Bile Acid Receptor Agonist Reverses Transforming Growth Factor-ß1-Mediated Fibrogenesis in Human Induced Pluripotent Stem Cells-Derived Kidney Organoids.

Chronic kidney disease progresses through the replacement of functional tissue compartments with fibrosis, a maladaptive repair process. Shifting kidney repair toward a physiologically intact architecture, rather than fibrosis, is key to blocking chronic kidney disease progression. Much research into the mechanisms of fibrosis is performed in rodent models with less attention to the human genetic context. Recently, human induced pluripotent stem cell (iPSC)-derived organoids have shown promise in overcoming the limitation. In this study, we developed a fibrosis model that uses human iPSC-based 3-dimensional renal organoids, in which exogenous transforming growth factor-ß1 (TGF-ß1) induced the production of extracellular matrix. TGF-ß1-treated organoids showed tubulocentric collagen 1α1 production by regulating downstream transcriptional regulators, Farnesoid X receptor, phosphorylated mothers against decapentaplegic homolog 3 (p-SMAD3), and transcriptional coactivator with PDZ-binding motif (TAZ). Increased nuclear TAZ expression was confirmed in the tubular epithelium in human kidney biopsies with tubular injury and early fibrosis. A dual bile acid receptor agonist (INT-767) increased Farnesoid X receptor and reduced p-SMAD3 and TAZ, attenuating TGF-ß1-induced fibrosis in kidney organoids. Finally, we show that TAZ interacted with TEA-domain transcription factors and p-SMAD3 with TAZ and TEA-domain transcription factor 4 coregulating collagen 1α1 gene transcription. In summary, we establish a novel, readily manipulable fibrogenesis model and posit a role for bile acid receptor agonism early in renal parenchymal fibrosis.

Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney.

A gradual decline in renal function occurs even in healthy aging individuals. In addition to aging, per se, concurrent metabolic syndrome and hypertension, which are common in the aging population, can induce mitochondrial dysfunction and inflammation, which collectively contribute to age-related kidney dysfunction and disease. This study examined the role of the nuclear hormone receptors, the estrogen-related receptors (ERRs), in regulation of age-related mitochondrial dysfunction and inflammation. The ERRs were decreased in both aging human and mouse kidneys and were preserved in aging mice with lifelong caloric restriction (CR). A pan-ERR agonist, SLU-PP-332, was used to treat 21-month-old mice for 8 weeks. In addition, 21-month-old mice were treated with a stimulator of interferon genes (STING) inhibitor, C-176, for 3 weeks. Remarkably, similar to CR, an 8-week treatment with a pan-ERR agonist reversed the age-related increases in albuminuria, podocyte loss, mitochondrial dysfunction, and inflammatory cytokines, via the cyclic GMP-AMP synthase-STING and STAT3 signaling pathways. A 3-week treatment of 21-month-old mice with a STING inhibitor reversed the increases in inflammatory cytokines and the senescence marker, p21/cyclin dependent kinase inhibitor 1A (Cdkn1a), but also unexpectedly reversed the age-related decreases in PPARG coactivator (PGC)-1α, ERRα, mitochondrial complexes, and medium chain acyl coenzyme A dehydrogenase (MCAD) expression. These studies identified ERRs as CR mimetics and as important modulators of age-related mitochondrial dysfunction and inflammation. These findings highlight novel druggable pathways that can be further evaluated to prevent progression of age-related kidney disease.

Primary Alveolar Soft-Part Sarcoma (ASPS) of the Prostate: Report of a Deceptive Case.

Alveolar soft-part sarcoma (ASPS) is a rare soft tissue tumor that primarily involves the extremities. We report a case of a 30-year-old never-smoker man who presented with hematuria, dysuria, and constipation at an outside hospital. He was diagnosed with and treated for multiple episodes of urinary tract infection. However, he continued to have voiding symptoms for which a cystoscopy was performed and revealed a bladder neck mass. He underwent transurethral resection of a bladder tumor and was diagnosed with muscle-invasive urothelial carcinoma, nested variant, at an outside hospital. Subsequent to this diagnosis he transferred his care to our center. In-house imaging revealed a large vascular mass involving the prostate and pushing against the bladder base. Prostate needle biopsies were performed and revealed an epithelioid neoplasm with a nested growth pattern composed of cells with a moderate amount of eosinophilic cytoplasm, mildly pleomorphic nuclei, and occasional prominent nucleoli. Since the findings were not classic for urothelial carcinoma or for prostate cancer, we included a wider differential of poorly differentiated carcinoma, sarcoma, and paraganglioma. A wide panel of keratin stains was negative, ETS (erythroblast transformation-specific)-related gene highlighted an extensive vascular network and neuroendocrine stains were all negative. A transcription factor E3 fluorescent in-situ hybridization was positive and subsequently, an ASPSCR1 gene rearrangement was demonstrated. The outside hospital transurethral resection of bladder tumor was obtained for review and the tumor was morphologically similar to that seen on the in-house prostate needle biopsies. Based on the above findings a final diagnosis of primary ASPS of the prostate with involvement of the bladder was made. The patient was later diagnosed with bilateral lung metastases. He was treated with pazopanib, radiation therapy, and cystoprostatectomy and is symptom-free on a 15-month follow-up.

