The impacts of dietary antioxidants on cardiovascular events in hemodialysis patients: An update on the cellular and molecular mechanisms.

Cardiovascular-related complications (CVCs) are the primary cause of death in patients undergoing hemodialysis (HD), accounting for greater than half of all deaths. Beyond traditional risk factors, chronic inflammation, extreme oxidative stress (OS), and endothelial dysfunction emerge as major contributors to accelerated CVCs in HD patients. Ample evidence shows that HD patients are constantly exposed to excessive OS, due to uremic toxins and pro-oxidant molecules that overwhelm the defense antioxidant mechanisms. The present study highlights the efficiency of natural antioxidant supplementation in managing HD-induced inflammation, OS, and consequently CVCs. Moreover, it discusses the underlying molecular mechanisms by which these antioxidants can decrease mitochondrial and endothelial dysfunction and ameliorate CVCs in HD patients. Given the complex nature of OS and its molecular pathways, the utilization of specific antioxidants as a polypharmacotherapy may be necessary for targeting each dysregulated signaling pathway and reducing the burden of CVCs.

An update on Glycerophosphodiester Phosphodiesterases; From Bacteria to Human.

The hydrolysis of deacylated glycerophospholipids into sn-glycerol 3-phosphate and alcohol is facilitated by evolutionarily conserved proteins known as glycerophosphodiester phosphodiesterases (GDPDs). These proteins are crucial for the pathogenicity of bacteria and for bioremediation processes aimed at degrading organophosphorus esters that pose a hazard to both humans and the environment. Additionally, GDPDs are enzymes that respond to multiple nutrients and could potentially serve as candidate genes for addressing deficiencies in zinc, iron, potassium, and especially phosphate in important plants like rice. In mammals, glycerophosphodiesterases (GDEs) play a role in regulating osmolytes, facilitating the biosynthesis of anandamine, contributing to the development of skeletal muscle, promoting the differentiation of neurons and osteoblasts, and influencing pathological states. Due to their capacity to enhance a plant's ability to tolerate various nutrient deficiencies and their potential as pharmaceutical targets in humans, GDPDs have received increased attention in recent times. This review provides an overview of the functions of GDPD families as vital and resilient enzymes that regulate various pathways in bacteria, plants, and humans.

Uncovering key molecular mechanisms in the early and late-stage of papillary thyroid carcinoma using association rule mining algorithm.

OBJECTIVE: Thyroid Cancer (TC) is the most frequent endocrine malignancy neoplasm. It is the sixth cause of cancer in women worldwide. The treatment process could be expedited by identifying the controlling molecular mechanisms at the early and late stages, which can contribute to the acceleration of treatment schemes and the improvement of patient survival outcomes. In this work, we study the significant mRNAs through Machine Learning Algorithms in both the early and late stages of Papillary Thyroid Cancer (PTC). METHOD: During the course of our study, we investigated various methods and techniques to obtain suitable results. The sequence of procedures we followed included organizing data, using nested cross-validation, data cleaning, and normalization at the initial stage. Next, to apply feature selection, a t-test and binary Non-Dominated Sorting Genetic Algorithm II (NSGAII) were chosen to be employed. Later on, during the analysis stage, the discriminative power of the selected features was evaluated using machine learning and deep learning algorithms. Finally, we considered the selected features and utilized Association Rule Mining algorithm to identify the most important ones for improving the decoding of dominant molecular mechanisms in PTC through its early and late stages. RESULT: The SVM classifier was able to distinguish between early and late-stage categories with an accuracy of 83.5% and an AUC of 0.78 based on the identified mRNAs. The most significant genes associated with the early and late stages of PTC were identified as (e.g., ZNF518B, DTD2, CCAR1) and (e.g., lnc-DNAJB6-7:7, RP11-484D2.3, MSL3P1), respectively. CONCLUSION: Current study reveals a clear picture of the potential candidate genes that could play a major role not only in the early stage, but also throughout the late one. Hence, the findings could be of help to identify therapeutic targets for more effective PTC drug developments.

Biofactors regulating mitochondrial function and dynamics in podocytes and podocytopathies.

