Comparison of different urinary diversions after radical cystectomy in Iran: Assessment of health-related quality of life and financial burden in a Middle Eastern country.

OBJECTIVES: To compare health-related quality of life (HRQOL), cost-effectiveness, and survival among different types of urinary diversion (UD) utilized after radical cystectomy (RC) for bladder cancer with consideration of the unique economic and cultural context in Iran. PATIENTS AND METHODS: In this retrospective study, we examined all patients who underwent RC from May 2017 to December 2021 at two specialized centers by the same surgical team. Patients were grouped based on their UD. Post-surgical HRQOL (obtained from EORTC QLQ-C30 and QLQBLM-30), financial burden, surgical complications, and survival were compared. Kruskal-Wallis H test, One-way ANOVA, and Kaplan-Meier analyses were utilized; accordingly. RESULTS AND LIMITATIONS: In total 187 patients were identified-orthotopic neobladder (ONB) (N = 75), ileal conduit (IC) (N = 57), and cutaneous ureterostomy (CU) (N = 55)-and were followed for a median 17.5 (Interquartile range: 7.0, 47.0) months. ONB was associated with better HRQOL, especially in the domains addressing physical, role and social functioning (p = 0.003, 0.011, 0.045) as well as better body image (p < 0.001), lower short- and long-term financial burden (p = 0.034 and <0.001, respectively), marginally lower complication rate (p = 0.049), and better 5-year overall survival (p < 0.001), in comparison with other UDs. Patients who underwent CU had the lowest HRQOL and worst survival. Limitations were retrospective design and possibility of selection bias. CONCLUSIONS: In this first study that assesses a Middle Eastern collective; ONB seems to be the UD of choice with regard to HRQOL and economic burden when there is no contraindication.

Postmortem Histopathologic Findings and SARS-CoV-2 Detection in Autopsy Kidneys of Patients With COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to investigate the prevalence of postmortem kidney histopathologic features of patients with coronavirus disease 2019 (COVID-19) in addition to the rate of renal tropism in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We searched Web of Science, PubMed, Embase, and Scopus up to September 2022 to identify eligible studies. A random-effects model was used to estimate the pooled prevalence. Cochran Q test and Higgins I2 were used to assess evidence of heterogeneity. RESULTS: In total, 39 studies were included in the systematic review. The meta-analysis included 35 studies consisting of a total of 954 patients, with an average age of 67.1 years. The pooled prevalence of acute tubular injury (ATI)-related changes was the predominant finding (85% [95% confidence interval, 71%-95%]), followed by arteriosclerosis (80%), vascular congestion (66%), and glomerulosclerosis (40%). Endotheliitis (7%), fibrin microthrombi (12%), focal segmental glomerulosclerosis (1%), and calcium crystal deposits (1%) were seen in a smaller number of autopsies. The overall average rate of virus detection was 47.79% in the pooled data of 21 studies (272 samples). CONCLUSIONS: The main finding-ATI-correlated to clinical COVID-19-associated acute kidney injury. The presence of SARS-CoV-2 in kidney samples in addition to vascular lesions in kidneys can be linked to direct kidney invasion by the virus.

The relationship between CT value and clinical outcomes in renal patients with COVID-19.

PURPOSE: Concomitant kidney diseases raise the mortality rate due to the SARS-CoV-2 virus as an independent factor. Although a qualitative PCR test's result is sufficient for diagnosis, Cycle threshold value may present relevant information to the physicians in providing faster treatment in patients with chronic conditions, including kidney diseases, to prevent morbidity and subsequent mortality. Thus, the present study was conducted to determine the relationship between the Cycle threshold value and clinical outcomes in renal patients with the coronavirus 2019. METHODS: This retrospective study was conducted on renal patients with the coronavirus 2019 infection admitted to Labbafinejad Hospital in Tehran, the capital of Iran, within a period of one year, from late February 2020 to February 2021. Data were collected per the prepared checklist. Cycle threshold values were measured by performing PCR on nasopharynx and oropharynx swab samples of patients. RESULTS: According to the adjusted analysis, having high viral load increased the odds of in-hospital mortality (aOR = 11.65, 95% CI 3.93-34.54), ICU admission (aOR = 5.49, 95% CI 2.16-13.97), and invasive ventilation (aOR = 7.18, 95% CI 2.61-19.74). Having high viral load also increased the odds of O2 therapy (aOR = 3.08, 95% CI 0.79-12.01), although the difference was not statistically significant (P = 0.105). CONCLUSION: Cycle threshold value was a significant predictor of mortality in renal patients. Nevertheless, further studies are required on how to render optimal use of the Cycle threshold value, given that the quality of the test sample and the different groups of patients under study affect the effectiveness of this marker in predicting disease severity.

