Case report: Endovascular treatment of transplant renal artery stenosis in patient with normal color duplex ultrasound of the renal artery.

Key Clinical Message: Proper diagnosis and treatment of vascular stenosis which is a possible complication of renal transplant is important in improving patients' quality of life and prognosis. Abstract: One known consequence among recipients of renal transplants is graft renal artery stenosis. Early identification and therapy are crucial to avoid graft malfunction and the serious consequences that might arise due to elevated hypertension in several organs. We report a rare case of transplant renal artery stenosis in a mid-aged woman who presented with edema, hypertension, and increased creatinine 2 months after kidney transplant. The patient had normal renal arterial resistive index (RI) and perfusion index (PI), and there was only a modest decrease in perfusion on duplex ultrasound. Following the patient's renal stenting treatment, angiographic resolution was observed. After 14 days of regulated blood pressure following renal artery stenting, she was discharged from the hospital with her edema resolved. Considering complications in patients with clinical manifestations such as hypertension resistant to treatment and graft dysfunction, vascular stenosis is a notable issue to consider even in the context of normal renal arterial RI, PI, and duplex ultrasound. Proper diagnosis and treatment are of importance to improve patients' quality of life and prognosis.

Urinary MicroRNAs, Possible Biomarkers for Early Detection of Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD).

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent renal disorder that causes abnormal growth of renal epithelial cells. The excessive expansion of renal epithelial cells can lead to cyst formation that is associated with serious renal complications. The early diagnosis of ADPKD makes the control of the disease somehow attainable. Regarding the diagnostic potential of microRNAs (miRs) as robust clinical biomarkers, the present study aimed to examine the potential of urinary miRs in early diagnosis of ADPKD in asymptomatic patients. METHODS: Urine samples were obtained from 20 asymptomatic ADPKD patients and 20 healthy control individuals and the miR content of the samples was extracted and converted to cDNA for the qRT-PCR experiment. The relative expressions of miR-17, miR-21, miR-143, and miR-223 were evaluated in ADPKD cases and healthy individuals. Serum levels of kidney function markers were also evaluated in the study participants. RESULTS: The urine samples of patients with ADPKD demonstrated higher levels of miR-17, miR-21, and miR-143 along with a lower miR-223 level compared to the healthy control group. CONCLUSION: This study revealed the differential expression of the studied miRs in ADPKD patients. Detection of miRs in urinary samples might provide a useful platform for early diagnosis of ADPKD in asymptomatic patients.  DOI: 10.52547/ijkd.7281.

Clostridium species diversity in gut microbiota of patients with renal failure.

The Pathology of digestive tract has long been known to be correlated with chronic kidney disease (CKD). The member of the major Firmicutes phylum especially Clostridium subcluster XIVa altered quantitatively and qualitatively in the gut microbiota of patients with End Stage Renal Disease (ESRD) and CKD. Therefore, in this study, the abundance of the species of Clostridium genus of Firmicutes phylum compared between intestine microbiota of patients with kidney failure and healthy individual. Fresh fecal specimens of 20 patients at different stages of CKD and 20 healthy individuals were collected. Bacterial DNA of samples were extracted to use for 16S ribosomal DNA sequencing targeting the V3-V4 region. Next generation sequencing (NGS) method at MiSeq system was used to find the diversity of gut microbiota composition. Totally, 11 (1.68%) of 651 bacterial strains which were isolated from forty fecal samples of both healthy volunteers and CKD/ESRD patients, were identified as Clostridium species. Eight genera of 11 Clostridium genera were related to Clostridium sensu stricto, and 3 other genera were as follows Vallitalea, Acidaminobacter and Caloramator. Among both group, the highest abundance was dedicated to Clostridium celatum genera. Sarcina maxima were not identified. The composition of Clostridium spp. showed the same frequency among CKD/ESRD and healthy groups (p < 0.05). The abundance of Clostridium spp. is virtually the same and not differs among healthy individuals and CKD/ESRD patients. Results of the present indicate despite of critical role of gut microbiota, some pathogens and their metabolites have no role on hemostasis and pathogenesis of kidney disorders.

