Assessing asymmetrical kidney function in living donors: a retrospective cohort study on CT metrics.

BACKGROUND: Live donor kidney transplantation is the preferred kidney replacement therapy for eligible patients but requires thorough donor evaluation to minimise risks. Contemporary guidelines recommend split kidney function measurement in living donors only when there is a significant kidney size discrepancy, yet the evidence for this is poor, and practice varies nationally. This study evaluates the efficacy of CT-derived kidney metrics in detecting significant functional asymmetry. METHODS: We conducted a retrospective cohort analysis of 123 prospective living kidney donors at a regional transplant centre from June 2011 to October 2014, utilising CT to determine kidney and cortical volumes and lengths. Asymmetric kidney function (AKF), defined by > 10% function difference on DMSA scans, was correlated with CT measurements to calculate the diagnostic accuracy of current guidelines. RESULTS: Among the prospective donors, the median age was 42 years, and 59.3% were female. The median split kidney function difference was 4%, with 25 individuals exhibiting > 10% AKF. Kidney length discrepancy proved to be a poor indicator of AKF (sensitivity: 28%, specificity: 84%). While negative predictive values for cortical and kidney volumes were high (96% and 93%, respectively), sensitivity was low, and specificity and positive predictive value did not meet satisfactory thresholds. CONCLUSIONS: CT-derived metrics of kidney length, cortical, and total volume show limited sensitivity and specificity in identifying significant AKF. These findings provide evidence to support revised guideline development in the assessment of living kidney donors.

Exstrophy-epispadias complex: are the kidneys and kidney function spared?

BACKGROUND: Exstrophy-epispadias complex (EEC) is a complex malformation of the lower abdominal wall, bladder, and pelvic floor, which necessitates multiple successive reconstruction procedures. Surgical and infectious complications are frequent. Our aim was to evaluate kidney function in these patients. METHODS: This cross-sectional study included patients with EEC, followed since birth in a pediatric urology clinic, who underwent nephrological evaluation (blood pressure (BP) measurement and blood and urine chemistries) and imaging studies (urinary tract ultrasound and DMSA kidney scan) during 2017-2020. RESULTS: Forty-three patients (29 males), median age 9 years (interquartile range 6-19), were included. Eleven (26%) used clean intermittent catheterization (CIC) for bladder drainage. At least one sign of kidney injury was identified in 32 (74%) patients; elevated BP, decreased kidney function (estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m2), and proteinuria/albuminuria were detected in 29%, 12%, and 36% of patients, respectively. Urinary tract dilatation (UTD) was found in 13 (37%) ultrasound examinations. Parenchymal kidney defects were suspected in 46% and 61% of ultrasound and DMSA scintigraphy, respectively. UTD was significantly associated with DMSA-proven kidney defects (p = 0.043) and with elevated BP, 39% vs. 20% in those without UTD. Decreased eGFR and elevated BP were less frequent among patients on CIC than among patients who voided spontaneously: 10% vs. 14% and 18% vs. 36%, respectively. Recurrent UTIs/bacteriuria and nephro/cystolithiasis were reported by 44% and 29% patients, respectively. CONCLUSION: The high rate of signs of kidney injury in pediatric patients with EEC dictates early-onset long-term kidney function monitoring by joint pediatric urological and nephrological teams. A higher resolution version of the Graphical abstract is available as Supplementary information.

The diagnostic value of DMSA scan in differentiating functional pseudo-tumors from malignancies in scarred kidneys: case series and literature review.