PodoCount: A Robust, Fully Automated, Whole-Slide Podocyte Quantification Tool.

Introduction: Podocyte depletion is a histomorphologic indicator of glomerular injury and predicts clinical outcomes. Podocyte estimation methods or podometrics are semiquantitative, technically involved, and laborious. Implementation of high-throughput podometrics in experimental and clinical workflows necessitates an automated podometrics pipeline. Recognizing that computational image analysis offers a robust approach to study cell and tissue structure, we developed and validated PodoCount (a computational tool for automated podocyte quantification in immunohistochemically labeled tissues) using a diverse data set. Methods: Whole-slide images (WSIs) of tissues immunostained with a podocyte nuclear marker and periodic acid-Schiff counterstain were acquired. The data set consisted of murine whole kidney sections (n = 135) from 6 disease models and human kidney biopsy specimens from patients with diabetic nephropathy (DN) (n = 45). Within segmented glomeruli, podocytes were extracted and image analysis was applied to compute measures of podocyte depletion and nuclear morphometry. Computational performance evaluation and statistical testing were performed to validate podometric and associated image features. PodoCount was disbursed as an open-source, cloud-based computational tool. Results: PodoCount produced highly accurate podocyte quantification when benchmarked against existing methods. Podocyte nuclear profiles were identified with 0.98 accuracy and segmented with 0.85 sensitivity and 0.99 specificity. Errors in podocyte count were bounded by 1 podocyte per glomerulus. Podocyte-specific image features were found to be significant predictors of disease state, proteinuria, and clinical outcome. Conclusion: PodoCount offers high-performance podocyte quantitation in diverse murine disease models and in human kidney biopsy specimens. Resultant features offer significant correlation with associated metadata and outcome. Our cloud-based tool will provide end users with a standardized approach for automated podometrics from gigapixel-sized WSIs.

The evolving story of apolipoprotein L1 nephropathy: the end of the beginning.

Genetic coding variants in APOL1, which encodes apolipoprotein L1 (APOL1), were identified in 2010 and are relatively common among individuals of sub-Saharan African ancestry. Approximately 13% of African Americans carry two APOL1 risk alleles. These variants, termed G1 and G2, are a frequent cause of kidney disease - termed APOL1 nephropathy - that typically manifests as focal segmental glomerulosclerosis and the clinical syndrome of hypertension and arterionephrosclerosis. Cell culture studies suggest that APOL1 variants cause cell dysfunction through several processes, including alterations in cation channel activity, inflammasome activation, increased endoplasmic reticulum stress, activation of protein kinase R, mitochondrial dysfunction and disruption of APOL1 ubiquitinylation. Risk of APOL1 nephropathy is mostly confined to individuals with two APOL1 risk variants. However, only a minority of individuals with two APOL1 risk alleles develop kidney disease, suggesting the need for a 'second hit'. The best recognized factor responsible for this 'second hit' is a chronic viral infection, particularly HIV-1, resulting in interferon-mediated activation of the APOL1 promoter, although most individuals with APOL1 nephropathy do not have an obvious cofactor. Current therapies for APOL1 nephropathies are not adequate to halt progression of chronic kidney disease, and new targeted molecular therapies are in clinical trials.

Diagnostic utility of a-methylacyl COA racemase in prostate cancer of the Iranian population.