Prevalence of SARS-CoV-2 Specific Antibodies in Asymptomatic Hemodialysis Patients.

BACKGROUND: Since the outbreak of the new coronavirus pandemic, the importance of carrying out an infection check to prevent acquisition and transmission among end-stage renal disease patients (ESRD) under maintenance hemodialysis (MHD) has become a major concern in the health care system. Applying serology screening tests could enlighten the view with regards to disease prevalence in dialysis wards. METHODS: We subjected 328 end-stage renal disease patients to maintenance hemodialysis. After dividing patients into suspicious and non-suspicious groups for COVID-19 infection based on their clinical manifestation, they were investigated for SARS-CoV-2 specific IgM and IgG screening against nucleoprotein (NP), spike protein (SP), and receptor-binding domain (RBD), utilizing our recently developed ELISA tests. RESULTS: We found that approximately 10.1% of asymptomatically tested cases were antibody positive. Although IgG positivity showed a higher prevalence than IgM across all three virus antigen subunits, there were no significant differences among mentioned immunoglobulins of the studied groups. The most prevalent antibody was from the IgG subtype against virus nucleoprotein (NP), while the lowest prevalence was attributed to receptor-binding domain (RBD) IgM. CONCLUSION: High seropositive rate among asymptomatic end-stage renal disease patients, as a sample of high-risk population, reflected the importance of considering SARS-CoV-2 specific antibody screening for disease containment.

Dialysis-Induced Immune Dysregulations and Their Possible Impacts on COVID-19.

Hemodialysis (HD) patients display metabolic and immunologic alterations that renders their immune responses to be dysregulated. These patients generally have problems in mounting effective immune responses against pathogens such as viruses. On the other hand they typically have higher levels of inflammatory cytokines in their peripheral blood. Both of these features may work in favor of COVID-19. Since robust immune responses are needed to prevent infection in the initial stages of COVID-19, the impaired immune system may not be able to cope effectively with the highly replicating SARS-CoV2. In advanced stages of the disease wherein the inflammation as well as the cytokine storm are the core players, a high baseline inflammatory cytokines could intensify and substantially exacerbate the immunopathological situation. Presence of COVID-19 in HD patients may also be a complex immunological condition. Immunological alterations in HD patients and their potential effects on the fate of the SARSCoV- 2 infection are discussed here. Case reports describing the occurrence of COVID-19 in HD patients have also been reviewed in this study.

Trend in creatinine determining methods: Conventional methods to molecular-based methods.

Renal failure (RF) disease is ranked as one of the most prevalent diseases with severe morbidity and mortality. Early diagnosis of RF leads to subsequent control of disease to reduce the poor prognosis. The level of sera creatinine is considered as a significant biomarker for kidney biofunction, which is routinely detected by the Jaffe reaction. The normal range for creatinine in the blood may be 0.84-1.21 mg/dL. Low accuracy, insufficient sensitivity, explosive and toxicity of picric acid, and pseudo-interaction with nonspecific elements such as ammonium ions in the Jaffe method lead to the development of various techniques for precise detection of creatinine such as spectroscopic, electrochemical, and chromatography approaches and sensors based on enzymes, molecular imprinted polymer and nanoparticles, etc. Based on previously established results, they are trying to construct sensors with high accuracy, optimum sensitivity, acceptable linear/calibration range, and limit of detection, which are small in size and applicable by the patient him/herself (point-of-care testing). By comparing the results of research, a molecularly imprinted electrochemiluminescence-based sensor with linear/calibration range of 5-1 mMconcentration of creatinine and the detection limit of 0.5 nM has the best detectable resolution with 2 million measurable points. In this paper, we will review the recently developed methods for measuring creatinine concentration and renal biofunction.

An optimal method for measuring biomarkers: colorimetric optical image processing for determination of creatinine concentration using silver nanoparticles.

