Reduction in Mean Glomerular Pore Size Coincides with the Development of Large Shunt Pores in Patients with Diabetic Nephropathy

Oberbauer, Rainer; Nenov, Vesselin D.; Weidekamm, Claudia; Haas, Martin; Szekeres, Thomas; Mayer, Gert

doi:10.1159/000020698

Cited by 26 publications

(21 citation statements)

References 13 publications

(15 reference statements)

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“…This is in contrast to the numerous nonrenal factors that influence the generation of creatinine, its tubular secretion, and backleak, which may result in inaccurate reflection of GFR by creatinine [12]. Another potential explanation emerges from recent observations that cystatin C and creatinine differ in regard to their glomerular filtration characteristics during pregnancy and diabetic nephropathy [47,48]. It remains speculative whether this phenomenon occurs also in ARF, but alterations in glomerular pore size could cause differences in the glomerular filtration of cystatin C and creatinine during ARF.…”

Section: Discussionmentioning

confidence: 99%

Early detection of acute renal failure by serum cystatin C

Herget–Rosenthal

Marggraf

Hüsing

et al. 2004

Kidney International

763

473

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Section: Discussionmentioning

confidence: 99%

Early detection of acute renal failure by serum cystatin C

Herget–Rosenthal

Marggraf

Hüsing

et al. 2004

Kidney International

763

473

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“…glomerular ltration slit size, despite a normal endothelium, with its negative surface charge probably plays a role in determining the access GFR determined as the clearance of iothalamate, a 613-Da low molecular mass marker [31 ].…”

Section: Discussionmentioning

confidence: 99%

Serum cystatin C for assessment of glomerular filtration rate in pregnant and non-pregnant women. Indications of altered filtration process in pregnancy

Strevens

Wide‐Swensson

Torffvit

et al. 2002

Scandinavian Journal of Clinical and Laboratory Investigation

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Serum cystatin C is believed to reflect the glomerular filtration rate (GFR) more closely than serum creatinine in many contexts and a reference interval for serum cystatin C in term pregnancy has been defined to enable its use also in pregnant women. However, serum cystatin C levels were not found to be decreased in term pregnancy, though GFR of low molecular mass substances is known to increase by at least 40% by the third trimester. The aim of this study was therefore to determine whether serum cystatin C is a reliable GFR marker also in pregnant women. GFR was determined by measurement of plasma clearance of iohexol in 48 previously healthy women in their third trimester and in 12 healthy nonpregnant women, and was compared with their serum levels of cystatin C and creatinine. Both serum cystatin C and creatinine levels were significantly related to GFR for both pregnant and non-pregnant women. However, the correlation between cystatin C and GFR was set at different levels for pregnant and nonpregnant women. Our results indicate a physiological difference between the filtration processes in kidneys of pregnant and non-pregnant women, whether it is size-dependent, configuration-dependent or charge-dependent. Nevertheless, serum cystatin C seems to reflect GFR reliably in both non-pregnant and pregnant, healthy and hypertensive women.

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“…The structural changes occurring during the development of early to late DNP involve thickening of the glomerular and tubular basement membranes and, later, a decreased filtration surface area combined with loss of podocytes, which is furthermore accompanied by a clearly reduced size selectivity of the glomerular filter (15,16,38). To date, the permselective properties of glomerular barrier in diabetic nephropathy have mainly been assessed by using dextran as a probe for glomerular permeability.…”

mentioning

confidence: 99%

Size and charge selectivity of the glomerular filter in early experimental diabetes in rats

Rippe¹,

Rippe²,

Torffvit³

et al. 2007

American Journal of Physiology-Renal Physiology

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Rippe C, Rippe A, Torffvit O, Rippe B. Size and charge selectivity of the glomerular filter in early experimental diabetes in rats. Am J Physiol Renal Physiol 293: F1533-F1538, 2007. First published August 15, 2007; doi:10.1152 doi:10. /ajprenal.00271.2007 is an early sign of diabetic nephropathy. The aim of the present study was to investigate whether the changes of the glomerular filtration barrier in early experimental diabetes are due to size-or charge-selective alterations. Wistar rats, made diabetic by streptozotocin (STZ) and having their blood glucose maintained at ϳ20 mM for 3 or 9 wk, were compared with age-matched controls. Glomerular clearances of native albumin (Cl-HSA) and neutralized albumin (Cl-nHSA) were assessed using a renal uptake technique. Glomerular filtration rate and renal plasma flow were assessed using 51 Cr-EDTA and [125 I]iodohippurate, respectively. In a separate set of animals, diabetic for 9 wk, and in controls, glomerular sieving coefficients () for neutral FITC-Ficoll (molecular radius: 15-90 Å) were assessed using size exclusion chromatography. At 3 wk of diabetes, Cl-HSA and Cl-nHSA remained unchanged, indicating no alteration in either size or charge selectivity. By contrast, at 9 wk of diabetes, there was a twofold increase of Cl-HSA, whereas Cl-nHSA remained largely unchanged, at first suggesting a glomerular charge defect. However, according to a two-pore model, the number of large pores, assessed from both Ficoll and Cl-HSA, increased twofold. In addition, a small reduction in proximal tubular reabsorption was observed at 3 wk, which was further reduced at 9 wk. In conclusion, no functional changes were observed in the glomerular filtration barrier at 3 wk of STZ-induced diabetes, whereas at 9 wk there was a decrease in size selectivity due to an increased number of large glomerular pores. sieving coefficient; proteinuria; capillary permeability; fractional clearance; macromolecules; diabetic nephropathy DIABETIC NEPHROPATHY (DNP) is currently the leading cause of end-stage renal disease in the Western world. In the early course of insulin-dependent diabetes, several functional and structural alterations occur in the kidney. Some of these alterations include glomerular hyperperfusion/hyperfiltration (34), hypertrophy of the nephrons and gross renal enlargement (3,25), and also changes in the glomerular extracellular matrix mass and composition. Microalbuminuria, i.e., moderately increased levels of albumin excretion (20 -200 g/min), is an early sign of DNP, reflecting either alterations in the glomerular barrier to (negatively charged) albumin or a reduction in the protein-reabsorbing properties of the proximal tubules, the latter supported by a recent study (29). According to the "Steno hypothesis," loss of negative charges in the filtration barrier, conceivably due to altered activity of the enzymes involved in the metabolism of extracellular matrix components, may be the cause of the microalbuminuria in early DNP (6). The Steno hypothesis is supported by the preferenti...

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Reduction in Mean Glomerular Pore Size Coincides with the Development of Large Shunt Pores in Patients with Diabetic Nephropathy

Cited by 26 publications

References 13 publications

Early detection of acute renal failure by serum cystatin C

Early detection of acute renal failure by serum cystatin C

Serum cystatin C for assessment of glomerular filtration rate in pregnant and non-pregnant women. Indications of altered filtration process in pregnancy

Size and charge selectivity of the glomerular filter in early experimental diabetes in rats

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