mohsen nafar

Antibody mediated rejection (AMR) is a major challenge in kidney transplantation and adversely affects allograft survival. Oxidative stress (OS) is implicated in AMR pathogenesis by triggering inflammation, apoptosis and fibrosis in the graft tissue. However, the status of OS and antioxidant defense in AMR patients remains unclear. We aimed to evaluate the levels of OS markers and antioxidant enzymes in AMR patients. 

We conducted a case-control study involving 22 biopsy-proven AMR patients (test group) and 14 kidney recipients with stable graft function (control group). Serum total oxidant status (TOS), total antioxidant capacity (TAC), total thiol groups, nitric oxide (NO), 8-isoprostane (8-IP) were determined and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured by spectrophotometric methods.

 Data analysis showed significant increases in TOS, TAC and 8-IP levels together with marked reductions in NO and total thiol groups in AMR patients. CAT and GPx activities did not differ between groups, however SOD activity was significantly lower in AMR patients.

Our study showed increased OS and impaired antioxidant defense in AMR patients. NO level may serve as a potential biomarker of OS severity and immune response in AMR. Further studies are required to elucidate the mechanisms and consequences of OS in AMR and to explore the therapeutic potential of antioxidants.

Tacrolimus is the mainstem of immunosuppressive therapy in kidney transplant patients. It has high intrapatient variability (Tac-IPV), which has been reported to affect graft function by predisposing patients to rejection or nephrotoxicity. We conducted this study with the aim of assessing the influence of Tac-IPV on 2-year graft function, biopsy-proven rejection, and infections in compliant renal recipients.

In this single-center retrospective analytic cross-sectional study, 250 patients who underwent transplantation from March 21, 2018, to March 20, 2020 and had at least three outpatient tacrolimus trough levels on the same daily dose 6 to 12 months after transplantation were recruited. Tac-IPV was defined as a coefficient variation of > 15%. Graft function, biopsy-proven rejection, cytomegalovirus (CMV) and BK virus viremia, and calcineurin inhibitor (CNI) toxicity were evaluated.

Of 202 transplant recipients, 128 were included with a mean age of 45.48 ± 13.14 years. The median Tac-IPV was 13.28% with 43.75% of patients with Tac-IPV > 15%. There were no significant differences in graft function, rejection, CNI toxicity, and CMV viremia among the groups during the 24-month study (P> .05). However, BK viremia was significantly higher among patients with Tac-IPV > 15% (13 vs. 2.9%, P = .042). The risk of antibody-mediated rejection alone (22.7 vs. 2.9%) or any kind of rejection (22.7 vs. 11.8%) was significantly higher in patients with higher Tac-IPV, and in those who had mean trough levels below 7 ng/mL (P = .015, .032; respectively).

Tac-IPV is low in adherent patients (with the median of 13.28%) and maintaining tacrolimus trough level above 7 ng/mL can overcome the adverse graft outcome of Tac-IPV in compliant kidney transplant recipients.

Chronic Kidney Disease (CKD) patients often face complex health challenges, including cardiovascular and pulmonary issues. Smoking is a recognized risk factor for these conditions, but its specific impact on CKD patients remains less understood.

In this cross-sectional study, we investigated the relationship between smoking habits and cardiopulmonary health among CKD patients. We examined baseline characteristics, including demographics, medical history, and biochemical markers, in a cohort of CKD patients. Cardiopulmonary parameters were assessed during exercise testing, including oxygen consumption, ventilation rates, ventilation-perfusion matching markers, and oxygen saturation levels.

Our findings revealed no statistically significant differences in cardiopulmonary parameters between smokers and non-smokers within the CKD patient population. This suggests that the relationship between smoking and exercise capacity in CKD patients is complex and influenced by multiple factors. Our analysis of demographics, comorbidities, and medication history provided critical context for interpreting these results.

