Investigation of the Effects of N-acetylcysteine and Selenium on Vesicoureteral Reflux Nephropathy: An Experimental Study.

INTRODUCTION: This study aimed to investigate the effects of N-acetylcysteine (NAC) and selenium (Se) on vesicoureteral reflux (VUR) nephropathy. METHODS: A total of 44 rabbits in 7 groups, namely group 1 (Control), group 2 (VUR + sterile urine), group 3 (VUR + sterile urine + NAC), group 4 (VUR + sterile urine + Se), group 5 (VUR + infected urine), group 6 (VUR + infected urine + NAC) and group 7 (VUR + infected urine + Se), were used. 99mTc Dimercaptosuccinic acid renal scan (DMSA), cystogram and urine culture were performed both at the beginning and end of the study. Left VUR was created surgically, and E. coli was inoculated in infected urine groups. NAC and Se were administered daily for 21 days. Malondialdehyde (MDA) measurement, inflammatory response scores (IRSs), and cicatrization response scores (CRSs) in renal tissues were evaluated. RESULTS: VUR did not reduce left renal uptake values in neither group 2 nor group 5. MDA levels of the left kidney were significantly higher in group 5 compared to group 1 (p = 0.001). There was no significant difference in MDA levels between group 5 and group 6, and between group 5 and group 7. Left kidney IRSs were found to be higher in all other groups except group 2 compared to the control group (p < 0.001). Left kidney CRSs were significantly higher in group 5 compared to group 2 (p = 0.026), group 6 (p < 0.001) and group 7 (p = 0.006). CONCLUSION: A decrease in renal functions was not observed in VUR, even if there was infection. When CRSs were evaluated, NAC and Se had protective effects in terms of scar formation in VUR nephropathy. TYPE OF STUDY: Experimental animal study. LEVELS OF EVIDENCE: N/A.

99mTc-DMSA and 99mTc-DTPA identified renal dysfunction due to microplastic polyethylene in murine model.

In the previous study (Im et al., 2022), we revealed microplastic (MP) was accumulated and cleared through the kidneys via PET imaging. Here, we aimed to identify the renal dysfunction due to polyethylene (PE) MP in the kidney tissue. Mice were exposed to 100 ppm (∼equivalent to 0.1 mg/mL)/100 µL of PE for 12 weeks (n = 10). PE uptake in the kidney tissues was confirmed using confocal microscopy. QuantSeq analysis was performed to determine gene expression. Renal function assessment was performed using 99mTc-Diethylene triamine penta acetic acid or 99mTc-Dimercaptosuccinic acid. Measurement of creatinine, BUN, and albumin levels in serum and urine samples was also estimated. [18F]-FDG was also acquired. PE increased expression of Myc, CD44, Programmed Death-Ligand 1 (PD-L1), and Hypoxia-Inducible Factor (HIF)-1α, which indicates a potential link to an increased risk of early-onset cancer. An increase in glucose metabolism of [18F]-FDG were observed. We assessed renal failure using 99mTc-Diethylene triamine penta acetic acid and 99mTc-Dimercaptosuccinic acid scintigraphy to determine the renal function. Renal failure was confirmed using serum and urine creatinine, serum blood urea nitrogen levels, serum albumin levels, and urine albumin levels in PE exposed mice, relative to the control. In sum, PE exposure induced renal dysfunction in a murine model.

Renal Cortical Imaging with Tc-99m DMSA in Children: An Institutional Review.

