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At least 19 recordsLinked to original sources
PubMed1992

[Key note comment on the determination of glomerular filtration rate].

Glomerular filtration rate (GRF) is the most fundamental renal function. Determination of GFR is the most important examination in clinical nephrology. Cin is accepted as the gold standard of GFR, but, continuous infusion and the determination method of inulin (method of anthrone) are very troublesome. Interference of glucose in the serum and urine of patients with diabetes mellitus on the determination of inulin should be avoided. Ccr is widely used in the clinical field. Recently, the dynamics of creatinine in the body have been clarified. Variation of pool, generation rate, extrarenal excretion and tubular excretion of creatinine are found to change daily in the patient. Additionally, classical Jaffé's reaction involves non creatinine chromogen particularly in the serum. Though Jaffé's reaction with kinetic analysis improves the reliability of this reaction, the result is still unsatisfactory. There are several methods of enzyme assay are now using an autoanalyser, but, if we use many enzymes and reagents, the reliability of this method could not exceed that of Jaffé's method. Recently, HPLC is recommended as the standard method. 24-hr urine collection is also troublesome in the measurement of Ccr. I have found a good correlation between the estimated Ccr using Cockcroft and Gault's formula and Cin. Such prediction using serum creatinine concentration and few parameters should be developed. Radiolabelled agents have been widely used for the determination of GFR. However, in Japan, the methods of clearance of non radiolabelled contrast agents should be developed. Furthermore, a physical determination of GFR is necessary. In this workshop, these issues will be discussed by each speaker.

Animals↗
PubMed1998

Application of newer clearance techniques for the determination of glomerular filtration rate.

Glomerular filtration rate (GFR) is the standard measure of renal function and is critical for the management of renal diseases. Rigorous assessment of GFR requires the measurement of renal clearance of a filtration marker, such as inulin. This method, however, is not suitable for routine clinical practice. Labelled compounds as alternative filtration markers provide accurate and precise GFR measurement, but their use may be limited for safety reasons. Thus investigators have proposed clearance procedures using minute doses of non-radioactive contrast agents, including iothalamate and iohexol. Their renal clearance provides similar accuracy as inulin clearance in GFR estimation, but the need of urine collection again poses certain limitations to the procedure. Thus, plasma clearance of suitable exogenous markers, such X-ray contrast media, has been suggested for measuring renal function, in which the elimination rate of the tracer after a single intravenous injection is evaluated. Plasma clearance of these markers estimated by multiple blood samples provides precise information, but repeated sampling makes this method cumbersome. Abbreviated kinetic profiles have been proposed to predict GFR from the plasma disappearance curve. The simplified method that uses a one-compartment model corrected by the Bröchner-Mortensen formula gives an excellent correlation with inulin clearance and is currently employed for measuring GFR in multi-centre clinical trials.

Contrast Media↗
PubMed1997

Measurement of glomerular filtration rate.

Glomerular filtration rate (GFR) is the standard measure of renal function and is critical for the diagnosis and management of renal diseases. Rigorous assessment of GFR requires the measurement of renal clearance of an exogenous marker that is freely filtered by the kidney, and that does not undergo metabolism, tubular secretion or absorption, such as inulin. While its clearance provides the most accurate method of measuring GFR, it is not suitable for routine clinical practice. Labeled compounds as alternative filtration markers, including 125I-iothalamate and 99mTc-diethylenetriaminepenta-acetic acid (DTPA), provide accurate and precise GFR measurements, but their use may be limited for safety reasons. To avoid exposing patients to radiation, investigators have proposed clearance procedures using minute doses of non-radioactive contrast agents, including iothalamate (ionic) and iohexol (non-ionic). This approach provides similar accuracy to inulin clearance. The most important limitation of all renal clearance methods is that urine is collected by spontaneous voiding, stimulated by water loading, and thus subject to errors due to incomplete emptying of the bladder. Thus, plasma clearance of a suitable exogenous marker (51Cr-EDTA, 125I-iothalamate, iohexol) has been suggested for measuring renal function, in which the elimination rate of the tracer after a single intravenous injection is evaluated. Plasma clearance of these markers estimated by multiple blood samples provides more precise information, but repeated sampling makes this method cumbersome. To overcome this drawback, abbreviated kinetic profiles have been proposed to predict GFR from the plasma disappearance curve (elimination phase). On analyzing the data with a simplified method that uses a one-compartment model (six blood samples only in the elimination phase), corrected with the Bröchner-Mortensen formula, an excellent correlation was found with inulin clearance. This method is currently employed for measuring GFR in multicenter clinical trials.