Creatinine concentration is one of the important elements in the body for diagnosing kidney failure, muscular dystrophy, glomerular filtration rate, and diabetic nephropathy. The disadvantages of recently introduced analytical techniques, such as Jaffe's, spectroscopic, colorimetric, and chromatographic methods, for quantifying creatinine in urine involve toxicity, the high cost, interference, and the complexity of the design. In this paper, we designed and fabricated a new colorimetric assay for the measurement of creatinine concentration based on color differentiation generated by mixing different concentrations of creatinine with synthesized silver nanoparticles (AgNPs) coated with polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA). An isolated box is designed for the uniform optical imaging of solutions, the captured images are processed in real time, and the quantitative and qualitative results are displayed. For colorimetric processing, a variety of color systems, such as RGB (red, green, blue), CMYK (cyan, magenta, yellow, black), and grayscale (Gr), have been evaluated, indicating that the combination of green (G) and grayscale (Gr) provides the best results for this experiment. TEM analysis and spectroscopy were used to confirm the results of the experiment. Linear range and limit of detection (LOD) were obtained for AgNPs/PVP 0.03-1 mg/dl and 0.024 mg/dl and for AgNPs/PVA 0.01-1 mg/dl and 0.014 mg/dl, respectively, indicating the superiority of our proposed method over recently introduced methods. In this experiment, the detectable resolution with AgNPs/PVP is 40, while it is 71 with AgNPs/PVA. The designed system is simple to use, small in size, and cost-effective for measuring creatinine concentration, while it can be used as a portable system.

Comparison of the effect of linear and step-wise sodium and ultrafiltration profiling on dialysis adequacy in patients undergoing hemodialysis.

Patients with chronic renal failure undergoing hemodialysis (HD) need to receive adequate dialysis. Dialysis inadequacy leads to an increase in the side effects and even frequent hospitalizations as well as increased therapeutic costs. Considering the fact that improving the adequacy of dialysis is one of the goals of nursing care in these patients, this study aimed to compare the effect of linear and step-wise sodium-ultrafiltration (UF) profiling on HD adequacy. This study is a clinical trial; a total of 32 patients from two dialysis centers in East Azerbaijan province were selected and randomly divided into two groups. Each patient underwent HD for three sessions by routine method, three sessions by linear sodium profile and UF, and three sessions by the step-wise sodium profile and UF. At the end of each HD method, Kt/V was calculated to determine the adequacy of dialysis. Data analysis was performed using Statistical Package for the Social Sciences software version 13 with generalized estimating equation statistical test. According to the results of this study, there was a statistically significant difference between the mean of adequacy of dialysis (Kt/V) in the three treatment methods (P <0.05), in which the mean score of dialysis adequacy in step-wise method was 0.14 more than the routine method, and in the linear method, it was 0.21 more than the routine method. The mean Kt/V scores were 1.24, 1.31, and 1.10 in the step-wise method, linear method, and routine method, respectively(P <0.05). The results of this study indicate that simultaneous application of sodium and UF profiles is effective in the hemodynamic stability of patients, which reduces uncomfortable complications during dialysis. Therefore, in order to improve dialysis adequacy and prevent the complications, usage of sodium and UF profiles is recommended.

An update on potentials and promises of T cell co-signaling molecules in transplantation.

The promising outcomes of immune-checkpoint based immunotherapies in cancer have provided a proportional perspective ahead of exploiting similar approaches in allotransplantation. Belatacept (CTLA-4-Ig) is an example of costimulation blockers successfully exploited in renal transplantation. Due to the wide range of regulatory molecules characterized in the past decades, some of these molecules might be candidates as immunomodulators in the case of tolerance induction in transplantation. Although there are numerous attempts on the apprehension of the effects of co-signaling molecules on immune response, the necessity for a better understanding is evident. By increasing the knowledge on the biology of co-signaling pathways, some pitfalls are recognized and improved approaches are proposed. The blockage of CD80/CD28 axis is an instance of evolution toward more efficacy. It is now evident that anti-CD28 antibodies are more effective than CD80 blockers in animal models of transplantation. Other co-signaling axes such as PD-1/PD-L1, CD40/CD154, 2B4/CD48, and others discussed in the present review are examples of critical immunomodulatory molecules in allogeneic transplantation. We review here the outcomes of recent experiences with co-signaling molecules in preclinical studies of solid organ transplantation.

