease

Sumida

Molnar

Potukuchi³

et al. 2017

CJASN

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Section: Discussionmentioning

confidence: 99%

Changes in Albuminuria and Subsequent Risk of Incident Kidney Disease

Sumida

Molnar

Potukuchi³

et al. 2017

CJASN

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“…2, right panel). In addition, hyperfiltration and albuminuria are also seen with greater frequency in individuals with prediabetes than in those with normal glucose tolerance (54,55) and are linked prospectively even in the general population (56). It therefore seems likely that, as in retinopathy, the process that leads to diabetic nephropathy starts before the onset of diabetes, at least in T2D.…”

Section: Diabetic Nephropathymentioning

confidence: 99%

Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences

2018

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Microvascular and metabolic physiology are tightly linked. This Perspective reviews evidence that ) the relationship between hyperglycemia and microvascular dysfunction (MVD) is bidirectional and constitutes a vicious cycle;) MVD in diabetes affects many, if not all, organs, which may play a role in diabetes-associated comorbidities such as depression and cognitive impairment; and ) MVD precedes, and contributes to, hyperglycemia in type 2 diabetes (T2D) through impairment of insulin-mediated glucose disposal and, possibly, insulin secretion. Obesity and adverse early-life exposures are important drivers of MVD. MVD can be improved through weight loss (in obesity) and through exercise. Pharmacological interventions to improve MVD are an active area of investigation.

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“…8–11 An increase in the single-nephron GFR is often inferred from an increase in the total GFR (since new nephrons are not generated). 12 However, to our knowledge, the determination of the actual single-nephron GFR in humans has not been possible.…”

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confidence: 99%

Single-Nephron Glomerular Filtration Rate in Healthy Adults

et al. 2017

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BACKGROUND The glomerular filtration rate (GFR) assesses the function of all nephrons, and the single-nephron GFR assesses the function of individual nephrons. How the single-nephron GFR relates to demographic and clinical characteristics and kidney-biopsy findings in humans is unknown. METHODS We identified 1388 living kidney donors at the Mayo Clinic and the Cleveland Clinic who underwent a computed tomographic (CT) scan of the kidney with the use of contrast material and an iothalamate-based measurement of the GFR during donor evaluation and who underwent a kidney biopsy at donation. The mean single-nephron GFR was calculated as the GFR divided by the number of nephrons (calculated as the cortical volume of both kidneys as assessed on CT times the biopsy-determined glomerular density). Demographic and clinical characteristics and biopsy findings were correlated with the single-nephron GFR. RESULTS A total of 58% of the donors were women, and the mean (±SD) age of the donors was 44±12 years. The mean GFR was 115±24 ml per minute, the mean number of nephrons was 860,000±370,000 per kidney, and the mean single-nephron GFR was 80±40 nl per minute. The single-nephron GFR did not vary significantly according to age (among donors <70 years of age), sex, or height (among donors ≤190 cm tall). A higher single-nephron GFR was independently associated with larger nephrons on biopsy and more glomerulosclerosis and arteriosclerosis than would be expected for age. A higher single-nephron GFR was associated with a height of more than 190 cm, obesity, and a family history of end-stage renal disease. CONCLUSIONS Among healthy adult kidney donors, the single-nephron GFR was fairly constant with regard to age, sex, and height (if ≤190 cm). A higher single-nephron GFR was associated with certain risk factors for chronic kidney disease and certain kidney-biopsy findings. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)

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Association of Increasing GFR with Change in Albuminuria in the General Population

Abstract: Increasing GFR is associated with an increase in albumin-to-creatinine ratio and incident albuminuria in the general nondiabetic population. These findings support single-nephron hyperfiltration as a risk factor for albuminuria in the general population.

Cited by 40 publications

References 51 publications

Changes in Albuminuria and Subsequent Risk of Incident Kidney Disease

Changes in Albuminuria and Subsequent Risk of Incident Kidney Disease

Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences

Single-Nephron Glomerular Filtration Rate in Healthy Adults

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