Diethylenetriamine Pentaacetic Acid Clearance Research Articles

The accuracy of estimating equations for the evaluation of kidney function in adult survivors of unilateral, nonmetastatic, non-syndromic Wilms tumor: A pilot study from the St. Jude Lifetime Cohort Study.

Adult survivors of unilateral, nonmetastatic, non-syndromic Wilms tumor (WT) treated with whole abdomen radiation therapy (WART) are at risk for impaired kidney function. The impact of bias and accuracy on estimated glomerular filtration rate (eGFR) among adult survivors of WT has not been well documented. We clinically evaluated male and female WT survivors with creatinine and cystatin C, calculated eGFR using the Chronic Kidney Disease-Epidemiology equations with and without cystatin C, and measured 99mTc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. WT survivors treated with unilateral nephrectomy (UN), non-nephrotoxic chemotherapy (NNC) and WART or treated with UN, no radiation therapy, and NNC were enrolled. Correlations between 99mTc DTPA clearance and eGFR were calculated. Bias and the percentage of eGFR calculations that differed from the 99mTc DTPA clearance by 10% or less (P10) or 30% or less (P30) (accuracy) were calculated. Among female WT survivors, none of the eGFR calculations was statistically significantly correlated with 99mTc DTPA clearance. Among both unirradiated and WART-treated male WT survivors, 99mTc DTPA clearance correlated well with eGFR calculations that included creatinine. eGFR calculations that included creatinine were positively biased among female participants compared to 99mTc DTPA clearance, and no P30 was greater than 90% among either irradiated males or females. Among female survivors of unilateral, nonmetastatic, non-syndromic WT who have undergone UN, eGFR is poorly correlated with, is positively biased, and lacks sufficient accuracy, compared to 99mTc DTPA clearance.

Abstract 6381: Long-term kidney function after treatment for unilateral, non-metastatic, non-syndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study

Abstract Background: We previously reported that the estimated glomerular filtration rate (eGFR) was decreased among survivors of unilateral, non-metastatic, non-syndromic Wilms tumor (WT) treated with whole abdomen radiation therapy (WART) compared to controls, but not compared to unirradiated WT survivors (Pediatr Blood Cancer 2020;67:e28271). The impact of sex on estimates of kidney function among adult survivors of WT has not been well-documented. Methods: We clinically evaluated male and female WT survivors with creatinine and cystatin C, calculated eGFR using the Chronic Kidney Disease - Epidemiology (CKD-EPI) equations with and without cystatin C and measured 99mTc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. WT survivors consisted of 20 treated with unilateral nephrectomy (UN), non-nephrotoxic chemotherapy (NNC) and whole abdomen radiation therapy (WART) (mean - 20.2 Gray (Gy); standard deviation (SD) - 9.12 Gy), and 20 treated with UN, no radiation therapy, and NNC. Correlations between 99mTc DTPA clearance and eGFR were calculated. Results: Among female WT survivors, none of the eGFR calculations was statistically significantly correlated with 99mTc DTPA clearance. Among male WT survivors, 99mTc DTPA clearance correlated well with eGFR calculations that included creatinine. Results are shown in the Table. Conclusions: Among female survivors of unilateral, non-metastatic, non-syndromic WT who have undergone UN, eGFR is poorly correlated with 99mTc DTPA clearance. Evaluation of treatment-related changes in body composition may provide insight into these results. Correlation between eGFR and 99mTc DTPA clearance Females eGFR(CKD-EPI) 99mTc DTPA clearance No radiation therapy (n=13) Whole abdomen radiation therapy(n=12) Pearson correlation coefficient p-value Pearson correlation coefficient p-value Creatinine only 0.109 0.723 -0.295 0.352 Cystatin C only 0.311 0.301 0.094 0.782 Creatinine and cystatin C 0.348 0.244 -0.028 0.935 Males No radiation therapy (n=6) Whole abdomen radiation therapy(n=6) Pearson correlation coefficient p-value Pearson correlation coefficient p-value Creatinine only 0.827 0.043 0.859 0.028 Cystatin C only 0.811 0.050 0.592 0.216 Creatinine and cystatin C 0.878 0.021 0.866 0.026 Citation Format: Daniel M. Green, Mingjuan Wang, Matthew J. Krasin, Andrew M. Davidoff, DeoKumar Srivastava, Dennis W. Jay, Kirsten K. Ness, Barry L. Shulkin, Jennifer Q. Lanctot, Kyla C. Shelton, Rachel C. Brennan, Matthew J. Ehrhardt, Stephanie Dixon, Beth A. Kurt, Leslie L. Robison, Melissa M. Hudson, Sheri L. Spunt. Long-term kidney function after treatment for unilateral, non-metastatic, non-syndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6381.

