Influence of glomerular filtration rate on the rate of para-aminohippurate secretion by the rat kidney: Micropuncture and clearance studies

Häberle, D. A.; Ober, Angelika; Ruhland, G. J.

doi:10.1038/ki.1975.56

Cited by 28 publications

(11 citation statements)

References 26 publications

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“…It is now recognized that one of the mechanisms serving to control the rate of glomerular filtration operates at the single nephron level and responds to changes in some correlate of the flow rate in the early distal nephron (13)(14)(15)(16)(17). In a general sense, the magnitude of a change in SNGFR, in relation to the magnitude of a change in loop of Henle flow rate, is an 1, suppression of SNGFR by native fluid flowing through the loop of Henle was 4.2 nl/min (50%) less in rats fed a high protein diet, compared with rats fed a low protein diet.…”

Section: Discussionmentioning

confidence: 99%

“…One mechanism capable of effecting changes in the determinants of GFR is the individual-nephron negative-feedback control pathway, the tubuloglomerular (TG) feedback system (13)(14)(15)(16)(17). This system serves to adjust glomerular vascular resistance (17)(18)(19) and Kf (17) in response to variations of some correlate of the early distal tubule flow rate, thereby altering the same determinants of filtration that are altered by protein feeding.…”

Section: Introductionmentioning

confidence: 99%

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Dietary protein suppresses feedback control of glomerular filtration in rats.

Seney¹,

Wright²

1985

J. Clin. Invest.

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We have examined the possibility that changes in glomerular filtration rate (GFR) after changes in dietary protein intake may depend on altered function of the tubuloglomerular (TG) feedback system. We studied male Sprague-Dawley rats after dietary pretreatment for 9.6±3.6 (SD) d with isocaloric diets containing either 6% or 40% casein. We found that GFR in rats fed the high protein diet was 24-29% higher than in rats fed the low protein diet. Simultaneous measurements of single nephron GFR (SNGFR) in the distal tubule were 6.3 nl/min or 21% higher in the rats fed the high protein diet whereas proximally measured SNGFR was not statistically different in the two groups. The higher distally measured SNGFR of rats receiving the high protein diet was associated with a 4.2 nI/ min or 50% smaller suppression of SNGFR by TG feedback (-4.3 vs. -8.5 nl/min, P < 0.001). Loop perfusion experiments demonstrated that in rats fed the high protein diet the TG feedback mechanism was less sensitive than in rats fed the low protein diet. The TG feedback response in rats fed the low protein diet, as assessed by reductions in stop-flow pressure and SNGFR, was half-maximal at flows of 14-15 nl/min. In contrast, the TG feedback response in rats fed the high protein diet was half-maximal at 22-24 nl/min. Maximal suppression of stop-flow pressure and SNGFR and the slope of the TG feedback response to increasing loop flow rates were not different in the two groups. We conclude that the sensing mechanism of the TG feedback system is rendered less responsive by a high protein intake, and that this change permits GFR to increase.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dietary protein suppresses feedback control of glomerular filtration in rats.

Seney¹,

Wright²

1985

J. Clin. Invest.

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“…The maintained net rate of PAH secretion following NTS is of interest in view of the recent report by Haberle [ 17] that net secretion of PAH in the proximal convoluted tubule in the rat changes concurrently with the single nephron GFR and intratubular flow rate. This is in contrast to the classical concept which implies that each proximal tubule cell pos sesses a limited number of PAH-transporting sites and the net rate of secretion occurs when all the sites are occupied.…”

Section: Discussionmentioning

confidence: 99%

Immediate Effect of Nephrotoxic Serum on Kidney Function in the Dog

Wagnild¹

1977

Nephron

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Nephrotoxic antibody rapidly fixes to glomerular basement membrane following systemic injection and immediately initiates histopathologic alterations. We studied the functional changes induced by nephrotoxic serum (NTS) in dogs starting 20 min after injection using three different protocols. By this time the GFR, U_NaV and FE_Na had decreased in each study. Volume expansion resulted in a significantly smaller absolute increase in FE_Na than in the pre-injection control study (1.1 vs. 2.8%, p < 0.005), while maximum tubular secretion of PAH (Tm_PAH) and reabsorption of glucose (Tm glucose) stayed constant following NTS; thus, Tm_PAH/ GFR and Tm glucose/GFR increased significantly. These studies demonstrate that glomerular function is rapidly affected by NTS while absolute tubular function is relatively well maintained. Since histologic and functional changes occurred simultaneously, it seems likely that the functional changes were the direct consequence of the pathologic alterations.

