Stop-flow analysis of creatinine excretion in the dog

1962 ◽  
Vol 203 (6) ◽  
pp. 980-984 ◽  
Author(s):  
Robert E. Swanson ◽  
Ali A. Hakim
Keyword(s):  
Creatinine Clearance ◽  
Competitive Inhibition ◽  
Flow Analysis ◽  
High Plasma ◽  
Free Flow ◽  
Inulin Clearance ◽  
Plasma Creatinine ◽  
Clearance Ratio ◽  
Creatinine Concentration ◽  
Stop Flow

Urinary excretion patterns of creatinine and inulin under stop-flow conditions in male mongrel dogs were compared. Evidence for a weak creatinine secretory mechanism at the proximal tubule level include the following: 1) Exogenous creatinine in the stop-flow samples appears prior to inulin when both are injected midway during a 10-min ureteral clamping period. 2) The ratio of creatinine/inulin U/P values (creatinine clearance ratio) shows a peak and a distribution coextensive with PAH/inulin clearance ratios. 3) Self-depression of the peak stop-flow creatinine clearance ratio was obtained at high plasma creatinine concentrations. 4) High plasma p-aminohippuric acid levels depressed the free-flow and peak stop-flow creatinine clearance ratios and, conversely, high plasma creatinine concentration depressed free-flow and peak stop-flow PAH clearance ratios (competitive inhibition). 5) Probenecid reduced free-flow and peak stop-flow creatinine clearance ratios (creatinine secretory mechanism blocked). The mean free-flow creatinine/inulin clearance ratios in 44 clearance periods was 1.2±0.1 (sd), compared to the peak stop-flow ratio of 1.8±0.4 (sd) (N = 20) at plasma creatinine concentrations less than 20 mg/100 ml.

Stop-flow analysis of tubular transport of uric acid in rabbits

1964 ◽  
Vol 207 (6) ◽  
pp. 1265-1272 ◽  
Author(s):  
E. C. Beechwood ◽  
W. O. Berndt ◽  
Gilbert H. Mudge
Keyword(s):  
Uric Acid ◽  
Flow Analysis ◽  
Distal Tubule ◽  
Free Flow ◽  
Transport Systems ◽  
Clearance Ratio ◽  
Renal Handling ◽  
Pronounced Increase ◽  
Secretory Transport ◽  
Stop Flow

Various physiological and pharmacological aspects of the renal handling of uric acid have been investigated. In the majority of rabbits the free-flow urate-to-inulin clearance ratio was found to be less than 1, although some animals (about 20%) demonstrated net secretion. Despite the predominance of net reabsorption under free-flow conditions, the usual stop-flow pattern showed only a proximal secretory peak. No distal tubular activity was evident under any of the experimental circumstances studied. The administration of chlorothiazide, lactic acid, creatinine, or pyrazinoic acid caused a pronounced increase in the proximal secretory peak. Probenecid produced a depression of the secretory peak resulting in a net reabsorptive dip. This reversal of proximal tubular activity is taken as evidence for the presence of both secretory and reabsorptive mechanisms. The following phenomena have been found to be involved in the renal handling of uric acid by the rabbit: 1) filtration of urate at the glomerulus; 2) proximal reabsorptive and secretory transport systems which are drug sensitive; and 3) relative impermeability of the distal tubule to urate.

Localization of urate transport in the nephron of mongrel and Dalmatian dog kidney

1959 ◽  
Vol 197 (3) ◽  
pp. 601-603 ◽  
Author(s):  
Richard H. Kessler ◽  
Klaus Hierholzer ◽  
Ruth S. Gurd
Keyword(s):  
Flow Analysis ◽  
Secretory Activity ◽  
Distal Segment ◽  
Free Flow ◽  
Proximal Segment ◽  
Urate Transport ◽  
Dog Kidney ◽  
Stop Flow ◽  
Urate Reabsorption ◽  
Dalmatian Dog