BACKGROUND: The terms "renal regenerating nodule" and "nodular compensatory hypertrophy" are used in the literature to describe functioning pseudo-tumors (FPT) in the setting of an extensively scarred kidney. FPTs are usually discovered incidentally during routine renal imaging. Differentiating these FPTs from renal neoplasms is critical but can be challenging in the setting of chronic kidney disease (CKD) given the limitations related to using contrast-based imaging. CASE SUMMARIES: We report a pediatric case series of 5 CKD patients, with history of urinary tract infections, in which tumor-like lesions evolved in scarred kidneys and were incidentally discovered on routine renal imaging. These were diagnosed as FPT by utilizing dimercaptosuccinic acid (DMSA) imaging and showed stable size and appearance upon follow-up with ultrasound and MRI. CONCLUSION: FPTs can be picked up on routine imaging of pediatric patients with CKD. Although larger cohort studies are needed to confirm these conclusions, our case series supports the evidence that DMSA scan showing uptake at the site of the mass can be a useful tool to suggest the diagnosis of FPTs in children with kidney scarring, and that SPECT DMSA scan adds more precision in picking up and accurately localizing FPTs compared to planar DMSA.

Acquisition time reduction in pediatric 99m Tc-DMSA planar imaging using deep learning.

PURPOSE: Given the potential risk of motion artifacts, acquisition time reduction is desirable in pediatric 99m Tc-dimercaptosuccinic acid (DMSA) scintigraphy. The aim of this study was to evaluate the performance of predicted full-acquisition-time images from short-acquisition-time pediatric 99m Tc-DMSA planar images with only 1/5th acquisition time using deep learning in terms of image quality and quantitative renal uptake measurement accuracy. METHODS: One hundred and fifty-five cases that underwent pediatric 99m Tc-DMSA planar imaging as dynamic data for 10 min were retrospectively collected for the development of three deep learning models (DnCNN, Win5RB, and ResUnet), and the generation of full-time images from short-time images. We used the normalized mean squared error (NMSE), peak signal-to-noise ratio (PSNR), and structural similarity index metrics (SSIM) to evaluate the accuracy of the predicted full-time images. In addition, the renal uptake of 99m Tc-DMSA was calculated, and the difference in renal uptake from the reference full-time images was assessed using scatter plots with Pearson correlation and Bland-Altman plots. RESULTS: The predicted full-time images from the deep learning models showed a significant improvement in image quality compared to the short-time images with respect to the reference full-time images. In particular, the predicted full-time images obtained by ResUnet showed the lowest NMSE (0.4 [0.4-0.5] %) and the highest PSNR (55.4 [54.7-56.1] dB) and SSIM (0.997 [0.995-0.997]). For renal uptake, an extremely high correlation was achieved in all short-time and three predicted full-time images (R2  > 0.999 for all). The Bland-Altman plots showed the lowest bias (-0.10) of renal uptake in ResUnet, while short-time images showed the lowest variance (95% confidence interval: -0.14, 0.45) of renal uptake. CONCLUSIONS: Our proposed method is capable of producing images that are comparable to the original full-acquisition-time images, allowing for a reduction of acquisition time/injected dose in pediatric 99m Tc-DMSA planar imaging.

A new recommendation for febrile urinary tract infection in children aged 2-24 months: Tepecik UTI Guideline-2.

AIM: Urinary tract infections (UTIs) represent a common febrile illness in infancy. The study compared two UTI guidelines in terms of number of imaging studies, presence of parenchymal damage and radiation exposure in patients with the first febrile UTI between 2 and 24 months of age. METHOD: The results of Tepecik UTI Guideline-1 used until 2012 (Group 1, n = 105) were retrospectively compared with Tepecik UTI Guideline-2 (Group 2) used after 2013. In Group 1, urinary tract ultrasonography (US), dimercaptosuccinic acid (DMSA) and voiding cystourethrography (VCUG) were made in all patients. In Group 2, if the US result was abnormal, patients were evaluated with VCUG and DMSA. If the US was normal, only DMSA was performed. If the DMSA was abnormal, the VCUG was undergone (n: 43, 40.9%). RESULTS: The abnormal VCUG detection rate was 69.2% in Group 1 and 30.8% in Group 2 (p = 0.09). Sensitivity and specificity of US in the diagnosis of vesicoureteral reflux (VUR) was 15.9% and 96.7% in Group 1 and 61.5% and 70.5% in Group 2, respectively. Abnormal DMSA findings were observed among 33.3% (Groups 1) and 66.7% (Groups 2) subjects, respectively (p > 0.05). The median radiation exposure (500 mrem) of patients in Group 1 was statistically significantly higher than those in Group 2 (200 mrem) (p < 0.001). CONCLUSION: The VCUG should not be the first examination to be considered in such patients. We think that Tepecik UTI Guideline-2 reduces unnecessary invasive procedure and radiation exposure and not missed VUR in the management of children with UTI at 2-24 months. Needs prospective follow-up studies before considering this recommendation.

