Glomerular Filtration Rate In Man Research Articles

Low Testosterone Accelerates Age-Associated Declines in Kidney Function Assessed via Estimated Glomerular Filtration Rate in Men

Kidney function declines with increasing age and more than 50% of seniors over the age of 75 years are believed to have overt kidney disease. Data regarding declines in kidney function around the age of menopause in women are consistent with what would be expected of age alone, suggesting that the loss of estrogens do not contribute to declines in kidney function. In contrast, reports indicate that androgen deprivation therapy reduces estimated glomerular filtration rate (eGFR) and increases the risk of acute kidney injury, highlighting a possible influence of testosterone (T) on kidney function. The influence of age-related declines in T on declines in kidney function in otherwise healthy aging men has yet to be determine. PURPOSE: To determine the influence of low T on age-related declines in eGFR in men. Methods: Healthy young (YM; 18-40 years) and middle-aged/older (MA/O; 50-75 years) men participated. MA/O men were categorized as having either low (<300 ng/dL) or normal (400-1000 ng/dL) T via a venous blood draw. Serum creatinine and blood urea nitrogen (BUN) were quantified and eGFR was calculated using the 2021 CKD-EPI creatinine equation. Differences in eGFR and BUN were examined using the Kruskal-Wallis test with Dunn’s multiple comparisons test in the case of a significant main effect. Results: 23 YM (age: 29±4 y, T: 508±60 ng/dL), 23 MA/O men with low T (age: 59±7 y, T: 267±44 ng/dL), and 58 MA/O men with normal T (age: 58±6 y, T: 480±72 ng/dL) participated. Serum creatinine was significantly higher in MA/O men with low T (1.05±0.12 mg/dL) compared to YM (0.95±0.14 mg/dL, p=0.043) and MA/O men with normal T (0.96±0.11 mg/d, p=0.019). There were no differences between YM and MA/O men with normal T (p=0.956). There were significant age-associated declines in eGFR (YM= 109.9±14.3 vs. MA/O men with normal T= 90.1±9.3 mL/min/1.73m2, p<0.001) that were exaggerated in MA/O men with low T (82.6±10.4 mL/min/1.73m2, p=0.044 vs. MA/O men with normal T). BUN was significantly higher in MA/O men (normal T=17.2±3.4 mg/dL, low T=19.2 mg/dL) compared to YM (15.1±3.7 mg/dL, p=0.033 vs. normal T and p<0.001 vs. low T), but there was no difference between MA/O men with normal or low T (p=0.110). CONCLUSIONS: These data suggest that age-associated declines in testosterone contribute to declines in kidney function in otherwise healthy men. These data contrast evidence in women suggesting that the loss of estrogen during the menopause transition does not accelerate kidney dysfunction, suggesting sex differences in the mechanisms of kidney dysfunction. This work was supported by NIH grants R01AG049762, K01HL164978, U54A062319, T32AG000279, the Colorado Clinical and Translational Sciences Institute UL1TR001082, Colorado Nutrition and Obesity Research Center P30DK048520, and the Eastern Colorado GRECC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cystatin C-Based Equations Underestimate Glomerular Filtration Rate in Men With or at Risk for Mesoamerican Nephropathy

Cystatin C-Based Equations Underestimate Glomerular Filtration Rate in Men With or at Risk for Mesoamerican Nephropathy

ANALYSIS OF ASSOCIATION OF rs9536314 OF THE KL GENE WITH ANTHROPOMETRIC AND BIOCHEMICAL INDICATORS IN MEN OF NOVOSIBIRSK (WEST SIBERIA)