Animals↗
PubMed1998

Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine protein excretion rate, glomerular filtration rate, and end stage renal failure in chronic renal disease in patients without diabetes.

OBJECTIVE: To evaluate whether the protein:creatinine ratio in spot morning urine samples is a reliable indicator of 24 hour urinary protein excretion and predicts the rate of decline of glomerular filtration rate and progression to end stage renal failure in non-diabetic patients with chronic nephropathy. DESIGN: Cross sectional correlation between the ratio and urinary protein excretion rate. Univariate and multivariate analysis of baseline predictors, including the ratio and 24 hour urinary protein, of decline in glomerular filtration rate and end stage renal failure in the long term. SETTING: Research centre in Italy. SUBJECTS: 177 non-diabetic outpatients with chronic renal disease screened for participation in the ramipril efficacy in nephropathy study. MAIN OUTCOME MEASURES: Rate of decline in filtration rate evaluated by repeated measurements of unlabelled iohexol plasma clearance and rate of progression to renal failure. RESULTS: Protein:creatinine ratio was significantly correlated with absolute and log transformed 24 hour urinary protein values (P = 0.0001 and P < 0.0001, respectively.) Ratios also had high predictive value for rate of decline of the glomerular filtration rate (univariate P = 0.0003, multivariate P = 0.004) and end stage renal failure (P = 0.002 and P = 0.04). Baseline protein:creatinine ratios and rate of decline of the glomerular filtration rate were also significantly correlated (P < 0.0005). In the lowest third of the protein:creatinine ratio (< 1.7) there was 3% renal failure compared with 21.2% in the highest third (> 2.7) (P < 0.05). CONCLUSIONS: Protein:creatinine ratio in spot morning urine samples is a precise indicator of proteinuria and a reliable predictor of progression of disease in non-diabetic patients with chronic nephropathies and represents a simple and inexpensive procedure in establishing severity of renal disease and prognosis.

Circadian Rhythm↗
PubMed1976

Influence of ureteral catheter size on urinary flow rate and glomerular filtration rate in the rat.

The influence of ureteral catheter diameter on renal function was studied in rats during different diuretic states. Urinary flow rate and glomerular filtration rate were measured on each rat using ureteral catheters of two different internal diameters. In non-diuretic rats, urinary flow rate and glomerular filtration rate did not change according to the catheter diameter. In diuretic rats, urinary flow rate was from 40 to 70% lower with the smaller catheter. Differences became more marked as urinary flow rate increased. Glomerular filtration rates were about 20% lower when measured with small catheters. These results clearly demonstrate that the use of small diameter ureteral catheters during diuretic states leads to a decrease in glomerular filtration rate and urinary flow rate. The results also emphasize the importance of using large diameter catheters during such experimental conditions.

Animals↗
PubMed2000

Altered podocyte structure in GLEPP1 (Ptpro)-deficient mice associated with hypertension and low glomerular filtration rate.

