Biophysical Basis of Glomerular Filtration

Thomson, Scott C.; Blantz, Roland C.

doi:10.1016/b978-0-12-381462-3.00021-5

Cited by 5 publications

(5 citation statements)

References 145 publications

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“…Re‐arranging these equations gives the well‐known (Deen et al, 1972; Öberg et al, 2017; Thomson et al, 2007) non‐linear ordinary differential equation.

\frac{d C_{pr}}{d y} = \frac{C_{pr}^{2}}{C_{pr} (0) Q (0)} J_{normalv} (y) .

…”

Section: Methodsmentioning

confidence: 99%

“…Above, J v ( y ) is the local filtration flux (Thomson et al, 2007) which is equal to the local Starling pressure (difference between hydraulic and oncotic pressure gradients, P drop [ y ] is drop in hydraulic pressure across the length of the glomerular capillary) multiplied by the ultrafiltration coefficient (L p A).

J_{normalv} (y) = {normalL}_{normalp} A ((P_{GC} ‐ P_{BS} ‐ P_{drop} (y)) ‐ ({normalΠ}_{GC} (y) ‐ {normalΠ}_{BS})) .

…”

Section: Methodsmentioning

confidence: 99%

“…We simulated these changes by (1) lowering the filtration coefficient (LpA) and solute diffusion capacity (half for twice the thickness and so on), (2) increasing the glomerular hydraulic pressure gradient to achieve, and (3) a single nephron GFR (SNGFR) of 90 nL/min. If the glomerular filtration coefficient, hydraulic pressure gradient, SNGFR, and (afferent) oncotic pressure are known, then the single nephron plasma flow profile Q(y) and the plasma protein concentration C pr (y) as functions of the relative position y (position/total length) along the glomerular capillary, can be determined by use of the conservation of mass equations Re-arranging these equations gives the well-known (Deen et al, 1972;Öberg et al, 2017;Thomson et al, 2007) nonlinear ordinary differential equation.…”

Section: Laboratory Measurements For Renal Functionmentioning

confidence: 99%

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Potential relationship between eGFR _{cystatin C} /eGFR _creatinine ‐ratio and glomerular basement membrane thickness in diabetic kidney disease

Öberg

Lindström

Grubb

et al. 2021

Physiological Reports

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Diabetic kidney disease (DKD) is a leading cause of end‐stage renal disease and renal replacement therapy worldwide. A pathophysiological hallmark of DKD is glomerular basal membrane (GBM) thickening, whereas this feature is absent in minimal change disease (MCD). According to fundamental transport physiological principles, a thicker GBM will impede the diffusion of middle‐molecules such as cystatin C, potentially leading to a lower estimated GFR (eGFR) from cystatin C compared to that of creatinine. Here we test the hypothesis that thickening of the glomerular filter leads to an increased diffusion length, and lower clearance, of cystatin C. Twenty‐nine patients with a kidney biopsy diagnosis of either DKD ( n = 17) or MCD ( n = 12) were retrospectively included in the study. GBM thickness was measured at 20 separate locations in the biopsy specimen and plasma levels of cystatin C and creatinine were retrieved from health records. A modified two‐pore model was used to simulate the effects of a thicker GBM on glomerular water and solute transport. The mean age of the patients was 52 years, and 38% were women. The mean eGFR cystatin C /eGFR creatinine ‐ratio was 74% in DKD compared to 98% in MCD ( p < 0.001). Average GBM thickness was strongly inversely correlated to the eGFR cystatin C /eGFR creatinine ‐ratio (Pearson's r = −0.61, p < 0.01). Two‐pore modeling predicted a eGFR cystatin C /eGFR creatinine ‐ratio of 78% in DKD. We provide clinical and theoretical evidence suggesting that thickening of the glomerular filter, increasing the diffusion length of cystatin C, lowers the eGFR cystatin C /eGFR creatinine ‐ratio in DKD.

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“…Re‐arranging these equations gives the well‐known (Deen et al, 1972; Öberg et al, 2017; Thomson et al, 2007) non‐linear ordinary differential equation.

\frac{d C_{pr}}{d y} = \frac{C_{pr}^{2}}{C_{pr} (0) Q (0)} J_{normalv} (y) .

…”

Section: Methodsmentioning

confidence: 99%

J_{normalv} (y) = {normalL}_{normalp} A ((P_{GC} ‐ P_{BS} ‐ P_{drop} (y)) ‐ ({normalΠ}_{GC} (y) ‐ {normalΠ}_{BS})) .