DTPA clearance test: a sensitive method for detecting radiation-induced lung fibrosis in lung cancer patients.

The aim of this study is to analyze the frequency of lung injury and the sensitivity of the diethylenetriamine penta-acetic acid (DTPA) clearance test in detecting lung injury in patients undergoing radiotherapy (RT) to the thorax. Twenty individuals scheduled for RT for lung cancer were included as the patient group. The healthy control group consisted of 20 age and gender-matched individuals who were nonsmokers with no history of comorbidities. We conducted follow-up with patients at 0-1-6 months, performing carbon monoxide diffusion test (DLCO), DTPA clearance test (excluding the first month), and high-resolution computed tomography of the thorax. The control group was followed up with DLCO between the baseline and 6th months. Ninety percent of the patient group was male, and the median age was 62 years. Seventy percent of the patients had squamous cell carcinoma and adenocarcinoma. Pneumonitis was detected in the patient group in the first month (100%) and fibrosis in the sixth month (%100) Both at the beginning and in the sixth month, the DLCO values of patients who received RT were lower than those of the control group ( P = 0.001 and P < 0.001, respectively). While DTPA clearance was similar between irradiated and non-radiated lungs at the beginning, there was a substantial decrease in the irradiated lung in the sixth month( P = 0.001). There was no significant correlation between malignancy type, RT dose, and tumor size( P > 0.05). The DTPA clearance test could be an alternative method for demonstrating radiation injury in patients receiving RT.

Impact of the New Glomerular Filtration Rate Formulas on Kidney Function Assessment in Living Kidney Donors and Candidates.

To address this, we conducted a single-center retrospective cohort study of 150 kidney donors and donor candidates. We calculated pre- and postdonation eGFR using the old and new equations and compared them with measured GFR by 2.8 mCi Tc-99m diethylene triamine penta-acetic acid clearance (mGFRDTPA) and 24-h creatinine clearance (mGFRCrCl). We evaluated the impact of the new equations on donation eligibility and postdonation eGFR. We found that using the new eGFR equations resulted in higher predonation eGFR compared with the old equations but remained significantly lower than mGFRDTPA and mGFRCrCl. We also found that using the new eGFR equations would not exclude any potential donors based on our center's GFR criteria for donation. At 6 mo postdonation, the new equations resulted in higher eGFR values compared with the old equations. The new eGFR equations continue to underestimate GFR in healthy donor candidates but would not exclude any potential donors from donation and resulted in higher eGFR predonation and postdonation in a predominantly White population. eGFR equations designed specifically for potential kidney donors are still needed for better kidney function assessment.

Genetic Modifiers Influencing the Development of Albuminuria in Children with Sickle Cell Anemia