Podocytes are terminally differentiated kidney cells acting as the main gatekeepers of the glomerular filtration barrier; hence, inhibiting proteinuria. Podocytopathies are classified as kidney diseases caused by podocyte damage. Different genetic and environmental risk factors can cause podocyte damage and death. Recent evidence shows that mitochondrial dysfunction also contributes to podocyte damage. Understanding alterations in mitochondrial metabolism and function in podocytopathies and whether altered mitochondrial homeostasis/dynamics is a cause or effect of podocyte damage are issues that need in-depth studies. This review highlights the roles of mitochondria and their bioenergetics in podocytes. Then, factors/signalings that regulate mitochondria in podocytes are discussed. After that, the role of mitochondrial dysfunction is reviewed in podocyte injury and the development of different podocytopathies. Finally, the mitochondrial therapeutic targets are considered.

Unraveling the link between PTBP1 and severe asthma through machine learning and association rule mining method.

Severe asthma is a chronic inflammatory airway disease with great therapeutic challenges. Understanding the genetic and molecular mechanisms of severe asthma may help identify therapeutic strategies for this complex condition. RNA expression data were analyzed using a combination of artificial intelligence methods to identify novel genes related to severe asthma. Through the ANOVA feature selection approach, 100 candidate genes were selected among 54,715 mRNAs in blood samples of patients with severe asthmatic and healthy groups. A deep learning model was used to validate the significance of the candidate genes. The accuracy, F1-score, AUC-ROC, and precision of the 100 genes were 83%, 0.86, 0.89, and 0.9, respectively. To discover hidden associations among selected genes, association rule mining was applied. The top 20 genes including the PTBP1, RAB11FIP3, APH1A, and MYD88 were recognized as the most frequent items among severe asthma association rules. The PTBP1 was found to be the most frequent gene associated with severe asthma among those 20 genes. PTBP1 was the gene most frequently associated with severe asthma among candidate genes. Identification of master genes involved in the initiation and development of asthma can offer novel targets for its diagnosis, prognosis, and targeted-signaling therapy.

Decoding the Possible Molecular Mechanisms in Pediatric Wilms Tumor and Rhabdoid Tumor of the Kidney through Machine Learning Approaches.

Objective: Wilms tumor (WT) and Rhabdoid tumor (RT) are pediatric renal tumors and their differentiation is based on histopathological and molecular analysis. The present study aimed to introduce the panels of mRNAs and microRNAs involved in the pathogenesis of these cancers using deep learning algorithms. Methods: Filter, graph, and association rule mining algorithms were applied to the mRNAs/microRNAs data. Results: Candidate miRNAs and mRNAs with high accuracy (AUC: 97%/93% and 94%/97%, respectively) could differentiate the WT and RT classes in training and test data. Let-7a-2 and C19orf24 were identified in the WT, while miR-199b and RP1-3E10.2 were detected in the RT by analysis of Association Rule Mining. Conclusion: The application of the machine learning methods could identify mRNA/miRNA patterns to discriminate WT from RT. The identified miRNAs/mRNAs panels could offer novel insights into the underlying molecular mechanisms that are responsible for the initiation and development of these cancers. They may provide further insight into the pathogenesis, prognosis, diagnosis, and molecular-targeted therapy in pediatric renal tumors.

The Impact of Single Nucleotide Polymorphisms on the Pharmacokinetics of Tacrolimus in Kidney Allograft Recipients of Northern-West, Iran.

Purpose: Calcineurin inhibitors (CNIs) such as tacrolimus are a major immunosuppressive therapy after renal transplantation, which inhibit cytokine expression. The pharmacokinetics of such drugs is influenced by cytochrome P450 (CYP) enzymes, multi-drug resistance-1 (MDR-1), and C25385T pregnane X receptor (PXR). This study aimed to investigate the impact of single nucleotide polymorphisms (SNP) in these genes on the ratio of tacrolimus level per drug dosage (C/D ratio), acute graft rejection, and viral infections. Methods: Kidney transplantation recipients (n=65) under similar immunosuppressive treatment were included. Amplification refractory mutation systempolymerase chain reaction (ARMS-PCR) method was applied to amplify the loci containing the SNPs of interest. Results: Overall, 65 patients with a male/female ratio of 37/28 were included. The mean age was 38±1.75 years. The variant allele frequencies of CYP3A5*3, MDR-1 C3435T, and PXR C25385T were 95.38, 20.77, and 26.92%, respectively. No significant correlations were found between the studied SNPs and the tacrolimus C/D ratios. However, there was a significant difference in the C/D ratios at 2 and 8 weeks in homozygote CYP3A5 *3/*3 carriers (P=0.015). No significant association was found between the studied polymorphisms and viral infections and acute graft rejection (P>0.05). Conclusion: Homozygote CYP3A5 *3/*3 genotype could influence the tacrolimus metabolism rate (C/D ratio).

