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.

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.

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.

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.

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.

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.

1 H NMR-based metabolomics study for identifying urinary biomarkers and perturbed metabolic pathways associated with severity of IgA nephropathy: a pilot study.

The severity of IgA nephropathy (IgAN), the most common primary glomerulonephritis, is judged on the basis of histologic and clinical features. A limited number of studies have considered molecular signature of IgAN for this issue, and no reliable biomarkers have been presented non-invasively for use in patient evaluations. This study aims to identify metabolite markers excreted in the urine and impaired pathways that are associated with a known marker of severity (proteinuria) to predict mild and severe stages of IgAN. Urine samples were analysed using nuclear magnetic resonance from biopsy-proven IgAN patients at mild and severe stages. Multivariate statistical analysis and pathway analysis were performed. The most changed metabolites were acetoacetate, hypotaurine, homocysteine, L-kynurenine and phenylalanine. Nine metabolites were positively correlated with proteinuria, including mesaconic acid, trans-cinnamic acid, fumaric acid, 5-thymidylic acid, anthranilic acid, indole, deoxyguanosine triphosphate, 13-cis-retinoic acid and nicotinamide riboside, while three metabolites were negatively correlated with proteinuria including acetoacetate, hypotaurine and hexanal. 'Phenylalanine metabolism' was the most significant pathway which was impaired in severe stage in comparison to mild stage of IgAN. This study indicates that nuclear magnetic resonance is a versatile technique that is capable of detecting metabolite biomarkers in combination with advanced multivariate statistical analysis. Copyright © 2017 John Wiley & Sons, Ltd.

Evaluating the Prevalence of the Epidermal Growth Factor Receptor in Transitional Cell Carcinoma of Bladder and its Relationship With Other Prognostic Factors.

BACKGROUND: The most common malignancy in the urinary system has been bladder cancer and the most predominant histologic subtype has been transitional cell carcinoma (TCC). There were many molecular risk factors, related with poor prognosis. One of these factors was expression of epidermal growth factor receptor (EGFR). OBJECTIVES: The aim of this study was to evaluate the prevalence of the epidermal growth factor receptor in transitional cell carcinoma of bladder and its relationship with other prognostic factors. PATIENTS AND METHODS: This analytic descriptive study has performed with 61 patients with TCC of bladder after radical cystectomy whom have been hospitalized in Labbafinejad hospital in Tehran, Iran between 2007 and 2010. We have used Chi-square and t-test to analyze our data samples. RESULTS: Records of 61 patients have studied. Fifty three of the total samples were positive for EGFR expression (86.9%). Fifty samples of these fifty-three belonged to men and three others were women's samples (P = 0.46). Among the group with EGFR expression the results were as follows: 25 patients (47.2%) were 60 years old or less and 28 patients (52.8%) were older than 60 (P = 0.023), 16 patients (30.2%) had invasion to lamina properia, and the rest of them had invasion to deeper layers (P = 0.56). For most patients we could not determine the invasion of tumoral cells into the lymph nodes (Nx) (P = 0.067). Thirty four patients (64.2%) had not lymphovascular invasion (P = 0.44) and in forty three of patients (81.1%), perineural invasion have not seen (P = 0.23). Finally, 36 patients (67.9%) were grade 3 (P = 0.27). CONCLUSIONS: In this study we have concluded that most patients had EGFR positive expression. Also, except for the age, there was not any significant relation between expression of EGFR and the other prognostic factors such as, gender, invasion of the tumor into the layers, involving the lymph nodes, lymphovascular or perineural invasion, and grading.

1 H NMR-based metabolomics exploring urinary biomarkers correlated with proteinuria in focal segmental glomerulosclerosis: a pilot study.

Focal segmental glomerulosclerosis (FSGS) is a common glomerulonephritis, and its rates of occurrence are increasing worldwide. Proteinuria is a clinical defining feature of FSGS which correlates with the severity of podocyte injury in patients with nephrotic-range protein excretion. Metabolite biomarkers corresponding with the level of proteinuria could be considered as non-invasive complementary prognostic factors to proteinuria. The urine samples of 15 patients (n = 6 women and n = 9 men) with biopsy-proven FSGS were collected and subjected to nuclear magnetic resonance (NMR) analysis for metabolite profiling. Multivariate statistical analyses, including principal component analysis and orthogonal projection to latent structure discriminant analysis, were applied to construct a predictive model based on patients with proteinuria >3000 mg/day and <3000 mg/day. In addition, random forest was performed to predict differential metabolites, and pathway analysis was performed to find the defective pathways responsible for proteinuria. Ten metabolites, significant in both statistical methods (orthogonal projection to latent structure discriminant analysis and random forest), were considered as prognostic biomarkers for FSGS: citrulline, dimethylamine, proline, acetoacetate, alpha-ketoisovaleric acid, valine, isobutyrate, D-Palmitylcarnitine, histidine, and N-methylnicotinamide. Pathway analysis revealed impairment of the branched-chain amino acid degradation pathways in patients with massive proteinuria. This study shows that metabolomics can reveal the molecular changes corresponding with disease progression in patients with FSGS and provide a new insight for pathogenic pathways. Copyright © 2016 John Wiley & Sons, Ltd.

Validation of Oxford Classification of Immunoglobulin A Nephropathy: an Iranian Experience.

