Single-injection Inulin Clearance Research Articles

Variables of interest to predict glomerular filtration rate in preterm newborns in the first days of life.

Measurement of neonatal renal function is challenging, and accurate, easy-to-use markers to estimate glomerular filtration rate (eGFR) are lacking. This study aimed to evaluate principal determinants of GFR in neonates and develop a predictive equation. GFR was measured, using single injection inulin clearance, at median day 3 of life in 48 newborns. Associations of clearance with height, gestational age, weight, creatinine, and cystatin C were explored and a multivariable model to estimate GFR developed. We also evaluated preexisting GFR equations (Schwartz, Zappitelli, combined Zappitelli). Forty-four clearances were measured, 36 very preterm neonates (28-32weeks); 5 extremely preterm (< 28weeks), and 3 term newborns. No patient presented acute renal insufficiency. Median inulin clearance in preterm infants was 18.83ml/min/1.73m2 (IQ 15.29; 24.99). Inulin clearance correlated with weight (ρ 0.74), gestational age (ρ 0.72), height (ρ 0.49), and creatinine (ρ - 0.42), but not cystatin C. In the multivariable model, predicted GFR equation was 2.32* (weight (g))0.64/(creatinine (mcmol/l))0.62. Mean error in predicting clearance was - 0.8ml/min/1.73m2 (- 3.0-1.4) ranging from - 14.9 to 13.3ml/min/1.73m2. Mean prediction error with Zappitelli and combined Zappitelli equations were 28.5ml/min/1.73m2 (95% CI 24.6-32.3) and 28.3ml/min/1.73m2 (95% CI 24.9-31.7), respectively, and 2ml/min/1.73m2 (95% CI - 0.6-4.6) for Schwartz equation. Weight and gestational age are crucial determinants of GFR in neonates. The Zappitelli models were not validated in our population. Our predictive model and Schwartz models performed better. Our model should be evaluated in another preterm population, particularly in those presenting renal insufficiency.

GFR-estimation by serum creatinine during glucocorticosteroid therapy

While glucocorticosteroids (GCS) are widely used in patients with kidney disease, little is known about their effect on serum creatinine, the most commonly used endogenous marker of kidney function. We assessed the effect of GCS on the relationship between estimated GFR using the Schwartz equation (eGFR) and measured GFR using a single-injection inulin clearance (Cin) in children both in a paired analysis and a cross-sectional study. Primary outcome variable was the difference between eGFR and Cin (ΔGFR) in a paired analysis involving 22 patients during and off GCS treatment (mean GFR 103.8ml/min/1.73m2, mean prednisone dose 34.8mg/m2/day). In a cross-sectional analysis in 42 patients receiving GCS (mean dose of 25.7mg/m2/day), a dose-dependent effect was explored using univariate and multivariate linear regression of various variables including GCS dosage with serum creatinine as dependent variable. The paired analysis showed no significant difference in ΔGFR with or without GCS [- 23 (SD 53) vs. - 9 (SD 41) ml/min/1.73m2, p = 0.203]. Stepwise multivariate linear regression analysis showed a significant correlation between age and Cin, while GCS dose was not related to serum creatinine. GCS use had no significant effect on serum creatinine as a marker for kidney function in a mixed population of renal outpatient clinic children.

Height-Independent Estimation of Glomerular Filtration Rate in Children: An Alternative to the Schwartz Equation

To compare the diagnostic performance of 2 height-independent equations used to calculate estimated glomerular filtration rate (eGFR), those of Pottel (eGFR-Pottel) and the British Columbia Children's Hospital (BCCH) (eGFR-BCCH), with the commonly used Schwartz equation (eGFR-Schwartz). We externally validated eGFR-Pottel and eGFR-BCCH in a well-characterized pediatric patient population (n = 152) and compared their diagnostic performance with that of eGFR-Schwartz using Bland-Altman analysis. All patients underwent glomerular filtration rate measurement using the gold standard single-injection inulin clearance method (GFR-inulin). Median GFR-inulin was 92.0 mL/min/1.73 m² (IQR, 76.1-107.4 mL/min/1.73 m²). Compared with GFR-inulin, the mean bias for eGFR-Schwartz was -10.1 mL/min/1.73 m(2) (95% limits of agreement [LOA], -77.5 to 57.2 mL/min/1.73 m(2)), compared with -12.3 mL/min/1.73 m² (95% LOA, -72.6 to 47.9 mL/min/1.73 m(2)) for eGFR-Pottel and -22.1 mL/min/1.73 m² (95% LOA, -105.0 to 60.8 mL/min/1.73 m(2)) for eGFR-BCCH. eGFR-Pottel showed comparable accuracy to eGFR-Schwartz, with 77% and 76% of estimates within 30% of GFR-inulin, respectively. eGFR-BCCH was less accurate than eGFR-Schwartz (66% of estimates within 30% of GFR-inulin; P < .01). The performance of eGFR-Pottel is superior to that of eGFR-BCCH and comparable with that ofeGFR-Schwartz. eGFR-Pottel is a valid alternative to eGFR-Schwartz in children and could be reported by the laboratory if height data are not available.

