Kidney Lesions Research Articles

Pure Metastatic Papillary Renal Cell Carcinoma Without Renal Mass: A Case Report and Literature Review

Renal cell carcinoma (RCC) is the most common solid lesion in the kidney and accounts for approximately 90% of all kidney malignancies. Metastasis usually occurs a few years after the diagnosis of RCC, but metastases can be seen at first presentation in some patients. Pure metastasis of RCC without kidney lesions is an extremely rare seen entity. Herein, we aimed to present a pure metastatic RCC (mRCC) in several lymph nodes without a kidney mass. A 41-year-old male was diagnosed with multiple lymphadenopathies based on imaging conducted after a work accident. No other lesion was detected. An excisional biopsy was performed on the supraclavicular lymph node. Histopathological examination of sample revealed a Type 2 papillary RCC metastasis. No primary lesion was observed in both kidneys in CT/MRI imaging. As a result, the patient was diagnosed as a pure metastatic papillary RCC and sunitinib treatment was started. After the treatment, metastatic lesions regressed, however, patient died due to COVID-19. In the literature, mRCC of unknown primary represents an aggressive metastatic malignancy and can be considered a poor prognostic factor in itself. However, in some cases as such in our patient, appropriate treatment could be beneficial in terms of metastatic regression. Pure metastatic RCC has been reported with only case reports and series. The treatment and prognosis in these patients are heterogeneous.

The role of CEUS as problem-solving technique when abdominal CT or MRI are inconclusive

PurposeTo evaluate the role of CEUS in the characterization of abdominal lesions compared to CT and MRI and whether it could be “problem-solving” when CT and/or MRI are inconclusive or contraindicated.MethodsA retrospective study was conducted on 39 patients (22 males; mean age: 64 years) with one or more abdominal focal lesions (total: 41; mean diameter: 2.9 cm) who underwent CEUS, had already undergone CT/MRI without a definitive diagnosis or had not undergone them due to contraindications. The frequency, out of the total lesions included, in which CEUS was problem-solving, confirmatory or inconclusive was evaluated.ResultsCEUS proved to be problem-solving for 20/41 (48.8%) lesions, confirmatory for 17/41 (41.5%) lesions and inconclusive for 4/41 (9.7%) lesions. Including problem-solving and confirmatory diagnosis, CEUS correctly identified 24/27 (88.9%) liver lesions, 11/11 (100%) kidney lesions, a gallbladder and a pancreatic lesion, while it did not provide useful information for 4/41 (9.7%) lesions, specifically three liver lesions and a testicular one.ConclusionsCEUS is a promising technique when CT and/or MRI are inconclusive or contraindicated and to increase the radiologist’s diagnostic confidence.

Impaired Glucose Metabolism, Primary Cilium Defects, and Kidney Cystogenesis in Glycogen Storage Disease Type Ia.

Glycogen Storage Disease type Ia (GSDIa) is a rare metabolic disorder caused by mutations in the catalytic subunit of glucose-6 phosphatase (G6PC1). This leads to severe hypoglycemia and most young GSDIa patients develop CKD. The kidney pathology is characterized by the development of cysts, which typically occur at an advanced stage of CKD. To elucidate the molecular mechanisms responsible for cyst formation, we characterized renal metabolism, molecular pathways involved in cell proliferation and integrity primary cilium integrity, using mice in which G6pc1 was specifically deleted in the kidney from in utero stage. GSDIa mice exhibited renal fibrosis, high-inflammation, and cyst formation, leading to kidney dysfunction. In addition, the loss of G6PC1 led to the ectopic accumulation of glycogen and lipids in the kidneys, and a metabolic shift towards a Warburg-like metabolism. This metabolic adaptation was due to an excess of glucose-6 phosphate, which supports cell proliferation, driven by the MEK/ERK and AKT/mTOR pathways. Treatment of GSDIa mice with rapamycin, a target of the mTOR pathway, reduced cell proliferation and kidney damage. Our results also identified lipocalin 2 as a contributor to renal inflammation and an early biomarker of CKD progression in GSDIa mice. Its inactivation partially prevented kidney lesions in GSDIa. Importantly, primary cilium defects were observed in the kidneys of GSDIa mice. Metabolic adaptations due to glucose-6 phosphate accumulation in GSDIa renal tubules, towards a Warburg-like metabolism, appeared to promote cell proliferation and cyst formation in a similar manner to that observed in various cystic kidney diseases. This was associated with down-regulation of primary cilium gene expression and consequently, altered cilium morphology.