Background: Nephropathy in sickle cell anemia (SCA) begins in childhood and portends chronic kidney disease, renal failure, and early mortality among affected adults. Individuals of African descent have disproportionately higher rates of developing non-diabetic renal disease. Several candidate genetic variants have been identified, including some specific to African Americans, which are associated with the development of albuminuria and renal disease. The influence of genetic polymorphisms on albuminuria and elevated glomerular filtration rate (GFR) in children with SCA, both early signs of sickle nephropathy, has not been investigated.Objectives: To determine the influence of selected single nucleotide polymorphisms (SNPs) on the development of albuminuria and elevated GFR in children with SCA; to identify novel genetic variants influencing albuminuria and GFR by whole exome sequencing (WES).Design/Methods: Genomic DNA was collected on children with SCA enrolled in two prospective studies with pre-hydroxyurea renal assessments (n=185): (1) Hydroxyurea Study of Long-Term Effects (HUSTLE, NCT00305175, n=79) with no prior disease-modifying therapy; and (2) Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH, NCT 01425307, n=106) on chronic transfusions for abnormal TCD velocities. Albuminuria was defined as ≥30mg albumin/gm creatinine on the pre-hydroxyurea urine specimen. GFR was measured in HUSTLE using plasma DTPA (technetium 99m-labeled diethylenetriaminepentaacetic acid) clearance, and estimated GFR (eGFR) in TWiTCH based on serum creatinine. DNA samples were genotyped for 8 candidate SNPs previously associated with renal disease, using PCR-based allelic discrimination, bidirectional Sanger sequencing, and analysis of variable number tandem repeats (VNTR). Associations between albuminuria and genetic polymorphisms were tested using an additive model and correlation trend test. Linked WES data from the same patients were analyzed to identify other variants associated with albuminuria and GFR.Results: Albuminuria was present in 13.1% of patients, including 16.3% in HUSTLE and 11.0% in TWiTCH. APOL1 genetic variants were common (G1 allele frequency = 21.9%, G2 allele = 16.0%, Table) and similar to published cohorts. Children with two APOL1 G1 alleles had an increased risk of albuminuria that approached statistical significance (p=0.053). Conversely, the presence of the DARC SNP that confers Duffy antigen expression had a protective effect (p=.038). WES analysis did not identify additional non-synonymous APOL1 variants linked with albuminuria. However, 93 non-synonymous variants were associated with DTPA GFR (p<0.001). Using patients with eGFR as a validation cohort, 7 variants in FUBP1, ZFAND4, CD163, GMFG and HLA-E maintained their association with kidney filtrative function (p<0.05). In particular, two variants in CD163, which is a macrophage scavenger receptor for hemoglobin-haptoglobin complexes, were strongly associated with increased GFR in both patient cohorts.Table 1Candidate genes associated with microalbuminuria. All SNPs were tested with either an additive or recessive genetic model. *The eNOS VNTR was analyzed by the chi-square method.GeneSNPLocationMAFAlbuminuria (Additive)Variant frequencyCasesControlsAPOL1 G1rs7388531922q1221.9%0.05332.0%20.3%APOL1 G2rs7178531322q1216.0%0.44510.0%16.0%DARCrs28147781q2313.6%0.0384.2%15.7%eNOS 4aVNTR7q3531.2%0.333*31.5%22.7%eNOSrs17999837q3512.5%0.66314.6%12.2%eNOSrs20707447q3515.6%0.29910.4%16.3%CUBNrs791897210p1216.2%0.45712.5%16.8%CUBNrs180123910p122.7%0.1990.0%3.1%Conclusion: Genetic polymorphisms associated with chronic kidney disease in African American adults may influence the development of early-onset albuminuria among children with SCA, including an increased risk among children with ≥1 APOL1 G1 alleles and a decreased risk associated with the DARC SNP. Previously published eNOS and CUBN variants had no measureable effects. WES analysis suggests novel genetic variants including CD163 SNPs may influence the development of elevated GFR in children with SCA, and provide candidate genes for future research. DisclosuresOff Label Use: Hydroxyurea is FDA approved for the treatment of sickle cell anemia in adults, but has not yet been approved in children. . Nottage:Janssen Pharmaceuticals: Employment. Ware:Biomedomics: Research Funding; Bristol Myers Squibb: Research Funding; Bayer Pharmaceuticals: Consultancy; Eli Lilly: Other: DSMB membership.

Measuring GFR: A Systematic Review

No comprehensive systematic review of the accuracy of glomerular filtration rate (GFR) measurement methods using renal inulin clearance as reference has been published. Systematic review with meta-analysis of cross-sectional diagnostic studies. Published original studies and systematic reviews in any population. Index and reference measurements conducted within 48 hours; at least 15 participants studied; GFR markers measured in plasma or urine; plasma clearance calculation algorithm verified in another study; tubular secretion of creatinine had not been blocked by medicines. Endogenous creatinine clearance; renal or plasma clearance of chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA), diethylenetriaminepentaacetic acid (DTPA), iohexol, and iothalamate; and plasma clearance of inulin. Renal inulin clearance measured under continuous inulin infusion and urine collection. Mean bias <10%, median bias <5%, the proportion of errors in the index measurements that did not exceed 30% (P30) ≥80%, and P10 ≥50% were set as requirements for sufficient accuracy. Based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, the quality of evidence across studies was rated for each index method. Renal clearance of iothalamate measured GFR with sufficient accuracy (strong evidence). Renal and plasma clearance of 51Cr-EDTA and plasma clearance of iohexol were sufficiently accurate to measure GFR (moderately strong evidence). Renal clearance of DTPA, renal clearance of iohexol, and plasma clearance of inulin had sufficient accuracy (limited evidence). Endogenous creatinine clearance was an inaccurate method (strong evidence), as was plasma clearance of DTPA (limited evidence). The evidence to determine the accuracy of plasma iothalamate clearance was insufficient. With the exception of plasma clearance of inulin, only renal clearance methods had P30 >90%. The included studies were few and most were old and small, which may limit generalizability. Requirements for sufficient accuracy may depend on clinical setting. At least moderately strong evidence suggests that renal clearance of 51Cr-EDTA or iothalamate and plasma clearance of 51Cr-EDTA or iohexol are sufficiently accurate methods to measure GFR.