BACKGROUND: Considering the great variations in the reported prevalence of prostate cancer across the world possibly due to different genetic and environmental backgrounds, we aimed to determine the expression pattern and the diagnostic utility of α-methylacyl coenzyme A racemase (AMACR) among Iranian patients with prostate adenocarcinoma. MATERIALS AND METHODS: In this cross-sectional study, formalin-fixed paraffin-embedded tissues of 58 patients with a definitive pathologic diagnosis of prostatic adenocarcinoma were evaluated. The expression of AMACR, intensity, and extensity of its staining was determined in selected samples by immunohistochemical technique. RESULTS: AMACR expression was significantly higher in neoplastic compared to normal tissue (P < 0.05). The expression of AMACR was significantly associated with the age of the patients (P = 0.04). The intensity of the staining was associated with the grade of the prostate adenocarcinoma (P = 0.04). There was no significant relationship between AMACR expression and perineural invasion. The sensitivity, specificity, positive predictive value, and negative predictive value of AMACR were 90%, 96%, 96%, and 90%, respectively. CONCLUSION: Findings from our study indicate that AMACR could be used as a diagnostic tool for the diagnosis of prostate adenocarcinoma. However, due to false-positive staining in the mimicker of prostatic adenocarcinoma, it is recommended to use it in combination with basal cell markers.

A review on the role of CAFs and CAF-derived exosomes in progression and metastasis of digestive system cancers.

Cancers evolve as a result of the accelerated proliferation of cancer cells in a complicated, enriched, and active microenvironment. Tumor microenvironment (TME) components are the master regulators of any step of cancer development. The tumor microenvironment is composed of many cellular and noncellular components that contribute to the evolution of cancer cells. Cancer-associated fibroblasts (CAFs) are activated fibroblasts in the TME that implicate in tumor progression and metastasis dissemination through secretion of oncogenic factors which are carried to the secondary metastatic sites through exosomes. In this review, we aimed to assess the role of CAF-derived exosomes in TME construction and pre-metastatic niche formation in different cancers of the digestive system in order to better understand some important mechanisms of metastasis and provide possible targets for clinical intervention. This review article is divided into two thematic parts explaining the general mechanisms of pre-metastatic niche formation and metastasis and the role of CAF-derived exosomes in different digestive system cancers including colorectal, gastric, esophageal, pancreatic, and liver cancers.

Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes.

BACKGROUND: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes. METHODS: Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages. RESULTS: Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted ß coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF. CONCLUSIONS: UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.

Aging and chronic high-fat feeding negatively affect kidney size, function, and gene expression in CTRP1-deficient mice.

C1q/TNF-related protein 1 (CTRP1) is an endocrine factor with metabolic, cardiovascular, and renal functions. We previously showed that aged Ctrp1-knockout (KO) mice fed a control low-fat diet develop renal hypertrophy and dysfunction. Since aging and obesity adversely affect various organ systems, we hypothesized that aging, in combination with obesity induced by chronic high-fat feeding, would further exacerbate renal dysfunction in CTRP1-deficient animals. To test this, we fed wild-type and Ctrp1-KO mice a high-fat diet for 8 mo or longer. Contrary to our expectation, no differences were observed in blood pressure, heart function, or vascular stiffness between genotypes. Loss of CTRP1, however, resulted in an approximately twofold renal enlargement (relative to body weight), ∼60% increase in urinary total protein content, and elevated pH, and changes in renal gene expression affecting metabolism, signaling, transcription, cell adhesion, solute and metabolite transport, and inflammation. Assessment of glomerular integrity, the extent of podocyte foot process effacement, as well as renal response to water restriction and salt loading did not reveal significant differences between genotypes. Interestingly, blood platelet, white blood cell, neutrophil, lymphocyte, and eosinophil counts were significantly elevated, whereas mean corpuscular volume and hemoglobin were reduced in Ctrp1-KO mice. Cytokine profiling revealed increased circulating levels of CCL17 and TIMP-1 in KO mice. Compared with our previous study, current data suggest that chronic high-fat feeding affects renal phenotypes differently than similarly aged mice fed a control low-fat diet, highlighting a diet-dependent contribution of CTRP1 deficiency to age-related changes in renal structure and function.

Diagnostic utility of high-risk human papillomavirus mRNA in situ hybridisation in squamous cell carcinoma of unknown primary in the head and neck and implementing American Society of Clinical Oncology guideline recommendations.