Targeting Lactobacillus johnsonii to reverse chronic kidney disease

Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease (CKD). However, no available therapy is effective in suppressing progressive CKD. Here, using microbiomics in 480 participants including healthy controls and patients with stage 1–5 CKD, we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression, whose abundance strongly correlated with clinical kidney markers. L. johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD. L. johnsonii supplementation ameliorated kidney lesion. Serum indole-3-aldehyde (IAld), whose level strongly negatively correlated with creatinine level in CKD rats, decreased in serum of rats induced using unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (NX) as well as late CKD patients. Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor (AHR) signal in rats with CKD or UUO, and in cultured 1-hydroxypyrene-induced HK-2 cells. Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells. Our further data showed that treatment with L. johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level. Taken together, targeting L. johnsonii might reverse patients with CKD. This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients.

Galectin-3 contributes to pathogenesis of IgA nephropathy

IgA nephropathy (IgAN) is the most common type of glomerulonephritis that frequently progresses to kidney failure. However, the molecular pathogenesis underlying IgAN remains largely unknown. Here, we investigated the role of galectin-3 (Gal-3), a galactoside-binding protein in IgAN pathogenesis and showed that Gal-3 expression by the kidney was significantly enhanced in patients with IgAN. In both TEPC-15 hybridoma-derived IgA-induced, passive, and spontaneous “grouped” ddY IgAN models, Gal-3 expression was clearly increased with disease severity in the glomeruli, peri-glomerular regions, and some kidney tubules. Gal-3 knockout (KO) in the passive IgAN model had significantly improved proteinuria, kidney function and reduced severity of kidney pathology, including neutrophil infiltration and decreased differentiation of Th17 cells from kidney-draining lymph nodes, despite increased percentages of regulatory T cells. Gal-3 KO also inhibited the NLRP3 inflammasome, yet it enhanced autophagy and improved kidney inflammation and fibrosis. Moreover, administration of 6-de-O-sulfated, N-acetylated low-molecular-weight heparin, a competitive Gal-3 binding inhibitor, restored kidney function and improved kidney lesions in passive IgAN mice. Thus, our results suggest that Gal-3 is critically involved in IgAN pathogenesis by activating the NLRP3 inflammasome and promoting Th17 cell differentiation. Hence, targeting Gal-3 action may represent a new therapeutic strategy for treatment of this kidney disease.

Tumor morphology evaluation using 3D-morphometric features of renal masses.

To assess the correlation between the general (gender, age, and maximum tumor size) and 3D morphotopometric features of the renal tumor node, following the MSCT data post-processing, and the tumor histological structure; to propose an equation allowing for kidney malignancy assessment based on general and morphometric features. In total, 304 patients with unilateral solitary renal neoplasms underwent laparoscopic (retroperitoneoscopic) or robotic partial or radical nephrectomy. Before the procedure, kidney contrast-enhanced MSCT followed by the tumor 3D-modeling was performed. 3D model of the kidney tumor, and its morphotopometric features, and histological structure were analyzed. The morphotopometric ones include the side of the lesion, location by segments, the surface where the tumor, the depth of the tumor invasion into the kidney, and the shape of tumor. Out of 304 patients, 254 (83.6%) had malignant kidney tumors and 50 (16.4%) benign kidney tumors. In total, 231 patients, out of 254 (90.9%) were assessed for the degree of malignant tumor differentiation. Malignant tumors were more frequent in men than in women (p < 0.001). Mushroom-shaped tumors were the most common shapes among benign renal masses (35.2%). The most common malignant kidney tumors had spherical with a partially uneven surface (27.6%), multinodular (tuberous (27.2%)), and spherical with a conical base (24.8%) shapes. Logistic regression model enabled the development of prognostic equation for tumor malignancy prediction ("low" or "high"). The univariate analysis revealed the correlation only between high differentiation (G1) and a spherical tumor with a conical base (p = 0.029). The resulting logistic model, based on the analysis of such predictors as gender and form of kidney lesions, demonstrated a large share (87.6%) of correct predictions of the kidney tumor malignancy.

