Impairment of the glomerular filtration rate by glomerular and interstitial factors in membranoproliferative glomerulonephritis with normal serum creatinine concentration.
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Creatinine↗
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Results for “glomerular filtration rate”
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Determination of glomerular filtration rate in advanced renal insufficiency.
The glomerular filtration rate (GFR) has been determined in 17 patients with advanced renal insufficiency (GFR less than 15 ml/min) by different clearance techniques using creatinine, inulin and 51Cr-EDTA as filtration markers. With renal inulin clearance as reference method for GFR, endogenous renal creatinine clearance overestimated GFR by an average of 30%. Renal clearance of 51Cr-EDTA and inulin were closely correlated and thus 51Cr-EDTA is a suitable GFR marker even at low filtration rates. However, it was found that the plasma clearance of 51Cr-EDTA overestimated the GFR often by more than 100% in the range 2.6--11.2 ml/min. Renal clearance measured during 24 h was lower than 4 h renal clearance with the patient well hydrated and resting in bed. It is concluded that the precise measurement of low glomerular filtration rates requires the use of renal clearance techniques. Four-hour 51Cr-EDTA renal clearance is a suitable method for measuring and following the development of renal function in advanced renal insufficiency.
Adult↗
Common charge-shift mutation Glu65Lys in K+ channel β₁-Subunit KCNMB1: pleiotropic consequences for glomerular filtration rate and progressive renal disease.
BACKGROUND: Glomerular filtration rate (GFR) is a heritable trait, and hyperfiltration (GFR increment in remnant nephrons) may accelerate renal functional decline in chronic kidney disease (CKD). Mesangial and vascular smooth myocytes control GFR by contraction, dependent on voltage-gated Ca(2+) influx, which is controlled by the regulatory β₁-subunit (KCNMB1) of large-conductance heteromeric K+ ('BK') channels. KCNMB1 gain-of-function variant Glu65Lys results in generalized vasorelaxation and thus protection against systemic hypertension. Here we asked whether the Glu65Lys variant influences GFR, in the basal state or during progressive renal decline. METHODS: We explored Glu65Lys effects on GFR in three populations spanning two ethnicities and two diseases (hypertension and nephrosclerosis). GFR was either estimated (eGFR from serum creatinine) or directly measured (iothalamate clearance). RESULTS: The 65Lys variant was relatively common, occurring on ∼5-10% of chromosomes in different biogeographic ancestry groups, and 65Lys carriers exhibited higher eGFR in two primary care populations: extreme BP values in Kaiser clinics (p = 0.029, accounting for ∼0.2% of trait variance), or treated hypertensives in VA clinics (p = 0.017, accounting for ∼0.9% of trait variance). In blacks with progressive renal disease (NIDDK AASK), 65Lys carriers displayed a steeper slope in GFR chronic decline (p = 0.030, accounting for ∼0.4% of trait variance), and Glu65Lys genotype also predicted time of onset of renal failure (log rank p = 0.019). CONCLUSIONS: Common KCNMB1 gain-of-function variant Glu65Lys influences GFR, and 65Lys carriers exhibit not only elevated baseline GFR, but also more rapid GFR decline (and consequent development of renal failure) in CKD. The results suggest that profiling patients at Glu65Lys can assist in gauging renal prognosis as well as selection of rational therapy in hypertension with progressive renal disease.
Black or African American↗
Postnatal development of renal function in piglets: glomerular filtration rate, clearance of PAH and PAH extraction.
Glomerular filtration rate (GFR), estimated as clearance of inulin, and clearance of p-aminohippuric acid (CPAH) were measured in 32 unanaesthetized piglets 1--62 days of age. During this period of time, GFR increased from 0.27 to 0.59 ml/min/g kidney and CPAH increased from 1.02 to 1.72 ml/min/g kidney. At 8 weeks of age, GFR and CPAH equaled adult values. In addition, renal PAH extraction (EPAH) was estimated in 12 anaesthetized piglets aged 1--79 days. EPAH increased from 0.75 at birth to 0.86 (adult value) at 3 weeks of age. The result shows a postnatal increase in renal functions in piglets, but the development from birth to adult level was less pronounced than seen in other animal species.
Animals↗
Microvascular permeability to albumin and glomerular filtration rate in diabetic and normal children.