Background Urinary tract infection (UTI) is one of the commonly encountered conditions in children. Dimercaptosuccinic acid (DMSA) scintigraphy is widely advocated for functional and morphological evaluation of the renal cortex including parenchymal defect. Moreover, only a small percentage of renal defects are detected by ultrasound. We aimed to examine DMSA scintigraphy of children and identify factors associated with cortical defect. Methods Patients aged ≤ 18 years old who underwent DMSA scintigraphy (November 18, 2019-February 2, 2023, 30 children) were included. All children received intravenous injections of 99m Tc-DMSA followed by static planar and single-photon-emission computed tomography imaging at 3 hours. Cortical findings and differential functions of the worst affected kidney were graded accordingly. Grade I has no more than two cortical defects, grade II has more than two cortical defects with normal parenchyma between the defects, while grade III is when generalized damage is noted, and grade IV is when a shrunken kidney is seen with no DMSA uptake. Normal functioning kidney is when the relative function at 45 to 55%, mildly reduced function at 40 to 44%, and substantially impaired function at 10 to 39%, while nonfunctioning is when the differential split renal function < 10%. All data were then statistically analyzed. Results Majority was female (53%). The mean age was 5.85 years. UTI episodes were 73%. Twenty-two children had congenital urinary tract anomalies. All patients with vesicoureteric refluxes (VURs) had positive defects. Scintigraphy showed abnormalities in 17 children affecting unilateral (64%) or both kidneys (36%). There were 17 children (57%) respectively in the abnormal DMSA scan findings category with normal until significant impairment of the functioning kidney category. VURs were significantly associated with abnormal scintigraphy ( p < 0.05). A significant association was found between abnormal DMSA scan findings and differential renal function ( p < 0.05). Conclusion Significant association was noted between VURs and abnormal DMSA scintigraphy, abnormal DMSA scan findings, and impaired differential renal function. Special consideration should be given to these cases.

Determining Split Renal Function in Children With Ureteropelvic Junction Stenosis: Technetium-99m Mercaptoacetyltriglycine (Tc-99m MAG-3) or Technetium-99m Dimercaptosuccinic Acid (Tc-99m DMSA)?

Background Ureteropelvic junction stenosis (UPJS) is the most common cause of clinically significant antenatal hydronephrosis. We compared separate renal function results obtained using technetium-99m-mercaptoacetyltriglycine (Tc-99m MAG-3) and technetium-99m-dimercaptosuccinic acid (Tc-99m DMSA) in pediatric patients with UPJS to evaluate the adequacy of Tc-99m MAG-3 scintigraphy and the necessity of additional Tc-99m DMSA scintigraphy during follow-up. Methodology Patients diagnosed with hydronephrosis in the Pediatric Nephrology Department of Pamukkale University Faculty of Medicine over a period of 10 years (2012-2022) were evaluated retrospectively. Patients who had been diagnosed with UPJS and underwent both Tc-99m MAG-3 and Tc-99m DMSA scintigraphy during follow-up were included in the study. Technetium-99m-labeled MAG-3 and DMSA scans were re-evaluated for all patients by the Department of Nuclear Medicine. Results The study included 52 children with unilateral UPJS (12 girls and 40 boys) with a mean age of 6.34 ± 4.81 years (range: 2.97-9.79 years). Thirty-six patients (69.2%) were diagnosed antenatally. Differential renal function in Tc-99m DMSA was 46.94 ± 10.64 and in Tc-99m MAG-3 was 43.08 ± 11.18; the functions were lower in Tc-99m MAG-3, but the values were within normal limits for both groups (p=0.0001, z=-3.893). When differential renal functions were compared between Tc-99m DMSA and Tc-99m MAG-3 results, a statistically significant positive and strong correlation was found in the kidney with ureteropelvic junction obstruction (UPJO) (p=0.0001, r=0.752). When classifying the Tc-99m MAG-3 and Tc-99m DMSA results in the kidney with UPJO (supranormal, normal, low function) for the determination of differential renal functions, there was a consistency of 76%, and it was correlated (p=0.0001, k=0.456). While two patients had supranormal function and 13 patients had low function in Tc-99m MAG-3, five patients had supranormal function, and eight patients had low function in Tc-99m DMSA. Conclusions Some studies in the literature have reported that Tc-99m MAG-3 causes supranormal function measurements in patients with UPJS; our results showed that Tc-99m DMSA resulted in a higher rate of supranormal values for affected kidneys. We believe that Tc-99m DMSA should not be performed in addition to Tc-99m MAG-3 scintigraphy in the follow-up of every patient with UPJS but can be utilized in select cases, such as patients with surgical indications and those suspected before surgery.

Review of the Clinical and Technical Aspects of 99mTc-Dimercaptosuccinic Acid Renal Imaging: The Comeback "Kit".