Antibody-mediated Rejection of Kidney Allografts Following COVID-19: A Report of Two Cases.

Increased risk of graft rejection could be the consequence of COVID-19 in kidney transplant recipients (KTRs). We report two cases of kidney transplant (KT) with stable graft function who experienced antibody-mediated rejection (ABMR) following recovery from COVID-19. It seems that reduced immunosuppression during the acute illness, is the main explanation for post-COVID-19 ABMR. However, the inflammatory state associated with COVID-19, as well as direct cytopathic effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can predispose the kidney allograft to rejection. There is no definite guideline for the modification of immunosuppressives during COVID-19 in kidney transplant recipients. However, re-institution of full-dose immunosuppressives soon after recovery from COVID-19 and frequent outpatient follow-up visits are recommended.  DOI: 10.52547/ijkd.7176.

Renal mucormycosis following transurethral resection of prostate in the time of COVID-19: Unique imaging features resembling emphysematous pyelonephritis.

We report a case of isolated renal mucormycosis 2 weeks following transurethral resection of prostate. The patient also mentioned history of admission for COVID-19, two months earlier. Symptoms progressed and patient underwent urgent nephrectomy. CT scan resembled imaging features of emphysematous pyelonephritis and therefore, patient did not receive timely treatment with amphotericin B in addition to nephrectomy and succumbed to the disease.

Combination of T-DM1 and platinum-based chemotherapy in patient-derived xenograft models of muscle-invasive bladder cancer.

Objectives: To assess the efficacy and safety of T-DM1, as an anti-HER2 antibody-drug conjugate (ADC), alone and in combination with two platinum-based chemotherapy regimens in patient-derived xenografts (PDXs) of muscle-invasive bladder cancer (MIBC) established in immunodeficient mice. Materials and Methods: After treatment initiation, tumor size was measured twice a week. Percent of tumor growth inhibition (TGI) and tumor response rates were calculated as efficacy endpoints. To evaluate treatment toxicity, relative body weight (RBW) was calculated for each group. For comparison of TGIs between treatment groups, the Kruskal-Wallis test was used. Also, the significance of the overall response (OR) rate between placebo groups with treatment groups was analyzed using Fisher's exact test. Immunohistochemistry and fluorescence in situ hybridization techniques were used to evaluate the level of HER2 expression. Results: Our data showed that T-DM1 alone induced a moderate antitumor activity. While chemotherapy regimens induced a slight TGI when administered alone, interestingly, they showed strong antitumor activity when administered combined with T-DM1. The OR rates were higher when T-DM1 was combined with chemotherapy regimens than T-DM1 alone. When compared with the placebo group, the OR rates of combination groups were statistically significant. Our data also showed that the administered dose of each drug was well tolerated in mice. Conclusion: The combination of T-DM1 and platinum-based chemotherapy may represent a new treatment option for bladder tumors with even low HER2 expression, and could also provide substantial novel insight into tackling the challenges of MIBC management.

The Prevalence of Vitamin D Deficiency, Its Predisposing Factors and Association with 24-hour Urine Metabolites Among Iranian Kidney Stone Formers.

INTRODUCTION: To study the prevalence of vitamin D deficiency in kidney stone formers and its predisposing factors and to assess the relationship between serum 25-Hydroxyvitamin D and urine metabolites. METHODS: Kidney stone formers were selected from the records of the kidney stone prevention clinic in Labbafinejad hospital, Tehran, Iran. Vitamin D deficiency was defined as 25-Hydroxyvitamin D < 20 ng/mL. The association between vitamin D deficiency and predisposing factors, serum, and urine metabolites was evaluated. RESULTS: In 1005 patients (66.4% men and 33.6% women), the prevalence of vitamin D deficiency was 44.8%. Vitamin D deficiency was more prevalent in patients under 50 years (P < .001) and patients with hyperparathyroidism (P < .05). The lowest prevalence of hyperparathyroidism was in the 25-Hydroxyvitamin D range of 40 to 49.9 ng/mL, followed by the range of 30 to 39.9 and 20 to 29.9 ng/mL. Patients with vitamin D deficiency had lower serum creatinine (P < .02), lower 24-hour urine calcium (P < .01), and lower 24-hour urine oxalate (P < .05). CONCLUSION: Iranian kidney stone formers have a relatively high prevalence of vitamin D deficiency. Our population seems to have different predisposing factors for vitamin D deficiency, i.e., higher prevalence among younger patients and no association between obesity and gender with vitamin D status. According to the parathyroid hormone, the favorable serum 25-Hydroxyvitamin D level was 20 to 49.9 ng/mL in our kidney stone formers.