…”

Section: Methodsmentioning

confidence: 99%

Section: Laboratory Measurements For Renal Functionmentioning

confidence: 99%

See 1 more Smart Citation

Potential relationship between eGFR _{cystatin C} /eGFR _creatinine ‐ratio and glomerular basement membrane thickness in diabetic kidney disease

Öberg

Lindström

Grubb

et al. 2021

Physiological Reports

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show abstract

“…26. A value for L p S of 0.44 ml·min Ϫ1 · mmHg Ϫ1 ·g Ϫ1 corresponds to a mean pressure gradient of only ϳ1.5 mmHg, which is very low compared with measured values (37). Figure 1 shows versus a e for the experimental data (dashed line) and the best fit for the regression of the distributed two-pore model (solid line).…”

Section: Resultsmentioning

confidence: 93%

A distributed two-pore model: theoretical implications and practical application to the glomerular sieving of Ficoll

Öberg

Rippe

2014

American Journal of Physiology-Renal Physiology

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In the present study, an extended two-pore theory is presented where the porous pathways are continuously distributed according to small- and large-pore mean radii and SDs. Experimental glomerular sieving data for Ficoll were analyzed using the model. In addition, several theoretical findings are presented along with analytic solutions to many of the equations used in distributed pore modeling. The results of the data analysis revealed a small-pore population in the glomerular capillary wall with a mean radius of 36.6 Å having a wide arithmetic SD of ∼5 Å and a large-pore radius of 98.6 Å with an even wider SD of ∼44 Å. The small-pore radius obtained in the analysis was close to that of human serum albumin (35.5 Å). By reanalyzing the data and setting the distribution spread of the model constant, we discovered that a narrow distribution is compensated by an increased mean pore radius and a decreased pore area-to-diffusion length ratio. The wide distribution of pore sizes obtained in the present analysis, even when considering electrostatic hindrance due to the negatively charged barrier, is inconsistent with the high selectivity to proteins typically characterizing the glomerular filtration barrier. We therefore hypothesize that a large portion of the variance in the distribution of pore sizes obtained is due to the molecular "flexibility" of Ficoll, implying that the true variance of the pore system is lower than that obtained using flexible probes. This would also, in part, explain the commonly noted discrepancy between the pore area-to-diffusion length ratio and the filtration coefficient.

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“…In the absence of charge, filtration (solvent flow) can be described as the sum of hydraulic flow and osmotic flow. Furthermore, solute flux is classically the sum of diffusion and convection and their mutual interactions, which can be described by the global non-linear flux equation (Patlak equation) (18)(19)(20). However, across charged membranes, the transport of charged solutes, such as albumin, is much more complicated due to the development of a variety of electrokinetic phenomena.…”

Section: Electrokinetic Effects Affecting Solute Transport Across Charged Membranesmentioning

confidence: 99%

Counterpoint: Defending Pore Theory

Rippe

Öberg

2015

Perit Dial Int

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Biophysical Basis of Glomerular Filtration

Cited by 5 publications

References 145 publications

Potential relationship between eGFR _{cystatin C} /eGFR _creatinine ‐ratio and glomerular basement membrane thickness in diabetic kidney disease

Potential relationship between eGFR _{cystatin C} /eGFR _creatinine ‐ratio and glomerular basement membrane thickness in diabetic kidney disease

A distributed two-pore model: theoretical implications and practical application to the glomerular sieving of Ficoll

Counterpoint: Defending Pore Theory

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Biophysical Basis of Glomerular Filtration

Cited by 5 publications

References 145 publications

Potential relationship between eGFR cystatin C /eGFR creatinine ‐ratio and glomerular basement membrane thickness in diabetic kidney disease

Potential relationship between eGFR cystatin C /eGFR creatinine ‐ratio and glomerular basement membrane thickness in diabetic kidney disease

A distributed two-pore model: theoretical implications and practical application to the glomerular sieving of Ficoll

Counterpoint: Defending Pore Theory

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Product

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Potential relationship between eGFR _{cystatin C} /eGFR _creatinine ‐ratio and glomerular basement membrane thickness in diabetic kidney disease

Potential relationship between eGFR _{cystatin C} /eGFR _creatinine ‐ratio and glomerular basement membrane thickness in diabetic kidney disease