Interventions for decreasing the risk of recurrent IgA nephropathy: A systematic review and meta-analysis.

Recurrent IgA nephropathy (rIgAN) is an important cause of kidney allograft loss. Till now, no proven strategies have been confirmed to prevent/decrease the rIgAN. Here, a systematic review and meta-analysis were performed on the available interventions impacting rIgAN. PubMed, Embase, Web of sciences, ProQuest, and Cochrane library databases along with Google Scholar were searched for articles evaluating the rIgAN after kidney transplantation (up to 23 February 2023). The main inclusion criteria were kidney transplantation because of primary IgAN and articles studying the rate of the rIgAN based on different therapeutic interventions to find their effects on the disease recurrence. Based on our criteria, 11 papers were included in this systematic review, two of which pleased the criteria for the meta-analysis. Meta-analysis showed that the risk of the rIgAN in the steroid-free group was 3.33 times more than that of the steroid-receiving group (Pooled Hazard Ratio = 3.33, 95% CI 0.60 to18.33, Z-value = 1.38, p-value = 0.16). Steroid-free therapy increases the risk of rIgAN in kidney transplant recipients with primary IgAN. High-quality trials with large sample sizes studies are needed to confirm the impact of the steroids on decreasing the rate of the rIgAN.

Circular RNAs as novel biomarkers in glomerular diseases.

Circular RNAs (circRNAs) regulate gene expression and biological procedures by controlling target genes or downstream pathways by sponging their related miRNA (s). Three types of circRNAs have been identified; exonic circRNAs (ecircRNAs), intronic RNAs (ciRNAs), and exon-intron circRNAs (ElciRNAs). It is clarified that altered levels of circRNAs have dynamic pathological and physiological functions in kidney diseases. Evidence suggests that circRNAs can be considered novel diagnostic biomarkers and therapeutic targets for renal diseases. Glomerulonephritis (GN) is a general term used to refer to a wide range of glomerular diseases. GN is an important cause of chronic kidney diseases. Here, we review the biogenesis of circRNAs, and their molecular and physiological functions in the kidney. Moreover, the dysregulated expression of circRNAs and their biological functions are discussed in primary and secondary glomerulonephritis. Moreover, diagnostic and therapeutic values of circRNAs in distinguishing or treating different types of GN are highlighted.

Ischemic tubular injury: Oxygen-sensitive signals and metabolic reprogramming.

The kidneys are the most vulnerable organs to severe ischemic insult that results in cellular hypoxia under pathophysiological conditions. Large amounts of oxygen are consumed by the kidneys, mainly to produce energy for tubular reabsorption. Beyond high oxygen demand and the low oxygen supply, different other factors make kidneys vulnerable to ischemia which is deemed to be a major cause of acute kidney injury (AKI). On the other hand, kidneys are capable of sensing and responding to oxygen alternations to evade harms resulting from inadequate oxygen. The hypoxia-inducible factor (HIF) is the main conserved oxygen-sensing mechanism that maintains homeostasis under hypoxia through direct/indirect regulation of several genes that contribute to metabolic adaptation, angiogenesis, energy conservation, erythropoiesis, and so on. In response to oxygen availability, prolyl-hydroxylases (PHDs) control the HIF stability. This review focuses on the oxygen-sensing mechanisms in kidneys, particularly in proximal tubular cells (PTCs) and discusses the molecules involved in ischemic response and metabolic reprogramming. Moreover, the possible roles of non-coding RNAs (microRNAs and long non-coding RNAs) in the development of ischemic AKI are put forward.

Glucocorticoid Receptor Polymorphisms and Avascular Osteonecrosis After Kidney Transplantation.

INTRODUCTION: Glucocorticoids (GCs) are commonly prescribed as immunosuppressive agents after kidney transplantation and their most common non-traumatic adverse effect is Avascular Necrosis (AVN) of the femoral head. In this regard, this study aimed to evaluate the glucocorticoid receptor (GR) polymorphisms among kidney transplant recipients and their potential role as a risk factor for the incidence of AVN. METHODS: In this study, 99 renal transplant recipients were evaluated for the correlations of GR polymorphisms including N363S (rs6195), BclI (rs41423247), ER22/23EK (rs6189/rs6190), and A3669G (rs6198) with AVN after renal transplantation. RESULTS: Results showed that none of the renal-transplanted patients neither with GC hypersensitive polymorphisms (N363S and BclI) nor with GC-resistant polymorphisms (A3669G and ER22/23EK) developed AVN (P > .05). In addition, the medications of the renal recipients with AVN were significantly different from the nonAVN patients (P < .001). CONCLUSION: The study results indicate that the GR polymorphisms have no critical roles in the susceptibility to AVN after renal transplantation. However, further studies to confirm the results are recommended.  DOI: 10.52547/ijkd.7221.