This study contributes to our understanding of the intricate relationship between smoking habits and cardiopulmonary health in CKD patients. While smoking is recognized as a risk factor, its specific impact on exercise capacity within this population may be influenced by individual variables. Further research is needed to explore these relationships in larger and more diverse cohorts. These findings underscore the importance of considering multiple variables when assessing the impact of smoking on the health of CKD patients.

 End-Stage Renal Disease (ESRD) is a severe nephrological condition that can lead to permanent kidney damage. Therefore, early disease diagnosis is key to preventing casualties. The gold standard method of diagnosis tends to evaluate changes in sodium, potassium, calcium, phosphorus, urea, creatinine, and parathormone hormones in blood after dialysis. However, serum evaluation is not always possible or easy for patients. Therefore, saliva evaluation has been proposed in recent years as an alternative.

 The current article aims to evaluate metabolite in the saliva of ESRD patients.

 In this descriptive-analytical study, 29 ESRD patients undergoing hemodialysis treatment were selected. Their saliva and serum samples were taken. The number of biochemical factors, including sodium, potassium, calcium, phosphorus, urea, creatinine, and parathormone hormone, was measured with an autoanalyzer device and related kits. Finally, the correlation of parameters in serum and saliva was examined using the Pearson test.

 The results showed a significant positive relationship between the levels of sodium, urea, and creatinine in serum and saliva samples (P < 0.05). On the other hand, there was no significant relationship between the serum and saliva levels of potassium, calcium, phosphorus, and PTH (P > 0.05).

 Due to the significant correlation between some prominent biochemical factors in saliva and serum after hemodialysis in ESRD patients, saliva could be considered a non-invasive diagnostic fluid for monitoring kidney disease in the future.

Graphene-based nanomaterials have shown some degrees of stem cell protection against cell death. Due to their distinctive function, the kidneys are exposed to many toxic substances. On the other hand, minor and trivial effects of stem cells have been reported for the treatment of acute kidney injury (AKI). Here, we explain the use of Graphene oxide (GO) for improving the efficacy of mesenchymal stem cells (MSCs) in the treatment of Cisplatin-induced AKI.

In this study, GO particles were synthesized in our lab. Cisplatin-induced AKI was modeled on rats. Thirty adults male Wistar Albino rats were divided into five groups: control group (did not receive any treatment), Cisplatin group (received 5 mg/ kg cisplatin intraperitoneally), sham group (received 500 µL saline intraperitoneally 5th days after Cisplatin injection), [Cisplatin + MSCs] group (received 5×106 /kg MSCs after Cisplatin injection), and [Cisplatin+ MSCs + GO] group (received 1.5 mg/kg GO + MSCs after Cisplatin injection. Biochemical analysis of serum creatinine (Cr) and blood urea nitrogen (BUN) levels, as well as histological study of the kidneys in diverse groups were compared. The oneway analysis of variance (ANOVA) and Dunnett’s test were used for comparisons between the study groups.

GO improved the effects of MSCs transplantation on serum Cr and BUN in AKI rat models. It also reduced cell death, hyaline casts, and cell debris in the animal models compared to the MSCs group.

It could be concluded that GO can enhance the efficacy of MSCs transplantation in the treatment of damaged kidneys.

The accurate assessment of the pre-donation glomerular filtration rate (GFR) is a crucial step in donor selection. We conducted a prospective cross-sectional study to identify the best equation to estimate GFR and the necessity of a radio-nuclear scan in GFR evaluation.

In this study, 154 potential donors were enrolled, and GFR equations (the MDRD study, the CKD-EPI study, and the full age spectrum [FAS]), and creatinine clearance were compared with measured GFR (mGFR) by the radio-nuclear method.

The study results indicate that Potential donors had an mGFR of 95.56 ± 15.57 mL/min per 1.73 m2. Though body surface area (BSA) adjusted full age spectrum (FAS) and CKD-EPI equations were most correlated with mGFR, the correlation coefficients were weak (ICC: 0.3 and 0.32, respectively). Misclassification at the cut-off of 80 cc/min/ 1.73 m2 was about 42% for both equations. Besides, 16.8% of donors with eGFR more than 80 cc/min/ 1.73 m2 had a difference in split renal function, and 57.1% of participants had a > 2% probability of having an mGFR < 90 mL/min per 1.73 m2.