Data-Driven Discovery of Molecular Targets for Antibody-Drug Conjugates in Cancer Treatment.

Antibody-drug conjugate therapy has attracted considerable attention in recent years. Since the selection of appropriate targets is a critical aspect of antibody-drug conjugate research and development, a big data research for discovery of candidate targets per tumor type is outstanding and of high interest. Thus, the purpose of this study was to identify and prioritize candidate antibody-drug conjugate targets with translational potential across common types of cancer by mining the Human Protein Atlas, as a unique big data resource. To perform a multifaceted screening process, XML and TSV files including immunohistochemistry expression data for 45 normal tissues and 20 tumor types were downloaded from the Human Protein Atlas website. For genes without high protein expression across critical normal tissues, a quasi H-score (range, 0-300) was computed per tumor type. All genes with a quasi H - score ≥ 150 were extracted. Of these, genes with cell surface localization were selected and included in a multilevel validation process. Among 19670 genes that encode proteins, 5520 membrane protein-coding genes were included in this study. During a multistep data mining procedure, 332 potential targets were identified based on the level of the protein expression across critical normal tissues and 20 tumor types. After validation, 23 cell surface proteins were identified and prioritized as candidate antibody-drug conjugate targets of which two have interestingly been approved by the FDA for use in solid tumors, one has been approved for lymphoma, and four have currently been entered in clinical trials. In conclusion, we identified and prioritized several candidate targets with translational potential, which may yield new clinically effective and safe antibody-drug conjugates. This large-scale antibody-based proteomic study allows us to go beyond the RNA-seq studies, facilitates bench-to-clinic research of targeted anticancer therapeutics, and offers valuable insights into the development of new antibody-drug conjugates.

Development and immunohistochemical characterization of patient-derived xenograft models for muscle invasive bladder cancer.

Objectives: Patient-derived xenograft (PDX) models have become a valuable tool to evaluate chemotherapeutics and investigate personalized cancer treatment options. The role of PDXs in the study of bladder cancer, especially for improvement of novel targeted therapies, continues to expand. In this study, we aimed to establish autochthonous PDX models of muscle-invasive bladder cancer (MIBC) to provide a useful tool to conduct research on personalized therapy. Materials and Methods: Tumors from MIBC patients undergoing radical cystectomy were subcutaneously transplanted into immunodeficient mice. The tumor size was measured by a caliper twice a week for up to five months. After the first growth in mice, they were serially passaged. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) of 11 markers (Ki67, P63, GATA3, KRT5/6, KRT20, E-cadherin, 34ßE12, PD-L1, EGFR, Nectin4, and HER2) were used to evaluate phenotype maintenance of original tumors. Results: From 10 MIBC patients, two PDX models (P8X20 and P8X26) were successfully established (20% success rate). These models mostly retained primary tumor characteristics including histology, morphology, and molecular nature of the original cancer tissues. IHC analysis showed that the expression level of 7 markers for the model P8X20, and 8 markers for the model P8X26 was exactly similar between the patient tumor and the next generations. Conclusion: We developed the first autochthonous PDX models of MIBC in Iran. Our data suggested that the established MIBC PDX models reserved mostly histopathological characteristics of primary cancer and could provide a new tool to evaluate novel biomarkers, therapeutic targets, and drug combinations.

Human cytomegalovirus infection in Iranian glioma patients correlates with aging and tumor aggressiveness.