Effect of Corticosteroid Therapy on Low-Molecular–Weight Protein Markers of Kidney Function

Serum cystatin C, β2-microglobulin, and β-trace protein are endogenous markers of glomerular filtration rate (GFR). Cystatin C, in particular, is a promising alternative to creatinine for the detection of incipient renal failure. However, corticosteroids affect the extrarenal metabolism of cystatin C, which limits the use of cystatin C as a marker of GFR in a variety of clinical settings. Low-molecular–weight (LMW) β-trace protein might be a useful alternative in this respect. The present study set out to compare the effect of corticosteroid therapy on the serum concentrations of cystatin C, β2-microglobulin, and β-trace protein. We studied a group of 108 children being treated or followed for malignancy (n = 41) or renal disease (n = 67). In the former group 14 patients (34%) were treated with glucocorticoids, in the latter 18 (27%). We compared single-injection inulin clearance studies in 76 patients not receiving steroids with 32 in patients receiving corticosteroid treatment (median dose 33.0 mg prednisone-equivalent per m2 body surface area per day, range 1.2–70.4). Mean (SD) age was 9.7 (5.8) years, mean (SD) GFR 92.8 (34.6) mL · min−1 · (1.73 m2)−1. Patients included in the …

Single-injection inulin clearance for routine measurement of glomerular filtration rate in cats

Glomerular filtration rate (GFR) was determined in 53 cats using an inulin single-injection method. Thirty healthy young adult cats were used to establish normal values. The procedure was also used in 23 cats that were either older than 10 years or had borderline serum creatinine levels. The total clearance was calculated from the decay of the serum inulin concentration after injection of 3000 mg/m 2body surface area using a two-compartment model. Concomitant inulin and iohexol clearance in nine cats showed excellent correlation between the two methods. Calculated normal values for GFR in 30 healthy cats were 35.9–58.5 (median 46.0) ml/min/m 2or 2.07–3.69 (median 2.72) ml/min/kg. A few cats with normal creatinine or blood urea nitrogen levels were detected as having reduced GFR and therefore being in a state of early renal dysfunction. The study indicates that single-injection inulin clearance is a valuable tool for routine GFR measurement in cats. An ‘inulin excretion test’ using only one blood sample 3 h after the administration of 3000 mg/m 2body surface area could prove an attractive alternative for the assessment of renal function in daily practice.

Middle molecule and small protein removal in children on peritoneal dialysis

Dialysis efficiency has a great influence on the outcome of patients. Few data are available on the removal of solutes with molecular weights higher than urea and creatinine. The aim of our study was to assess the transport and the removal of substances with molecular weights up to 15 kD and to evaluate the contribution of residual renal function in peritoneal dialysis (PD) children. Seventeen patients of 12 +/- 4 years undergoing automated PD were studied. Ten patients had 563 +/- 355 mL/day of urine output, and 7 were anuric. During a standardized nightly intermittent PD (NIPD) session, a single-injection inulin clearance was performed. Urea, creatinine, inulin (measured by HPLC), cystatin C and beta2-microglobulin (beta2m) were measured in blood, urine and dialysate. Clearances (L/week/1.73 m2) and weekly solute removal index (SRI) were calculated for all the solutes; weekly Kt/V was calculated for urea. In non-anuric versus anuric patients the total clearances were: urea 82.6 +/- 18.3 versus 71.3 +/- 26.4; creatinine 82.7 +/- 28.6 versus 47.8 +/- 18.8; inulin 42.8 +/- 11.3 versus 32.8 +/- 20.4; beta2m 14.2 +/- 13.8 versus 9.2 +/- 8.3; cystatin C 20.2 +/- 9.4 versus 9.7 +/- 4.8. In the patients with residual diuresis, the urea was removed mainly by PD (69.2%), while inulin, beta2m and cystatin C were removed by renal clearance (64.0%, 79.5% and 62.8%, respectively). Total, peritoneal and renal weekly Kt/V values in the subjects with residual renal function, were 2.86 +/- 0.70, 1.99 +/- 0.40 and 0.87 +/- 0.43, respectively. Peritoneal weekly Kt/V in the anuric patients was 2.36 +/- 0.85; total weekly Kt/V in the total group was 2.65 +/- 0.78. Weekly SRIs in non-anuric versus anuric patients were: urea 2.56 +/- 0.58 versus 2.09 +/- 0.74; creatinine 2.66 +/- 0.73 versus 1.46 +/- 0.56; inulin 2.36 +/- 0.92 versus 1.64 +/- 1.60; beta2m 1.26 +/- 1.10 versus 1.20 +/- 1.90; cystatin C 1.72 +/- 0.83 versus 1.58 +/- 1.62. Solutes removed during PD tend to decrease following an increase in molecular weight of the substance. Since anuric patients are at higher risk of middle molecule and small protein accumulation, more attention should be paid to the removal of middle molecules. Further studies should be undertaken to evaluate whether removing them has a clinical impact and to determine their threshold levels.