If the nuclear scan is easily available, we suggest measuring GFR by 99mTc -DTPA scan as the preferred method. Otherwise, our data suggest utilizing mGFR in patients with high body mass index, size asymmetry in CT-scan, eGFR less than 90 mL/min per 1.73 m2 with FAS and/or CKD-EPI equation as these factors deviated the estimated GFR, and also in those with inaccurate creatinine clearance measurements or with posttest probability of having mGFR less than 90 mL/min per 1.73 m2 more than 2%.

Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies.

This study aimed to evaluate prospectively the influence of low dose ATG induction therapy with two different protocols (Sirolimus versus Mycophenolate mofetil) on the expression of functional markers (LAG-3, CD39, and intracellular CTLA-4) on conventional Tregs in renal recipients.

Thirty-eight renal transplant recipients were enrolled in this study. The patients were randomly assigned into two groups, including TMP: Tacrolimus (Tac), Mycophenolate mofetil (MMF), and Prednisolone (n=23); and TSP: Tac, Sirolimus (SRL), and Prednisolone (n=15). The frequency of LAG-3, CD39, and intracellular CTLA-4 on circulating Tregs was analyzed by flow cytometry before and after transplantation.

Analysis of the flow cytometry data showed that the frequency of CD4+CD25+FOXP3+ Tregs increased 4 months post-transplantation compared to pre-transplantation in both groups, although this increase was only significant in TMP group. In TMP treated patients, the frequency of LAG-3+ Tregs and CD39+ Tregs increased, whereas the frequency of intracellular CTLA-4+ Tregs decreased 4 months post-transplantation. In TSP group, while the frequency of CD39+ Tregs increased, the frequency of CTLA-4+ Tregs decreased in post-transplantation compared to pre-transplantation.

it seems that both treatment regimen protocols with a low dose ATG induction therapy may be clinically applicable in kidney transplant recipients.

Identification of latent tuberculosis (TB) infection is important in kidney transplant candidates. Due to the absence of a gold standard, both tuberculin skin test (TST) and interferon‑gamma release assays (IGRA) are used to screen patients. The aim of this study was to evaluate the agreement of these two tests in patients undergoing renal transplantation.

Two hundred kidney transplant candidates at a referral center in 2014–2017 were included in this study. TST and Quantiferon‑Gold (QFT‑G) tests were performed for all patients before transplantation. In case of a positive result in any of the tests, patients were administered a 9‑month prophylaxis treatment using isoniazid. Cohen’s kappa coefficient (k) test was used to determine the agreement between the two tests.

The mean age of patients was 40.72 ± 18.33. Nine (4.5%) patients had positive TST and 16 (8%) had positive IGRA. Concordance of the two tests was evaluated as medium (κ = 0.44 and P < 0.001). No association was found between the underlying causes of renal failure and skin test positive or IGRA. The tests showed a poor agreement among diabetics, candidates of re‑transplantation, and those who were on dialysis for longer than a year (κ < 0.20).

TST or IGRA can be used to screen TB in kidney transplant candidates with a moderate agreement. However, we suggest using both TST and QFT‑G in diabetics, re‑transplant candidates, and those on dialysis for >1 year.

Cytomegalovirus (CMV) infection is the most common complications following kidney transplantation. Natural killer (NK) cells demonstrated critical anti-viral role in controlling and elimination of CMV after transplantation. Interleukin-15 (IL-15) is a pleiotropic cytokine that promotes the activity of NK cells and strengthens the acquired immune system. Also, IP10 (CXCL10) is a chemotactic factor which regulates NK cell recruitment and antiviral immune response. We aimed to determine the correlation between the serum levels of IL-15 and IP-10 cytokines with CMV infection, CMV viral load, and cyclosporine as a major immunosuppressive treatment after transplantation.