Purpose of the study. To determine the frequency of the rs9536314 (F325V) polymorphism of the KL gene and the association of this variant with a number of biochemical and anthropometric parameters in men of the study group and in the Caucasian population of Western Siberia. Materials and methods. The study group (69 men, average age 61.2 ±11.5 years) was randomly formed from a sample of persons who applied to the clinic and polyclinic of NIITPM - a branch of the ICG SB RAS and GBUZ NSO Hospital of war veterans No. 3 (178 men, aged 50-65 years old and over 80 years old). The population group was randomly selected (219 people) from the sample surveyed within the framework of the International Multicenter Project Risk Factors for Cardiovascular Diseases in Eastern Europe HAPIEE (9360 participants, 45–69 years old, mean age 53.8±7 years old, Caucasians > 90 %). Biochemical parameters were determined by standard enzymatic methods. Serum concentration of Klotho protein was measured by ELISA. Genomic DNA was amplified by polymerase chain reaction in a standard reaction mixture and further digested with TaqI B restriction enzyme. Results. The frequency of genotypes (TT, TG, and GG) and alleles (T and G) rs9536314 of the KL gene in the study group corresponds to the data in the population of Western Siberia, as well as the population of Western and Eastern Europe. There were no statistically significant differences in the mean values of the studied clinical and biochemical parameters depending on the rs9536314 genotypes of the KL gene in the study group and in the population. In the study group, the level of Klotho protein in the blood and the glomerular filtration rate in men with coronary heart disease and arterial hypertension did not differ in the autosomal dominant and autosomal recessive models for the rs9536314 KL gene. Conclusion . Thus, the frequency of the rs9536314 polymorphism of the KL gene in the study group corresponds to the frequency of the rs9536314 polymorphism of the KL gene in the Caucasian population of Western Siberia. Biochemical and anthropometric parameters, as well as the Klotho protein, do not have statistically significant differences depending on the genotypes of rs9536314 of the KL gene in the examined men.

Anderson-Fabry disease.

Anderson-Fabry disease.

Effects of Atorvastatin Dose and Concomitant Use of Angiotensin-Converting Enzyme Inhibitors on Renal Function Changes over Time in Patients with Stable Coronary Artery Disease: A Prospective Observational Study.

Angiotensin-converting enzyme inhibitors (ACEI) and statins are widely used in patients with coronary artery disease (CAD). Our aim was to compare changes in glomerular filtration rate (GFR) over time in subjects with stable CAD according to atorvastatin dose and concomitant use of ACEI. We studied 78 men with stable CAD referred for an elective coronary angiography who attained the then-current guideline-recommended target level of low-density lipoproteins (LDL) cholesterol below 2.5 mmol/L in a routine fasting lipid panel on admission and were receiving atorvastatin at a daily dose of 10–40 mg for ≥3 months preceding the index hospitalization. Due to an observational study design, atorvastatin dosage was not intentionally modified for other reasons. GFR was estimated during index hospitalization and at about one year after discharge from our center. Irrespective of ACEI use, a prevention of kidney function loss was observed only in those treated with the highest atorvastatin dose. In 38 subjects on ACEI, both of the higher atorvastatin doses were associated with increasing beneficial effects on GFR changes (mean ± SEM: −4.2 ± 2.4, 1.1 ± 1.6, 5.2 ± 2.4 mL/min per 1.73 m2 for the 10-mg, 20-mg and 40-mg atorvastatin group, respectively, p = 0.02 by ANOVA; Spearman’s rho = 0.50, p = 0.001 for trend). In sharp contrast, in 40 patients without ACEI, no significant trend effect was observed across increasing atorvastatin dosage (respective GFR changes: −1.3 ± 1.0, −4.7 ± 2.1, 4.8 ± 3.6 mL/min per 1.73 m2, p = 0.02 by ANOVA; rho = 0.08, p = 0.6 for trend). The results were substantially unchanged after adjustment for baseline GFR or time-dependent variations of LDL cholesterol. Thus, concomitant ACEI use appears to facilitate the ability of increasing atorvastatin doses to beneficially modulate time-dependent changes in GFR in men with stable CAD.

The association of serum lipids and inflammatory biomarkers with renal function in men with type II diabetes mellitus