The Clinicopathological Characteristics and Prognosis of 55 Patients With TFE3-Rearranged Renal Cell Carcinomas

ObjectiveTo explore the clinicopathological features and prognosis of TFE3-rearranged renal cell carcinomas (TFE3-rRCC). MethodsIn this retrospective observational study, the data of patients with TFE3-rRCC admitted to Xijing Hospital from January 2010 to October 2023 were collected, encompassing the general information, pathological diagnosis, immunohistochemistry, and the results of FISH detection. The treatment information and survival data of the patients were recorded during the follow-up. ResultsA total of 55 patients with TFE3-rRCC were enrolled, among whom 25 were males and 30 were females. TFE3 FISH assay suggested the disruption of the TFE3 gene. Fifty-four patients underwent surgical resection of kidney lesions, while 1 patient did not. By the end of follow-up in December 2023, 3 patients were lost to follow-up, 28 patients remained alive, and 24 patients had died. Among the 52 patients followed up, 31 developed metastases, involving lymph nodes, liver, bone, lung, peritoneum, pleura, adrenal gland, and brain. The 1-year and 5-year survival rates of the patients were 84.6% and 50.6%, respectively. In this study, there were 31 patients with TFE3-rRCC recurrence or metastasis. Median PFS was 7 and 13 months in the VEGFR-TKI and VEGFR-TKI+ ICI groups, respectively. The median OS was 12 months in the VEGFR-TKI treatment group. The median OS data of VEGFR-TKI+ ICI group has not been reached. The ORR and DCR was 25%, 66.7% in the VEGFR-TKI group. The ORR and DCR was 33.3%, 77.8% in the VEGFR-TKI+ ICI group. ConclusionTFE3-rRCC is a rare subtype of malignant renal tumor. The diagnosis mainly relies on pathological morphology, immunohistochemistry, and the detection of TFE3 gene disruption by FISH. In terms of treatment, surgery is the primary approach, and lymph nodes, liver, and bone are the main metastatic sites. VEGFR-TKI+ICI treatment might be an option of recurrent or metastatic TFE3-rRCC.

Effect of Ultrasound-Guided Renal Biopsies on Urinary N-Acetyl-Beta-D-Glucosaminidase Index Activity in Dogs with Diffuse Parenchymal Nephropathies.

Ultrasound-guided kidney biopsy is an essential diagnostics method that can increase the accuracy of the differential diagnosis between acute and chronic nephropathies. In addition, it will help clinicians perform an etiologic diagnosis, issue a prognosis, and orient therapy for the majority of parenchymal nephropathies. Due to the relative invasiveness and potential adverse effects, the use of kidney biopsies is limited among practitioners. Twenty-eight dogs, of mixed breed and variable ages, of which 11 (39, 29%) were males and 17 (60, 71%) were females, were examined and underwent an ultrasound-guided kidney biopsy to establish a definitive diagnosis. The patients were presented with a variety of diffuse nephropathies, such as kidney lymphoma: 1 (3.57%), glomerulonephritis: 13 (46.43%), tubulointerstitial nephritis: 11 (39.29%), and nephrocalcinosis. A total of 3 (10.71%) of 18 (64.29%) were in acute kidney injury, and 10 (35.71%) were CKD patients. The type and the severity of the kidney lesions were correlated with changes in the urinary n-acetyl-beta-d-glucosaminidase index (iNAG. To quantify the side effects of percutaneous kidney biopsy, the magnitude of post-biopsy hematuria and changes in urinary iNAG activity were evaluated. The results indicate a significant post-biopsy increase in the urinary iNAG activity in all the patients that underwent this procedure (100.08 ± 34.45 U/g), with a pre-biopsy iNAG vs. 147.65 ± 33.26 U/g post-biopsy iNAG (p < 0.001), suggesting an intensification in the kidney tubular damage that comes consecutives to kidney puncture and sampling. Transitory macro- or microhematuria were constant findings in all the dogs that underwent ultrasound-guided kidney biopsy, but the magnitude and extent could not be associated with the platelet count (PLT 109/L), aPTT (s), and PT (s) levels in our patients, and they were also resolved after 12-24 h without therapeutic interventions. Ultrasound-guided renal biopsy was shown to be a minimally invasive diagnostic procedure that causes transient and limited effects on kidney structures. Although these effects were minor and resolved without intervention, we feel that the benefit of obtaining higher-quality biopsied tissue outweighs the higher risks associated with this procedure.