Apigenin-Loaded PLGA-DMSA Nanoparticles: A Novel Strategy to Treat Melanoma Lung Metastasis.

The flavone apigenin (APG), alone as well as in combination with other chemotherapeutic agents, is known to exhibit potential anticancer effects in various tumors and inhibit growth and metastasis of melanoma. However, the potential of apigenin nanoparticles (APG-NPs) to prevent lung colonization of malignant melanoma has not been well investigated. APG-loaded PLGA-NPs were surface-functionalized with meso-2,3-dimercaptosuccinic acid (DMSA) for the treatment of melanoma lung metastasis. DMSA-conjugated APG-loaded NPs (DMSA-APG-NPs) administered by an oral route exhibited sustained APG release and showed considerable enhancement of plasma half-life, Cmax value, and bioavailability compared to APG-NPs both in plasma and the lungs. DMSA-conjugated APG-NPs showed comparably higher cellular internalization in B16F10 and A549 cell lines compared to that of plain NPs. Increased cytotoxicity was observed for DMSA-APG-NPs compared to APG-NPs in A549 cells. This difference between the two formulations was lower in B16F10 cells. Significant depolarization of mitochondrial transmembrane potential and an enhanced level of caspase activity were observed in B16F10 cells treated with DMSA-APG-NPs compared to APG-NPs as well. Western blot analysis of various proteins was performed to understand the mechanism of apoptosis as well as prevention of melanoma cell migration and invasion. DMSA conjugation substantially increased accumulation of DMSA-APG-NPs given by an intravenous route in the lungs compared to APG-NPs at 6 and 8 h. This was also corroborated by scintigraphic imaging studies with radiolabeled formulations administered by an intravenous route. Conjugation also allowed comparatively higher penetration as evident from an in vitro three-dimensional tumor spheroid model study. Finally, the potential therapeutic efficacy of the formulation was established in experimental B16F10 lung metastases, which suggested an improved bioavailability with enhanced antitumor and antimetastasis efficacy of DMSA-conjugated APG-NPs following oral administration.

Renal SPECT/CT with 99mTc-dimercaptosuccinic acid is a non-invasive predictive marker for the development of interstitial fibrosis in a rat model of renal insufficiency.

BACKGROUND: Chronic kidney disease (CKD) increases cardiovascular risk and mortality. Renal fibrosis plays a major role in the progression of CKD but, to date, histology remains the gold standard to assess fibrosis. Non-invasive techniques are needed to assess renal parenchymal impairment and to perform the longitudinal evaluation of renal structure. Thus we evaluated renal isotopic imaging by single-photon emission computed tomography/computed tomography (SPECT/CT) with technetium-99m (99mTc)-dimercaptosuccinic acid (DMSA) to monitor renal impairment during renal insufficiency in rats. METHODS: Renal insufficiency was induced by an adenine-rich diet (ARD) at 0.25 and 0.5% for 28 days. Renal dysfunction was evaluated by assaying biochemical markers and renal histology. Renal parenchymal impairment was assessed by SPECT/CT isotopic imaging with 99mTc-DMSA on Days 0, 7, 14, 21, 28, 35 and 49. RESULTS: Compared with controls, ARD rats developed renal dysfunction characterized by increased serum creatinine and blood urea nitrogen, fibrosis and tubulointerstitial damage in the kidneys, with a dose-dependent effect of the adenine concentration. 99mTc-DMSA SPECT-CT imaging showed a significant decrease in renal uptake over time in 0.25 and 0.5% ARD rats compared with control rats (P = 0.011 and P = 0.0004, respectively). 99mTc-DMSA uptake on Day 28 was significantly inversely correlated with Sirius red staining evaluated on Day 49 (r = 0.89, P < 0.0001, R2 = 0.67). CONCLUSIONS: 99mTc-DMSA renal scintigraphy allows a longitudinal follow-up of risk of renal fibrosis in rats. We found that the reduction of renal parenchyma in ARD rats is inversely proportional to newly formed fibrous tissue in the kidney. Our results suggest that 99mTc-DMSA renal scintigraphy may be a useful non-invasive prognostic marker of the development of renal fibrosis in animals and should be tested in humans.