In order to examine the permeability of microvessels in diabetic children, the glomerular filtration rate, urinary excretion rates of albumin and beta 2-microglobulin, intravascular mass of albumin, and transcapillary escape rate of albumin were studied in 26 diabetic children without clinical signs of microangiopathy (age: 7-14 years; duration of disease: 3-14 years). Similar measurements were made in 28 healthy school children (age: 8-14 years). Mean glomerular filtration rate in the diabetic children was higher than in the normal children (138 versus 109 ml/min per 1.73 m2, p less than 0.01). Urinary excretion rates of albumin and beta 2-microglobulin did not differ in diabetics. Mean intravascular albumin mass in the diabetic girls (1.64 g/kg body weight) was lower (p less than 0.01) than in the diabetic boys (1.89 g/kg body weight) and also lower (p less than 0.02) than in the normal girls (1.94 g/kg body weight). Mean transcapillary escape rate of albumin in the twenty diabetics with duration of diabetes less than 10 years (7.14%/h) was lower (p less than 0.01) than that in normal children (8.90%/h); the escape rate showed a positive correlation with duration of diabetes (r=0.47; p less than 0.02). Thus glomerular filtration rate in diabetic children is elevated to the same extent as in adult short-term juvenile diabetics while the permeability of the glomerular membrane to macromolecules is normal. Interpretation of the results on intravascular albumin mass and transcapillary escape rate of albumin requires further investigation.
Adolescent↗
Intrarenal renin and autoregulation of renal plasma flow and glomerular filtration rate.
Autoregulatory responses of renal plasma flow (RPF) and glomerular filtration rate (GFR) to reductions in renal artery pressure (RAP) were studied in both kidneys of two-kidney, one-clamp dogs and in dogs treated with deoxycorticosterone acetate (DOCA; 25 mg/kg) plus high sodium diets with and without renal arterial clamping. In non-DOCA-treated animals, unilateral renal artery constriction resulted in a significant difference (P = 0.004) in renal renin activity (RRA) between the clamped (171 +/- 37 ng AI.mg-1.h-1) and the contralateral (57 +/- 23 mg AI.mg-1.h-1) kidneys with no change in their relative autoregulatory ability. In dogs treated with DOCA/high sodium there were no differences in RRA between the clamped and contralateral kidneys. The dogs treated with DOCA/high sodium were able to autoregulate both RPF and GFR even though their RRA was only 5.4 ng AI.mg-1.h-1. DOCA/high sodium treatment, however, reduced basal RPF (22%) and GFR (23%) below those in non-DOCA-treated animals. Analysis of the autoregulatory ability of individual kidneys showed no relationship to either RRA or renin secretory rates. These results support the conclusion that the renin-angiotensin system is not necessary component in the autoregulation of RPF or GFR.
Animals↗
Digoxin clearance and glomerular filtration rate.
The authors have studied the correlation between digoxin clearance and glomerular filtration rate. This correlation was better than between digoxin clearance and creatinine clearance without reducing the error of a programed therapy.
Aged↗
Glomerular filtration rate and kidney blood flow in alloxan and streptozotocin diabetic rats.
Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow.
Alloxan↗
Further observations on the response of the glomerular filtration rate to glucagon: comparison with secretin.
Glucagon causes marked elevations of glomerular filtration rate (GFR) in dogs when administered intravenously (i.v.) in small doses. The associated natriuresis is thought to be entirely due to increments in the filtered sodium load. In this study, renal denervation, thyroparathyroidectomy, and blockade of cholinergic, alpha- and beta-adrenergic, dopaminergic and histaminergic receptors did not prevent the usual glucagon-induced elevations of GFR or rate of sodium excretion (UNaV). This effect of glucagon was not mediated through the release of cyclic AMP, or by plasma compositional changes of Ca-2+, K+, or amino acids. Pure porcine secretin, in doses of 5--10 mug/min delivered either i.v. or into the left renal artery did not alter GFR; clearance of the p-aminohippurate (CPAH) or UNaV in either hydropenic or saline-loaded dogs. Nor did this polypeptide, structurally very similar to glucagon, abolish the effect of glucagon on GFR. It did, however, partially inhibit the glucagon-induced natriuresis, presumably by preventing a previously undetected glucagon action on tubular reabsorption of sodium.
Amino Acids↗
The renal blood flow and the glomerular filtration rate of anaesthetized dogs during acute changes in plasma sodium concentration.