Liquid hyper-absorption as a cause of increased DTPA clearance in the cystic fibrosis airway

BackgroundAirway liquid hyper-absorption is a key pathophysiological link between the genetic mutations of cystic fibrosis (CF) and the development of lung disease. Here we consider whether the clearance of radiolabeled diethylene triamine pentaacetic acid (DTPA) might be used to detect changes in airway liquid absorption.MethodsTc99m-DTPA was added to the apical (luminal) surface of primary human bronchial epithelial cell cultures from CF and non-CF lungs. Liquid absorption rates were assessed using an optical method and compared to DTPA absorption rates. Measurements of transepithelial electrical resistance (TER) were made to determine the effect of epithelial permeability. DTPA absorption was assessed after stimuli known to influence liquid absorption (volume addition and osmotic gradients) and in cultures containing different proportions of CF and non-CF cells.ResultsDTPA absorption rate was increased in CF cultures matching previous in vivo studies in individuals with CF. DTPA and liquid absorption rates were proportional. There was no relationship between TER and DTPA absorption rate when measured in individual cultures. Apical volume addition increased both DTPA and liquid absorption rates. DTPA absorption increased in a dose-dependent manner after basolateral mannitol addition was used to create transepithelial osmotic gradients favoring liquid absorption. Conversely, apical mannitol (a candidate therapy) slowed DTPA absorption in CF cultures.ConclusionsThese results imply that DTPA absorption is directly related to liquid absorption, consistent with increased rates of airway surface liquid absorption in the CF airway, and that modification of liquid absorption from osmotic therapies might be detectable through DTPA absorption measurements in vivo.Trial registrationnone

Updated height- and creatinine-based equation and its validation for estimation of glomerular filtration rate in children from developing countries

Since the original Schwartz formula overestimates glomerular filtration rate (GFR), it is proposed that the constant (k) that accounts for the method of creatinine estimation be derived locally. We derived a new k for height (cm)/serum creatinine (mg/dl) (ht/scr) equation by regression analysis. In a cross-sectional observational study, 197 children (2-18 years) with chronic kidney disease (CKD), who underwent reference GFR measurement by plasma clearance of diethylenetriamine pentaacetic acid (dGFR) at a tertiary care hospital, formed the index dataset for deriving the prediction equations for estimating GFR. Serum creatinine was estimated by the kinetic Jaffe method. The prediction equations were validated on a separate cohort of 225 children with CKD. The median creatinine was 0.7 mg/dl and dGFR was 80.5 (interquartile range 18.1-137.5) ml/min/1.73 m(2). The new k (regression coefficient of height/creatinine) was 0.42 (R(2) = 0.61) and the updated equation was GFR = 0.42 × (ht/scr). Addition of age and mid-arm circumference (MAC) to this equation improved R (2) to 62.3%. Based on the above parameters, the new equation for estimating GFR was GFR (ml/min/1.73 m(2)) = 0.257 × [ht/scr](0.95) × [age (year)](-0.19) × [MAC (cm)](0.397). The two equations performed comparably, with a mean bias <2 ml/min/1.73 m(2). The updated ht/scr equation yielded 74% and 24% estimated GFR values that were within 30% and 10% of the measured dGFR, respectively. The updated equation, with a k value of 0.42, provides a reasonably accurate bedside estimate of GFR in children in countries where creatinine is estimated by the kinetic Jaffe method.

Abdominal ultrasound with scintigraphic and clinical correlates in infants with sickle cell anemia: baseline data from the BABY HUG trial.

The purpose of this study is to perform and evaluate baseline abdominal ultrasound in infants with sickle cell anemia who participated in the BABY HUG multiinstitutional randomized placebo-controlled trial of hydroxyurea therapy and to examine the potential relationships among ultrasound results and clinical, nuclear medicine, and laboratory data. After local institutional review board approval and with informed guardian consent, 116 girls and 87 boys (age range, 7.5-18 months) with sickle cell anemia underwent standardized abdominal sonography at 14 institutions. Imaging was centrally reviewed by one radiologist who assessed and measured the spleen, kidneys, gallbladder, and common bile duct. Baseline physical assessment of spleen size, serum alanine aminotransferase and bilirubin levels, (99m)Tc sulfur colloid liver-spleen scans, and (99m)Tc diethylenetriaminepentaacetic acid clearance glomerular filtration rates (GFRs) were obtained. Analysis of variance and the Student test were performed to compare sonographic findings to published results in healthy children and to clinical and laboratory findings. The mean (± SD) spleen volume (108 ± 47 mL) was significantly greater than published normal control values (30 ± 14 mL; p < 0.0001). There was no correlation between spleen volume and function assessed by liver-spleen scan. The mean GFR (125 ± 34 mL/min/1.73 m(2)) was elevated compared with control GFRs (92 ± 18 mL/min/1.73 m(2)). Renal volumes (right kidney, 29 ± 8 mL; left kidney, 31 ± 9 mL) were significantly greater than control volumes (right kidney, 27 ± 3 mL; left kidney, 27 ± 3 mL; p < 0.0001) and were positively correlated with GFR (p = 0.0009). Five percent of patients had sonographic biliary abnormalities (sludge, n = 6; dilated common bile duct, n = 2; and cholelithiasis and thickened gallbladder wall, n = 1 each). There was no correlation between biliary sonographic findings and laboratory results. In infants with sickle cell anemia, sonographic spleen volume does not reflect function, but increased renal volume correlates with GFR and is consistent with hyperfiltration. Sonographic biliary abnormalities can occur early in life, while remaining clinically silent.