Kidney, ureter, and urinary bladder segmentation based on non-contrast enhanced computed tomography images using modified U-Net

This study was performed to segment the urinary system as the basis for diagnosing urinary system diseases on non-contrast computed tomography (CT). This study was conducted with images obtained between January 2016 and December 2020. During the study period, non-contrast abdominopelvic CT scans of patients and diagnosed and treated with urinary stones at the emergency departments of two institutions were collected. Region of interest extraction was first performed, and urinary system segmentation was performed using a modified U-Net. Thereafter, fivefold cross-validation was performed to evaluate the robustness of the model performance. In fivefold cross-validation results of the segmentation of the urinary system, the average dice coefficient was 0.8673, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9651, 0.7172, and 0.9196, respectively. In the test dataset, the average dice coefficient of best performing model in fivefold cross validation for whole urinary system was 0.8623, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9613, 0.7225, and 0.9032, respectively. The segmentation of the urinary system using the modified U-Net proposed in this study could be the basis for the detection of kidney, ureter, and urinary bladder lesions, such as stones and tumours, through machine learning.

Abscopal Effect Demonstrated on [18F]FDG PET/CT in a Case of Renal Cell Carcinoma Postnephrectomy

Renal cell carcinoma accounts for 3% of all malignancies with many of them presenting with metastasis at the time of presentation. The abscopal effect, a phenomenon characterized by systemic bystander effects on nontargeted lesions due to local therapy, has been extensively studied in the context of radiotherapy and immunotherapy. However, documentation of the abscopal effect following surgery remains limited. We present a case of a 67-year-old Indian male diagnosed with clear cell renal cell carcinoma (RCC), who underwent left radical nephrectomy. Baseline staging and postnephrectomy follow-up scans with fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) revealed an FDG-avid primary lesion in the left kidney with metastasis to the left lung. Surprisingly, the follow-up FDG PET-CT scan demonstrated the resolution of the left lung metastasis, indicating the occurrence of the abscopal effect resulting from the local nephrectomy. This rare clinical observation highlights the potential of surgery to induce immunogenic tumor neoantigens release and inflammatory factors, leading to systemic antitumor effects. While the abscopal effect has been extensively studied in the context of radiotherapy and immunotherapy, there is a scarcity of studies reporting nephrectomy promoting such systemic effects. The combination of radiotherapy and immunotherapy has shown promising results in enhancing tumor immunosuppression and facilitating the abscopal effect. We report a case of RCC with lung metastasis showing abscopal effect with resolution of lung nodule postnephrectomy on 18-F-FDG PET-CT.

Contrast-Enhanced Ultrasound in the Diagnosis of Solid Renal Lesions.

The availability of imaging methods has enabled increased detection of kidney lesions, which are a common clinical problem. It is estimated that more than half of patients over the age of 50 have at least one undetermined mass in the kidney. The appropriate characterization and diagnosis of lesions imaged in the kidney allows for proper therapeutic management. Previously, contrast-enhanced computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI) have been used in their extended diagnosis. However, the limitations of these techniques, such as radiation exposure, renal toxicity, and allergies to contrast agents, must be considered. Contrast-enhanced ultrasound (CEUS) is increasingly being used as an examination to resolve interpretive doubts that arise with other diagnostic methods. Indeed, it can be considered both as a problem-solving technique for diagnosing and distinguishing lesions and as a technique used for observation in preservative treatment. Evaluation of the enhancement curve over time on CEUS examination can help to differentiate malignant renal cell carcinoma (RCC) subtypes that should be resected from benign lesions, such as oncocytoma or angiomyolipoma (AML), in which surgery can be avoided. It allows for distinguishing between benign and malignant tumors, renal and pseudotumors, and solid and cystic tumors. Therefore, with recent advances in ultrasound technology, CEUS has emerged as a fast, reliable, and cost-effective imaging tool in the preoperative evaluation and diagnosis of solid renal masses.

Comparison of Age-Related Decline and Behavioral Validity in C57BL/6 and CB6F1 Mice.

