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PubMed1999

Comparison of iothalamate clearance methods for measuring GFR.

STUDY OBJECTIVE: To evaluate the bias and precision of three methods of measuring glomerular filtration rate (GFR) relative to a standard method. DESIGN: Prospective, outpatient study. SETTING: University-affiliated general clinical research center. PATIENTS: Twenty-six patients with various degrees of renal function (GFR range 25-151 ml/min/1.73 m2). INTERVENTIONS: Each patient received iothalamate twice during the study visit, first as a bolus injection and then as a priming dose followed by a constant-rate infusion for 2.5 hours. MEASUREMENTS AND MAIN RESULTS: Plasma (ClpIVB) and renal clearances (ClrIVB) after bolus injection and plasma clearance during constant-rate infusion (ClpINF) were compared with standard renal clearance during constant-rate infusion (ClrINF). All three measures were highly correlated with ClrINF (r>0.90, p<0.001). The mean ClrIVB was not significantly different from ClrINF (106.3+/-30.4 vs 104.2+/-28.5 ml/min/1.73 m2) and provided a precise (8.8%, 95% CI 6.5-11.1%) and unbiased measure of GFR. Both ClpIVB and ClpINF were positively biased; values exceeded ClrINF by 11.8+/-11.1 (p=0.0001) and 10.5+/-12.5 ml/min/1.73 m2 (p=0.0003), respectively. Use of a nonrenal correction factor of 9.8 and 10.5 ml/min/1.73 m2 for infusion and bolus plasma clearance values, respectively, eliminated bias and improved the precision of these methods. CONCLUSIONS: Iothalamate renal clearance after bolus injection is a simple, accurate, and precise measurement of GFR and may be a useful alternative to the standard infusion method in clinical investigations. The corrected plasma clearance provides a simple index of GFR for clinical practice.

Adult↗
PubMed2005

An alternative formula to the Cockcroft-Gault and the modification of diet in renal diseases formulas in predicting GFR in individuals with type 1 diabetes.

Chronic kidney disease is currently on the rise and not only leads to ESRD necessitating dialysis or transplantation but also increases cardiovascular disease risk. Measurement of the GFR, the gold standard for assessing kidney function, is expensive and cumbersome. Several prediction formulas that are based on serum creatinine are currently used to estimate the GFR, but none has been validated in a large cohort of individuals with diabetes. The performance of two commonly used formulas, the abbreviated Modification of Diet in Renal Disease (MDRD) study formula for the GFR and the Cockcroft-Gault estimate of creatinine clearance, were examined against GFR measured by the renal clearance of iothalamate in 1286 individuals with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT). The performance of these formulas was assessed by computing bias, precision, and accuracy. The DCCT participants had normal serum creatinine, unlike the MDRD patients, and somewhat lower creatinine excretion than subjects in the original cohort Cockcroft Gault, which led to biased and highly variable estimates of GFR when these formulas were applied to the DCCT subjects. The MDRD substantially underestimated iothalamate GFR, whereas the Cockcroft Gault formula underestimated it when it was <120 ml/min per 1.73 m(2) and overestimated it when iothalamate GFR was >130 ml/min per 1.73 m(2). Overall, only one third of the formula's estimates were within +/-10% of iothalamate GFR. By underestimating GFR, these formulas were likely to flag early declines in kidney function. Refitting the MDRD formula to the DCCT data gave a more accurate and unbiased prediction of GFR from serum creatinine; percentage of estimate within 10% of measured GFR increased to 56%. A substantial variability in the estimates, however, remained.

Adult↗
PubMed1991

Radiocontrast increases plasma and urinary endothelin.

Recent studies indicate that endothelin (ET), a potent endogenous systemic and renal vasoconstrictor peptide, may mediate decreases in GFR in models of acute renal dysfunction. Moreover, in an animal model of radiocontrast-induced nephropathy (RCIN), it was recently demonstrated that early renal hemodynamic responses to radiocontrast are attenuated by intra-arterial atrial natriuretic factor (ANF), which prevents subsequent RCIN. The studies presented here were therefore designed to determine whether i.v. infusion of radiocontrast produces increases in endogenous plasma and urinary ET and whether these responses are modulated by intra-arterial ANF in an animal model of RCIN. In these studies, dogs with pacing-induced heart failure received i.v. radiocontrast in the presence and absence of an intra-aortic infusion of ANF. Significant increases in both plasma and urinary ET were observed during and after radiocontrast. Although coadministration of ANF did not prevent increases in plasma and urinary ET, ANF preserved renal function acutely in this model of RCIN by increasing GFR above baseline levels.

Acute Kidney Injury↗
PubMed1992

Radiocontrast agents induce endothelin release in vivo and in vitro.