Demographic, clinical, and laboratory factors associated with renal parenchymal injury in Iranian children with acute pyelonephritis.

BACKGROUND: The association between renal parenchyma changes on dimercaptosuccinic acid (DMSA) scans and demographic, clinical, and laboratory markers was assessed in pediatric patients with acute pyelonephritis. METHODS: A retrospective study of 67 Iranian babies and children aged 1-month to 12-year with APN was conducted between 2012 and 2018. The presence of renal parenchymal involvement (RPI) during APN was determined using technetium-99m DMSA during the first 2 weeks of hospitalization. The association of DMSA results with demographic data, clinical features (hospitalization stay, fever temperature and duration), and laboratory parameters such as pathogen type, and hematological factors (ESR, CRP, BUN, Cr, Hb, and WBC) was evaluated. RESULTS: 92.5% of children with an average age of 43.76 ± 5.2 months were girls. Twenty-four children (35.8%) did not have renal parenchymal injury (RPI), while 26 (38.8%) and 17 (25.4%) patients showed RPI in one and both kidneys, respectively. There was no significant association between RPI and mean ESR, CRP, BUN, and WBC. However, there were significant associations between RPI and higher mean levels of Cr, Hb, and BMI. CONCLUSIONS: Low BMI and Hb levels and increased Cr levels might be indicative of the presence of RPI in children with APN.

Comparison of Urinary Tract Dilatation and Society of Fetal Urology systems in the detection of vesicourethral reflux and renal scar.

PURPOSE: The presence and degree of hydronephrosis is very important in the management of many diseases of the urinary tract. In this study, we aim to compare the sensitivity and specificity of 2 classification systems that are used for hydro-nephrosis grading in ultrasound, for reflux and scar detection. The classification systems were the Society of Fetal Urology (SFU) and Urinary Tract Dilatation (UTD). MATERIAL AND METHODS: Ultrasounds and dimercaptosuccinic acid scintigraphies (DMSA) of all patients who underwent voiding cystourethrogram (VCUG) due to urinary tract infection were examined retrospectively. DMSA was accepted for scar detection and VCUG for reflux detection as reference methods. SFU classification was used for hydronephrosis in ultrasound reports, and UTD classification was made over the reports. Sensitivity, specificity, and positive and negative predictive values of UTD and SFU classification systems for reflux and scar detection were calculated, and these 2 systems were compared. RESULTS: 103 (39%) of the patients were male and 162 (61%) were female. Pathologies were detected in 192 (35%) of 530 kidneys in ultrasound. In 110 (42%) of the children, reflux was detected in VCUG. Scars in DMSA were detected in only 16% (44) of 266 kidneys. Sensitivity, positive and negative predictive values of the UTD classification system were statistically significantly higher than the SFU system for scar and reflux detection (p < 0.01). CONCLUSIONS: If we use the UTD system in ultrasounds of patients with urinary tract infections, children reported as UTD 0 may not need VCUG, which reduces radiation exposure to children and the cost of the diagnostic interventions.

Effects of combined administration of calcium, iron, zinc, chrysanthemum flavonoids, and DMSA on the treatment of lead intoxication in mice.