Localization of urate transport within the nephrons of mongrel and Dalmatian dogs was studied by stop-flow analysis. In mongrel dogs urate concentrations and clearance ratios were lowest in the segment in which PAH was secreted. Urate clearance ratios of 0.7 in free-flow samples were reduced to about 0.3 in stop-flow samples from the proximal segment. In the distal segment urate clearance ratios did not differ significantly from ratios obtained in free-flow. Probenecid, in doses sufficient to block PAH secretion, inhibited urate reabsorption thereby increasing urate clearance. In contrast to these findings with mongrel dogs, the Dalmatians exhibited weak but definite urate secretion within the proximal segment. The action of probenecid in this strain of dogs was to stop all proximal secretory activity for urate thereby reducing urate clearance. It was suggested that mongrel and Dalmatian dogs transport urate by systems that are identical except for direction of urate movement.

Creatinine Secretion by the Frog Renal Tubule

1956 ◽  
Vol 184 (3) ◽  
pp. 527-534 ◽  
Author(s):  
Robert E. Swanson
Keyword(s):  
Sodium Azide ◽  
Sodium Arsenite ◽  
Renal Tubule ◽  
Inulin Clearance ◽  
Clearance Ratio ◽  
Creatinine Concentration ◽  
Urinary Creatinine ◽  
Intact Kidney

Simultaneous creatinine and inulin clearance measurements were carried out in Ringer-perfused and intact kidneys of the bullfrog ( R. catesbiana). For the perfusion series the median creatinine/inulin clearance ratio was 1.27. The ratio was elevated above unity for the majority of intact kidney experiments. Perfusion with poisons such as phlorizin, sodium azide, sodium arsenite and 2, 4-dinitrophenol, as well as elevation of the creatinine concentration in perfusing fluids, generally depressed the clearance ratio toward unity. It is concluded that a portion of the urinary creatinine of bullfrogs can be excreted by active tubular participation.

Iohexol Plasma Clearance in Animal Models: The Clear Choice for Measuring Early Renal Dysfunctio

2018 ◽  
Author(s):  
Mandy Turner
Keyword(s):  
Renal Function ◽  
Animal Models ◽  
Kidney Function ◽  
Kidney Failure ◽  
Plasma Clearance ◽  
Inulin Clearance ◽  
Plasma Creatinine ◽  
Creatinine Concentration ◽  
Plasma Creatinine Concentration ◽  
Iohexol Plasma Clearance

Glomerular filtration rate is a measure of the kidney’s ability to filter blood. In animal models of early kidney failure, there is no routine method to accurately measure GFR. The expensive gold standard of GFR measurement is exogenous inulin clearance. The commonly used method, endogenous plasma creatinine concentration, is unreliable and insensitive, especially at normal levels of renal function. This study investigates the utility of iohexol, an inexpensive radio-contrast agent as a promising exogenous marker for plasma clearance kidney function evaluation in rats. Early stages of progressive kidney failure were induced with a 0.25% adenine diet in male Sprague Dawley rats (N=8) over 5 weeks. Both plasma clearance of iohexol and inulin and creatinine concentration were evaluated following weekly venous injections and blood sampling. Plasma iohexol clearance and plasma inulin clearance strongly correlate (R2=0.95). However, plasma creatinine concentration correlated weakly with iohexol(R2=0.53) and inulin(R2=0.58). Iohexol plasma clearance accurately measures changes in kidney function, especially in in comparison to creatinine analysis. The data demonstrates creatinine is an inappropriate marker for renal function in early adenine-induced CKD rat models. Ongoing analysis of this data suggests refinement of the protocol will yield a simple method for routine measure of kidney function in murine lab animals. This tool will facilitate advancement in kidney disease onset and allow for more accurate interpretation of kidney function in the various animal models.

scholarly journals Diagnostic Value of Plasma Cystatin C as a Glomerular Filtration Marker in Decompensated Liver Cirrhosis