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“…It has been shown that PAH concentration profile along the length of the proximal convolution does not change markedly with variations in GFR. 23 The fraction of PAH that passes the glomerulus and enters tubular cells of the nephron (via peritubular capillaries) is completely secreted. 9 Consequences of renal dysfunction for pharmacotherapy in SCI For proper pharmacotherapy after SCI, early renal dysfunction detection is critical.…”

Section: Reduced Glomerular Filtration Ratementioning

confidence: 99%

Changes in renal function during acute spinal cord injury: implications for pharmacotherapy

et al. 2013

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Study design: Laboratory investigation in rats submitted to experimental spinal cord injury (SCI). Objective: To characterize changes in renal function during acute SCI. Methods: Sprague Dawley rats were subjected to severe spinal cord contusion at T8 level or to laminectomy as control. Twenty-four hours after spine surgery, clearance assessments of a single dose of iohexol (120 mg kg À1 ) or of p-aminohippuric acid (PAH, 100 mg kg À1 ) were used to evaluate glomerular filtration rate (GFR) and tubular secretion (TS), respectively. Blood sampling was used to determine concentrations of both compounds by high-performance liquid chromatography for pharmacokinetic measurements. Results: Iohexol clearance decreased significantly after injury, which resulted in increased concentrations and half-life of iohexol in blood; PAH clearance remained unchanged. Conclusion: GFR but not TS is altered during spinal shock. These observations should be of interest to professionals caring for early cord-injured patients, in order to prevent toxicity and therapeutic failure when administering drugs eliminated by the kidney. Spinal Cord (2013) 51, 528-531; doi:10.1038/sc.2013.35; published online 23 April 2013Keywords: glomerular filtration rate; iohexol; renal dysfunction; tubular secretion INTRODUCTION Spinal cord injury (SCI) causes numerous systemic and metabolic alterations that can interfere with the efficacy and security of drug use. 1 Changes in drug disposition and kinetics have been documented in patients and animal models of SCI as a consequence of autonomic nervous system dysfunction. [2][3][4] Precise understanding of the pathophysiological mechanisms involved in pharmacokinetic and pharmacodynamic alterations associated with SCI is required to optimize pharmacological treatments.The kidney is the major regulator of internal fluid environment; therefore, physiologic changes associated with renal dysfunction can have pronounced effects on drug performance, particularly of drugs eliminated by the kidney such as aminoglycosides and quinolones, which are widely used after SCI.There are reports that show decrease of glomerular filtration rate (GFR) in patients with chronic cord injury. 5,6 However, information on GFR during early stages of SCI is scarce and wrongly based on creatinine measurements, 7 which are faulty because they are affected by muscle mass catabolism occurring at this stage of SCI.Our objective here was to assess renal function in the acute stage of experimental SCI by determining (1) GFR from clearance of an exogenous compound unrelated to endogenous compounds derived from muscle catabolism, and (2) tubular secretion (TS). We have hypothesized that during spinal shock produced after experimental SCI, renal function is altered showing decreased GFR and increased TS as a compensatory mechanism.

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Influence of glomerular filtration rate on the rate of para-aminohippurate secretion by the rat kidney: Micropuncture and clearance studies

Cited by 28 publications

References 26 publications

Dietary protein suppresses feedback control of glomerular filtration in rats.

Dietary protein suppresses feedback control of glomerular filtration in rats.

Immediate Effect of Nephrotoxic Serum on Kidney Function in the Dog

Changes in renal function during acute spinal cord injury: implications for pharmacotherapy

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