Human cytomegalovirus (HCMV), as a ubiquitous and opportunistic virus, is a matter for consideration in broad-spectrum diseases, specifically in immunocompromised individuals. In recent decades, many studies that have evaluated the role of HCMV in inflammation and malignancies, especially in high-grade gliomas, have reported inconsistent results. Thus, this study was conducted to analyze 97 primary gliomas for human CMV UL83 gene and protein through TaqMan real-time polymerase chain reaction and immunohistochemistry, respectively. The results were positive for the UL83 gene and pp65 protein in 71% and 24% of samples, respectively. The frequency of HCMV was significantly higher in glioblastomas than other glioma grades (P < .01 and P < .05 for the UL83 gene and protein, respectively). In addition, the association between the prevalence of HCMV and aging strengthened the virus reactivation hypothesis in gliomas. In conclusion, a high frequency of HCMV infection was found in gliomas that correlated with tumor aggressiveness and age. This study recommends a thorough investigation to determine HCMV infection in gliomas to improve the existing knowledge of its role in glial tumors, its prognostic value, and possible efficient antiviral target therapy.

Metabolomic Analysis of Membranous Glomerulonephritis: Identification of a Diagnostic Panel and Pathogenic Pathways.

BACKGROUND: Primary membranous glomerulonephritis (MGN) is a major cause of nephrotic syndrome in adults. Its diagnosis is based on invasive biopsy, and the current traditional serum or urinary biomarkers, such as the anti-phospholipase A2 receptor, are not adequately sensitive or specific. AIM OF THE STUDY: Our purpose is to identify a sensitive and specific noninvasive panel of biomarkers for the diagnosis of MGN by using metabolomic techniques and to explore the pathogenic pathways that are involved in disease development. METHODS: The urine metabolome of 66 MGN patients, 31 healthy controls, and 72 disease controls, were analyzed using nuclear magnetic resonance (NMR) and gas chromatography-tandem mass spectrometry (GC-MS/MS). Advanced multivariate statistical analyses were performed for the construction of diagnostic models and biomarker discovery. Receiver operating characteristic (ROC) curve analysis was used to suggest the most sensitive and specific diagnostic panel. RESULTS: The NMR-based diagnostic model showed allantoic acid and deoxyuridine as the most overrepresented and underrepresented biomarkers, respectively differentiating MGN from both control groups. The GC-MS/MS-based diagnostic model showed oxalic acid as the most overrepresented biomarker and 2-hydroxyglutaric acid lactone as the only underrepresented specific biomarker. A panel of a combination of the most accurate predictors of NMR and GC-MS/MS was composed of α-hydroxybutyric acid, 3,4-Dihydroxymandelic acid, 5α-cholestanone, 2-hydroxyglutaric acid lactone, nicotinamide, epicoprostanol, and palmitic acid. Nine impaired pathways were identified in MGN, such as pyrimidine metabolism and NAD salvage. CONCLUSIONS: This comprehensive metabolomic study of MGN indicates a panel of promising biomarkers, which is complementary to current traditional biomarkers, and needs to be validated in a larger cohort.

Chondroitin sulfate degradation and eicosanoid metabolism pathways are impaired in focal segmental glomerulosclerosis: Experimental confirmation of an in silico prediction.

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease, is a diverse clinical entity that occurs after podocyte injury. Although numerous studies have suggested molecular pathways responsible for the development of FSGS, many still remain unknown about its pathogenic mechanisms. Two important pathways were predicted as candidates for the pathogenesis of FSGS in our previous in silico analysis, whom we aim to confirm experimentally in the present study. Methods: The expression levels of 4 enzyme genes that are representative of "chondroitin sulfate degradation" and "eicosanoid metabolism" pathways were investigated in the urinary sediments of biopsy-proven FSGS patients and healthy subjects using real-time polymerase chain reaction (RT-PCR). These target genes were arylsulfatase, hexosaminidase, cyclooxygenase-2 (COX-2), and prostaglandin I2 synthase. The patients were sub-divided into 2 groups based on the range of proteinuria and glomerular filtration rate and were compared for variation in the expression of target genes. Correlation of target genes with clinical and pathological characteristics of the disease was calculated and receiver operating characteristic (ROC) analysis was performed. Results: A combined panel of arylsulfatase, hexosaminidase, and COX-2 improved the diagnosis of FSGS by 76%. Hexosaminidase was correlated with the level of proteinuria, while COX-2 was correlated with interstitial inflammation and serum creatinine level in the disease group. Conclusion: Our data supported the implication of these target genes and pathways in the pathogenesis of FSGS. In addition, these genes can be considered as non-invasive biomarkers for FSGS.