INTRODUCTION: The American Society of Clinical Oncology (ASCO)-endorsed College of American Pathologists guideline recommends high-risk human papillomavirus (HPV) testing for metastatic squamous cell carcinoma (SCC) of lymph nodes level II/III of unknown primary. Herein, the performance of HPV-RNA in situ hybridisation (ISH) in detection of HPV-related SCC is evaluated implementing the ASCO guideline recommendations. METHODS: Eighty head and neck (HN) SCC fine needle aspirations, which utilized HPV-RNA ISH/P16, were evaluated at Johns Hopkins Hospital (2015-2018) to investigate their performance and concordance with histology. The results were compared to a prior study of 59 HNSCCs, which HPV-DNA ISH. RESULTS: Of the 80 reviewed fine needle aspirations, 65 (50 male, 15 female) were included. The mean age was 63.2 ± 14.0 years. The most common site was neck lymph nodes (47, 72.3%). Fifty-five cases (84.6%) were accompanied by concurrent core biopsy, and 48 cases (59.4%) had surgical follow-ups. HPV-RNA ISH was positive in 44 (67.7%), and P16 was strongly positive in 46 (70.8%). The HPV-RNA ISH/ P16 concordance rate was 92.3% on cytology material. The cytology/surgical concordance rate for HPV-RNA ISH was 88.9% (16/18). There was a discordance between the results in five cases (7.7%; HPV-RNA ISH-/P16+). CONCLUSION: HPV-RNA ISH is a robust and reliable method for detecting HPV-related HNSCC on cytology material showing concordance rate of 92.3% between HPV-RNA ISH and P16, which is a sensitive but non-specific marker. Compared to HPV-DNA ISH, HPV-RNA ISH reproducibly identifies HPV-related HNSCC with fewer discrepancies between cytology and histology. The findings of this study are in agreement with the ASCO recommendations.

APOL1 renal risk variants exacerbate podocyte injury by increasing inflammatory stress.

BACKGROUND: Apolipoprotein L1, APOL1, is a trypanosome lytic factor present in human and certain other primates. APOL1 gene variants, present in individuals of recent sub-Saharan African descent, increase risk for glomerular disease and associate with the disease progression, but the molecular mechanisms have not been defined. OBJECTIVES: We focus on the mechanism how APOL1 variant proteins enhance podocyte injury in the stressed kidney. METHODS: First, we investigated the expression of APOL1 protein isoform and the localization of APOL1 protein in the kidney. Next, we examined the role of APOL1 in the podocyte stress and the inflammatory signaling in the kidney after hemi-nephrectomy. RESULTS: We identified a novel RNA variant that lacks a secretory pathway signal sequence and we found that the predicted APOL1-B3 protein isoform was expressed in human podocytes in vivo and by BAC-APOL1 transgenic mice. APOL1-B3-G2 transgenic mice, carrying a renal risk variant, manifested podocyte injury and increased pro-IL-1ß mRNA in isolated glomeruli and increased IL-1ß production in the remnant kidney after uninephrectomy. APOL1-B3 interacted with NLRP12, a key regulator of Toll-like receptor signaling. CONCLUSIONS: These results suggest a possible mechanism for podocyte injury by which one of the APOL1 protein isoforms, APOL1-B3 and its renal risk variants, enhances inflammatory signaling.

Water intake and intra-meal fluid consumption in relation to general and abdominal obesity of Iranian adults.

OBJECTIVE: The aim of this study was to examine the association between whole-day water intake and intra-meal fluid consumption and odds of general and abdominal obesity among adults. METHODS: This cross-sectional study was conducted among 7958 adults in Isfahan, Iran. Daily water consumption was assessed through the use of a pre-tested questionnaire by asking questions about the average number of glasses of water consumed in a day. Intra-meal fluid consumption was also analysed. Data regarding height, weight and waist circumference were collected using a validated self-administered questionnaire. Obesity was defined as body mass index ≥30 kg/m2, and abdominal obesity was defined as waist circumference >88 cm for women and >102 cm for men. RESULTS: After taking potential confounders into account, individuals who were taking more than eight glasses of water in a day had 78% greater odds of general obesity (OR: 1.78; 95% CI: 1.08-2.94) compared with those who were taking less than two glasses of water. Individuals with much water intake had no significant greater odds of abdominal obesity. Compared with those who were consuming less than a glass of intra-meal fluids, subjects with 1-2 glasses of fluids between meals had 34% greater odds of general obesity (OR: 1.34; 95% CI: 1.04-1.59). Although subjects with greater intra-meal fluid intake had greater odds of abdominal obesity in crude model, this association became non-significant after adjustment for potential confounders (comparing > 4 glasses vs. ≤1 glass: OR: 1.65; 95% CI: 0.81-3.34). CONCLUSIONS: We observed that taking more than eight glasses of water in a day and consuming 1-2 glasses of fluids between meals was associated with greater odds of general obesity.