The effect of combined administration of calcium (Ca), iron (Fe), zinc (Zn), chrysanthemum flavonoids, and meso-2,3-dimercaptosuccinic acid (DMSA) on the treatment of lead (Pb) intoxication in mice was studied. One hundred ninety female mice (SPF level, aged 18-22 days) were randomly divided into two groups as experimental animals. Mice in group I (10 mice) served as normal control animals, and were administered deionized water containing 12.5 µL/L acetate acid for 6 weeks, whereas mice in group II (180 mice) were exposed to 0.1% (wt/vol) of lead acetate in deionized water for 6 weeks and served as experimental animals. After 6 weeks of successful modeling, 180 mice from group II (lead-exposed) were divided into 18 groups of 10 mice each, 16 of which were treated by the combined administration of Ca, Fe, Zn, chrysanthemum flavonoids, and DMSA by L16 (215 ) orthogonal design. The remaining two groups were given treatment with low and high doses of DMSA, respectively. After three weeks of intervention (ig), the optimal treatment group was identified according to its blood lead level, as well as some antioxidant indices in the blood, liver, and hippocampus. The results indicated that the combined administration of Fe, Zn, chrysanthemum flavonoids, and DMSA with low dosage had the most significant effect on increasing the activities of blood delta-aminolevulinic acid dehydratase and superoxide dismutase (SOD), hepatic SOD and hippocampus nitric oxide synthase while decreasing the blood lead level, the content of hepatic malondialdehyde and hippocampus nitric oxide; this was considered the optimal treatment group. There was no difference in the level of blood hemoglobin between the optimal treatment group and the model control group (the first group of the orthogonal experiment). The activities of blood glutathione (GSH), hepatic GSH and glutathione peroxidase of the optimal treatment group were the same as other groups', and the recovery of the related indexes in the optimal effect group closely resembled the high dosage DMSA group. It can be concluded that the coadministration of Fe, Zn, and chrysanthemum flavonoids along with a low-dose DMSA effectively reduces Pb poisoning and lead-induced oxidative damage in lead-exposed mice; the result may provide a theoretical reference for the treatment of Pb poisoning.

Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial.

BACKGROUND: To evaluate the efficacy of adjuvant systemic corticosteroids in reducing kidney scarring. A previous study suggested that use of adjuvant systemic corticosteroids reduces kidney scarring in children radiologically confirmed to have extensive pyelonephritis. Efficacy of corticosteroids for children with febrile urinary tract infection (UTI) has not been studied. METHODS: Children aged 2 months to 6 years with their first febrile UTI were randomized to corticosteroids or placebo for 3 days (both arms received antimicrobial therapy); kidney scarring was assessed using 99mTc-dimercaptosuccinic acid kidney scan 5-24 months after the initial UTI. RESULTS: We randomized 546 children of which 385 had a UTI and 254 had outcome kidney scans (instead of the 320 planned). Rates of kidney scarring were 9.8% (12/123) and 16.8% (22/131) in the corticosteroid and placebo groups, respectively (p = 0.16), corresponding to an absolute risk reduction of 5.9% (95% confidence interval: - 2.2, 14.1). CONCLUSION: While children randomized to adjuvant corticosteroids tended to develop fewer kidney scars than children who were randomized to receive placebo, a statistically significant difference was not achieved. However, the study was limited by not reaching its intended sample size. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov , NCT01391793, Registered 7/12/2011 Graphical abstract.

Antenatally detected urinary tract dilatation: a 12-15-year follow-up.

BACKGROUND: Antenatally diagnosed urinary tract dilatation (UTD) still burdens healthcare providers and parents. This study was conducted to establish long-term outcome in an unselected group of children with antenatally detected UTD. METHODS: Seventy-one out of 103 children born in 2003-2005 and diagnosed with antenatal UTD agreed to participate in a 12-15-year follow-up including blood and urine samples, a kidney ultrasound exam, and kidney scintigraphy. The records were searched for previous urinary tract infections. RESULTS: Among children with an anteroposterior diameter (APD) ≤ 7 mm and no calyceal, kidney, ureteral, or bladder pathology in the early postnatal period, no one tested had reduced estimated glomerular filtration rate (eGFR), albuminuria, or UTD at the follow-up at a mean age of 13.6 years. One child had kidney damage not affecting kidney function. Among children with postnatal APD > 7 mm and/or kidney, calyceal, ureteral, or bladder pathology, 15% had persistent UTD and 32-39% (depending on the method used) had kidney damage. Major postnatal urinary tract ultrasound abnormalities and a congenital anomalies of the kidney and urinary tract (CAKUT) diagnosis were factors associated with an increased risk for permanent kidney damage (odds ratios 8.9, p = 0.016; and 14.0, p = 0.002, respectively). No one had reduced eGFR. One child (1/71, 1%) had a febrile urinary tract infection after the age of 2. CONCLUSIONS: We conclude that in children with postnatal APD ≤ 7 mm, no calyceal dilatation, normal bladder, ureters, and kidney parenchyma, the outcome is excellent. There is no need for long-term follow-up in these patients.