Key therapeutic targets implicated at the early stage of hepatocellular carcinoma identified through machine-learning approaches.

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer. Early-stage detection plays an essential role in making treatment decisions and identifying dominant molecular mechanisms. We utilized machine learning algorithms to find significant mRNAs and microRNAs (miRNAs) at the early and late stages of HCC. First, pre-processing approaches, including organization, nested cross-validation, cleaning, and normalization were applied. Next, the t-test/ANOVA methods and binary particle swarm optimization were used as a filter and wrapper method in the feature selection step, respectively. Then, classifiers, based on machine learning and deep learning algorithms were utilized to evaluate the discrimination power of selected features (mRNAs and miRNAs) in the classification step. Finally, the association rule mining algorithm was applied to selected features for identifying key mRNAs and miRNAs that can help decode dominant molecular mechanisms in HCC stages. The applied methods could identify key genes associated with the early (e.g., Vitronectin, thrombin-activatable fibrinolysis inhibitor, lactate dehydrogenase D (LDHD), miR-590) and late-stage (e.g., SPRY domain containing 4, regucalcin, miR-3199-1, miR-194-2, miR-4999) of HCC. This research could establish a clear picture of putative candidate genes, which could be the main actors at the early and late stages of HCC.

Protective effect of Eprosartan against ischemic acute renal injury: Acting on NF-κB, caspase 3, and Sirtuin 1.

Kidney ischemia/reperfusion (I/R) injury is a leading cause of acute kidney injury (AKI) occurring frequently under major surgeries and sepsis. This study aimed to evaluate the effect of Eprosartan, an angiotensin II receptor type-1 (AT-1) antagonist, on the kidney I/R rat model. Male Wistar rats (n = 24) were allocated into (i) Sham, (ii) Eprosartan, (iii) I/R, and (iv) Eprosartan + I/R groups. Animals in the last group received a single dose of Eprosartan (60 mg/kg) 1 h before kidney I/R. Renal oxidant/antioxidant, inflammatory (NF-κB p65, COX-2, IL-6, TNF-α), and apoptotic (caspase-3, Bax, Bcl2) factors along with Sirtuin 1, Klotho, and mitochondrial biogenesis (PGC-1α, and Sirtuin 3) factors were evaluated by Western blotting. Significant recovery of kidney function and increased levels of antioxidant markers were observed in the Eprosartan + I/R group. The Eprosartan anti-inflammatory activity was demonstrated by significant downregulation of NF-κB and its downstream pro-inflammatory factors. Eprosartan pretreatment could also abolish I/R-induced alterations in the apoptotic parameters. Moreover, Eprosartan + I/R rats significantly presented higher levels of Sirtuin 1 content. In conclusion, Eprosartan exhibited nephroprotective effects against kidney damage induced by I/R in rats by decreasing oxidative stress, inflammatory, and apoptotic pathways along with increasing Sirtuin1 level.

The effect of Fingolimod on patients with moderate to severe COVID-19.

Hyper-inflammation, cytokine storm, and recruitment of immune cells lead to uncontrollable endothelial cell damage in patients with coronavirus disease 2019 (COVID-19). Sphingosine 1-phosphate (S1P) signaling is needed for endothelial integrity and its decreased serum level is a predictor of clinical severity in COVID-19. In this clinical trial, the effect of Fingolimod, an agonist of S1P, was evaluated on patients with COVID-19. Forty patients with moderate to severe COVID-19 were enrolled and divided into two groups including (1) the control group (n = 21) receiving the national standard regimen for COVID-19 patients and (2) the intervention group (n = 19) that prescribed daily Fingolimod (0.5 mg) for 3 days besides receiving the standard national regimen for COVID-19. The hospitalization period, re-admission rate, intensive care unit (ICU) administration, need for mechanical ventilation, and mortality rate were assessed as primary outcomes in both groups. The results showed that re-admission was significantly decreased in COVID-19 patients who received Fingolimod compared to the controls (p = .04). In addition, the hemoglobin levels of the COVID-19 patients in the intervention group were increased compared to the controls (p = .018). However, no significant differences were found regarding the intubation or mortality rate between the groups (p > .05). Fingolimod could significantly reduce the re-admission rate after hospitalization with COVID-19. Fingolimod may not enhance patients' outcomes with moderate COVID-19. It is necessary to examine these findings in a larger cohort of patients with severe to critical COVID-19.