Late-onset renal hypertrophy and dysfunction in mice lacking CTRP1.

Local and systemic factors that influence renal structure and function in aging are not well understood. The secretory protein C1q/TNF-related protein 1 (CTRP1) regulates systemic metabolism and cardiovascular function. We provide evidence here that CTRP1 also modulates renal physiology in an age- and sex-dependent manner. In mice lacking CTRP1, we observed significantly increased kidney weight and glomerular hypertrophy in aged male but not female or young mice. Although glomerular filtration rate, plasma renin and aldosterone levels, and renal response to water restriction did not differ between genotypes, CTRP1-deficient male mice had elevated blood pressure. Echocardiogram and pulse wave velocity measurements indicated normal heart function and vascular stiffness in CTRP1-deficient animals, and increased blood pressure was not due to greater salt retention. Paradoxically, CTRP1-deficient mice had elevated urinary sodium and potassium excretion, partially resulting from reduced expression of genes involved in renal sodium and potassium reabsorption. Despite renal hypertrophy, markers of inflammation, fibrosis, and oxidative stress were reduced in CTRP1-deficient mice. RNA sequencing revealed alterations and enrichments of genes in metabolic processes in CTRP1-deficient animals. These results highlight novel contributions of CTRP1 to aging-associated changes in renal physiology.

Morphological and functional characteristics of aging kidneys based on two-photon microscopy in vivo.

Age-related kidney disease, which is chronic and naturally occurring, is a general term for a set of heterogeneous disorders affecting kidney structures and characterized by a decline in renal function. Age-related renal insufficiency has important implications with regard to body homeostasis, drug toxicity and renal transplantation. In our study, two-photon microscopy was used to image kidney morphological and functional characteristics in an age-related rat model in vivo. The changes in morphology are analyzed based on autofluorescence and Hoechst 33342 labeling in rats with different ages. Structural parameters including renal tubular diameter, cell nuclei density, size and shape are studied and compared with Hematoxylin and Eosin histological analysis. Functional characteristics, such as blood flow, and glomerular filtration rate are studied with high-molecular weight (MW) 500-kDa dextran-fluorescein and low-MW 10-kDa dextran-rhodamine. Results indicate that morphology changes significantly and functional characteristics deteriorate with age. These parameters are potential indicators for evaluating age-related renal morphology and function changes. Combined analyses of these parameters could provide a quantitative, novel method for monitoring kidney diseases and/or therapeutic effects of kidney drugs.

Discrepancies Between Biopsy Gleason Score and Radical Prostatectomy Specimen Gleason Score: An Iranian Experience.

PURPOSE: Considering the importance of treatment decisions for prostate cancer (PCa) and the utility of Gleason scoring system (GS) in this field, we aimed to assess the percent of agreement and disagreement between needle biopsy (NB) Gleason score and radical prostatectomy (RP) specimen Gleason score. MATERIALS AND METHODS: In this retrospective study, consecutive patients with PCa, who underwent NB and subsequently RP were enrolled. GS of both NB and RP specimens were recorded for each patient. Patients were classified according to the GS as low-grade (? 3+3), intermediate-grade (3+4 and 4+3), and high-grade (GS?8-10). The levels of agreement and discrepancy of NB GS was compared to its corresponding RP GS using Kappa coefficient of agreement. Over-grading and under-grading of NB GS were also determined. RESULT: A total of 100 embedded RP and corresponding NB were analyzed. The rate of discrepancy for group and individual scoring of GS was 41% and 56%, respectively. The rate of under and over-grading was 34% and 7%, respectively. Kappa value for group and individual scoring was .443 (95%CI: .313 - .573) and .411 (95%CI: .291 - .531), respectively. CONCLUSION: The findings of our study indicate that though the agreement between NB GS and RP GS are fair to moderate, but the feature of discrepancy, i.e. under-grading in low and intermediate grades and over-grading in high grades of NB GS, could help us in making more appropriate clinical decision especially considering other biochemical and pathological factors such as the level of PSA or peri-neural invasion.

A six-year survey of the spectrum of renal disorders on native kidney biopsy results in Central Iran and a review of literature.