Glomerular epithelial protein 1 (GLEPP1) is a receptor tyrosine phosphatase present on the apical cell surface of the glomerular podocyte. The GLEPP1 gene (PTPRO:) was disrupted at an exon coding for the NH(2)-terminal region by gene targeting in embryonic stem cells. Heterozygote mating produced the expected genotypic ratio of 1:2:1, indicating that the Ptpro(-/-) genotype does not lead to embryonic or neonatal lethality. Kidney and glomerular structure was normal at the gross and light microscopic levels. Scanning and transmission electron microscopy showed that Ptpro(-/-) mice had an amoeboid rather than the typical octopoid structure seen in the wild-type mouse podocyte and that there were blunting and widening of the minor (foot) processes in association with altered distribution of the podocyte intermediate cytoskeletal protein vimentin. Reduced filtration surface area in association with these structural changes was confirmed by finding reduced glomerular nephrin content and reduced glomerular filtration rate in Ptpro(-/-) mice. There was no detectable increase in the urine albumin excretion of Ptpro(-/-) mice. After removal of one or more kidneys, Ptpro(-/-) mice had higher blood pressure than did their wild-type littermates. These data support the conclusion that the GLEPP1 (Ptpro) receptor plays a role in regulating the glomerular pressure/filtration rate relationship through an effect on podocyte structure and function.

Albumins↗
PubMed1993

Effect of aldose reductase inhibitor (tolrestat) on urinary albumin excretion rate and glomerular filtration rate in IDDM subjects with nephropathy.

OBJECTIVE: To explore the possible link between diabetic nephropathy and the enhanced activity of the polyol pathway, known to occur in IDDM subjects. RESEARCH DESIGN AND METHODS: We studied the effects of the aldose reductase inhibitor tolrestat (200 mg/day) on urinary albumin excretion rate and glomerular filtration rate in 20 IDDM patients with diabetic nephropathy. RESULTS: Six months of placebo treatment produced no significant changes in glomerular filtration rate, urinary albumin excretion rate, and renal plasma flow. Consequently, filtration fraction remained unchanged. During tolrestat treatment, glomerular filtration rate decreased from the basal value of 156 +/- 14 ml.min-1.1.73 m2 to 142 +/- 13.7 ml.min-1.1.73 m2 (P < 0.001) at 2 mo; 128 +/- 12.4 ml.min-1.1.73 m2 (P < 0.001) at 4 mo; and 123.7 +/- 13.0 ml.min-1.1.73 m2 at 6 mo. A significant decrease of urinary albumin excretion rate was observed during the trial (basal values 219 +/- 32.5 vs. 196.9 +/- 28.5 micrograms/min at 2 mo [P < 0.05]; 171.6 +/- 25.5 micrograms/min at 4 mo [P < 0.001]; and 58.6 +/- 19.3 micrograms/min at 6 mo [P < 0.001]). No significant change in renal plasma flow was seen during tolrestat treatment. Filtration fraction significantly decreased in the tolrestat group from the basal value of 0.23 +/- 0.02 to 0.21 +/- 0.01 at 2 mo (P < 0.005); 0.18 +/- 0.02 at 4 mo (P < 0.001); and 0.17 +/- 0.02 at 6 mo (P < 0.001). CONCLUSIONS: The polyol pathway is implicated in hemodynamic changes associated with early diabetic nephropathy, and aldose reductase treatment can positively influence these parameters.

Adult↗
PubMed2006

Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.

BACKGROUND: Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease but require calibration of the serum creatinine assay to the laboratory that developed the equation. The 4-variable equation from the Modification of Diet in Renal Disease (MDRD) Study has been reexpressed for use with a standardized assay. OBJECTIVE: To describe the performance of the revised 4-variable MDRD Study equation and compare it with the performance of the 6-variable MDRD Study and Cockcroft-Gault equations. DESIGN: Comparison of estimated and measured GFR. SETTING: 15 clinical centers participating in a randomized, controlled trial. PATIENTS: 1628 patients with chronic kidney disease participating in the MDRD Study. MEASUREMENTS: Serum creatinine levels were calibrated to an assay traceable to isotope-dilution mass spectrometry. Glomerular filtration rate was measured as urinary clearance of 125I-iothalamate. RESULTS: Mean measured GFR was 39.8 mL/min per 1.73 m2 (SD, 21.2). Accuracy and precision of the revised 4-variable equation were similar to those of the original 6-variable equation and better than in the Cockcroft-Gault equation, even when the latter was corrected for bias, with 90%, 91%, 60%, and 83% of estimates within 30% of measured GFR, respectively. Differences between measured and estimated GFR were greater for all equations when the estimated GFR was 60 mL/min per 1.73 m2 or greater. LIMITATIONS: The MDRD Study included few patients with a GFR greater than 90 mL/min per 1.73 m2. Equations were not compared in a separate study sample. CONCLUSIONS: The 4-variable MDRD Study equation provides reasonably accurate GFR estimates in patients with chronic kidney disease and a measured GFR of less than 90 mL/min per 1.73 m2. By using the reexpressed MDRD Study equation with the standardized serum creatinine assay, clinical laboratories can report more accurate GFR estimates.