Variability of glomerular filtration rate estimation using single injection methods in Type 1 diabetic patients.

Single-injection inulin clearance (SIIC) methods without urine collection have often been compared with classical constant-infusion inulin clearance methods. Therefore, we used repeated SIIC measurements to prove the hypothesis of a possible overestimation or variability of inulin clearance in Type 1 diabetic patients. Two SIIC periods, glomerular filtration rate 1 and 2 (GFR 1, GFR 2) were performed consecutively on the same day. In diabetic patients, GFR 3 was measured several days later at the same time of day as the GFR 1 had been done. The calculation used a two-compartment modelling system (TCM) which showed excellent agreement to ratio of dose over area under the curve (D/AUC) calculation. Twelve normotensive Type 1 diabetic patients (mean and SD), age 39 (10.7) years, diabetes duration 20 (10.7) years, HbA1c 8.5% (0.82%), albuminuria 13.8 (15.7) mg/24 h and six controls, age 26 (2.6) years were examined. Healthy controls showed an excellent repeatability between GFR 1 111.8 (11.44) and GFR 2 110.8 (11.41) ml.min-1.1.73 m2-1. However, in diabetic patients there was a highly significant decrease between GFR 1 129.4 (11.86) and GFR 2 118.1 (13.05) ml.min-1.1.73 m2-1. GFR 1 with 129.4 (11.86) ml.min-1.1.73 m2-1 did not differ significantly from GFR 3 with 129.9 (12.40) ml.min-1.1.73 m2-1 in diabetic patients (P < 0.839). In contrast to normal subjects, in Type 1 diabetic patients single-injection inulin clearance technique showed a clinically relevant decrease in GFR on two repeated measurements on the same day. Overestimation of GFR by the first inulin clearance may be caused by incomplete inulin distribution in the slow compartment. Diabet. Med. 18, 464-468 (2001)

Glomerular filtration rate by single-injection inulin clearance: definition of a workable protocol for children.

The total serum clearance of inulin after a single intravenous injection is an established method for the determination of the glomerular filtration rate (GFR). To optimize this procedure in children, we analyzed 117 serum inulin time-decay curves in 59 children (age range 1.3-15.2 years)with renal disease. It was found that the two-compartment model fitted statistically better to the disappearance curves of serum inulin than the one-compartment model. The sampling frequency could be reduced from 12 to a minimum of seven data points (t=0, 10, 20, 30, 65, 120 and 240 min) in 4 h without a relevant change in the fit of the two-compartment model to the date or in the calculated clearance of serum inulin. We conclude that, by using a standardized 'seven-sample schedule', followed by a two-compartment analysis, the single-injection serum clearance of inulin is a suitable compromise between practical convenience and clinical accuracy for the determination of the GFR in children.

Single-injection inulin clearance — a simple method for measuring glomerular filtration rate in dogs

The glomerular filtration rates (GFR) of 93 dogs of different breeds with a broad range of bodyweight were determined using an inulin single-injection method. Fifty-two dogs were used as controls, 21 dogs had suspected renal disease but serum creatinine in the normal range, and 20 dogs had elevated serum creatinine levels and a low urine specific gravity due to renal disease. Inulin was injected intravenously at a dosage of 100 mg kg −1 bodyweight or 3000 mg m −2 body surface. Blood samples were taken before and three, 20, 40, 80 and 120 minutes after injection. The total clearance was calculated from the decrease in the serum concentration of inulin using a two-compartment model. The range of GFR values was 83-5–144-3 ml min −1 m −2 in control dogs, 60–96.7 ml min −1 m −2 in dogs with suspected renal disease, 50-0–76-2 ml mine M-2 in dogs with suspected renal disease and polyuria/polydipsia, and 16-3–63-0 ml mine m−2 in dogs with azotaemic renal disease. The study indicates that single-injection inulin clearance is a cheap and simple tool for GFR measurements in small animal practice.

Growth hormone treatment in children with preterminal chronic renal failure: no adverse effect on glomerular filtration rate.