Fifty-eight kidney transplant recipient patients without evidence of CMV virus disease before transplantation surgery were included in the study. From the day of transplant surgery, the patients were evaluated based on the presence of CMV Ag pp65, CMV viral load, serum levels of IL-15 & IP-10, Cyclosporine levels (C0 & C2), Glomerular Filtration Rate (GFR), and hematological & biochemical Index, up to 75 days.

Comparison analysis of serum levels of IL-15 and IP-10 showed no significant association with CMV infection in kidney transplant recipients. In addition, CMV viral load and cyclosporine levels at C0 and C2 did not affect patientschr('39') IL-15 and IP-10 levels.

The levels of IP-10 and IL-15 cytokines are not affected with CMV infection, even if a viral infection occurs in the early days after transplantation or long afterwards. In addition, taking the different levels of cyclosporine did not affect the cytokines levels. Other mechanisms may play a role in maintaining the levels of these cytokines.

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematous (SLE). With no specific clinical or laboratory manifestation to predict response to treatment, this study was aimed to provide a panel of predictive biomarkers of response before initiation of treatment.

Liquid chromatography tandem mass spectrometry (LCMS/MS) analysis was performed on plasma and urine samples of 11 patients with biopsy proven proliferative LN at the time of biopsy. Unsupervised principal component analysis (PCA), orthogonal projection to latent structures discriminant analysis (OPLS-DA), gene ontology annotation and protein mapping were performed on 326 proteins in plasma and 1381 proteins in urine samples.

Samples of eight patients achieved complete remission and three reached partial remission were analyzed. The mean 24- hour protein excretion was 3259 mg/d and the mean eGFR was 87.73 cc/min. OPLS-DA analysis of plasma samples showed a clear discrimination for complete and partial remission patients. Twenty plasma proteins and ten urine proteins with the highest fold changes and AUCs were selected as candidate biomarkers (IGHV1-18, PI16, IGHD, C3, FCER2, EPS8L2, CTTN, BLVRB). This plasma and urine biomarker panel is involved in oxidative stress, acute inflammation, reduction in regulatory T cells, complement pathway consumption, and proximal tubule bicarbonate reclamation.

Our suggested panel of plasma and urine biomarkers can precisely discriminate patients with possibility of complete response to treatment. It seems that the higher indices of inflammation will associate with better chance of achieving complete remission.

Autosomal dominant polycystic kidney disease (ADPKD), a multisystem disorder, is the most prevalent type of hereditary kidney disease. Here, we aimed to evaluate methylation of the PKD1 gene (PKD1) promoter and its correlation with PKD1 expression in peripheral blood.

In this case-control study methylation of the PKD1 promoter was evaluated using methylation-sensitive high-resolution melt (MS-HRM) analysis. PKD1 expression was assessed by quantitative real-time PCR. The correlation was evaluated using the Pearson correlation test.

Twenty subjects from both the patient and control groups (n= 40 for each) were methylated at the PKD1 promoter to various levels (18.9% in patients and 62.5% in controls). This difference was statistically significant (p< 0.0001). PKD1 expression in blood samples was significantly greater in ADPKD patients than in controls (p= 0.0081). Significant correlation was seen between PKD1 expression and its promoter methylation status in peripheral blood (r case= -0.5300, p= 0.0162, and r control = -0.6265, p= 0.0031).

Methylation of the PKD1 promoter in ADPKD patients was inversely correlated with PKD1 expression.

Background:

 Oxidative stress as a major mediator of adverse outcomes in kidney transplant recipients who are prone to oxidative stress-mediated injury by pre-transplant and post-transplant conditions.
Objectives: The purpose of this study was to assess the effects of Pioglitazone on oxidative stress biomarkers and blood glucose control in diabetic patients receiving insulin after kidney transplantation.