Female Urethral Cavernous Hemangioma, A Rare Entity: Two Case Reports and Review of The Literature.

Genitourinary hemangiomas are very rare. To our knowledge few cases of female urethral hemangiomas have been reported and presenting cases are the first reports in Iran.They should be considered as differential diagnosis of any female patient with microscopic or gross hematuria or bloody urethral discharge, especially when other parts of urinary system are radiologically intact. Thorough physical examination of genital area is highly recommended in order not to miss any urethral lesions. Herein we report two cases of female urethral cavernous hemangioma, their management and a review of literature.

Metabolomics approach reveals urine biomarkers and pathways associated with the pathogenesis of lupus nephritis.

OBJECTIVES: lupus nephritis (LN) is a severe form of systemic lupus erythematosus (SLE) with renal complications. Current diagnosis is based on invasive renal biopsy and serum antibodies and complement levels that are not specific enough. The current study aims to identify new biomarker candidates for non-invasive diagnosis of LN and explore the pathogenic mechanisms that contribute to renal injury. MATERIALS AND METHODS: A metabolomics approach using 1H-nuclear magnetic resonance (1H-NMR), was developed for comparison of urine metabolic profile of 14 LN patients, 10 SLE patients, and 11 healthy controls (HCs). Differential biomarker candidates were identified by using multivariate modeling, and their diagnostic accuracy was evaluated by receiver operating characteristic analysis (ROC). RESULTS: Three metabolites were common in differentiating all three groups including beta-alanine, 2,2-dimethylsucssinic acid, and 3,4-Dihydroxyphenylacetaldehyde and suggested as a diagnostic panel for LN with AUC of 0.89, sensitivity of 81 %, and specificity of 100 %. Complementary analyses on pathways indicated that nicotinate and nicotinamide metabolism is the most important perturbed pathway in LN. CONCLUSION: Metabolomics is a useful tool for identification of biomarkers with the ability to diagnose LN patients and predict perturbed pathways responsible for renal injury.

Bone morphogenetic protein-7 incorporated polycaprolactone scaffold has a great potential to improve survival and proliferation rate of the human embryonic kidney cells.

Renal failures treatment has been faced with several problems during the last decades. Kidney tissue engineering has been created many hopes to improve treatment procedures with scaffold fabrication that can modulate kidney cells/stem cells migration to the lesion site and increase the survival of these cells at that site with imitating the role of the kidney extracellular matrix. In this study, bone morphogenetic protein-7 (BMP7) as a vital factor for kidney development and regeneration was incorporated in the polycaprolactone (PCL) nanofibers and after morphological, mechanical, and biocompatible characterization, proliferation, and survival of the human embryonic kidney cells (HEK) were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and gene expression while cultured on scaffolds. Mechanical properties of the PCL nanofibers modulated after combining with BMP7 and hydration degree, protein adsorption and cell adhesion were enhanced in PCL-BMP7 compared to the pure PCL. Proliferation rate and growth increased significantly in HEK cells cultured on PCL-BMP7 when compared with that of PCL and tissue culture plate, whereas these data were also confirmed via significant decrease in apoptotic genes expression level in HEK cell cultured on PCL-BMP7. According to the results, PCL-BMP7 demonstrated positive effects on the survival and proliferation rate of the kidney cells and showed has also a great potential to use as a bioimplant for kidney tissue engineering applications.

Prevalence of virulence determinants and antibiotic resistance patterns of Enterococcus faecalis strains in patients with community-acquired urinary tract infections in Iran.

The aim of this study was to characterize virulence factors and antibiotic resistance patterns in E. faecalis strains obtained from community-acquired urinary tract infections. A total of 70 E. faecalis isolates from Labbafinejad Hospital in Tehran were collected. Antibiotic resistance and virulence determinants were examined by phenotypic and molecular methods. Among 70 E. faecalis isolates, efba (97.1%), ace (95.7%), and gelE (94.3%) were the most prevalent virulence genes. The most common antibiotic resistance pattern was tetracycline (88.6%) and minocycline (87.1%). Multi-drug resistant phenotype was detected among 10% of them. Our results showed capability of E. faecalis strains for infection of the urinary tract in community. Involvement of virulence determinants in the pathogenesis of community acquired E. faecalis strains was proposed due to their high prevalence rates. Food producing animals were proposed as their environmental reservoirs, due to dominance of tetracycline resistance phenotype among them.