2002 ◽  
Vol 48 (6) ◽  
pp. 850-858 ◽  
Author(s):  
Rocco Orlando ◽  
Michele Mussap ◽  
Mario Plebani ◽  
Pierpaolo Piccoli ◽  
Sara De Martin ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Creatinine Clearance ◽  
Glomerular Filtration ◽  
Cystatin C ◽  
Plasma Creatinine ◽  
Decompensated Liver Cirrhosis ◽  
Creatinine Concentration ◽  
Plasma Creatinine Concentration ◽  
Calculated Creatinine Clearance ◽  
Cirrhotic Patients

Abstract Background: Plasma creatinine concentration and calculated creatinine clearance are of limited value as glomerular filtration rate (GFR) markers in patients with decompensated liver cirrhosis. We assessed plasma cystatin C as an indicator of GFR in such patients. Methods: We studied 36 patients with decompensated liver cirrhosis and 56 noncirrhotic controls, both groups including individuals with normal and impaired renal function. GFR was measured in all individuals by inulin clearance, with values <72 mL · min−1 · 1.73 m−2 considered decreased. We measured cystatin C and creatinine in plasma and calculated (from plasma concentrations) and measured creatinine clearances, using for them decision points of 1.25 mg/L, 115 μmol/L, and 72 and 72 mL · min−1 · 1.73 m−2, respectively. Results: Plasma cystatin C concentrations were similar in controls and cirrhotics and, at the usual cutpoint, could detect decreased GFR with similar sensitivities in the two groups (73% and 88%, respectively). Serum creatinine was markedly lower in cirrhotics and remained mostly within the reference interval at all GFR values; the diagnostic sensitivity of creatinine was much lower in cirrhotics than in controls (23% vs 64%). Lower diagnostic sensitivity was also observed for calculated creatinine clearance (53% vs 100% in controls), whereas similar sensitivities were found for measured creatinine clearance (86% and 81%) in controls and cirrhotics, respectively. ROC analysis showed that all four variables had similar diagnostic accuracies in cirrhotic patients. However, it also revealed that good diagnostic accuracies for plasma creatinine and calculated creatinine clearance can be obtained only if reference intervals different from those used for the general population are adopted. Conclusions: Plasma cystatin C concentration is an accurate GFR marker in cirrhotic patients. Plasma creatinine concentration and calculated creatinine clearance are of no practical value, as their reference values vary with the severity of the liver disease.

scholarly journals Comparison of inulin clearance with 2-h creatinine clearance in Japanese pediatric patients with renal disease: open-label phase 3 study of inulin

2021 ◽  
Author(s):  
Osamu Uemura ◽  
Kenji Ishikura ◽  
Koichi Kamei ◽  
Riku Hamada ◽  
Masaki Yamamoto ◽  
...  
Keyword(s):  
Renal Disease ◽  
Creatinine Clearance ◽  
Primary Endpoint ◽  
Pediatric Patients ◽  
Pediatric Nephrology ◽  
Inulin Clearance ◽  
Clearance Ratio ◽  
Open Label ◽  
Maintenance Rate ◽  
Starting Point

Abstract Background There is no approved dosage and administration of inulin for children. Therefore, we measured inulin clearance (Cin) in pediatric patients with renal disease using the pediatric dosage and administration formulated by the Japanese Society for Pediatric Nephrology, and compared Cin with creatinine clearance (Ccr) measured at the same time. We examined to what degree Ccr overestimates Cin, using the clearance ratio (Ccr/Cin), and confirmed the safety of inulin in pediatric patients. Methods Pediatric renal disease patients aged 18 years or younger were enrolled. Inulin (1.0 g/dL) was administered intravenously at a priming rate of 8 mL/kg/hr (max 300 mL/hr) for 30 min. Next, patients received inulin at a maintenance rate of 0.7 × eGFR mL/min/1.73 m2 × body surface area (max 100 mL/hr) for 120 min. With the time the maintenance rate was initiated as a starting point, blood was collected at 30 and 90 min, while urine was collected twice at 60-min intervals. The primary endpoint was the ratio of Ccr to Cin (Ccr/Cin). Results Inulin was administered to 60 pediatric patients with renal disease; 1 patient was discontinued and 59 completed. The primary endpoint, Ccr/Cin, was 1.78 ± 0.52 (mean ± standard deviation). Regarding safety, five adverse events were observed in four patients (6.7%); all were non-serious. No adverse reactions were observed in this study. Conclusions The results in this study on the dosage and administration of inulin showed that inulin can safely and accurately determine GFR in pediatric patients with renal disease. ClinicalTrials.gov identifier NCT03345316.