Methods: 

In a triple-blind randomized placebo-controlled trial, sixty-two kidney transplanted diabetic patients (40 men and 24 women) were followed for 4 months after randomly assigned to the placebo group and Pioglitazone group (30 mg/d). All of the patients continued their insulin therapy irrespective of the group that they were assigned to evaluate the effects of the addition of pioglitazone on blood glucose and oxidative stress biomarkers, Malondialdehyde (MDA) and total protein carbonyls (TPC) serum levels.

Results:

At baseline, there were no statistically significant differences in glycemic control levels and oxidative markers between the two groups. After 4 months of intervention, a significant improvement occurred in Hemoglobin A1c (HBA1c) in the Pioglitazone group. The changes of HBA1c during 4 months of follow up in the Pioglitazone group show improvement in glucose control were as HBA1c in the placebo group increased by 0.3% (P = 0.0001). Moreover, at the end of the study, the MDA level was significantly lower in the Pioglitazone group (P < 0.0001, 1.22 - 3.90). Regarding the serum level of TPC, the changes were not statistically different at baseline and also at the end of the study between two groups.

Conclusions:

 Administration of Pioglitazone in addition to insulin in diabetic kidney transplant patients not only improved glycemic control (evidenced by HBA1c) but also significantly decreased oxidative stress markers such as MDA.

Membranous nephropathy (MN) as one of the most common glomerulonephritis still relies on an invasive procedure of kidney biopsy for precise recognition. Over the recent past years noninvasive methods using wide range of biomarkers have been developed in order to diagnose and estimating the final prognosis of MN. Plasma, urine and tissue are readily accessible specimens for identification of these biomarkers. In order to utilize a single biomarker or a panel of them for detection of a specific entity, many factors should taking into consideration like the accuracy, precision, and validity, accompanying with being available and cost effective. This review is focused on recently developed biomarkers and their application on the diagnosis besides determining the prognosis of MN. The clinical utilities and limitations of each biomarker are discussed in details.

In this study, we aimed to evaluate the presentation and outcome of COVID-19 in patients with chronic kidney disease (CKD).

We included 43 patients with a past history of CKD and confirmed diagnosis of COVID-19. Patients were evaluated for demographic characteristics, clinical and laboratory data and findings of initial chest computed tomography (CT) and were followed until either death or discharge occurred. Then, study variables were compared based on final outcome and stage of CKD.

Mean age ± SD of patients was 60.65 ± 14.36 years; 65.1% were male. Five of 43 patients (11.6%) died on follow-up and the rest were discharged. Disease outcome did not differ across CKD stages (P > .05). More than half of the patients (58.1%) presented with severe disease on admission. Clinical symptoms were similar to those of non-CKD individuals. Mean duration of hospitalization was higher in those who died, although not significant (16.6 ± 8.38 vs. 11 ± 6.26, P > .05). The only hematologic parameter that significantly differed between survivors and non-survivors was lactase dehydrogenase level (P < .05). Ground-glass opacification and reticular pattern were the most frequent patterns on CT and pleural effusion existed in about one-fifth of all patients. A greater lower zone score was noted in deceased patients (P < .05).

Patients with CKD are vulnerable to a more severe form of COVID-19 and experience a higher mortality rate than the general population; however, higher CKD stage is not related to worse prognosis or different imaging manifestation compared with lower stage.

Since in the reports presented about COVID-19, patients receiving kidney transplantation have not been specifically studied and based on national flowchart, this population is classified as highrisk group, thus it is necessary to be aware of the step-by-step treatment approach of these patients. Suspicious cases included patients with a history of dry cough, chills or sore throat accompanying by shortness of breath with or without fever, patients with upper/lower respiratory symptoms with radiological manifestations as single or double-sided multilobular infiltrations on CT scan or plain chest radiography, any one that has a history of close contact with a definite COVID-19 case within the last 14 days, any one with a history of presence in COVID-19 epidemic regions within the last 14 days and patient with pneumonia that despite of proper treatment has an inappropriate clinical response and clinical condition becomes more severe in an unusual way or unexpectedly.