Variability in physical resilience to aging prompts a comprehensive examination of underlying mechanisms across organs and individuals. We conducted a detailed exploration of behavioral and physiological differences between C57BL/6 and CB6F1 mice across various age groups. In behavioral assays, B6 mice displayed superior performance in rotarod tasks but higher anxiety while CB6F1 mice exhibited a decline in short-term memory with age. Grip strength, long-term memory, and voluntary wheel running declined similarly with age in both strains. Examining physiological phenotypes, B6 mice exhibited lower body fat percentages across ages compared to CB6F1 mice, though cataract severity worsened with age in both strains. Analysis of cardiac functions revealed differences between strains, with worsening left ventricular hypertrophy and structural heart abnormalities with age in CB6F1 mice along with higher blood pressure than B6. Lesion scores showed an age-related increase in heart, kidney, and liver lesions in both strains, while lung lesions worsened with age only in CB6F1 mice. This study underscores the validity of behavioral assays and geropathology assessment in reflecting age-related decline and emphasizes the importance of considering strain specificity when using mouse models to study human aging.

Evaluating Single-Nucleotide Polymorphisms in Inflammasome Proteins and Serum Levels of IL-18 and IL-1β in Kidney Interstitial Damage in Anti-Neutrophilic Cytoplasmic Antibody-Associated Vasculitis.

The inflammasome regulates the innate inflammatory response and is involved in autoimmune diseases. In this study, we explored the levels of IL-18 and IL-1β in serum and urine and the influence of various single-nucleotide polymorphisms (SNPs) on kidney lesions at diagnosis in patients with ANCA-associated vasculitis (AAV) and their clinical outcomes. Ninety-two patients with renal AAV were recruited, and blood and urine were collected at diagnosis. Serum and urine cytokine levels were measured by ELISA. DNA was extracted and genotyped using TaqMan assays for SNPs in several inflammasome genes. Lower serum IL-18 (p = 0.049) and the IL-18 rs187238 G-carrier genotype (p = 0.042) were associated with severe fibrosis. The IL-18 rs1946518 TT genotype was associated with an increased risk of relapse (p = 0.05), whereas GG was related to better renal outcomes (p = 0.031). The rs187238 GG genotype was identified as a risk factor for mortality within the first year after AAV diagnosis, independent of the requirement for dialysis or lung involvement (p = 0.013). We suggest that decreased cytokine levels could be a surrogate marker of scarring and chronicity of the renal lesions, together with the rs187238 GG genotype. If our results are validated, the rs1946518 TT genotype predicts the risk of relapse and renal outcomes during follow-up.

The extent of kidney involvement in paediatric tuberous sclerosis complex

BackgroundTuberous sclerosis (TSC)–associated kidney disease is a leading cause of mortality in adults with TSC. This study aimed to understand TSC features in children, particularly kidney involvement, to inform clinical care for this specific group.MethodsThis retrospective cohort study included all paediatric (< 19 years) TSC cases at a large tertiary paediatric nephrology centre. Relevant data were collected from patients’ records, statistical analyses were performed to identify associations between variables, survival probabilities were estimated with Kaplan‒Meier curves, and log-rank tests were conducted to assess survival differences among genetic mutations.ResultsA total of 182 children with TSC were included. Among the 145 children with available kidney imaging data, 78.6% (114/145) exhibited kidney lesions. Angiomyolipomas (AMLs) were significantly more prevalent in the TSC2 mutation group (p = 0.018). Children with TSC2 mutations generally had poorer lesion-free survival than those with TSC1 mutations, but this difference was only significant for AMLs (p = 0.030). The change in size of largest AMLs increased with age and doubled in children above 9 years; a similar pattern was observed when stratified by genetic mutation. In contrast, kidney cysts exhibited two peaks: one in children under 5 years (2.31 mm/year) and the second in children between 15–19 years (2.82 mm/year). Chronic kidney disease was observed in 12.3% (10/81) of children, and high-risk AMLs above 3 cm were observed in 9% (13/145).ConclusionsWhile TSC kidney disease emerges later in the disease course than neurological features, our findings emphasise the importance of kidney surveillance during childhood, including routine kidney imaging, kidney function, and blood pressure monitoring.Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Sex-Specific Analysis of Mid-Term Outcomes of Atherectomy-Assisted Endovascular Treatment in Severe Peripheral Arterial Disease.