Eplerenone reduces renal ischaemia/reperfusion injury by modulating Klotho, NF-κB and SIRT1/SIRT3/PGC-1α signalling pathways.

OBJECTIVES: Acute kidney injury (AKI) is a sudden impairment in kidney function that is associated with high morbidity and mortality. Inflammation, oxidative stress, mitochondrial impairment and energy depletion, along with organ dysfunction are hallmarks of AKI. This study aimed to evaluate the effects of Eplerenone, an aldosterone receptor antagonist, on the kidney injury caused by ischaemia/reperfusion (I/R). METHODS: Male Wistar rats (n = 24) were randomly allocated into four groups: sham, IR, Eplerenone and Eplerenone+IR. Rats in the two last groups 1 h before I/R induction, were treated with Eplerenone (100 mg/kg) via intraperitoneal injection. Protein levels of Klotho, heat shock protein 70 (HSP70), sirtuin1 (SIRT1), SIRT3 and peroxisome proliferator-activated receptor-gamma coactivator 1-α (PGC-1α) along with antioxidant, apoptotic (caspase 3, Bax and Bcl2) and inflammatory [nuclear factor kappa-B (NF-κB) p65, Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2)] factors were evaluated in the kidney tissues of the experimental groups. KEY FINDINGS: Eplerenone pre-treatment significantly could improve IR-induced pathological changes and kidney function and increase the renal antioxidant factors compared to the IR group (P < 0.05). Furthermore, in the Eplerenone + IR group, significant elevation of the Klotho, SIRT1, SIRT3 and PGC-1α at the protein level was identified compared to the IR group. Eplerenone pretreatment could not only downregulate NF-κB signalling and its downstream inflammatory factors (IL-6, COX-2 and TNF-α) but also could decrease apoptotic factors (P ≤ 0.01). CONCLUSIONS: The results recommended that Eplerenone exerts a protective effect against kidney IR injury by up-regulating Klotho, HSP70, sirtuins and PGC-1α to preserve mitochondrial function and cell survival. Moreover, it hinders renal inflammation by suppressing NF-κB signalling. These results offer insight into the prevention or treatment of AKI in the future.

A diagnostic miRNA panel to detect recurrence of ovarian cancer through artificial intelligence approaches.

BACKGROUND: Ovarian Cancer (OC) is the deadliest gynecology malignancy, whose high recurrence rate in OC patients is a challenging object. Therefore, having deep insights into the genetic and molecular mechanisms of OC recurrence can improve the target therapeutic procedures. This study aimed to discover crucial miRNAs for the detection of tumor recurrence in OC by artificial intelligence approaches. METHOD: Through the ANOVA feature selection method, we selected 100 candidate miRNAs among 588 miRNAs. For their classification, a deep-learning model was employed to validate the significance of the candidate miRNAs. The accuracy, F1-score (high-risk), and AUC-ROC of classification test data based on the 100 miRNAs were 73%, 0.81, and 0.65, respectively. Association rule mining was used to discover hidden relations among the selected miRNAs. RESULT: Five miRNAs, including miR-1914, miR-203, miR-135a-2, miR-149, and miR-9-1, were identified as the most frequent items among high-risk association rules. The identified miRNAs may target genes/proteins involved in epithelial-mesenchymal transition (EMT), resistance to therapy, and cancer stem cells; being responsible for the heterogeneity and plasticity of the tumor. Our conclusion presents mir-1914 as the significant candidate miRNA and the most frequent item. Current knowledge indicates that the dysregulated miR-1914 may function as a tumor suppressor or oncogene in the development of cancer. CONCLUSION: These candidate miRNAs can be considered a powerful tool in the diagnosis of OC recurrence. We hypothesize that mir-1914 might open a new line of research in the realm of managing the recurrence of OC and could be a significant factor in triggering OC recurrence.

Salivary biomarkers in cancer.

