Gamma-variate plasma clearance versus urinary plasma clearance of 51 Cr-EDTA in patients with cirrhosis with and without fluid retention.

In patients with fluid retention, the plasma clearance of 51 Cr-EDTA (Clexp obtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma-variate plasma clearance (Clgv) with the urinary plasma clearance of 51 Cr-EDTA (Clu ) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of 51 Cr-EDTA followed by plasma and quantitative urinary samples for 5 h. Clgv was determined from the injected dose relative to the plasma concentration-time area, obtained by a gamma-variate iterative fit. Clexp and Clu were determined by standard technique. In patients without fluid retention, Clgv , Clexp and Clu were closely similar. The difference between Clgv and Clu (Clgv - Clu  = ΔCl) was mean -0·6 ml min-1  1·73 m-2 . In patients with ascites, ΔCl was significantly higher (11·8 ml min-1  1·73 m-2 , P<0·0001), but this value was lower than Clexp - Clu (17·5 mL min-1  1·73 m-2 , P<0·01). ΔCl increased with lower values of GFR (P<0·001). In conclusion, in patients with fluid retention and ascites Clgv and Clexp overestimates GFR substantially, but the overestimation is smaller with Clgv . Although Clu may underestimate GFR slightly, patients with ascites should collect urine quantitatively to obtain a reliable measurement of GFR.

Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases.

Total plasma clearance versus urinary plasma clearance of (51)Cr-EDTA in patients with cirrhosis with and without fluid retention.

BACKGROUND AND AIM: In patients with fluid retention, the total plasma clearance of (51)Cr-EDTA (ClP) may overestimate the glomerular filtration rate (GFR). The present study was therefore undertaken in order to compare ClP with the urinary plasma clearance of (51)Cr-EDTA (ClU) in patients with cirrhosis with and without fluid retention. MATERIAL AND METHODS: A total of 136 patients with cirrhosis (24 without fluid retention, 112 with ascites) received a quantitative intravenous injection of (51)Cr-EDTA followed by plasma and quantitative urinary samples for 5 hours. ClP was determined from the injected dose relative to the plasma concentration-time area, extrapolated to infinity. ClU was determined as urinary excretion relative to the plasma concentration-time area up to voiding. RESULTS: In patients without fluid retention, the difference between ClP and ClU (ClP - ClU = ClΔ) was mean 4.5 mL/min/1.73 m(2). In patients with ascites, ClΔ was significantly higher (17.6 mL/min/1.73 m(2), p < 0.0001). ClΔ increased with lower values of GFR (r = - 0.458, p < 0.001). Repeated measurements of ClU in a subgroup of patients with fluid retention (n = 25) gave almost identical values. Different types of corrections of one-pool clearance were almost identical with ClP, except for higher clearance values, which were somewhat underestimated by the former. CONCLUSION: In patients with fluid retention and ascites ClP and corrected one-pool clearance overestimates GFR substantially. Although ClU may underestimate GFR slightly, patients with ascites should collect urine quantitatively in order to obtain a reliable measurement of GFR.

The clearance concept with special reference to determination of glomerular filtration rate in patients with fluid retention.

In subjects without fluid retention, the total plasma clearance of a renal filtration indicator (inulin, (99m) Tc-DTPA, (51) Cr-EDTA) is close to the urinary plasma clearance. Conversely, in patients with fluid retention (oedema, pleural effusions, ascites), there is a substantial discrepancy between the total plasma clearance and the urinary plasma clearance. This is owing to delayed indicator distribution to smaller or larger parts of the interstitial space, which in patients with ascites may simulate a peritoneal dialysator. In patients with fluid retention, urinary plasma clearance should be assessed to obtain a correct measurement of the glomerular filtration rate (GFR). In theory, total plasma clearance with late samples (24-h, 48-h) may be applied in patients with fluid retention, but validation hereof has not been performed. Until such studies are completed, it is recommended that patients with fluid retention have their GFR measured by a urinary plasma clearance technique with controlled quantitative urinary sampling within a few hours after indicator injection.

One-sample determination of glomerular filtration rate (GFR) in children. An evaluation based on 75 consecutive patients.

BACKGROUND AND AIM: From a clinical point of view determination of glomerular filtration rate (clearance) is important. The aim of the present study was to compare the one-sample clearance to reference multiple-sample (51)Cr-EDTA clearance in consecutively referred children suspected of or with established nephro-urological disorders. MATERIAL AND METHODS: A total of 75 children, age ½-13 years, received a quantitative intravenous injection of (51)Cr-EDTA followed by six plasma samples 10-120 min after injection. The multiple-sample clearance was measured as injected dose relative to the area under the plasma radioactivity curve. The one-sample clearance was determined from a single plasma sample collected at 60, 90 or 120 min after injection according to the one-pool method. RESULTS: The overall accuracy of one-sample clearance was excellent with mean numeric difference to the reference value of 0.7-1.7 mL/min. In 64 children, the one-sample clearance was within ± 4 mL/min of the multiple-sample value. However, in 11 children the numeric difference exceeded 4 mL/min (4.4-19.5). Analysis of age, body size, distribution volume, indicator retention time, clearance level, curve fitting, and sampling time could not explain the observed large difference between one-sample and multiple-sample clearance in these 15% of the children. CONCLUSION: In the majority of children there is an excellent agreement between one-sample clearance and multiple-sample clearance. However, unexpectedly in a small fraction (15%) larger discrepancies are found. If an accurate clearance value is essential a multiple-sample determination should be performed.