Investigating the effectiveness of the Trigonella foenum-graecum L. (fenugreek) seeds in mild asthma: a randomized controlled trial.

BACKGROUND: Asthma is one of the important chronic diseases. The asthma prevalence is increasing in last decades. Despite the presence of good controller drugs like corticosteroids, about 60% of asthmatic patients use alternative medicine. This study was done to determine the effectiveness of Tregonella foenum graceum (fenugreek) seeds in mild asthma. METHODS: It is a double blind trial with placebo effect. One of the ancient prescriptions from Persian Medicine was selected. The participants were divided to three groups randomly. On group received fenugreek syrup one received honey syrup and the third received placebo. Duration of treatment was 4 weeks. Quality of life, Lung function tests and IL-4 levels were evaluated before and after treatment. RESULTS: From 90 participants to study 79 completed the process. After study there was significant increase in quality of the life and lung function tests and IL-4 levels in fenugreek and honey groups. CONCLUSION: FEV1 level was improved more than 10% in fenugreek group. Treatment was well tolerated. No serious side effects were reported during the study. The aqueous extract of fenugreek seeds appears to be effective and safe in treatment of mild asthma.Trial registration The study was recorded with the Iranian Registry of Clinical trials [http://www.irci.ir], registration code: IRCT2016011325991N1.

N-acetylcysteine decreases urinary level of neutrophil gelatinase-associated lipocalin in deceased-donor renal transplant recipients: a randomized clinical trial.

CONTEXT: Acute kidney injury (AKI) is a common complication after kidney transplantation (KT), especially in recipients from deceased donors. Urinary neutrophil gelatinase-associated lipocalin (u-NGAL) is an early and sensitive marker of AKI after transplantation. OBJECTIVES: We assessed the renoprotective effect of N-acetylcysteine (NAC) on u-NGAL levels as an early prognostic marker of graft function immediately after transplantation. MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled trial was conducted on 70 deceased-donor KT recipients ( www.irct.ir , trial registration number: IRCT2014090214693N4). Patients received 600 mg oral NAC or placebo twice daily from day 0 to 5 and urine samples were taken before, and on the first and fifth days after transplantation. U-NGAL and early graft function were compared between the two groups. RESULTS: NAC significantly reduced u-NGAL levels compared to placebo (p value = 0.02), while improvement in early graft function with NAC did not reach statistical significance. CONCLUSIONS: This study showed that NAC administration in deceased-donor KT recipients can reduce tubular kidney injury, evidenced by u-NGAL measurements. Improvement in early graft function needs a larger sample size to reach a statistical conclusion.

Application of Sparse Linear Discriminant Analysis and Elastic Net for Diagnosis of IgA Nephropathy: Statistical and Biological Viewpoints

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis diagnosed based on renal biopsy. Mesangial IgA deposits along with the proliferation of mesangial cells are the histologic hallmark of IgAN. Non-invasive diagnostic tools may help to prompt diagnosis and therapy. The discovery of potential and reliable urinary biomarkers for diagnosis of IgAN depends on applying robust and suitable models. Applying two multivariate modeling methods on a urine proteomic dataset were obtained from IgAN patients, and comparison of the results of these methods were the purpose of this study. Methods: Two models were constructed for urinary protein profiles of 13 patients and 8 healthy individuals, based on sparse linear discriminant analysis (SLDA) and elastic net (EN) regression methods. A panel of selected biomarkers with the best coefficients were proposed and further analyzed for biological relevance using functional annotation and pathway analysis. Results: Transferrin, α1-antitrypsin, and albumin fragments were the most important up-regulated biomarkers, while fibulin-5, YIP1 family member 3, prasoposin, and osteopontin were the most important down-regulated biomarkers. Pathway analysis revealed that complement and coagulation cascades and extracellular matrix-receptor interaction pathways impaired in the pathogenesis of IgAN. Conclusion: SLDA and EN had an equal importance for diagnosis of IgAN and were useful methods for exploring and processing proteomic data. In addition, the suggested biomarkers are reliable candidates for further validation to non-invasive diagnose of IgAN based on urine examination.