Adult↗
PubMed2001

Of mice and men and elephants: metabolic rate sets glomerular filtration rate.

Allometric scaling deals with the functional consequences of changes in size or scale among geometrically dissimilar animals (ie, animals differing in proportions). For adult mammals ranging in size and proportion from mouse to elephant, the data describe an interdependent set of functions consisting of metabolism (measured as metabolic rate), glomerular filtration rate (GFR), effective renal plasma flow, excretion of nitrogenous waste products, cardiac output, and pulmonary function-related variables. Within this set of functions, evidence indicates that metabolic rate is the primary process. One important design feature is given by the ratio of GFR to metabolic rate. Because this ratio is independent of size, it can be generalized to all mammals in this series. The numeric value of this ratio gives the optimal GFR for each unit of metabolic rate. A simple hypothesis is proposed: metabolic rate, the primary process, sets GFR. This relationship is unidirectional. A decrease in GFR, for example, caused by nephron loss, should not lead to a change in metabolic rate. This hypothesis was tested in four natural experiments: human growth and development, thyroid dysfunction, chronic renal failure, and hibernation. The results are consistent with this hypothesis.

Age Factors↗
PubMed2001

Chromium-51 ethylenediamine tetraacetic acid glomerular filtration rate: a better predictor than glomerular filtration rate calculated by the Cockcroft-Gault formula for renal involvement in systemic lupus erythematosus patients.

OBJECTIVE: To investigate whether the ethylenediamine tetraacetic acid (EDTA) glomerular filtration rate (GFR) is a better indicator of the degree of renal involvement than serum creatinine concentration or creatinine clearance calculated by the Cockroft-Gault formula. METHODS: We studied prospectively all systemic lupus erythematosus (SLE) patients with normal or borderline serum creatinine concentration (<110 micromol/l) and urinary sediment abnormalities and/or proteinuria in the last 2 yr. EDTA-GFR, serum creatinine concentration, calculated creatinine clearance (Cockroft-Gault formula) and 24-h urine protein were determined at the same time. Renal biopsies were performed in patients with low values of EDTA-GFR or significant proteinuria. RESULTS: Twenty-three patients were identified, of whom 22 were females. The average age of the patients was 31.6+/-8.2 yr. Biopsies were assigned to WHO classes as follows: class II, 1 patient; class III, 6 patients; class IV, 10 patients; class V, 6 patients. The average serum creatinine concentration, EDTA-GFR and calculated creatinine clearance were 79.8+/-mol/l, 74.5 ml/min and 97 ml/min respectively. EDTA-GFR showed abnormal values (<80 ml/min) in 15 of the 23 patients (65.2%) while calculated creatinine clearance was abnormal (<80 ml/min) in three of the 23 patients (13%) (P<0.001). Using the Pearson correlation test, we did not find any correlation between EDTA-GFR or creatinine clearance values and the sum of activity and chronicity indices. CONCLUSION: GFR performed by EDTA-GFR correctly predicted renal involvement in SLE patients, whereas GFR calculated by the Cockcroft-Gault formula may have underestimated renal function. Significant numbers of patients with WHO class III, IV or V lupus nephritis may be missed if biochemical creatinine clearance or serum creatinine concentration alone is used to assess renal disease.

Adolescent↗
PubMed1986

Effect of experimental diabetes on glomerular filtration rate and glomerular prostanoid production in the rat.