1. The effects of acute changes in plasma Na concentration (P(Na)) on renal blood flow (RBF) and glomerular filtration rate (GFR) were studied in anaesthetized greyhounds. Saline was infused at a constant rate (0.1 ml. kg(-1) min(-1)) either into a renal artery or into a systemic vein. Plasma Na concentration was altered by varying the Na concentration of the infused saline from 0.154 to 0.077, 0.616 or 1.232 M.2. Blood pressure (B.P.), packed cell volume (PCV), concentration of plasma solids (PS) and the plasma concentration of H(+) and K (P(K)) ions were measured but no attempt was made to contain their fluctuation.3. An infusion of hypertonic saline into a renal artery usually led to an ipsilateral increase in RBF for 5-15 min, followed by a progressive fall. Over-all, mean values of RBF fell with P(Na) throughout the range studied (120-190 m-mole l.(-1)). Glomerular filtration rate rose with P(Na) to reach maximal values at P(Na) levels of 140-160 m-mole l.(-1), but fell thereafter. The combined fall in RBF and GFR, without change in filtration fraction, at P(Na) values above 160 m-mole l.(-1) is consistent with an alteration in afferent arteriolar resistance. The fall in GFR despite a rise in RBF noted when P(Na) was reduced below 140 m-mole l.(-1) requires an additional explanation.4. Renal blood flow was independent of P(K); it was inversely related to [H(+)] and directly related to PS. Glomerular filtration rate was independent of PCV and P(K). It was also inversely related to [H(+)] and directly related to PS up to a value of 6 g 100 g(-1) plasma, after which the relationship was reversed. These results suggest that the renal vascular responses to acute changes in P(Na) may be mediated in part, at least, by concurrent change in PS and [H(+)].
Animals↗
The renal plasma flow and glomerular filtration rate as estimated through double radiocompound renography.
In order to estimate the renal plasma flow and glomerular filtration rate during the course of renography, a method was developed using simultaneously 131I Hippuran and 169Yb DTPA. First results obtained in a survey of approximately 200 patients are encouraging. The method permits an accurate evaluation of the renal function. In addition, by comparing the clearance rate of the two radiocompounds one can also obtain some interesting diagnostic information which can contribute usefully to the interpretation of renographic tracings and/or gamma camera sequential images.
Acute Disease↗
Inhibitory effect of methylxanthines on feedback control of glomerular filtration rate in the rat kidney.
Microperfusion experiments were performed in rats to assess the effect of luminal application of theophylline and the more lipophilic 3-isobutyl-1-methylxanthine (IBMX) on feedback regulation of glomerular filtration rate. Elevation of loop of Henle flow from 0 to 40 nl/min caused a 20.3 +/- 4.5% reduction of stop flow pressure (SFP) and a 32.2 +/- 3.7% reduction of early proximal flow rate (EPFR) when the perfusate was a 140 mM NaCl solution. When theophylline was added in a concentration of 5mM SFP fell by only 5.3 +/- 1.8% and EPFR by 7.9 +/- 33%, changes which were significantly smaller than in the control perfusions (P less than 0.01). An identical change of loop of Henle flow in the presence of IBMX in concentration of 1 and 5 mM was associated with a 4.5 +/- 3.9% decrease and a 12.1 +/- 2.7% increase of EPFR. In orthograde perfusion experiments full inhibition of the feedback response was noted at an IBMX concentration of about 1 mM while during retrograde perfusion a concentration of 0.4 mM was sufficient to produce the same effect. This indicates that methylxanthines diffuse out of the loop of Henle to a considerable extent. Methylxanthines reduced absolute and fractional water absorption along the loop of Henle to some extent while Cl absorption rates and early distal Cl concentrations were not significantly altered. Cyclic AMP applied from the luminal side in a concentration of 10 mM did not affect the feedback response of EPFR to flow elevation from 0 to 40 nl/min. Luminal application of dibutyryl cyclic AMP at 10 mM induced a small, but significant reduction of the feedback response when tested by paired t-test (P less than 0.05). Our results show that luminal application of methylxanthines strongly interfere with feedback regulation of glomerular filtration rate. It is unclear at present whether this effect is related to inhibition of cyclic nucleotide phosphodiesterase and a rise in tissue cyclic AMP levels or to interference with a mechanism involving the local action of adenosine or 5'-AMP.
Animals↗
Instantaneous measurement of glomerular filtration rate in the isolated perfused rat kidney.
In perfusion studies on the isolated cellfree perfused rat kidney, the glomerular filtration rate (GFR) can be controlled if the GFR can be measured instantaneously. This paper reports on a GFR meter which opens this possibility. Vitamin B12 is used as a marker for the GFR. A bubble flow meter determines urine flow rates ranging from 10 up to 200 microliter-min-1. A fiberoptic colorimeter measures vitamin B12 concentrations in the urine up to 400 mg-l-1. The flow meter and the colorimeter are described in detail. The reliability of vitamin B12 as a marker for the GFR is demonstrated and, moreover, the identity of GFR values obtained with the GFR meter and those from B12 spectrophotometry is demonstrated.
Animals↗
[Effect of angioprotectors on the glomerular filtration rate and vascular permeability in diabetic angiopathies].