The intravascular administration of the ionic radiocontrast agent sodium iothalamate (2.9 g of iodine/kg body wt) to rats induced an increase in plasma concentration of immunoreactive endothelin from 21.3 +/- 1.2 to 36 +/- 3 fmol/mL, preceded by a transient rise in the plasma level of atrial natriuretic peptide and associated with a fall in RBF. Equi-iodine amounts of the nonionic agents ioxaglate and iohexol elicited similar or more marked changes in plasma endothelin, but hypertonic solutions of NaCl, mannitol, or glucose did not. Comparable levels of endothelin produced by infusions of endothelin-1 induced a reduction of up to 29% in RBF. Iothalamate and iohexol stimulated endothelin release from cultured bovine endothelial cells, suggesting a direct effect of ionic and nonionic agents on vascular endothelium. The data invite speculation that under some circumstances endothelin release might play a role in the circulatory changes caused by these compounds and in the pathogenesis of radiocontrast nephropathy.

Animals↗
PubMed1992

Acute unilateral nephrectomy elicits a specific increase in plasma of peptides derived from the N-terminal region of proopiomelanocortin.

Acute unilateral nephrectomy (AUN) causes natriuresis from the contralateral kidney through neurohumoral reflex pathways that involve an increase in the plasma of peptides derived from the N-terminal region of the adrenocorticotropic hormone (ACTH)/beta-endorphin precursor proopiomelanocortin (POMC). To determine the specificity of these humoral changes, the concentrations in plasma of ACTH and two peptides arising from the N-terminal fragment (NTF) of POMC, NTF32-49 and gamma-melanocyte-stimulating hormone (gamma-MSH), and of another natriuretic peptide, atrial natriuretic peptide (ANP), were measured by RIA with highly specific antisera to these epitopes. Group I experiments followed the course of sodium excretion (UNaV) for 120 min after AUN or sham nephrectomy. UNaV more than doubled within 60 min of AUN, and this natriuresis was maintained for the remainder of the experiment, whereas UNaV in sham rats did not change. There was no difference in plasma immunoreactive (ir) ACTH or ir-ANP concentrations between sham and AUN rats 120 min after the procedure, but plasma ir-NTF concentration was double in AUN rats compared with sham (P < 0.03). In Group II experiments, animals were killed 30, 60, 90, or 120 min after AUN and the urinary response related to peptide concentrations in plasma. UNaV rose rapidly after AUN, reaching a maximum value within 45 min that again was double the control value and remained stable for the duration of the experiment, up to 120 min after AUN. There was no significant change in ir-ACTH or ir-ANP at any point after AUN compared with values in sham AUN rats. However, plasma concentrations of both ir-NTF and ir-gamma-MSH were elevated 30 min after AUN and reached values at 120 min that were again double the values in sham rats (P < 0.05 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1996

Effects of diet and antihypertensive therapy on creatinine clearance and serum creatinine concentration in the Modification of Diet in Renal Disease Study.

Factors other than the glomerular filtration rate (GFR) can affect creatinine clearance (Ccr) and serum creatinine concentration (Pcr). The effect of dietary protein and antihypertensive therapy on Ccr the reciprocal of the Pcr (1/Pcr). and their determinants (GFR, creatinine clearance from tubular secretion (CTScr), and creatinine excretion (UcrV) values) was assessed in patients participating in the Modification of Diet in Renal Disease (MDRD) Study. This study compared the effects of assignment to a low versus usual-protein diet and to a low versus usual-blood pressure goal on the decline in these measurements over 3 yr in 585 patients with baseline GFR of 25 to 55 mL/min per 1.73 m2 (Study A). This study also assessed correlations and associations of these measurements with each other and with protein intake, blood pressure, class of antihypertensive agents, and renal diagnosis in 840 patients with baseline GFR of 13 to 55 mL/min per 1.73 m2 (Studies A and B). In Study A, the estimated mean decline in GFR at 3 yr did not differ significantly between the low and usual-protein diet groups (-10.9 versus -12.1 mL/min). In contrast, CTScr declined more in the low-protein diet group (-7.8 versus -3.6 mL/min, P < .05). Consequently, the low-protein diet group had a greater decline in Ccr (-17.6 versus -14.4 mL/min, P < .05). The low-protein diet group also had a greater decline in UcrV (-306 versus -92 mg/day, P < .05). The decline in UcrV was proportionately greater than the decline in CTScr hence the decline in 1/Pcr was less in the low-protein diet group (-0.091 versus -0.122 dl/mg, P < .05). Similarly, in Study A, there was no significant difference in the decline in GFR at 3 yr between the low and usual-blood pressure groups (-10.7 versus -12.3 mL/ min). However, there was a lesser decline in CTScr in the low blood pressure group (-4.7 versus -6.7 mL/ min, P < .05). Consequently, the decline in Ccr was less in the low blood pressure group (-14.2 versus -17.8 mL/min, P < .05). There was no significant difference in UcrV between the blood pressure groups (-192 versus -205 mg/day). Hence, the decline in 1/Pcr paralleled the decline in Ccr; it was less in the low blood pressure group (-0.091 versus -0.122 dL/mg, P < .05). In Studies A and B, correlations of rates of decline in Ccr and GFR were 0.64 and 0.79, respectively (P < 0.001). Correlations of rates of decline in 1/Pcr and GFR were 0.79 and 0.85, respectively (P < 0.001). In Studies A and B combined, baseline GFR, CTScr and UcrV correlated significantly with protein intake (r = 0.45, 0.47, and 0.36, respectively; P < 0.001), but not with blood pressure. Baseline CTScr was significantly lower in patients with polycystic kidney disease and tubulointerstitial diseases or urinary tract diseases, compared with glomerular and other diseases (P < 0.05). It was also lower in patients who were taking calcium channel blockers, compared with patients not taking these agents, and in patients not taking diuretics, compared with patients taking diuretics (P < 0.05). These results show that creatinine secretion and excretion are affected by protein intake. Creatinine secretion is also affected by antihypertensive therapy and renal diagnosis. In the MDRD Study, the low-protein diet reduced creatinine secretion and excretion, and the low blood pressure goal slowed the decline in creatinine secretion. These effects caused differences between the diet groups and between the blood pressure groups in Ccr and 1/Pcr that were not the result of differences in GFR. Studies assessing the effects of these interventions on the progression of renal disease should measure GFR in addition to Ccr and Pcr.