Lysozyme Excretion as a Measure of Renal Tubular Dysfunction in Children

1970 ◽  
Vol 39 (3) ◽  
pp. 457-465 ◽  
Author(s):  
T. M. Barratt ◽  
Rita Crawford
Keyword(s):  
Molecular Weight ◽  
Creatinine Clearance ◽  
Healthy Adults ◽  
Low Molecular Weight ◽  
Tubular Dysfunction ◽  
Renal Tubular Dysfunction ◽  
Clearance Ratio ◽  
Creatinine Concentration ◽  
Heavy Load ◽  
Protein Reabsorption

1. Activity of the low molecular weight enzyme lysozyme was measured in the plasma and urine of healthy adults and children and of children with renal disease. 2. No difference was detected between lysozyme excretion (expressed as the lysozyme/creatinine clearance ratio) of healthy adults and neonates, implying that the proximal tubular function of protein reabsorption is mature in the neonate. 3. The lysozyme/creatinine clearance ratio was not elevated in the nephrotic syndrome: thus a heavy load of filtered albumin does not interfere with low molecular weight protein reabsorption. 4. Very high values of lysozyme/creatinine clearance were observed in children with the Fanconi syndrome; there was no overlap with any other group studied. 5. Children with pyuria had a very slight increase in urine lysozyme/creatinine concentration ratio.

scholarly journals The Effect of Cadmium on GFR Is Clarified by Normalization of Excretion Rates to Creatinine Clearance

2021 ◽  
Vol 22 (4) ◽  
pp. 1762
Author(s):  
Soisungwan Satarug ◽  
David A. Vesey ◽  
Muneko Nishijo ◽  
Werawan Ruangyuttikarn ◽  
Glenda C. Gobe ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Tubular Injury ◽  
Creatinine Concentration ◽  
Thai Subjects ◽  
Urine Creatinine ◽  
Wide Range ◽  
Nephron Loss ◽  
Urine Cadmium ◽  
Excretion Rates ◽  
Cd Exposure

Erroneous conclusions may result from normalization of urine cadmium and N-acetyl-β-D-glucosaminidase concentrations ([Cd]u and [NAG]u) to the urine creatinine concentration ([cr]u). In theory, the sources of these errors are nullified by normalization of excretion rates (ECd and ENAG) to creatinine clearance (Ccr). We hypothesized that this alternate approach would clarify the contribution of Cd-induced tubular injury to nephron loss. We studied 931 Thai subjects with a wide range of environmental Cd exposure. For x = Cd or NAG, Ex/Ecr and Ex/Ccr were calculated as [x]u/[cr]u and [x]u[cr]p/[cr]u, respectively. Glomerular filtration rate (GFR) was estimated according to the Chronic Kidney Disease (CKD) Epidemiology Collaboration (eGFR), and CKD was defined as eGFR < 60 mL/min/1.73m2. In multivariable logistic regression analyses, prevalence odds ratios (PORs) for CKD were higher for log(ECd/Ccr) and log(ENAG/Ccr) than for log(ECd/Ecr) and log(ENAG/Ecr). Doubling of ECd/Ccr and ENAG/Ccr increased POR by 132% and 168%; doubling of ECd/Ecr and ENAG/Ecr increased POR by 64% and 54%. As log(ECd/Ccr) rose, associations of eGFR with log(ECd/Ccr) and log(ENAG/Ccr) became stronger, while associations of eGFR with log(ECd/Ecr) and log(ENAG/Ecr) became insignificant. In univariate regressions of eGFR on each of these logarithmic variables, R2 was consistently higher with normalization to Ccr. Our tabular and graphic analyses uniformly indicate that normalization to Ccr clarified relationships of ECd and ENAG to eGFR.

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