Background: Endovascular treatment of lower-extremity peripheral disease (PAD) is associated with higher complication rates and suboptimal outcomes in women. Atherectomy has shown favourable outcomes in calcified lesions, minimising the incidence of stent placement caused by recoil or flow-limiting dissection. To date, there are no published mid-term outcomes evaluating the performance of atherectomy differentiated by sex. This study aims to evaluate sex-specific outcomes and prognostic factors affecting the results of atherectomy-assisted endovascular treatment in severe PAD. Methods: A retrospective analysis was conducted at a single centre in Germany, initiated by physicians and not sponsored by industry, on patients presenting with Rutherford categories ranging from III to V and featuring de novo occlusive or stenotic lesions of the superficial femoral (SFA) and/or popliteal arteries. The intervention involved rotational atherectomy-assisted angioplasty utilising the Jetstream (Boston, US®) device. The point of interest of this study was postinterventional clinical improvement as well as mid-term outcomes, including primary patency, over a targeted 2-year follow-up period. Statistical analysis utilised Cox regression (survival analysis) to calculate hazard ratios according to sex category. Comparative survival analysis was performed using the log-rank test and visually represented through Kaplan-Meier curves. Risk factors associated with absence of clinical improvement were examined across both sex groups utilising the chi-square or Fisher exact test, as appropriate. Results: A total of 98 patients (103 limbs) were initially included, with >75% having moderate-to-severe lesion calcification (>50%). A total of 84 patients (97 limbs, 62 male and 35 female) proceeded to a 2-year follow-up (mean 16.4 months for males and 16.1 for females) after a successful index procedure. Age distribution, Rutherford class, diabetes, chronic kidney disease (CKD), target vessel, lesion type, and length were balanced among both groups. Similar primary patency rates, of 89% among female and 91% among male limbs, were observed (p = 0.471). Female patients exhibited a lower rate of clinical improvement based on the Rutherford scale in comparison to males (80.6% vs. 94.5%, p = 0.048). CDK was the only significant prognostic factor across pooled data (odds ratio for CKD: 15.15, p < 0.001). Conclusions: Rotational atherectomy showed comparably high rates of mid-term primary patency, with low rates of bailout stent placement. These findings highlight the beneficial use of atherectomy in female patients who are per se at risk for higher rates of complications during and after endovascular interventions.

A step toward simplified dosimetry of radiopharmaceutical therapy via SPECT frame duration reduction

Despite being time-consuming, SPECT/CT data is necessary for accurate dosimetry in patient-specific radiopharmaceutical therapy. We investigated how reducing the frame duration (FD) during SPECT acquisition can simplify the dosimetry workflow for [177Lu]Lu-PSMA radioligand therapy (RLT). We aimed to determine the impact of shortened acquisition times on dosimetric precision. Three SPECT scans with FD of 20, 10, and 5 second/frame (sec/fr) were obtained 48 h post-RLT from one metastatic castration-resistant prostate cancer (mCRPC) patient's pelvis. Planar images at 4, 48, and 72 h post-therapy were used to calculate time-integrated activities (TIAs). Using accurate activity calibrations and GATE Monte Carlo (MC) dosimetry, absorbed doses in tumor lesions and kidneys were estimated. Dosimetry precision was assessed by comparing shorter FD results to the 20 sec/fr reference using relative percentage difference (RPD). We observed consistent calibration factors (CFs) across different FDs. Using the same CF, we obtained marginal RPD deviations less than 4% for the right kidney and tumor lesions and less than 7% for the left kidney. By reducing FD, simulation time was slightly decreased. This study shows we can shorten SPECT acquisition time in RLT dosimetry by reducing FD without sacrificing dosimetry accuracy. These findings pave the way for streamlined personalized internal dosimetry workflows.