End-stage renal disease (ESRD) is a foremost health issue with major consequences in various parts of the world. In Iran, the prevalence/incidence of ESRD has increased during the past decades. The economic burden of ESRD treatment on patients, their families, and the whole healthcare system is huge as well. Hence ESRD is considered emerging public health problem in developing countries, including Iran, requiring short- and longterm changes in healthcare policies. Developing a national registry system for dialysis patients in Iran now enables us to summarize certain clinical characteristics of these patients and compares the present situation with the late 1990s when dialysis services just began to expand in the country. In this paper, the authors provide information regarding the process of establishing dialysis registry in Iran along with the report of the output of such a registry. Focusing on such an important measure in the whole country of around along with the data that it has produced is a gateway to further progress.

Reduced graft function (RGF) in donor renal transplant recipients is caused by oxidative damage due to extensive ischemia-reperfusion (I/R) injury during transplantation. Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker to detect tubular injury early after renal transplantation. N-acetylcysteine (NAC) is a potent antioxidant that can reduce I/R injury by improving oxidative damage. The aim of the present study is to assess the efficacy of NAC in improving graft function and reducing renal tubular injury in deceased donor renal transplant recipients. A double-blind, randomized clinical trial was conducted on 50 deceased donor renal transplant recipients. Patients were randomized into two groups, receiving either 600 mg NAC twice daily, or placebo (days 0 to 5). Results were assessed based on the rate of RGF, levels of plasma NGAL (p-NGAL) and the estimated glomerular filtration rate (eGFR). The rate of RGF was significantly lower in patients receiving NAC vs. placebo (21.4% vs. 50%). The measurement of p-NGAL levels showed that patients in the NAC group had significantly greater reduction of p-NGAL by both days 1 and 5 post-transplantation than those in the placebo group. A near steady-state eGFR level was reached by week 1 in the NAC group, however, the improvement of eGFR was significantly slower in the placebo group and a near steady-state was only achieved by week 4. NAC has promising potential in reducing tubular injury and improving graft function, evidenced by significant reduction in the rate of RGF and levels of p-NGAL.

Delayed graft function (DGF) is a form of acute renal failure which results in increased post-transplantation allograft immunogenicity and risk of rejection episodes in addition to decreased long-term survival. Its incidence and risk factors have been extensively studied, especially after deceased donation. However until now, only few data has been published on DGF in living donor kidney transplant recipients. The present study was performed to investigate the frequency and risk factors of DGF among living- kidney transplant recipients.

In this retrospective study, 500 living kidney transplant recipients recruited and data collected from hospital registries in three countries (Iran, Kingdom of Saudi Arabia (KSA) , and Kuwait ).

Incidence of DGF revealed to be %95) %2.3 CI: %3.6-%0.9). DGF group showed significant older age for the recipients and in “without DGF” group, there were more females, and lower weight for the recipients. It was found that patients with DGF had longer pre transplant dialysis duration, cold ischemic and anastomosis time during surgery .

DGF after living-donor kidney transplantation is a multifactorial complication which donor, recipient, and technical factors would lead toward. Consideration and optimization of these risk factors may drive through better long-term patient and graft outcomes in living kidney transplant recipients.

Long non-coding RNAs (lncRNAs) include a vast portion of human transcripts. They exert regulatory roles in immune responses and participate in diverse biological functions. Recent studies indicated dysregulation of lncRNAs in the process of transplant rejection. In the current study, we aimed at identification of the expression of five lncRNAs (OIP5-AS1, FAS-AS1, TUG1, NEAT1 and PANDAR) in association with the process of transplant rejection.

We assessed expression of these lncRNAs in the peripheral blood of 61 kidney transplant receivers including 29 transplant rejected patients and 32 transplant non-rejected patients using real time PCR technique.