INTRODUCTION: In 2009, the Oxford classification of immunoglobulin A (IgA) nephropathy was proposed by the working group of the International IgA Nephropathy Network and Renal Pathology Society. It established specific pathologic features that predict the risk of progression of disease. This study aimed to evaluate the interobserver reproducibility of the Oxford classification of IgA nephropathy between Iranian nephropathologists. MATERIALS AND METHODS: We included 100 patients with primary IgA nephropathy diagnosed between 2001 and 2011. Histologic slides were circulated among 4 pathologists. A score sheet was answered by each individual pathologist for each biopsy, according to the instruction of the Oxford classification. Reproducibility was determined for each variable, using intraclass correlation coefficient (ICC). RESULTS: The ICC values calculated for each major category of the Oxford classification were as follows: the highest score of 0.94 for tubular atrophy and interstitial fibrosis; 0.8 for glomerular basement membrane duplication, extracapillary proliferation, and segmental endocapillary proliferation; and 0.1 to 0.3 for arterial lesions, especially for hyalinosis of arterioles and intimal thickening of arcuate vessels and interlobar arteries. CONCLUSIONS: The Oxford classification of IgA nephropathy is a useful tool and evidenced-based method with high interobserver reproducibility in pathology reporting. Our data suggest that Oxford classification may be used as a model for classification of other renal pathologies in the future.

A Significant Upregulation of miR-886-5p in High Grade and Invasive Bladder Tumors.

PURPOSE: To investigate the expression alteration of miR-886-5p in bladder tumors and evaluating its expression level as a potential biomarker in this type of cancer. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) samples of bladder tumors belonging to 70 patients whom had been referred to the Shahid Labbafi-Nejad medical center were obtained from the archival collection of pathology department. After RNA extraction and cDNA synthesis, expression levels of miR-886-5p were quantified by a real-time reverse transcription polymerase chain reaction (RT-PCR) approach. RESULTS: Our data revealed a significant upregulation (~3 times) of miR-886-5p in high grade bladder tumors, compared to the low grade ones (P < .05). Moreover, its expression level could significantly discriminate noninvasive (Ta, T1) from invasive (T-2T4) tumor stages. CONCLUSION: Our data suggests a potential role for miR-886-5p in progression of bladder cancer.

Diagnostic urinary proteome profile for immunoglobulin a nephropathy.

INTRODUCTION: Immunoglobulin A (IgA) nephropathy, the most common type of glomerulonephritis, is only diagnosed by invasive kidney biopsy. Urine proteome panel might help in noninvasive diagnosis and also better understanding of pathogenesis of IgA nephropathy. MATERIALS AND METHODS: Second mid-stream urine samples of 13 patients with biopsy-proven IgA nephropathy and 8 healthy controls were investigated by means of nanoscale liquid chromatography tandem mass spectrometry. Multivariate analysis of quantified label-free proteins was performed by the principal component analysis and partial least squares models. RESULTS: A total number of 493 unique proteins were quantified by nanoscale liquid chromatography tandem mass spectrometry, of which 46 proteins were considered as putative biomarkers of IgA nephropathy, after multivariate analysis and additional filter criterion and comparing the patients and the controls. Some of the significant differentially expressed proteins were CD44, glycoprotein 2, vasorin, epidermal growth factor, CLM9, protocadherin, utreoglobin, dipeptidyl peptidase IV, NHL repeat-containing protein 3, and SLAM family member 5. These proteins were related to various involved pathogenic pathways of inflammatory response and complement system. CONCLUSIONS: This proteome profile could be utilized in the diagnosis of IgA nephropathy. In addition, providing a noninvasive diagnostic tool, it may shed light on the pathogenesis of IgA nephropathy.

Association of programmed cell death 1 and programmed cell death 1 ligand gene polymorphisms with delayed graft function and acute rejection in kidney allograft recipients.

INTRODUCTION: The genetic variations of co-stimulatory molecules can affect the extent of T cell activity during T-cell mediated immunity, especially in transplant patients. This study aimed to investigate the association of programmed cell death 1 (PDCD1) and programmed cell death 1 ligand 1 (PDCD1LG1) gene polymorphisms with clinical outcome of kidney transplantation. MATERIALS AND METHODS: A total of 122 patients with a kidney transplant were included in this retrospective study. Patients were classified into two groups of biopsy-proven acute allograft rejection (AAR) and stable graft function (SGF) during the 5-year follow-up period. Four single nucleotide polymorphisms in PDCD1 and PDCD1LG1 were determined in the groups of patients as well as in 208 healthy control individuals. RESULTS: The frequencies of PD-1.3 (+7146 G>A), PD-1.9 (+7625 C>T), PD-L1 (8923 A>C), and PD-L1 (+6777 C>G) genotypes and alleles were not significantly different between the AAR and SGF groups. In comparison with healthy controls, PD-1.9 (+7625 C>T) genotype and T allele were significantly more frequent in all of the patients and in those with SGF. Overall, 27 of 122 kidney allograft recipients experienced delayed graft function, and a higher frequency of PD-1.9 (+7625 C>T) genotype and T allele was observed in this group versus those without delayed graft function. Similarly, a significant high frequency of this genotype was found among the AAR subgroup of patients with delayed graft function. CONCLUSIONS: Our results indicate that potentially functional genetic variation in PDCD1 can influence the outcome of kidney transplantation.