Doppler Ultrasound-guided Percutaneous Nephrolithotomy: A Prospective Randomized Study

To evaluate the role, safety, and effectiveness of Doppler ultrasound-guided percutaneous nephrolithotomy (PCNL). The present study was a prospectively randomized controlled trial performed from March 2007 to February 2010. A total of 131 patients, scheduled for PCNL to remove huge renal stones (diameter>35 mm) and staghorn stones, were enrolled and prospectively randomized using a random numbers table into 2 groups. Of the 131 patients, 54 were randomized to ultrasound-guided puncture PCNL (group 1). Group 2 included 57 patients who received Doppler ultrasound-guided PCNL. A total of 30 patients were excluded from the study. The preoperative data included urinalysis, urine culture, complete blood count, biochemistry study, renal ultrasonography, intravenous urography, and technetium-99m diethylenetriaminepentaacetic acid to determine the selective glomerular filtration rate. The intraoperative findings, operative time (from insertion of the puncture needle to the end of the procedure), and outcomes were also recorded. The complete blood count and serum creatinine were also checked. The modified Clavien grading system was used to evaluate the perioperative morbidity of PCNL. No difference was found between the 2 groups with regard to the serum creatinine change, length of stay, return to normal activity, Clavien grade, relative perfusion rate, or glomerular filtration rate, as determined by technetium-99m diethylenetriaminepentaacetic acid clearance, preoperatively and postoperatively. However, the hemoglobin decrease (2.33±0.46 g/dL) in the ultrasound-guided puncture group was greater than that in the Doppler ultrasound-guided group, with statistically significant difference. Doppler ultrasound-guided PCNL is accurate and safe and was associated with less blood loss. We believe that Doppler ultrasound can be an important alternative to B-mode ultrasound guidance.

Clinical investigations of 99mTc–p-aminohippuric acid as a new renal agent

99mTc-p-aminohippuric acid (PAH) is a new radiopharmaceutical rapidly secreted by the kidneys in a manner consistent with tubular secretion. A comparative study of renal scintigraphy and clearance with 99mTc-PAH, diethylene triamine pentaacetic acid (DTPA) and mercaptoacetyltriglycine (MAG,) was performed. 99mTc-PAH was prepared from a lyophilized kit by addition of sodium pertechnetate in the presence of DTPA. Ten healthy individuals were injected with 110 MBq of 99mTc-PAH. A dynamic study was repeated with 99mTc-DTPA and 99mTc-MAG3 several days later, after a 1-day interval. Clearance measurements were performed in five individuals. The mean values of time-to-peak activity (Tmax) and the time from peak to 50% of peak activity (T(1/2)) for 99mTc-PAH (3.6 +/- 0.9 and 6.9 +/- 2.7 min, respectively) and 99mTc-MAG3 (3.5 +/- 0.8 and 6.8 +/- 2.1 min, respectively) were significantly lower in comparison with those of s99mTc-DTPA (4.9 1.7 and 11.7 +/- 1.9 min, respectively). The mean value of 99mTc-PAH clearance (186.9 +/- 12.2 ml/min) was significantly lower in comparison with MAG3 clearance (303.9 +/- 19.5 ml/min) and significantly higher than DTPA clearance (85.0 +/- 24.1 ml/min). Our preliminary results indicate the potential usefulness of 99mTc-PAH for routine renal scintigraphy. Owing to its fast kinetics, excretion properties and high-quality images, it could be a suitable substitute for 99mTc-DTPA. 99mTC-PAH clearance values, however, were significantly lower than those of MAG3, and could not be used for the estimation of renal plasma flow.