Dyslipidemia and inflammation may promote renal disease via mechanisms of vascular endothelial cell dysfunction in type II diabetes mellitus (DM). Sparse data, however, are available on the relation of lipids and inflammatory biomarkers and glomerular filtration rate (GFR) in type II DM. We performed a cross-sectional study of 732 men with type II DM enrolled in the Health Professionals' Follow-Up Study. Plasma creatinine was used to estimate GFR by the simplified Modification of Diet in Renal Disease (MDRD) equation. In men with a GFR <60 ml/min/1.73 m(2), triglycerides, non-high-density lipoprotein (HDL), apoprotein B, fibrinogen, soluble tumor necrosis factor receptor (sTNFR-2) and vascular cell adhesion molecule-1 (VCAM) were significantly higher when compared to the referent group (GFR> or =90 ml/min/1.73 m(2)). In multivariable logistic regression, those in the highest quartiles of the following biomarkers had increased odds of having a GFR <60 ml/min/1.73 m(2) when compared to those in the lowest quartiles: triglycerides (odds ratio (OR) 3.11; 95% CI, 1.52-6.36), fibrinogen (OR 5.40; 95% CI 2.14-13.65), sTNFR-2 (OR 8.34; 95% CI 3.50-19.88) and VCAM (OR 4.50; 95% CI 1.98-10.23). An inverse association was observed for HDL (OR 0.48; 95% CI 0.24-0.98). We found no association between C-reactive protein and GFR. The results were similar when creatinine clearance by Cockcroft-Gault was used to estimate kidney function. We conclude that several potentially modifiable lipid and inflammatory biomarkers are elevated in the setting of moderately decreased GFR in men with type II DM and may be the link between renal insufficiency and increased risk for cardiovascular events in this population.

Relationship between nutritional status and the glomerular filtration rate: Results from the MDRD Study

The relationship between the protein-energy nutritional status and renal function was assessed in 1785 clinically stable patients with moderate to advanced chronic renal failure who were evaluated during the baseline phase of the Modification of Diet in Renal Disease Study. Their mean +/- SD glomerular filtration rate (GFR) was 39.8 +/- 21.1 mL/min/1.73 m2. The GFR was determined by 121I-iothalamate clearance and was correlated with dietary and nutritional parameters estimated from diet records, biochemistry measurements, and anthropometry. The following parameters correlated directly with the GFR in both men and women: dietary protein intake estimated from the urea nitrogen appearance, dietary protein and energy intake estimated from dietary diaries, serum albumin, transferrin, percentage body fat, skinfold thickness, and urine creatinine excretion. Serum total cholesterol, actual and relative body weights, body mass index, and arm muscle area also correlated with the GFR in men. The relationships generally persisted after statistically controlling for reported efforts to restrict diets. Compared with patients with GFR > 37 mL/min/1.73 m2, the means of several nutritional parameters were significantly lower for GFR between 21 and 37 mL/min/1.73 m2, and lower still for GFRs under 21 mL/min/1.73 m2. In multivariable regression analyses, the association of GFR with several of the anthropometric and biochemical nutritional parameters was either attenuated or eliminated completely after controlling for protein and energy intakes, which were themselves strongly associated with many of the nutritional parameters. On the other hand, few patients showed evidence for actual protein-energy malnutrition. These cross-sectional findings suggest that in patients with chronic renal disease, dietary protein and energy intakes and serum and anthropometric measures of protein-energy nutritional status progressively decline as the GFR decreases. The reduced protein and energy intakes, as GFR falls, may contribute to the decline in many of the nutritional measures.

Reassessment of the single intravenous injection method with inulin for measurement of the glomerular filtration rate in man

1. Factors influencing the total body and renal clearances of inulin were investigated in a total of 37 healthy adult volunteers and 10 patients with stable chronic renal failure after the single intravenous injection of a dose of 70 mg/kg given over 5 min. 2. The elimination of inulin was highly concentration-dependent, and in healthy volunteers the renal clearance fell from 103.7 +/- 14.4 ml min-1 1.73 m-2 during the first hour after administration to 49.1 +/- 20.9 ml min-1 1.73 m-2 over the period 6-8 h. In the patients with renal failure the renal clearance fell correspondingly from 39.7 +/- 16.5 to 26.6 +/- 8.6 ml min-1 1.73 m-2. There were no changes in the simultaneously measured clearances of creatinine. 3. The values obtained for the total body clearance of inulin after a single injection depend critically on dose, the number and timing of blood samples, the choice of pharmacokinetic model, the number of data points chosen for estimation of the slope of the terminal elimination phase for analysis by the methods of residuals, and the weighting used for curve fitting by non-linear regression analysis. 4. With standardized conditions of sampling from 0 to 2 h and weighted non-linear regression analysis of the plasma concentration-time data, the total body and renal clearances of inulin were almost identical in subjects with normal renal function at 105.2 +/- 10.2 and 102.9 +/- 13.0 ml min-1 1.73 m-2. In the patients with chronic renal failure sampling was continued for 3 h and the corresponding clearances were 40.4 +/- 15.3 and 38.9 +/- 15.7 ml min-1 1.73 m-2. 5. The 0-2 h total body and renal clearances of inulin were measured by the single injection method and the renal clearance was measured by the standard constant infusion method on different occasions in 10 healthy volunteers. The respective clearances were similar at 101.4 +/- 6.6, 94.9 +/- 11.9 and 88.4 +/- 12.1 ml min-1 1.73 m-2. 6. The reproducibility of the single injection and constant infusion methods was compared by measuring the inulin clearance with both techniques on three occasions in separate groups of eight and nine healthy volunteers. The mean coefficient of variation for the total body clearance with the single injection method was only 3.9% compared with 9.5% for the renal clearance determined the same way and 12.0% for the renal clearance during constant infusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Response of adenylate cyclase to parathyroid hormone and prostaglandins by human isolated glomeruli.