#2284 Clinical characteristics and renal survival of patients with monoclonal gammopathy of renal significance (MGRS)

Abstract Background and Aims Monoclonal gammopathy of renal significance (MGRS) comprises a diverse group of renal disorders related to a nephrotoxic monoclonal immunoglobulin. Due to the rarity of the disease and the recent definition of MGRS-associated kidney lesions, data about long-term clinical outcomes remain limited. Method A single-center, retrospective cohort study was conducted including data of all patients with biopsy-proven MGRS who were followed at our center between 2005 and 2023. We examined the clinicopathologic characteristics and renal survival of the patients. Disease progression was defined as an eGFR decline &amp;gt;30% or end-stage kidney disease (ESKD). Univariate Cox regression analysis was used to assess the relationship between clinical features and disease progression. Results A total of 23 adults (males 43.5%) with a median age of 65 years (IQR 55-70) were included in our study. At presentation, median eGFR was 51 ml/min/1.73 m2 (IQR 40-80) and proteinuria 3.94 g/24 h (IQR 2.00-6.26). Serum or urine monoclonal protein was not detected in 4 patients (18.2%). MGRS-associated renal lesions included Ig-related amyloidosis (n = 8), monoclonal immunoglobulin deposition disease (n = 7), cryoglobulinemic glomerulonephritis (n = 2), C3 glomerulopathy (n = 2), proliferative glomerulonephritis with monoclonal IgG deposits (n = 1), immunotactoid glomerulopathy (n = 1) and miscellaneous (n = 2). Most patients were treated with a plasma cell-directed regimen (77.3%) and the rest with B-cell-directed (13.6%) or conservative therapy (9.1%). Median follow-up for the cohort was 45 months (IQR 27-67). Thirteen patients responded to treatment (52.1%), achieving a reduction in proteinuria (0.44 vs 3.94 g/24 h, p:001) and maintenance of eGFR (60 vs 56 ml/min, p:0.363) at the last follow-up visit. All responders had received clone-directed therapy. Disease progression occurred in 8 patients (34.8%), three of whom reached ESKD (13.0%). Renal survival, defined as survival without ESKD, was 84.6% at 48 months (CI 73.3-101.7). Factors that were associated with disease progression were Ig-related amyloidosis (HR: 6.94, CI: 1.30-36.84, p:0.023) and eGFR &amp;lt; 45 ml/min at diagnosis (HR: 14.73, CI: 1.62-132.95, p:0.017). Conclusion MGRS is a heterogeneous clinical entity manifesting with varying degrees of proteinuria and kidney injury. Impaired kidney function at diagnosis and Ig-related amyloidosis correlated with worse renal prognosis in our cohort. Early identification and clone-directed treatment of MGRS may improve long-term renal survival.

#2615 Altered peroxidasin expression pattern in IgA nephropathy

Abstract Background and Aims PXDN is a multifunctional heme peroxidase responsible for the crosslinking of type IV collagen protomers at basement membranes, playing a crucial role in the extracellular matrix dynamics. In renal pathophysiology, increased PXDN expression has been associated with pro-fibrotic and pro-carcinogenic mechanisms and we have shown that PXDN is expressed throughout all kidney compartments since the early stages of nephrogenesis. However, the role of PXDN in kidney health and disease remains largely unknown. In this work we performed a comparative analysis of PXDN expression between renal biopsy samples from IgA nephropathy (IgAN) patients and healthy kidney biopsy samples. IgAN was the selected CKD model due to its straightforward diagnosis by standard protocols for histopathological evaluation of kidney biopsies, and to the fact that the renal outcomes are consistently associated with several key pathologic features, including tubular atrophy and interstitial fibrosis. Correlations between PXDN expression and IgAN disease and kidney function parameters as well as with ECM proteins were also explored. Method Fluorescence immunohistochemistry for PXDN was performed in biopsy samples from IgAN patients (n = 20) and in biopsies from healthy kidney donors (n = 7). Proximal tubules were assessed by anti-CD15 fluorescent staining. Collagen III (COLIII) deposition was investigated in IgAN samples (n = 7) by immunofluorescence. Brightfield images were manually segmented into glomeruli, proximal and distal tubules, and interstitium, using QuPath software, and the fluorescence intensity measurements were obtained with ImageJ/Fiji. Results Results showed that, in comparison with healthy kidney samples, PXDN is significantly decreased in proximal and distal tubules of IgAN patients (P &amp;lt; 0.001 and P &amp;lt; 0.05, respectively) whereas it is increased in IgAN interstitium (P &amp;lt; 0.001). When IgAN samples were stratified by the presence or absence of chronic lesions (glomerular sclerosis and interstitial fibrosis) we observed that in the proximal tubules, PXDN is decreased even in areas without lesions while in the distal tubules the expression is compromised only in the lesioned areas. In the interstitium, PXDN shows a tendency of increase from healthy tissue to IgAN in areas without and with tubulointerstitial fibrosis, presenting a significant increase in the lesioned areas (P &amp;lt; 0.001). Concerning ECM deposition, results showed a significant correlation between the expression of PXDN and COLIII in sclerotic glomeruli (R = 0.8214; P = 0.0341) and in the tubulointerstitial fibrotic areas (R = 0.93; P = 0.0067). Moreover, although no differences were observed in the glomerular expression of PXDN between healthy and IgAN samples, when considering eGFR, a significant increase of PXDN was observed in both non-lesioned and sclerotic glomeruli from IgAN patients with eGFR bellow 60 ml/min/1,73 m2. In the interstitium, the expression of PXDN was also increased in tubulointerstitial fibrotic areas of IgAN patients with eGFR bellow 60 ml/min/1,73 m2, in comparison with the same areas in patients with higher eGFR values. Conclusions Overall, our study shows a differential expression of PXDN in IgAN, with loss in the tubular region that relates with the state of interstitial fibrosis, and gain in the glomerular and interstitial region where it correlates with COLIII compartment-specific deposition and with kidney function as assessed by eGFR. These data support, for the first time, the enrollment of PXDN in the topographic mechanism of IgA-mediated kidney lesion that deserves further investigations. Given that sclerosis and fibrosis are a common pathogenic mechanism of CKD, irrespective of the underlying etiology, we postulate that PXDN may serve as a novel therapeutic target for this disease.