Antihypertensive Agents↗
PubMedDate not supplied

Plasma exogenous creatinine clearance test in dogs: comparison with other methods and proposed limited sampling strategy.

Plasma clearance of creatinine was evaluated for assessment of glomerular filtration rate (GFR) in dogs. In 6 healthy dogs (Experiment 1), we determined 24-hour urine clearance of endogenous creatinine, plasma, and urine clearances of exogenous creatinine administered at 40, 80, and 160 mg/kg in a crossover design (linearity study), plasma iothalamate clearance, and plasma and urine clearances of 14C-inulin. In Experiment 2, plasma creatinine and iothalamate clearances were compared, and a linearity study was performed as for Experiment 1 in 6 dogs with surgically induced renal impairment. Experiment 3 compared plasma creatinine clearance with plasma iothalamate clearance before and 3 weeks after induction of moderate renal impairment in 6 dogs. Plasma creatinine clearances were calculated by both noncompartmental and compartmental analyses. In Experiment 1, plasma inulin clearance was higher (P < .001) than other clearance values. Plasma creatinine clearances at the 3 dose rates did not differ from urine inulin clearance and each other. In Experiment 2, plasma creatinine clearances were about 14% lower than plasma iothalamate clearance (P < .05). In Experiment 3, decreases in GFR assessed by plasma clearances of iothalamate and creatinine were similar. Renal failure decreased the daily endogenous input rate of creatinine by 25%. Limiting sampling strategies for optimizing GFR calculation were proposed, allowing an error lower than 6.5% with 4 blood samples. These results suggest that determination of plasma creatinine clearance by a noncompartmental approach offers a reliable, inexpensive, rapid, and convenient means of estimating GFR in routine practice.

Animals↗
PubMed2004

Studies on experimental iodine allergy: 2. Iodinated protein antigens and their generation from inorganic and organic iodine-containing chemicals.

We hypothesize that iodine allergy is an immune response to iodinated autologous proteins generated in vivo from iodine-containing organic and inorganic chemicals. In this report, effects of protein iodination on elicitogenic activity in guinea pig iodine allergy model and iodinated protein antigen generation in vitro from iodine-containing chemicals were investigated. Active cutaneous anaphylaxis (ACA) and delayed-type hypersensitivity (DTH) tests were performed in guinea pigs immunized with iodine. The amount of iodine (I2) reacted to proteins for giving them an eliciting activity of ACA was > or = 0.15 micromol for 1 mg of albumin. DTH reactions were provoked by intradermal injection of 10(6) PECs reacted with > or = 0.075 micromol of I2. I2 was generated from a potassium iodide (KI) solution or iodinated contrast media by UV light irradiation. X-ray irradiation of KI and iodinated contrast media in the presence of protein resulted in the generation of iodinated protein antigens. The generation of iodinated protein antigens was inhibited in the presence of reducing agents. Therefore, it is noteworthy that iodine allergy of the present hypothesis is dependent on reactive oxygens. By presenting these ex vivo and in vitro data, we discuss the possibilities for the generation of iodinated protein antigens in vivo.

Adoptive Transfer↗