A role for hormonal substances and other biochemical messengers in the regulation of the glomerular filtration rate has been inferred from the results of micropuncture studies in the rat and from the demonstration of hormone-responsive adenylate cyclase activity in glomeruli isolated from the renal cortex of rats and rabbits. To investigate whether such hormonal factors may contribute to the regulation of glomerular function in humans, we studied the response of adenylate cyclase activity to the administration of human PTH-(1-34) and prostaglandins (PG) by glomeruli isolated from the renal cortex of four human kidneys. PTH and PGs (PGE2, PGI2, and, to a lesser extent, PGF2 alpha) stimulated human glomerular adenylate cyclase activity. Basal adenylate cyclase activity ranged from 0.2-1.2 nmol 20 min-1 mg-1. For each agonist, the percent increase above basal values (at the maximum concentration tested) and the concentration of the agonist that elicited 50% of the maximum stimulation (ED50) were as follows: for PTH 300-460% (10,000 mIU/ml); ED50, 100-550 mIU/ml; for PGE2, 160-380% (10 microM); ED50, 0.4-1.6 microM; and for PGI2, 180-650% (10 microM); ED50, 0.09-0.46 microM. The synthetic guanylnucleotide 5'-guanylylimidodiphosphate [Gpp(NH)p] potentiated the effect of PTH and PGI2, since the combined effects were greater than the sums of the effects of the individual agonists, and there was a significant interaction between Gpp(NH)p and PTH or PGI2, as indicated by three-factor analysis of variance. Additivity, but not potentiation, was observed for PGE2. The effects of PTH plus PGE2 or PGI2 were also additive, a finding that suggests that PTH and PGs are not linked to the same pool of adenylate cyclase. In contrast, the combination of PGE2 and PGI2 resulted in a significantly lower effect than the sum of their individual effects, a finding indicating that these PGs share in part a common pool of adenylate cyclase. Demonstration of PTH- and PG-dependent adenylate cyclase activity in human isolated glomeruli suggests a role for these agonists in the regulation of the glomerular filtration rate in man.

Angiotensin II Receptors in Human Isolated Renal Glomeruli*

125I-Labeled angiotensin II ([125I]A II) binds specifically to glomeruli isolated from human kidneys that were obtained at nephrectomy or early autopsy. Equilibrium was reached after 30 min, and specific binding represented more than 90% of the total binding. Dissociation after dilution with the addition of an excess of unlabeled hormone was more rapid than after dilution alone. The effect increased as a function of the A II concentration. The Scatchard plot derived from saturation experiments was curvilinear, with an upward concavity. Two groups of receptor sites could be defined by the Kd values (0.1 and 2 nM, respectively) and the number of receptor sites (40 and 300 fmol mg glomerular protein-1, respectively). Alternatively, binding could be considered to follow a negative cooperative type of hormone-receptor interaction. [Asn1, Val5]A II, [Asp1,Ile5]A II, [des, Asp1,Ile5]A II, [Sar1, Ala8]A II, and [Sar1, Ile8]A II were all equally effective as competitive inhibitors of [125I]A II binding. Both calcium and magnesium (0.5-5 mM) produced an increase in [125I]A II specific binding, whereas guanylylimidodiphosphate, an analog of GTP, inhibited it. Degradation of the [125I]A II present in the incubation medium was estimated by three different techniques. It increased linearly with time and reached 20% at 30 min. Specific binding of A II to human glomeruli at plasma concentrations observed in man under physiological conditions and during the iv administration of A II demonstrates that human renal glomeruli include target cells for A II and thus suggests a role for A II in regulation of the glomerular filtration rate in man.