In recent years, the comprehensive analysis of saliva, i.e., salivaomics, has played an increasing role in biomarker discovery for disease detection in general and cancer specifically. Saliva is a readily accessible, non-invasive and low-cost specimen that can be used to detect biomarkers of clinical relevance. Saliva-based "omics" technologies, which include proteomics, transcriptomics, metabolomics and microbiomics, have rapidly evolved and may be applicable in point-of-care detection, liquid biopsy and nanoscience. Advances in analytical methods has increased the scope and application of salivaomics from solely the oral cavity to the entire physiologic system, and accordingly to personalized medicine. In this chapter, we highlight recent advances in analytical approaches to identify and detect biomarkers in saliva and their potential use as diagnostic, prognostic and therapeutic markers with a focus on cancer.

Microbiota and glomerulonephritis: An immunological point of view.

Glomerular injury is the major cause of chronic kidney diseases (CKD) worldwide and is characterized by proteinuria. Glomerulonephritis (GN) has a wide spectrum of etiologies, the intensity of glomerular damage, histopathology, and clinical outcomes that can be associated with the landscape of the nephritogenic immune response. Beyond impaired immune responses and genetic factors, recent evidence indicates that microbiota can be contributed to the pathogenesis of GN and patients' outcomes by impacting many aspects of the innate and adaptive immune systems. It is still unknown whether dysbiosis induces GN or it is a secondary effect of the disease. Several factors such as drugs and nutritional problems can lead to dysbiosis in GN patients. It has been postulated that gut dysbiosis activates immune responses, promotes a state of systemic inflammation, and produces uremic toxins contributing to kidney tissue inflammation, apoptosis, and subsequent proteinuric nephropathy. In this review, the impact of gastrointestinal tract (GI) microbiota on the pathogenesis of the primary GN will be highlighted. The application of therapeutic interventions based on the manipulation of gut microbiota with special diets and probiotic supplementation can be effective in GN.

Evaluating the effect of Edaravone on clinical outcome of patients with severe COVID-19 admitted to ICU: a randomized clinical trial.

Cytokine storm is the most prominent hallmark in patients with coronavirus disease 2019 (COVID-19) that stimulates the free radical storm, both of which induce an overactive immune response during viral infection. We hypothesized that owning to its radical-scavenging and anti-inflammatory properties, Edaravone could reduce multi-organ injury, clinical complications, and mortality in severe COVID-19 cases. This single-center randomized clinical trial was accompanied in the intensive care units (ICUs) of the teaching hospital of Tabriz University of Medical Sciences to evaluate the effect of Edaravone on the outcome of patients with severe COVID-19. Thirty-eight patients admitted to ICU were included and randomized into two control and intervention arms. Patients in the intervention group received 30 mg Edaravone by slow intravenous infusion for three days in addition to receiving national therapy. The primary outcome was the need for intubation, the intubation length, and mortality rate. Secondary endpoints were clinical improvement. Edaravone administration improved the primary outcomes; it decreased the need for endotracheal intubation and mechanical ventilation [10.52% (n = 2) versus 42.1% (n = 8); p = 0.03] and intubation length [3 (1-7) versus 28 (4-28), p = 0.04] compared to control group. Baseline characteristics and laboratory tests were similar between the studied groups. No marked differences were observed in secondary endpoints (p > 0.05). Administration of Edaravone could decrease the need for mechanical ventilation and length of intubation in severe COVID-19 patients admitted to ICU.

The Role of Cytokines in Nephrotic Syndrome.

Idiopathic nephrotic syndrome (INS) is an important primary glomerular disease characterized by severe proteinuria. Evidence supports a role for T cell dysfunction in the pathogenesis of INS. Glucocorticoids are the primary therapy for INS; however, steroid-resistant NS (SRNS) patients are at a higher risk of drug-induced side effects and harbor poor prognosis. Although the exact mechanism of the resistance is unknown, the imbalances of T helper subtype 1 (Th1), Th2, and regulatory T cells (Tregs) and their cytokines may be involved in the pathogenesis of glucocorticoid responsiveness. Up to now, no confirmed biomarkers have been able to predict SRNS; however, a panel of cytokines may predict responsiveness and identify SRNS patients. Thus, the introduction of distinctive cytokines as novel biomarkers of SRNS enables both preventions of drug-related toxicity and earlier switch to more effective therapies. This review highlights the impacts of T cell population imbalances and their downstream cytokines on response to glucocorticoid responsiveness state in INS.