Expression of FAS-AS1 was significantly higher in rejected group compared to non-rejected group in males, however, differences between case and control groups were insignificant among females. For other lncRNAs no significant differences were detected between two study groups. Quantile regression model showed that patients’ gender was an important parameter in determination of FAS-AS1 expression (Beta = - 9.46, t =- 2.82, P = 0.007) but not for other lncRNAs expressions. Significant pairwise correlations were detected between expression levels of lncRNAs in a disease related manner.

Based on the higher expression of FAS-AS1 in patients with transplant rejection, this lncRNA might be associated with the pathogenesis of renal transplant rejection.

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. 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).   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. Metabolomics is a useful tool for identification of biomarkers with the ability to diagnose LN patients and predict perturbed pathways responsible for renal injury.

Many studies have clearly reported the advantages of colonoscopy screening in terms of reducing the mortality rate of colorectal cancers in general population. However, the importance of colonoscopy screening in improving the survival rate of kidney transplant recipients is still unclear. So, the aim of this study is to survey the importance and feasibility of colonoscopy screening in kidney transplant recipients.

This clinical study was conducted from February 2015 to November 2016. All participants received polyethylene glycolelectrolyte solution (PEG-ES) or magnesium hydroxide for bowel preparation. Colonoscopy was done and the location and the size of any lesions were recorded in all participants.

Among 247 post-kidney transplant patients who were visited routinely in Labbafi-Nejad Hospital in Tehran, 30 individuals with any signs or symptoms of malignant or non-malignant colorectal diseases and patients who had a colonoscopy during the previous year or had a failed transplant procedure and subsequent return to dialysis were excluded. Finally, 217 kidney transplant recipients were enrolled in this study, of which 121 patients completed the study.

The results of this study, for the first time, confirm the safety and efficiency of colonoscopy as a routine gastrointestinal screening method among post-kidney transplant recipients in Iran, and suggest that it can be highly proficient in detecting gastrointestinal lesions and its implementation is without significant adverse effects in such patients.

Evaluation of gene expression in urinary sediment has been considered as a promising non-invasive approach for biomarker identification of kidney diseases. Nonetheless, there are several challenges in extraction of RNA from this valuable source of biomarkers, mostly because of the factors that have influence on quality of isolated RNA such as low cellular content. Accordingly, we compared the quality of RNA from urine sediment samples that was isolated by four different methods. TRIzol reagent with basic protocol (method 1), modified procedure of TRIzol (method 2), a column-based protocol (method 3) and combination of method 1 and 3 (method 4) were applied for isolation of RNA from identical aliquots of five healthy urine samples. The quality and yield of isolated RNA were evaluated based on concentration and purity. Expression levels of GAPDH and miR-21 were studied by quantitative RT-PCR. Methods 1 and 2 showed the highest RNA yield while no difference in purity of RNA in different methods was noticed. Quantitative RT-PCR findings indicated that Ct values in samples of method 1 had the lowest level. Although higher concentrations of RNA were isolated by method 2, the declined Ct values in this method might indicate degradation of isolated RNA. Column based protocols (method 3 and 4) were failed to show significant recovery of RNA. It seems that isolation procedure using TRIzol, as a phenol based method, is the most efficient, robust and reliable procedure for RNA isolation from urinary sediment cells.

Chronic kidney disease (CKD), characterized by progressive loss of renal function, is becoming a growing problem in the general population. New analytical technologies such as “omics”-based approaches, including metabolomics, provide a useful platform for biomarker discovery and improvement of CKD management. In metabolomics studies, not only prediction accuracy is attractive, but also variable importance is critical because the identified biomarkers reveal pathogenic metabolic processes underlying the progression of chronic kidney disease. We aimed to use k-important neighbors (KIN), for the analysis of a high dimensional metabolomics dataset to classify patients into mild or advanced progression of CKD.