Pharmacokinetics of Rocephin, a highly active new cephalosporin with an exceptionally long biological half-life.

The total (bound and unbound) plasma concentration time profiles following the three intravenous doses of Rocephin (150, 500 and 1,500 mg) declined in a biphasic manner. A simple compartment analysis was inappropriate since a dose-disproportional increase in the area under the total drug concentration time curve (AUCT,0(-8)) occurred. This resulted in unstable, dose-dependent total systemic clearance (9.7-13.0 ml/min) and volume of distribution (7.0-8.6 litres) values. The dose-dependent pharmacokinetic changes could be completely explained in terms of the concentration-dependent plasma protein binding (fp ranging from 0.04 to 0.17 in the concentration range from 0.5 to 300 micrograms/ml). Hence, the pharmacokinetics of free (unbound) Rocephin was linear and dose-independent. With reference to free (unbound) drug the mean total clearance was 255 ml/min and the mean renal clearance about 160 ml/min. The renal clearance was therewith slightly higher than the average glomerular filtration rate in man (approximately 125 ml/min). Consequently the coadministration of probenecid (1 g) had no effect on the pharmacokinetics of Rocephin. The mean plasma half-life of Rocephin was not influenced by dose and averaged 8 h. It was therewith the longest ever reported one for a cephalosporin in healthy volunteers.

Comparison between [ 14C] Inulin and [ 51Cr] EDTA measurement of glomerular filtration rate in man

Comparison between [ 14C] Inulin and [ 51Cr] EDTA measurement of glomerular filtration rate in man

Renal clearance of oxipurinol, the chief metabolite of allopurinol

Oxipurinol (4,6-dihydroxypyrazolo(3,4-d)pyrimidine; alloxanthine) is the chief metabolite of allopurinol in vivo. Like allopurinol, although to a lesser degree, oxipurinol suppresses xanthine oxidase and lowers the serum and urinary uric acid levels; indeed, for reasons indicated, much of the effect of allopurinol may well be due to oxipurinol. Unlike allopurinol, but like uric acid, oxipurinol appears to be reabsorbed by the tubules, since its renal clearance is much less than the glomerular filtration rate in man and the mongrel dog, although it is not bound to plasma proteins. Moreover, uricosuric drugs increase the clearance of oxipurinol in man, but not in the Dalmatian dog. Oxipurinol apparently is not secreted by the tubules. In the presence of marked kidney damage the renal clearance of oxipurinol is impaired and the plasma oxipurinol concentration in patients given usual allopurinol dosages is elevated. Patients with marked renal insufficiency appear to exhibit a higher incidence of side reactions than do patients with normal renal function.

Iothalamate Sodium I 125 vs Cyanocobalamin Co 57 as a Measure of Glomerular Filtration Rate in Man

The simultaneous renal clearances of iothalamate sodium I 125, cyanocobalamin Co 57, and inulin were compared in 19 patients with a variety of renal diseases. The renal clearances of both iothalamate sodium I 125 and cyanocobalamin Co 57 are not statistically different from the clearance of inulin or from each other. Plasma protein binding was insignificant with iothalamate sodium I 125 but averaged 22% with cyanocobalamin Co 57 with a considerable variation between patients. These observations, as well as a lower cost per study, suggest that iothalamate sodium I 125 is an excellent radioactive material to substitute for inulin clearance when measuring the glomerular filtration rate in man.

Iothalamate sodium I 125 vs cyanocobalamin Co 57 as a measure of glomerular filtration rate in man

Iothalamate sodium I 125 vs cyanocobalamin Co 57 as a measure of glomerular filtration rate in man

Inulin, 57Co-labelled vitamin B12 and endogenous creatinine clearances in the measurement of glomerular filtration rate in man.