Glomerular hyperfiltration is an early functional renal lesion seen both in experimental and human diabetes mellitus. This increase in the glomerular filtration rate has been thought to be mediated, in part, by changes in vasoregulatory hormones such as the prostanoids. The present study was designed to measure glomerular prostanoid production in rats with experimental diabetes to determine whether the biochemical changes in prostanoid production could be consistent with the hemodynamic alterations noted. Sprague-Dawley rats were studied either 7 or 28 days after intravenous streptozotocin administration (60 mg/kg). Measurements of the glomerular filtration rate were performed in two groups of diabetic animals 28 days after streptozotocin administration: one group with intact prostanoid production, the other having received a cyclooxygenase inhibitor for the 4-week period. Similar studies were performed in nondiabetic control rats. Measurements of glomerular prostanoid production were performed in control and diabetic animals 7 days after streptozotocin administration. The results of these studies indicate that experimental diabetes mellitus is associated with an increase in the glomerular filtration rate and that this increase can be blocked by the administration of a cyclooxygenase inhibitor. In addition, the determination of levels of various glomerular prostanoids indicated an increased production of prostacyclin and a decreased production of thromboxane during this period of hyperfiltration. Thus, these data support the premise that altered prostanoid biosynthesis may be one of the biochemical mediators of the hyperfiltration seen in early experimental diabetes mellitus.

Animals↗
PubMed2006

Autologous hematopoietic stem cell transplant with melphalan and thiotepa is safe and feasible in pediatric patients with low normalized glomerular filtration rate.

Normalized glomerular filtration rate (nGFR) <60 mL/min/1.73 m(2) often precludes hematopoietic stem cell transplant (HSCT) in pediatric patients. Three patients with nGFR < 60 mL/min/1.73 m(2) enrolled on an institutional phase I trial of HSCT preparative therapy for advanced and recurrent solid tumors with escalating melphalan, ranging from 135 to 180 mg/m(2), thiotepa (600 mg/m(2)), and vincristine (2 mg/m(2)). An additional patient with low nGFR was treated with the same preparative therapy. None of the patients developed acute renal failure, excess toxicities during HSCT or delayed engraftment. These cases demonstrate that it is feasible and safe to perform HSCT in pediatric patients with low nGFR using melphalan- and thiotepa-based preparative therapy.

Antineoplastic Agents, Alkylating↗
PubMed1974

Experience with the cumulative integral method for measurement of glomerular filtration rate.

The glomerular filtration rate (GFR) was estimated using (125)I-iothalamate by the cumulative integral method in 95 subjects - 16 normal subjects and 79 patients with suspected or proved renal disease. This method is accurate, simple to perform and theoretically sound. It minimizes errors due to transit time and bladder storage. The normal range of GFR was determined to be 71 +/- 10 (two standard deviations) ml/min/m(2). In 66 patients serum creatinine levels were compared with the GFR value expressed per square metre. For any given serum creatinine level there is a wide range of GFR values. A serum creatinine value in the normal range, i.e. between 0.7 and 1.3 mg/dl, cannot be used to predict the patient's GFR. The micro blood sampling technique makes this method particularly useful in infants.

Adult↗
PubMed2005

Low calorie commercial sugar is a sensitive marker of glomerular filtration rate.

BACKGROUND: Glomerular filtration rate (GFR) in humans and animals might be determined with precision by measuring the clearance of an ideal marker, such as inulin. However, the use of inutest, an inulin analog, is limited by its cost and accessibility. The present study tested whether low calorie commercial sugar (LC sugar) can be used to measure GFR during normal and renal dysfunction. METHODS: Two groups of 6 male Wistar rats weighing 300 to 350 g were included. One group was treated with a daily dose of cyclosporine (CsA) 30 mg/kg subcutaneously for 7 days and the other group was formed by nontreated control rats. In one half of each group, GFR was evaluated by using inutest and in the other half by using LC sugar. GFR was also evaluated by using a wide LC sugar plasma concentration range in an additional group. RESULTS: In nontreated rats, the mean GFR evaluated with LC sugar was 2.2 +/- 0.1 mL/min. This value is equal to that obtained with inutest: 2.3 +/- 0.1 mL/min. CsA administration produced a significant reduction of renal blood flow and renal function. The GFR reduction induced by CsA was similarly determined by both LC sugar and inutest to be at 1.0 +/- 0.2 and 1.1 +/- 0.2 mL/min (P= NS), respectively. In addition, GFR did not change when LC sugar plasma concentration gradually increased. CONCLUSION: Our results show that in both normal and pathophysiologic conditions, LC sugar is a good marker of GFR similar to the gold standard inutest.