Preparation and anti-Raji lymphoma efficacy of a novel pH sensitive and magnetic targeting nanoparticles drug delivery system.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) is a heterogeneous class of cancers that arises in lymph nodes or other lymphatic tissues, which causes many deaths worldwide and its incidence is increasing. METHODS: In this study, a pH-responsive DMSA-Fe3O4 magnetic nanoparticles (MNPs) covalently connect with ADM and As2O3 as a drug delivery system was invented to discuss the anticancer efficacy in non-Hodgkin's lymphoma (NHL) cell line--Raji. RESULTS: Detailedly, according to the chelation of ADM and Fe2+, the release rate of ADM was accelerated in acidic environment, and slowed down/blocked in neutral environment. The inhibitory effect to induce apoptosis of Fe3O4/As2O3+Doxil on Raji cells was obvious compared with that of single-drug group. Furthermore, the expression of Bcl-2 gene in Raji cells was suppressed under the action of MNPs. CONCLUSION: Taken together, the novel pH-responsive MNPs was proven to be a promising synergistic form of magnetic targeted drugs for clinical treatment of human Raji lymphoma.

THE ROLE OF TUMOR-SEEKING RADIOPHARMACEUTICALS IN THE DIAGNOSIS AND MANAGEMENT OF ADRENAL TUMORS.

CONTEXT: The variety of tumor-seeking radiopharmaceuticals, which are currently in clinical use, may have a potential role as imaging agents for adrenal gland tumors, due to physiological characteristics of this organ. OBJECTIVE: The purpose of this study was to evaluate the diagnostic potential of 99mTc-HYNIC-TOC, 99mTc(V)-DMSA, and 99mTc-MIBI in the assessment of adrenal tumors, by correlating with imaging findings and histopathologic results. DESIGN: The research is designed as a cross-sectional prospective study. PATIENTS AND METHOD: The study included 50 patients with adrenal tumors (19 hormone-secreting and 31 nonfunctioning) and 23 controls without adrenal involvement. In all patients, single-photon emission computed tomography (SPECT) was performed, using qualitative and semiquantitative analysis. The tumor to non-tumor tracer uptake was conducted by using a region-of-interest technique. Adrenal to background (A/B) ratio was calculated in all cases. RESULTS: 99mTc-HYNIC-TOC scintigraphy showed a high statistical significance between A/B ratios, while other two tracers resulted in a lower sensitivity, specificity and accuracy. Futhermore, 99mTc-HYNIC-TOC could have a high diagnostic yield to detect adrenal tumors (the receiver-operating-characteristic curve analysis, A/B ratio cut-off value of 8.40). CONCLUSION: A semiquantitative SPECT analysis showed that 99mTc-HYNIC-TOC is a highly sensitive tumor-seeking agent for the accurate localization of adrenal tumors.

Impacts of lead exposure and chelation therapy on bone metabolism during different developmental stages of rats.