Pathology of co-contamination of mycotoxins in poultry farms of Aizawl district of Mizoram

The study was conducted to investigate the naturally occurring pathology of co-contamination of mycotoxins in poultry farms in Aizawl, Mizoram. During the investigation, different chicken farms (n=73) were surveyed for occurrence of disease and mortality. The feed samples collected from affected farms were tested for the presence of aflatoxin, ochratoxin and zearalenone by ELISA kits. The dead birds were subjected to necropsy. Visceral organs from the dead birds were processed for histopathological studies. Fourteen feed samples, out of 49 tested (28.5%) were found affected by co-contamination with aflatoxin, ochratoxin and zearalenone. In this study, the mean level of aflatoxin, ochratoxin and zearalenone was 13.49693 ppb, 4.296286 ppb and 81.74543 ppb, respectively. Clinical signs were ruffled feathers, depression, dullness, huddling, poor growth, anorexia. Necropsy revealed pathological lesions in visceral and lymphoid organs. Histopathological findings were inflammations, degenerative, and necrotic lesions in liver and kidneys. A perusal of available literature did not reveal any study on the presence of co-contamination of Mycotoxicosis in poultry and poultry feed in Aizawl.

Clinical spectrum and outcome of Takayasu's arteritis in children

ObjectivesWe aimed to compare clinical spectrum and outcome between adults and children with Takayasu's arteritis (TAK) in a European population. MethodsWe made a nationwide retrospective observational study between 1988 and 2019. All adult patients met the ACR diagnostic criteria for TAK and all children met the EULAR/PRINTO/PRES criteria for paediatric TAK. ResultsWe identified 46 children and 389 adults with TAK. The male to female ratio was 34/46 (0.74) in the paediatric group compared to 241/274 (0.88) in the adult group (P<0.05). Children presented with significantly more systemic symptoms; i.e., fever (P<0.05), fatigue (P<0.001), weight loss (P<0.001), abdominal pain (P<0.05), and myalgia (P<0.05) while adults had more upper limb claudication (P<0.01). Topography of the lesions differed significantly between the two groups: adults had more damage at the cerebral vasculature (P<0.01), upper and lower limbs (P<0.001) while children had more kidney lesions (P<0.05). Children TAK had more frequent (P<0.01) and higher (P<0.001) biological inflammation than adults. Children received higher dose-weight of corticosteroids (P=0.001) and less biotherapy (P<0.010) at diagnosis. Relapses (P<0.05) and death (8.6% vs 4.9%) were more frequent in children TAK than in adults. ConclusionPaediatric TAK seems more severe than adult TAK. Therefore, paediatrics patients may require closer monitoring and systemic use of biological treatment.