Animals↗
PubMed2002

Cystatin C: an improved estimator of glomerular filtration rate?

BACKGROUND: Glomerular filtration rate (GFR) is routinely assessed by measuring the concentrations of endogenous serum markers such as blood urea nitrogen and serum creatinine (SCr). Although widely used, these endogenous markers are not ideal and do not perform optimally in certain clinical settings. The purpose of this review is to critically review the potential utility of cystatin C (CysC), especially in patient populations in which CysC may have an advantage over routinely used endogenous markers of GFR. APPROACH: In a narrative approach, we extensively review publications, primarily from the last 5 years, that address the development of methods to measure CysC, reference intervals, and the diagnostic accuracy of CysC to assess GFR. Between June 2000 and September 2001 Medline was searched using "cystatin c" as a textword, and articles that examined >75 individuals (except for renal transplant studies) and/or used accepted "gold standards" for assessing GFR were selected for inclusion. A total of 17 studies are reviewed that provide reference interval data for several populations. A total of 24 studies make conclusions about the utility of CysC vs SCr and/or creatinine clearance, with 20 providing data on the sensitivity and specificity of CysC for detecting impaired GFR. These publications are organized into subgroups that deal with specific patient populations or clinical situations. CONTENT: This review focuses on two areas: (a) the evolution of immunoassays used to determine the concentration of CysC in serum, their analytic sensitivity, and reference intervals; and (b) the diagnostic performance of CysC against other renal markers in the general population and in specific subpopulations of patients. SUMMARY: Studies of reference intervals for CysC overwhelmingly demonstrated that CysC values in blood are independent of age and sex. Of the 24 studies that examined clinical utility, 15 concluded that CysC is superior to SCr, whereas 9 concluded that CysC is equivalent but provides no advantage. Summary ROC plot analysis of 20 studies that provide sensitivity and specificity data strongly suggests that CysC will be superior to SCr for detecting impaired GFR. Taken together, it is clear that CysC performs at least as well as SCr in the population at large and that it is likely to be superior to SCr in specific patient populations.

Biomarkers↗
PubMed1990

Autoregulation of the glomerular filtration rate and the single-nephron glomerular filtration rate despite inhibition of tubuloglomerular feedback in rats chronically volume-expanded by deoxycorticosterone acetate.

Tubuloglomerular feedback (TGF) function and autoregulation (renal blood flow RBF; glomerular filtration rate, GFR; single-nephron glomerular filtration rate, SNGFR) were examined in rats chronically treated with deoxycorticosterone acetate (DOCA) and given isotonic saline to drink. DOCA treatment depressed arterial plasma renin activity, expanded plasma volume by 25% and increased arterial blood pressure. Autoregulation of RBF and GFR was maintained in the DOCA animals above 90 mm Hg and 110 mm Hg respectively, whereby both GFR and RBF were lower than in controls. Micropuncture experiments demonstrated the absence of TGF in the DOCA animals. There was no difference between SNGFR values measured in the distal and proximal tubules, nor was there a significant response of SNGFR when loops of Henle were perfused with Ringer's solution at 20 nl/min. Loop perfusion in control rats with tubular fluid collected in DOCA rats elicited a normal TGF response, showing that TGF inhibition in the DOCA animals is due to changes in the function of the juxtaglomerular apparatus. In contrast to control rats, proximal SNGFR was perfectly autoregulated. These results suggest that TGF is not primarily responsible for autoregulation and that the vasodilatation normally resulting from acute TGF interruption is therefore compensated by some other mechanism such that RBF and GFR are lower than in controls.

Animals↗