Tubulointerstitial nephritis as an extraintestinal manifestation of Crohn's disease

A 12-year-old boy presented to hospital with a 6-month history of crampy pre-defecation abdominal pain, non-bloody diarrhea, anorexia and weight loss. Investigations revealed hypochromic microcytic anemia, a low serum iron level, a low serum ferritin level and an elevated serum creatinine level. Histopathological examination of tissue specimens obtained at esophagogastroduodenoscopy and colonoscopy revealed features of Crohn's disease, and a renal biopsy demonstrated tubulointerstitial nephritis. A second case of tubulointerstitial nephritis in a patient with Crohn's disease, is also presented. Physical examination, laboratory tests including full blood count, electrolytes, renal function, serum albumin, urinalysis and 24 h urinary protein, esophagogastroduodenoscopy, colonoscopy, abdominal ultrasonography, dimercaptosuccinic acid scan, renal diethylene triamine pentaacetic acid clearance study and renal biopsy. Tubulointerstitial nephritis secondary to Crohn's disease. Prednisone therapy (60 mg/day) for 1 month followed by a tapering schedule over 3 months.

Technetium 99m‐diethylene triamine penta‐acetic acid aerosol clearance in the evaluation of pulmonary involvement in sickle cell disease

Pulmonary clearance of inhaled technetium (Tc) 99m-labeled diethylene triamine penta-acetic acid (DTPA) aerosol is a sensitive non-invasive marker of alveolar permeability and patients with interstitial lung diseases show enhanced clearance. However, a previous study in adult patients with diabetes mellitus showed delayed clearance. To investigate DTPA clearance in steady-state, otherwise healthy adult sickle cell disease (SCD) patients and correlate it with pulmonary function tests (PFTs), hematologic and clinical parameters. The subjects were randomly selected from the Hematology Clinic of Mubarak Hospital, Kuwait. Hematologic and pulmonary function data were collected with standard methods. DTPA radio-aerosol clearance studies were performed using ultrafine nebulizer containing 35 mCi (1295 MBq) of Tc 99m-DTPA in its reservoir and t(1/2) clearance in minutes was determined. Average values for both lungs were calculated and compared with normal values for our population. Forty-three subjects (24 SS and 19 S-beta(0)thal) aged between 16 and 45 yr (mean of 27.1 +/- 9.7) were studied. Twenty-two subjects (51.2%) had delayed, while only 10 (23.3%) showed enhanced DTPA clearance. Patients with enhanced clearance showed better PFTs than those with normal or delayed clearance. There was significant negative correlation of DTPA clearance with forced expiratory volume in 1 s, forced vital capacity and total lung capacity and significant positive correlation with age. Majority of adult SCD patients have delayed DTPA clearance unlike in inflammatory lung diseases, but similar to diabetes mellitus. DTPA clearance may be a useful modality for monitoring pulmonary involvement in SCD.

Sequential pulmonary effects of radiotherapy detected by functional and radiological end points in women with breast cancer

To determine the pulmonary effects of locoregional irradiation on clinical and sub-clinical radiographic and functional end points in women with breast cancer, and whether the course of these end points is affected by laterality. Twenty patients (10 irradiated on the left side and 10 irradiated on the right side) were prospectively evaluated for changes in pulmonary function tests, Tc-99m DTPA (diethylenetriamine pentaacetic acid) lung clearance scintigraphy and high-resolution computed tomography (HRCT) at 6, 16 and 52 weeks after radiotherapy. Tc-99m DTPA clearance, expressed as the biological half-time, T(1/2), was computed from the time-activity curves for 10 min for each lung. The irradiated lung volume was calculated for each patient. The mean irradiated lung volume was 6.4% +/- 2 (range 3-11%) for the entire population. In the whole study population, two (10%) patients, who were irradiated on the left side, had mild symptomatic radiation pneumonitis in the follow-up period. There was a statistically significant gradual reduction in all pulmonary function test values during the follow-up period. For patients irradiated on the left side, Tc-99m DTPA clearance T(1/2) values were statistically significantly decreased during the follow-up period (P = 0.03), but the decrease was not statistically significant for patients irradiated on the right side (P = 0.62). Tc-99m DTPA clearance T(1/2) values were statistically significantly decreased in the irradiated lung compared with the opposite lung, and no improvement was seen at week 52 after radiotherapy. The number of patients with changes on HRCT scans increased after radiotherapy, reaching a maximum at 16 weeks, when 80% of patients had changes. There was subsequent partial recovery 52 weeks after radiotherapy. Locoregional irradiation for breast cancer may cause sub-clinical irreversible impairment of radiological and functional pulmonary parameters. The increase in clearance rate of Tc-99m DTPA may be more prominent for patients with left-sided breast cancer.