99mTc-labeled dimercaptosuccinic acid (99mTc-DMSA) imaging is a well-established and highly sensitive method for the diagnosis of several renal cortical disorders affecting children and adults. Beginning in 2014, 99mTc-DMSA availability was severely impaired when it was added to the Drug Shortages List of the U.S. Food and Drug Administration and was commercially unavailable thereafter. The agent shortage negatively impacted practitioners' ability to evaluate renal cortical defects in children and adults and changed renal imaging practice. A survey among pediatric nuclear medicine clinicians confirmed the clinical need for 99mTc-DMSA. Finally, in early 2023 the Food and Drug Administration again approved 99mTc-DMSA in the United States. During the 99mTc-DMSA shortage, established practitioners may not have had the opportunity of using 99mTc-DMSA as they were accustomed in their experience. Also, newer imaging specialists and referring physicians and technologists may not have benefited from having 99mTc-DMSA in their training. Therefore, it is time to bring back 99mTc-DMSA into the armamentarium of imaging methods available to evaluate regional cortical renal function.

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.

The potential ameliorative role of Dimercaptosuccinic acid against the toxicity of Titanium Dioxide Nanoparticles on Caelatura nilotica clams.

The prevalent use of nanoparticles has adverse negative effects on biosystems. Subsequently, this study aimed to use Caelatura nilotica to assess the ecotoxicity of TiO2 NPs and how Dimercaptosuccinic acid (DMSA) improves these effects. Two concentrations of TiO2 NPs (25 and 150 µg/L) were used for 28 days. TiO2 NPs bioaccumulation, gonadal weight, gonado-somatic index, and histopathological alterations of gonads were determined. The tissues' accumulation of TiO2 NPs was concentration-time-dependent: it was 78.5 ± 28.93 µg/g dry weight in the exposed clams to 150 µg/L TiO2 NPs after 4 weeks of exposure. The gonadal weight and gonado-somatic index significantly decreased of the exposed group to 150 µg/L TiO2 NPs over the experimental period that they ended with values (1.01 ± 0.57 gm, 19.15 ± 7.75%, respectively). There are some histological alterations in the gonads of C. nilotica such as necrosis, deteriorated connective tissue, increased fibrous tissue, a reduced presence of mature sperms and mature ova, and irregular shapes of testicular/ovarian follicles. When using Dimercaptosuccinic acid (DMSA), this led to a reduction in accumulation of TiO2 NPs by the end of the experiment. So, C. nilotica is a promising model to reflect the adverse nano-toxics. DMSA emerges as a potentially valuable chelating agent that abolishes the negative effects of these nanoparticles.

The Intrarenal Reflux Diagnosed by Contrast-Enhanced Voiding Urosonography (ceVUS): A Reason for the Reclassification of Vesicoureteral Reflux and New Therapeutic Approach?

Vesicoureteral reflux (VUR) is defined as the urine backflow from the urinary bladder to the pyelo-caliceal system. In contrast, intrarenal reflux (IRR) is the backflow of urine from the renal calyces into the tubulointerstitial space. VURs, particularly those associated with IRR can result in reflux nephropathy when accompanied by urinary tract infection (UTI). The prevalence of IRR in patients with diagnosed VUR is 1-11% when using voiding cystourethrography (VCUG), while 11.9-61% when applying the contrast-enhanced voiding urosonography (ceVUS). The presence of IRR diagnosed by VCUG often correlates with parenchymal scars, when diagnosed by a 99mTc dimercaptosuccinic acid scan (DMSA scan), mostly in kidneys with high-grade VURs, and when diagnosed by ceVUS, it correlates with the wide spectrum of parenchymal changes on DMSA scan. The study performed by both ceVUS and DMSA scans showed IRRs associated with non-dilated VURs in 21% of all detected VURs. A significant difference regarding the existence of parenchymal damage was disclosed between the IRR-associated and IRR-non-associated VURs. A higher portion of parenchymal changes existed in the IRR-associated VURs, regardless of the VUR grade. That means that kidneys with IRR-associated VURs represent the high-risk group of VURs, which must be considered in the future classification of VURs. When using ceVUS, 62% of places where IRR was found were still unaffected by parenchymal changes. That was the basis for our recommendation of preventive use of long-term antibiotic prophylaxis until the IRR disappearance, regardless of the VUR grade. We propose a new classification of VURs using the ceVUS method, in which each VUR grade is subdivided based on the presence of an IRR.