Impaired growth and stunting remains a major therapeutic problem in children with chronic renal failure (CRF). Recombinant human growth hormone (rhGH) treatment may be beneficial, but concern has been raised about possible side-effects, i.e. deterioration of renal function and glucose intolerance. We have treated 10 prepubertal children with CRF (median age 7.5 [1.7-10.0] years) with 4 IU rhGH/m2 per day s.c. over a period of 1 year. Height velocity increased significantly (P less than 0.03) from basal 4.6 (2.0-14.0) cm/year to 9.7 (6.8-17.6) cm/year. Height velocity SDS for chronological age and for bone age increased in all children from basal median -2.3 to +3.8 (P less than 0.005). Median glomerular filtration rate (GFR) measured by single injection inulin clearance at onset was 18 (11-66) ml/min per 1.73 m2 and did not change significantly during the treatment year. The loss of GFR as estimated by creatinine clearance was similar during the treatment year (median loss 1.3 ml/min per 1.73 m2) compared to the year before treatment (median loss 3.7 ml/min per 1.73 m2). Serum glucose levels during an oral glucose tolerance test did not change, but fasting as well as stimulated insulin levels increased significantly with time during the study period. It is concluded that the rhGH regimen employed was remarkably effective in improving growth velocity in children with CRF without adversely affecting GFR. Glucose homeostasis remained stable, but at the expense of increased serum insulin levels.

Practical Approach for Determining Glomerular Filtration Rate by Single-Injection Inulin Clearance

We compared the glomerular filtration rate as measured by a single-injection inulin clearance with that measured by a standard isotope method with 99mTc-labeled diethylenetriaminopentaacetic acid in 21 subjects with glomerular filtration rates greater than 35 mL/min. After a bolus injection of 5 g of inulin, blood samples were taken 20, 45, 90, 120, 145, 180, and 240 min afterwards. Inulin was measured by optimized chemical or enzymatic methods of high analytical sensitivity to determine inulin at low concentrations. We used the one-compartment model and inulin concentrations measured at two sampling times to calculate the glomerular filtration rate from the data of the disappearance curve of inulin. Inulin concentrations at 20 and 240 min after injection of the inulin bolus were suited to estimate glomerular filtration rate by this procedure, resulting in values (y) comparable with those obtained by isotope technique (x). The relationship to the isotope technique was characterized by the equation y = +4.80 mL/min + 0.92x (r = 0.97). The single-injection inulin clearance determination can detect a decrease of glomerular filtration rate at the beginning of kidney damage, given that our study included subjects with glomerular filtration rates greater than 35 mL/min. We conclude that the glomerular filtration rate can be determined by analyzing only two blood samples after a bolus injection of inulin.

Single-Injection Inulin Clearance Using Only One Blood Sample as a Suitable Procedure to Measure Glomerular Filtration Rate

Single-Injection Inulin Clearance Using Only One Blood Sample as a Suitable Procedure to Measure Glomerular Filtration Rate

A simple estimate of glomerular filtration rate in low birth weight infants during the first year of life: Noninvasive assessment of body composition and growth

The management of the preterm infant often requires rapid assessment of glomerular filtration rate (GFR). We sought to develop a screening test using GFR = kL/Pcr, where GFR is expressed as ml/min/1.73 m2, L is body length in centimeters, Pcr is plasma creatinine concentration, and k is a constant that depends on muscle mass. The value for k in 118 appropriate for gestational age preterm infants (0.34 +/- 0.01 SE) was significantly less than that of full-term infants (0.43 +/- 0.02, P less than 0.001). There was no difference between 12- to 24-hour single-injection inulin clearance and either 0.33 L/Pcr or creatinine clearance in preterm infants. We compared the body habitus of preterm and full-term infants using the assessment of muscle mass from urinary creatinine excretion (UcrV) and from upper arm muscle area (AMA) and volume (AMV), and that of fatness from the sum of five skinfold thickness measurements. During the first year of life, premature infants were found to have a lower percentage of muscle mass than term infants did. On the other hand, they took on a relatively greater amount of subcutaneous fat. There was a very good correlation between AMA or AMV and urinary creatinine excretion (r = 0.91 and 0.94, respectively) in 68 infants with heterogeneous body composition during the first year, indicating the validity of the urinary creatinine measurement. Absolute GFR (ml/min) was also well estimated from AMA or AMV factored by Pcr. We conclude that GFR can be well estimated from 0.33 L/Pcr in preterm infants. The lower value for k reflects the smaller percentage of muscle mass in preterm versus term infants. As a screening test, 1.5 X k or 0.05 L/Pcr predicted low values of GFR with an efficiency of 73%, specificity of 67%, and sensitivity of 88%.