Detection of alveolar epithelial injury by99mTc-DTPA radioaerosol inhalation lung scan following blunt chest trauma

DTPA clearance rate is a reliable index of alveolar epithelial permeability, and is a highly sensitive marker of pulmonary epithelial damage, even of mild degree. In this study, 99mTc-DTPA aerosol inhalation scintigraphy was used to assesss the pulmonary epithelial membrane permeability and to investigate the possible application of this permeability value as an indicator of early alveolar or interstitial changes in patients with blunt chest trauma. A total of 26 patients was chest trauma (4 female, 22 male, 31-80 yrs, mean age; 53+/-13 yrs) who were referred to the emergency department in our hospital participated in this tsudy. Technetium-99m diethylene triamine pentaacetic acid (DTPA) aerosol inhalation scintigraphy was performed on the first and thirtieth days after trauma. Clearance half times (T1/2) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. On the first day, mean T1/2 value of the whole lung was 63+/-19 minutes (min), and thirtieth day mean T1/2 value was 67+/-21 min. On the first day, mean PI values of the lung and 30th day mean PI value were 0.60+/-0.05, and 0.63+/-0.05, respectively. Significant changes were observed in radioaerosol clearance and penetration indices. Following chest trauma, clearance of 99mTc-DTPA increased owing to breakdown of the alveolar-capillary barrier. This increase in the epithelial permeability of the lung appears to be an early manifestation of lung disease that may lead to efficient therapy in the early phase.

Can 99mTc-DTPA aerosol scanning predict radiation pneumonitis?

Purpose To investigate whether changes in diethylenetriamine pentaacetic acid (DTPA) aerosol clearance lung scans predict the development of radiation pneumonitis. Methods and materials Thirty-three patients with advanced non–small-cell lung cancer were treated with palliative radiation therapy to thorax. All patients were subjected to pretreatment and post-treatment DTPA aerosol clearance lung scans. The clearance t 1/2 values were compared using the paired t test. Changes in percentage aerosol deposition were also compared. The patients were serially assessed clinically and radiologically for development of radiation pneumonitis. Results For the whole group, the mean DTPA clearance t 1/2 for the diseased lung fell from 36.33 to 28.85 min ( p = 0.17). Twelve patients developed radiation pneumonitis, 8 Grade 1, 2 Grade 2, 1 Grade 3, and 1 Grade 4. In patients who developed radiation pneumonitis, the clearance t 1/2 for the diseased lung decreased from 37.50 min to 29.00 min after treatment ( p = 0.50). Other subgroups analyzed, including smokers, nonsmokers, those with and without endobronchial disease, as well as those free from radiation pneumonitis, also showed no significant change in the clearance of the aerosol. The difference between the percentage aerosol deposition of the diseased lung (37.92%) and that of the opposite lung (62.08%) for the entire sample was significantly different both before and after treatment ( p < 0.01). Delivery of radiation did not significantly change the aerosol deposition in either lung. Conclusions We conclude that, in patients with advanced non–small-cell lung cancer, significant change in the pulmonary clearance of 99mTc-DTPA aerosol could not be demonstrated after radiation therapy. In such patients, clearance of the aerosol does not predict the development of radiation pneumonitis.

Maximal rowing has an acute effect on the blood-gas barrier in elite athletes.

The purpose of the study was to evaluate the effects of maximal exercise on the integrity of the alveolar epithelial membrane using the clearance rate of aerosolized 99mTc-labeled diethylenetriaminepentaacetic acid as an index for the permeability of the lung blood-gas barrier. Ten elite rowers (24.3 +/- 4.6 yr of age) completed two 20-min pulmonary clearance measurements immediately after and 2 h after 6 min of all-out rowing (initial and late, respectively). All subjects participated in resting control measurements on a separate day. For each 20-min measurement, lung clearance was calculated for 0-7 and 10-20 min. Furthermore, scintigrams were processed from the initial and late measurements of diethylenetriaminepentaacetic acid clearance. Compared with control levels, the pulmonary clearance measurement after rowing was increased from 1.2 +/- 0.5 to 2.4 +/- 1.0%/min (SD) at 0-7 min (P < 0.01) and from 0.8 +/- 0.3 to 1.5 +/- 0.4%/min at 10-20 min (P < 0.0005), returning to resting levels within 2 h. In 6 of 10 subjects, ventilation distribution on the lung scintigrams was inhomogeneous at the initial measurement. The study demonstrates an acute increased pulmonary clearance after maximal rowing. The ventilation defects identified on the lung scintigrams may represent transient interstitial edema secondary to increased blood-gas barrier permeability induced by mechanical stress.