Urine samples were collected from CKD patients (n=73). The patients were classified based on metabolite biomarkers into the two groups: mild CKD (glomerular filtration rate (GFR)> 60 mL/min per 1·73 m2) and advanced CKD (GFR<60 mL/min per 1·73 m2). Accordingly, 48 and 25 patients were in mild (class 1) and advanced (class 2) groups respectively. Recently, KIN was proposed as a novel approach to high dimensional binary classification settings. Through employing a hybrid dissimilarity measure in KIN, it is possible to incorporate information of variables and distances simultaneously.

The proposed KIN not only selected a few number of biomarkers, it also reached a higher accuracy compared to traditional k-nearest neighbors (61.2% versus 60.4%) and random forest (61.2% versus 58.5%) which are currently known as the best classifieres.

Real metabolomics dataset demonstrate the superiority of proposed KIN versus KNN in terms of both classification accuracy and variable importance.

Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease, is a diverse clinical entity that occurs after podocyte injury. Although numerus studies suggested molecular pathways responsible for development of FSGS, many unknowns still remain about its pathogenic mechanism. Two important pathways were predicted as candidates for pathogenesis of FSGS in our previous in silico analysis that we aim to confirm these pathways experimentally in the present study. The expression level of four enzyme genes that are representative of "chondroitin sulfate degradation" and "eicosanoid metabolism" pathways were investigated in the urinary sediment of biopsy proven FSGS patients and healthy subjects using real-time polymerase chain reaction (RT-PCR). These target genes were arylsulfatase, hexosaminidase, cyclooxygenase-2 and prostaglandin I2 synthase. The patients were sub-divided into two groups based on 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. A combined panel of arylsulfatase, hexosaminidase and cyclooxygenase-2 improved the diagnosis of FSGS to 76%. Hexosaminidase was correlated with the level of proteinuria, while cyclooxygenase-2 was correlated with interstitial inflammation and serum creatinine level in the disease group. Our data supported the implication of these target genes and pathways in the pathogenesis of FSGS. Besides, these genes can also be considered as non-invasive biomarkers for FSGS.

Mineral bone disorder is one of the major factors affecting mortality and morbidity in dialysis patients, which is called chronic kidney disease-mineral and bone disorder (CKD-MBD). This study aimed to evaluate the laboratory parameters of mineral bone disorder in hemodialysis patients in Iran and their relationship with malnutrition and inflammation. This multicenter observational study was conducted in 2016 in 58 dialysis centers in Iran. Data of a total number of 7191 chronic hemodialysis patients aged older than 18 years with a dialysis duration of > 3 months were collected. Idiopathic hypercalcemia and history of parathyroidectomy were considered as the exclusion criteria. The serum levels of calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) were measured over a period of three months, and the findings were compared with the K/DOQI (National Kidney Foundation Dialysis Outcomes Quality Initiative) guidelines. Moreover, the serum level of C-reactive protein (CRP) and nutritional status based on geriatric nutritional risk index (GNRI) were assessed. The percentage of the patients who had a serum iPTH level of < 150 pg/mL was 46% while that of patients with iPTH of > 300 pg/mL was 29.3%. Hypercalcemia and hyperphosphatemia were observed in 20.6% and 34.2% of the patients, respectively. Moreover, 51.7%, 61.3%, 24.7%, and 84.7% of the patients, respectively, reached the K/DOQI target range of Ca, P, iPTH, and Ca × P product. The percentages of mild-to-severe malnutrition based on GNRI in patients whose iPTH level was within, below, and above the recommended range of K/DOQI guidelines were 30.7%, 34.1%, and 25.9%, respectively (P < 0.001). Furthermore, the serum level of CRP was significantly higher in low-serum PTH patients than in the other two groups. In total, only could 8.3% of the patients reach the four KDOQI target levels of CKD-MBD. The findings showed a significant percentage of patients had a low serum PTH level, which might be attributed to inflammatory and nutritional factors. Only had a small percentage of patients reached all the K/DOQI targets. Therefore, the effects of inflammatory and nutritional factors should also be considered, particularly in developing countries.