Native kidney biopsy reports in previous studies that are mostly originated in Western countries show various results in different parts of the world. In this study, we aimed to determine the prevalence of renal biopsy disorders in Iran and compare it with that of other studies in the world. This cross-sectional study evaluated consecutive native kidney biopsies performed in four centers in Isfahan, Iran, from 2009 to 2014. We also reviewed other relevant studies in Iran and the world. Overall, 1547 renal biopsies were reviewed; 493 cases were excluded (transplant or re-biopsy cases) and 1054 cases (43.3% female) were included in our study with a mean (±standard deviation) age of 33.1 (±18.5) years. The first three most prevalent diagnoses were focal and segmental glomerulosclerosis (FSGS) (24.8%), minimal change disease (MCD) (14.2%), and membranous glomerulonephritis (MGN) (9.6%). IgA nephropathy (IgAN) was more prevalent among men, whereas lupus nephritis had a higher prevalence among women. In three out of six previous studies conducted in Iran, the most prevalent pathological diagnosis was MGN; in two others, MCD predominated; and in the third study, FSGS had the highest prevalence. In Europe and Western Pacific Region, IgAN was by far the most prevalent GN, while studies in other parts of the world show conflicting results. The most prevalent diagnosis in our study was FSGS, which was consistent with previous studies in Iran, which seems to have an increasing prevalence. It is recommended that having a national registry is crucial to determine the current status and for better planning and management of renal disorders.

Pathological assessment of allograft nephrectomy: An Iranian experience.

BACKGROUND: The aim of this study was to determine the pathologic causes of renal allograft failure in transplant nephrectomy specimens. MATERIALS AND METHODS: In this cross-sectional study performed in the referral transplant center of Isfahan, Iran, medical files of all patients who underwent nephrectomy in 2008-2013 were studied. Age at transplantation, sex, donor's characteristics, causes of primary renal failure, duration of allograft function, and pathologic reasons of nephrectomy were extracted. Slides of nephrectomy biopsies were evaluated. Data were analyzed using SPSS. RESULTS: Medical files of 39 individuals (male: 56.4%; mean age: 35.1 ± 16.0 years) were evaluated. The main disease of patients was hypertension (17.9%), and most cases (64.1%) were nephrectomized < 6 months posttransplantation. Renal vein thrombosis (RVT) (51.3%) and T-cell-mediated rejection (TCMR) (41.0%) were the most prevalent causes of transplanted nephrectomy. Cause of primary renal failure was correlated to nephrectomy result (P = 0.04). TCMR was the only pathologic finding in all of patients nephrectomized >2 years posttransplantation. There were 14 cases in which biopsy results showed a relationship between primary disease of patients and pathologic assessment of allograft (P = 0.04). A significant relationship between transplantation-nephrectomy interval and both the nephrectomy result and histopathologic result existed (P < 0.0001). A relationship between primary allograft biopsy appearance and further assessment of nephrectomized specimen (P < 0.001) existed as well. CONCLUSION: The most pathologic diagnoses of nephrectomy in a period of less than and more than 6 months posttransplantation were RVT and TCMR, respectively. Early obtained allograft protocol biopsy is suggested, which leads to better diagnosis of allograft failure.

Risk factors of bloating and its association with common gastrointestinal disorders in a sample of Iranian adults.

BACKGROUND/AIMS: Bloating is an unpleasant but common gastrointestinal symptom that is experienced by many people at some stage in their lives. The current survey was conducted to investigate the epidemiology and risk factors of bloating and functional bloating (FB). In addition, we aimed to assess the association between bloating and functional gastrointestinal disorders (FGIDs). MATERIALS AND METHODS: In this cross-sectional study, the self-administered modified Rome III questionnaire was used to assess gastrointestinal symptoms and FGIDs. Severity of bloating, demographic and anthropometric measurements, physical activity level, psychological distress, and depression and anxiety were also assessed. RESULTS: Among the 4763 participants, 52.9% reported having experienced bloating at least occasionally in the past three months (among which 14.1% had severe or very severe symptoms); 19.7% of subjects were found to have FB. After adjusting for multiple variables, female gender, university degree, obesity, and anxiety were associated with both bloating and FB, while depression and psychological distress were only associated with bloating. The positive predictive value and negative predictive value of bloating for the diagnosis of functional bowel disorder were 92.9% and 80.1%, respectively. CONCLUSION: Bloating and FB are highly prevalent in the study population. We also identified several demographic, psychological, and lifestyle-related risk factors of bloating in this population.