Renal effects of hyperinsulinaemia in subjects with two hypertensive parents

The aim of this investigation was to study the effects of isoglycaemic hyperinsulinaemia on the renal metabolism of electrolytes and water in subjects with a strong genetic predisposition to essential hypertension, compared with that in non-predisposed subjects. We studied 25 normotensive subjects aged 18–35 years whose parents both had essential hypertension, and 22 age- and sex-matched subjects whose parents were both normotensive. Diabetes or morbid obesity in any subject or parent excluded the family. The 24-h blood pressure was measured. The subjects received an isocaloric diet with a fixed content of sodium and potassium for 4 days before the study. An isoglycaemic, hyperinsulinaemic clamp with infusion of insulin (40 munits·min -1 ·m -2 ) was performed. We measured the renal clearance of diethylenetriaminepenta-acetic acid, sodium, potassium and lithium both under basal conditions and during hyperinsulinaemia. In response to hyperinsulinaemia, renal sodium clearance decreased to a significantly greater extent in the hypertension-prone subjects [0.57 (0.74, 0.36) ml·min -1 ·1.73 m 2 (median and quartiles)] than in the controls [0.34 (0.56, 0.18) ml·min -1 ·1.73 m 2 ] ( P = 0.04). Compared with the controls, the subjects predisposed to hypertension had a higher 24-h diastolic blood pressure [78 (70, 82) mmHg, compared with 73 (68, 77) mmHg], but a similar insulin sensitivity index {10 7 ×[313 (225, 427)] compared with 10 7 ×[354 (218, 435)] l 2 ·min -1 ·pmol -1 ·kg -1 }. Thus the sodium-retaining effect of insulin was more pronounced in subjects with a strong genetic predisposition to essential hypertension than in subjects with normotensive parents. This effect may contribute to the development of hypertension in subjects with a genetic predisposition to hypertension.

Renal effects of hyperinsulinaemia in subjects with two hypertensive parents

The aim of this investigation was to study the effects of isoglycaemic hyperinsulinaemia on the renal metabolism of electrolytes and water in subjects with a strong genetic predisposition to essential hypertension, compared with that in non-predisposed subjects. We studied 25 normotensive subjects aged 18-35 years whose parents both had essential hypertension, and 22 age- and sex-matched subjects whose parents were both normotensive. Diabetes or morbid obesity in any subject or parent excluded the family. The 24-h blood pressure was measured. The subjects received an isocaloric diet with a fixed content of sodium and potassium for 4 days before the study. An isoglycaemic, hyperinsulinaemic clamp with infusion of insulin (40 munits.min(-1).m(-2)) was performed. We measured the renal clearance of diethylenetriaminepenta-acetic acid, sodium, potassium and lithium both under basal conditions and during hyperinsulinaemia. In response to hyperinsulinaemia, renal sodium clearance decreased to a significantly greater extent in the hypertension-prone subjects [0.57 (0.74, 0.36) ml.min(-1).1.73 m(2) (median and quartiles)] than in the controls [0.34 (0.56, 0.18) ml. min(-1).1.73 m(2)] (P=0.04). Compared with the controls, the subjects predisposed to hypertension had a higher 24-h diastolic blood pressure [78 (70, 82) mmHg, compared with 73 (68, 77) mmHg], but a similar insulin sensitivity index ¿10(7)x[313 (225, 427)] compared with 10(7)x[354 (218, 435)] l(2).min(-1).pmol(-1).kg(-1)¿. Thus the sodium-retaining effect of insulin was more pronounced in subjects with a strong genetic predisposition to essential hypertension than in subjects with normotensive parents. This effect may contribute to the development of hypertension in subjects with a genetic predisposition to hypertension.

Pulmonary technetium-99m diethylene triamine penta-acetic acid aerosol clearance as an index of lung injury.

Although the clearance of an inhaled nebulised radioaerosol has long been employed as a measure of lung function, this test has not found favour in nuclear medicine units to the extent that might originally have been anticipated. In this review the theoretical basis of solute transfer is considered and the measurement of radioaerosol clearance discussed. Thereafter the various clinical applications of alveolar permeability measurement are outlined. Finally, possible reasons for the restricted clinical use of the diethylene triamine penta-acetic acid clearance technique are considered. It is concluded that the technique should provide a rapid screening evaluation of the HIV+ve patient presenting predominantly with chest symptoms.