OBJECTIVE: To explore the impacts of Pb exposure and the dimercaptosuccinic acid (DMSA) chelation therapy on bone metabolisms in young rats of different ages, as well as the potential mechanisms. METHOD: Young rats were exposed to 0.05%-0.1% Pb acetate for 19 days, during infanthood (postnatal day, PND2-20), childhood (PND21-39) and adolescenthood (PND40-58) respectively. In each developmental stage, rats were further divided into three subgroups: lead-exposed, one-course and two-course DMSA chelation therapy subgroups. Blood/bone lead concentrations, serum calciotropic hormones concentrations, and mRNA and protein expressions of bone turnover markers in the serum and bones were measured. Bone microstructures were analyzed using Micro-CT. RESULTS: Compared with lead-exposed during childhood and adolescenthood, increases in blood/bone lead levels, and the changes of blood/bone lead and trabecular bone microstructures after one-course DMSA chelation were most significant in rats lead-exposed during infanthood (P < .05). The serum osteocalcin (OC) concentrations, mRNA/protein expressions of OC and runt-related transcription factor 2 (RUNX2) in bones all decreased after Pb exposure, along with significant increases in serum C-terminal telopeptide of type I collagen (CTX) concentrations (P < .05). These effects were accompanied by changes of serum parathormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25-(OH2)-D3) concentrations. DMSA chelation partially reversed the changes of bone microarchitectures, bone formation and resorption markers, and calciotropic-hormones, and the efficiency was greatest when the therapy was provided during infanthood. CONCLUSION: Developmental Pb exposure impaired bone microstructures and interfered bone metabolism, and the exposure effect was more obvious during infanthood than during childhood and adolescenthood. Lead effects were partially reversed by chelation therapy, and the efficacy may be most significant when the therapy was provided at younger ages.

A Review on Coordination Properties of Thiol-Containing Chelating Agents Towards Mercury, Cadmium, and Lead.

The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg. Its toxicity is also lower than that of DMPS (dimercaptopropane sulfonate), although DMPS is the recommended agent in acute poisonings with Hg salts. It is suggested that intracellular Cd deposits and cerebral deposits of inorganic Hg, to some extent, can be mobilized by a combination of antidotes, but clinical experience with such combinations are lacking. Alpha-lipoic acid (α-LA) has been suggested for toxic metal detoxification but is not considered a drug of choice in clinical practice. The molecular mechanisms and chemical equilibria of complex formation of the chelators with the metal ions Hg2+, Cd2+, and Pb2+ are reviewed since insight into these reactions can provide a basis for further development of therapeutics.

Protective effect of melatonin and agomelatine on adriamycin-induced nephrotoxicity in rat model: a renal scintigraphy and biochemical study.

OBJECTIVE: We aimed to determine the possible protective effects of melatonin and agomelatine on an animal model of adriamycin nephrotoxicity by 99mTc DMSA renal scintigraphy and biochemical methods. METHODS: Ten weeks old 49 male Wistar rats were randomly separated into seven groups; namely control (CON), adriamycin (ADR), melatonin (MEL), agomelatine (AGO), melatonin + adriamycin (MEL+ADR), agomelatine + adriamycin (AGO+ADR) and melatonin + agomelatine + adriamycin (MEL+AGO+ADR) groups. Nephrotoxicity was induced by a three-dose of 18 mg/kg adriamycin, i.p. at a 24 h interval on the 5th, 6th and 7th days. A dose of melatonin and agomelatine (40 mg/kg/i.p, the same doses) were injected for 7 days before and after the injected of ADR (18 mg/kg, i.p.), respectively. On the 8th day of the experiment, all animals were evaluated and scintigraphic and biochemical parameters were assessed, respectively. RESULTS: ADR significantly increased blood urea nitrogen (1040 %) and plasma creatinine (1020 %), and decreased 99mTc DMSA uptake levels (59 %) compared to the control (p < 0.001). Pretreatment with MEL, AGO, MEL+AGO mitigated these abnormalities produced by ADR in the kidney (p < 0.001). CONCLUSION: 99mTc DMSA for the early determination of ADR-induced nephrotoxicity had an important role. Also, a significant correlation was found between biochemical and scintigraphy parameters. Adriamycin caused significant damages to kidneys that were reduced with MEL and AGO (Tab. 2, Fig. 3, Ref. 39).

Hypermanganesemia with dystonia, polycythemia and cirrhosis in 10 patients: Six novel SLC30A10 mutations and further phenotype delineation.