Prevalence of malocclusions requiring treatment according to the KIG classification : A multipart cross-sectional study over a 20-year period in the district of Viersen/North Rhine.

BACKGROUND AND AIM: In Germany, the reimbursement of orthodontic treatment costs within the framework of the statutory health insurance (GKV) was restricted on 01 January 2002 by the introduction of the orthodontic indication groups (KIG). The aim of this study was to evaluate the prevalence of findings requiring treatment in a specialist practice over a 20-year period. The results were then compared with data from existing older studies. PATIENTS AND METHODS: The distribution of treatment-eligible KIG (KIG classifications grades 3-5) among patients with statutory health insurance in an orthodontic practice in North Rhine was determined over a 20-year period (2002-2021) after the introduction of the KIG system. This period was additionally scrutinized in four 5­year periods according to the operating cycles of the practice. Findings were classified into the highest of 19 possible KIG treatment needs levels. Multiple classifications were not made. RESULTS: Orthodontic treatment was indicated in a total of 4537 (2393 female, 2144 male) patients according to current statutory health insurance guidelines. The KIG classification "D" (increased overjet) was the most frequent within the observed 20 years with 24.3%. Among 11 KIG classifications, 86.1% of the 6 most frequent and 13.9% of the 5 rarest findings were observed constantly over all periods. Of 19 possible indications, "D4" was the most frequent with 19.6%. Of 4537 patients, 20.7% had KIG grade 3, 63.6% KIG grade 4 and 15.7% KIG grade 5. The prevalence of sagittal deviations "D" and "M" was 35.0%, transverse "B" and "K" 17.9% and vertical "O" and "T" 3.7%. Tooth position anomalies "E" and "P" had a share of 24.6%. CONCLUSIONS: The present study confirms existing findings as well as the nationwide data of the National Association of Statutory Health Insurance Dentists (KZBV) from 2020: The sagittal deviations "D" (increased overjet) and "M" (negative overjet) represented the most frequent findings with KIG D4 as the most common classification. The prevalence and age distribution of KIG grades 3-5 requiring treatment corresponded to nationwide comparative data.

Prevalence of KIG-grades 3-5 in an orthodontic practice in North Rhine Westphalia compared with results of the DMS•6 and with KZBV data.

BACKGROUND AND AIM: The prevalence of tooth and jaw malocclusions in 8- to 9-year-olds was surveyed in a nationwide setting as part of the orthodontic module of the Sixth German Study on Oral Health (DMS•6), using the orthodontic indication groups (KIG) as index. Aim of this study was the detection of the prevalence of malocclusions requiring treatment according to the KIG index in statutorily insured patients of an orthodontic practice in North Rhine Westphalia, Germany, and to compare results with corresponding DMS•6 and KZBV data. PATIENTS AND METHODS: Between 2017-2021, n = 953 statutorily insured patients called for an initial consultation and subsequent determination of the KIG-classification and -grades. The malocclusions were classified and graded in the highest possible KIG-grade according to valid SHI guidelines. Multiple classifications were not recorded. KIG-grade > 3 according to the valid guidelines was detected in n = 815 patients. Since the DMS•6 does not contain information on KIG classifications "U" and "S", their inclusion was waived despite evaluation, leaving data from n = 683 patients for analysis and comparison. RESULTS: During the study period, n = 235 patients (34.4%) had KIG-classification "D". More than 10% were classified as "K" (120 patients, 17.6%), "P" (98 patients, 14.2%), "M" (89 patients, 13.0%), and "E" (81 patients, 11.9%). Of 16 possible classifications with KIG-grade > 3, "D4" was the most common with 26.6% (182 patients). The results confirm the findings from the multicentric DMS•6 from2021 and corresponding KZBV data from 2020. CONCLUSIONS: Sagittal deviations described by classifications "D" and "M" represent with 47.4% almost half of the malocclusions with treatment need. KIG-grade D4 is the most frequent classification. There were no regional deviations of the prevalence of KIG-grades 3-5 in the district of Viersen / North Rhine compared with the national average, not even when scrutinizing a five-year-period.