SUMMARY In 14 cases, simultaneous clearances of inulin (range 39 to 160 ml. per minute) and endogenous creatinine were measured, and in 11 of these cases, the results were compared with the simultaneous clearance of radioactive (57Co) vitamin B12. The clearance of free (dialysable) 57Co vitamin B12 correlates closely with inulin clearance (ρ=0·985), and can be used as a measure of glomerular filtration rate. [Clearance of vitamin B12 (free)=1·07 clearance of inulin—10·9±5·48 (2 S.D.). ] The protein bound (non‐dialysable) fraction of the plasma 57Co vitamin B12 varied from patient to patient, and in the same patient at different times (range, 9·6% to 35·7%; mean, 17·7% of total), in spite of presaturation with stable vitamin B12. Because of this, the clearance of vitamin B12 is a valid measure of glomerular filtration rate only when correction is made for plasma protein binding as measured in the individual subject. The correlation between inulin and endogenous creatinine clearance was less precise. [Ratio of clearance of creatinine to clearance inulin=1·20±0·38 (2 S.D.).]

Deterioration of stored inulin solutions.

WHILE using a batch of inulin for determination of glomerular filtration rate in man, we found that some ampoules were giving much lower serum inulin-levels than were expected from the dose given. The inulin had been stored in the dark at 20°–25° C, in sealed ampoules, and from the batch number it was established that it had been manufactured thirteen years ago by Thomas Kerfoot and Co., Barnsley. We investigated the deterioration of inulin with time by determining the inulin content by the acid hydrolysis and resorcinol technique1 in fifteen ampoules of the thirteen-year-old batch of inulin, in seven ampoules of inulin one year old and in inulin recrystallized from the one-year-old batch, after washing with distilled water at 20° C. The ages of the inulin batches were kindly provided by the manufacturers.

RENAL EXCRETION OF VIAMIN B12 AND ITS USE IN MEASUREMENT OF GLOMERULAR FILTRATION RATE IN MAN.

Abstract In physiologic amounts vitamin B 12 was firmly bound by plasma proteins. When the binding sites were saturated by addition of vitamin B 12 the renal excretion of free (dialyzable) vitamin was by glomerular filtration, without evidence of either tubular secretion or reabsorption. In patients with normal renal function as well as in those with severely impaired function, the ratio of the clearance of free Co 57 vitamin B 12 to the clearance of inulin was 0.99 ± 0.8 (mean ± 1 S.D.). Stop-flow studies in dogs during the simultaneous infusion of inulin and Co 57 vitamin B 12 indicated that vitamin B 12 was not secreted or reabsorbed by the renal tubules. A lack of tubular secretion of vitamin B 12 was demonstrated in the aglomerular toadfish. Total body counting of fish injected with 2000 μg of Co 60 -labeled vitamin B 12 revealed that 94 per cent was retained after 38 days. Measurement of the radioactive vitamin B 12 clearance provided a simple and accurate method for determining the glomerular filtration rate in man. By presaturating the B 12 binding sites with stable vitamin B 12 and infusing the radiovitamin with a low specific activity (1 μc per 2000 μg) plasma protein binding of the radiovitamin was sufficiently low (8 per cent) that the glomerular filtration rate could be accurately measured even without dialysis of the plasma samples. Radiation exposure from the procedure was minimal, and counting of the plasma and urine samples could be performed readily in standard radiation detection equipment.

The measurement of the glomerular transference rate in man

AbstractIt is commonly but not unanimously held that the renal clearance of inulin measures the glomerular filtration rate in man, and that creatinine is partly excreted by the renal tubules.Results obtained from infusion experiments indicate that both substances are excreted at rates proportional to the respective plasma concentrations. The creatinine/inulin clearance ratio is never less than 1.0 and tends to decrease when the concentrations of creatine and inulin are high, sometimes as a result of slight increases in the inulin clearance and more commonly due to slight decreases in the creatinine clearanceThe interpretation of these findings is discussed in relation to the problem of the measurement of the glomerular filtration rate in man. It is concluded that there is at present no conclusive evidence in favour of the acceptance of the use of either substance.

Allantoin Clearance as a Measure of Glomerular Filtration Rate in Man.

ConclusionsThe average renal clearance of allantoin in 6 normal human subjects was found to be 123 cc per minute. The similarity of this value to that now accepted for the renal clearance of inulin...