Biallelic mutations in the SLC30A10 gene cause an inborn error of Mn metabolism characterized by hypermanganesemia, polycythemia, early-onset dystonia, and liver cirrhosis (HMDPC). To date, only 14 families from various ethnic groups have been reported. Here, we describe 10 patients from 7 unrelated Egyptian families with HMDPC. Markedly elevated blood Mn levels, the characteristic basal ganglia hyperintensity on T1-weighted images, and variable degrees of extrapyramidal manifestations with or without liver disease were cardinal features in all patients. Eight patients presented with striking early diseased onset (≤2 years). Unexpectedly, early hepatic involvement before the neurological regression was noted in 3 patients. Mutational analysis of SLC30A10 gene revealed 6 novel homozygous mutations (c.77T > C (p.Leu26Pro), c.90C > G (p.Tyr30*), c.119A > C (p.Asp40Ala), c.122_124delCCT (p.Ser41del), c.780_782delCAT (p.Iso260del) and c.957 + 1G > C). Treatment using 2,3 dimercaptosuccinic acid as a manganese chelating agent showed satisfactory results with improvement of biochemical markers, hepatic manifestations and relative amelioration of the neurological symptoms. Our findings present a large cohort of patients with HMDPC from same ethnic group. The majority of our patients showed severe and early presentation with clear phenotypic variability among sibship. Moreover, we extend the phenotypic and mutational spectrum and emphasize the importance of early diagnosis and treatment of this potentially fatal disorder.

CLINICAL SIGNS, DIAGNOSIS, AND TREATMENT OF LEAD INTOXICATION IN AN ELECTRIC EEL ( ELECTROPHORUS ELECTRICUS).

An adult, wild-caught electric eel ( Electrophorus electricus), weighing 18 kg and measuring 2 m in length, presented with bilateral swellings behind the pectoral fins, lethargy, and anorexia for 2 days. Anesthesia was performed with immersion in tricaine methanesulphonate and supplemented with 0.11 mg/kg medetomidine and 2.2 mg/kg ketamine intramuscularly. Endoscopy revealed blood in the oral and gastric cavity. The stomach was grossly enlarged, flaccid, and contained a lead wire which was removed manually. Blood lead values were severely elevated. The fish was treated with 28 mg/kg calcium disodium ethylenediaminetetraacetate intramuscularly every 72 hr for 5 doses, which resulted in an improved clinical condition. Because lead values had not decreased to normal values within 4 wk of initial presentation, 35 mg/kg dimercaptosuccinic acid was given orally twice weekly for 3 wk. The electric eel made a full recovery.

Comparison of 99mTc-DMSA renal scintigraphy with biochemical and histopathological findings in animal models of acute kidney injury.

Biochemical and histological assays are currently used for the diagnosis and characterization of kidney injury. The purpose of this study was to compare technetium-99m-labeled dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy, as a non-invasive method, with common biochemical and histopathological methods in two animal models of acute kidney injury. Nephrotoxicity was induced either by gentamicin (100 mg/kg/day for one week) or unilateral ureteral ligation (UUO). Renal scintigraphy was performed 1 h after intravenous injection of 99mTc-DMSA (3 mCi). Furthermore, plasma levels of blood urea nitrogen (BUN), creatinine, sodium, and potassium were determined using an autoanalyzer. At the end of experiments, kidneys were excised for the measurement of activity uptake (mCi/gr) using a dose calibrator as well as histopathological examinations with hematoxylin and eosin (H&E) staining. There was a significant decrease in 99mTc-DMSA uptake in both gentamicin (P value = 0.049) and UUO (P value = 0.034) groups, and it was more significant in the former. The levels of BUN and creatinine increased in both gentamicin and UUO groups, while the levels of sodium and potassium remained unchanged. Furthermore, a strong correlation was found between DMSA uptake and histopathological findings. Scintigraphy with 99mTc-DMSA is capable of detection of kidney injury in both gentamicin and UUO groups. Moreover, a significant correlation was found between scintigraphy parameters and histopathological findings. This suggests 99mTc-DMSA as a non-invasive method for the evaluation of kidney injury induced by drugs or anatomical disorders.