Renal function (glomerular filtration) and vascular permeability under the effect of an angioprotector were studied by means of labeled renotropic compounds in 55 patients with diabetic angiopathies. The patients were divided into 3 groups: the first group comprised 23 patients treated with anginin or prodectin alone; the second one--16 patients given dicinon or docsium, and the third one--16 patient who were given combined treatment. The best effect was noted in the latter group of patients.
Adolescent↗
Genetic overlap between estimated glomerular filtration rate and cardiovascular disease identifies potential targets for cardiorenal syndrome.
Heart and kidney diseases frequently coexist, but the genetic basis of this relationship remains unclear. We analyzed genetic data from large-scale studies to investigate how kidney function (estimated glomerular filtration rate, eGFR) and six common cardiovascular diseases share genetic risk factors. Using MiXeR method, and conjunctional false discovery rate (conjFDR) to identify overlapping genetic regions, we found 478 shared genomic loci between eGFR and cardiovascular diseases. These shared genes are involved in tissue development and structure. We also identified 29 genes that could be targeted by existing medications approved by the US Food and Drug Administration, such as PRKAG2, PDE1A, and IGF1R. Among these, genetically predicted higher level of IGF1R expression is associated with a higher eGFR, which reflects good kidney function and is protective against cardiorenal diseases, such as atrial fibrillation, and myocardial infarction. These findings reveal genetic overlap between kidney function and cardiovascular diseases, highlighting potential targets for understanding and treating cardiorenal syndrome.
Humans↗
[Effect of saralasin infusion on glomerular filtration rate and sodium excretion in hypertensive patients (author's transl)].
Saralasin (S) infusion, at a dose of 10 micrograms/kg/min IV, decreased Glomerular Filtration Rate (GFR) in 18 hypertensive patients. This effect was more pronounced in those patients with angiotensinogenic hypertension due to the somation of the effects of S upon renal vasculature and systemic arterial pressure. A decrease in urinary sodium excretion was also observed being more intense in those patients whose systemic pressure also decreased during S infusion. In group II (10 hypertensive patients) infusion of S in increasing doses (0.1, 0.5, 1.0, 5.0 and 10.0 micrograms/kg/min) a progressive decrease in GFR was observed only when the arterial pressure also decreased. However urinary sodium excretion decreased progressively as S doses increased. This effect was not related to S effect upon arterial pressure. This observation indicates that S, like angiotensin II, has a direct effect upon the renal tubules evoking an increase of sodium reabsorption.
Angiotensin II↗
Increased glomerular filtration rate after converting-enzyme inhibition in essential hypertension.
To test the influence of an inhibitor of angiotensin-converting enzyme, teprotide (SQ 20881), we administered it to seven patients with essential hypertension and normal renal function and nine with an unequivocal reduction in creatinine clearance, caused by bilateral renal-artery stenosis in two and by essential hypertension in seven. Despite the fall in blood pressure (112.7 +/- 4.5 to 100.3 +/- 3.9 mm Hg, mean +/- S.E.M., P less than 0.01), there were prompt increases in both creatinine clearance (95.9 +/- 10.5 to 109.9 +/- 9.5 ml per minute per 1.73 m2 of body-surface area, P less than 0.01) and sodium excretion (17.0 +/- 5.9 to 31.7 +/- 7.2 mumol per minute, P less than 0.01) in patients with essential hypertension. The increase in glomerular filtration rate was most striking, averaging 33 per cent (66.0 +/- 10.3 to 88.0 +/- 9.2 ml per minute per 1.73 m2, P less than 0.001) in patients in whom an initial reduction was evident and hypertension was more severe. These observations suggest that a functional element, perhaps involving angiotensin-mediated renal vasoconstriction, frequently has a role in the reduction in glomerular filtration rate that occurs in essential hypertension. This class of agent may improve renal excretory function as it controls hypertension.
Angiotensin-Converting Enzyme Inhibitors↗
Influence of glomerular filtration rate on renal PAH secretion rate in the rat kidney. Dependency of PAH extraction on renal filtration fraction.
PAH secretion (TPAH) was studied in rats at spontaneously occurring glomerular filtration rate (GFR). At saturated transport, TPAH was found to be correlated to GFR. This relationship was also observed at unsaturated transport where TPAH depends upon the PAH concentration in arterial plasma. However, no significant correlation between TPAH and renal PAH load or renal plasma flow rate was found when the effects of GFR were removed by partial correlation analysis. A dependency of TPAH on GFR explains the correlations found between filtration fraction (FF) and renal PAH extraction (EPAH) or renal tubular PAH extraction fraction (EPAH--FFPAH). Thus, even at low PAH concentration in a. plasma, renal PAH extraction may only be assumed to be constant if the filtration fraction is constant.
Aminohippuric Acids↗