Cytokine profile, Treg/Th17 cell frequency changes during different posttransplantational time points in patients undergoing renal transplantation.

Renal transplantation is the best therapeutic approach for end stage renal dysfunction patients. There are direct relationships between proportions of Treg cells, Treg/Th17 cells ratio and secreted immunosuppressive cytokines with increased survival rate of the transplanted organ. The aim of this study was the measurement of Treg and Th17 cells frequency and their secreted cytokines. Ninety renal-transplanted patients were divided in three groups based on times after transplantation (1-6 month, 6-36 month, and more than 3 years). Treg and Th17 cells frequency, expression level of their transcription factors and cytokines, and their secreted cytokines level were measured in these groups. Higher expression level of Interleukin (IL)-10 and FoxP3 mRNA were observed in patients who had longer posttransplantation time. In contrast, lower mRNA expressions of IL-6, IL-17, IL-23, and TGF-ß were observed in this group. Receptor γt showed no significant changes in studied groups. In addition IL-10 level was increased and IL-6, IL-17, IL-23, and TGF-ß level were decreased in patients who had longer posttransplantation time. Treg cells frequency was raised in mentioned group whereas no remarkable changes were observed in Th17 cell frequency. The present study declared that in stable renal transplantation, over time, the percentage of Treg cells and Treg/Th17 ration is increased. This increase in ratio induces a change in cytokine profile, resulting in an increased immunosuppressive cytokines such as IL-10 leading to increase in the survival rate of the transplanted organ.

Effects of fermentable high fiber diet supplementation on gut derived and conventional nitrogenous product in patients on maintenance hemodialysis: a randomized controlled trial.

INTRODUCTION: Gut derived toxins such as p-cresol, p-cresyl sulfate (pCS) and indoxyl sulfate (IS), which belong to protein-bound uremic toxins that promote development of fibrosis inflammatory state associated with chronic kidney disease. One possible way to suppress the production of IS and pCS is to increase dietary fiber intake. The aim of the present study was to assess whether increasing dietary fiber, as high amylose diet, can affect the level of conventional and protein bound nitrogenous products. METHODS: Fifty patients with end stage renal disease (ESRD) on maintenance hemodialysis were randomly assigned to receive a diet containing resistant starch (HAM-RS2) or placebo over 8 weeks spanning February and September 2017 in the 29 Bahman hospital hemodialysis ward in Tabriz, Iran. Of these, 44 patients (23 from HAM-RS2 and 21 control) completed the study. Plasma levels of urea, creatinine, uric acid and other routine parameters were measured at the beginning and after 8 weeks of starting the supplementation. The levels of IS and p-cresol in the collected serum samples were also determined by HPLC at baseline and after intervention. RESULTS: There was significant reduction of creatinine and uric acid levels in HAM-RS2 supplemented patients when compared with control group (P < 0.05). Serum levels of IS was not changed significantly in both HAM-RS2 treated and control patients, whereas p-cresol level was reduced significantly during the study period in HAM-RS2 treated patients (P = 0.039). The change of other parameters including Hb, lipids, bone markers and hs-CRP were non-significant during the study in both groups. CONCLUSION: Administration of fermentable high fiber diet as HAM-RS2 decreased serum levels of some nitrogenous products such as serum creatinine and p-cresol as a gut derived nitrogenous product without change in IS levels in maintenance hemodialysis patients. Due to safety, without important side effects the administration of diet enriched with fermentable fiber is suitable for patients on maintenance dialysis.

Renal structural image processing techniques: a systematic review.

BACKGROUND AND OBJECTIVE: Renal disease, such as nephritis and nephropathy, is very harmful to human health. Accordingly, how to achieve early diagnosis and enhance treatment for kidney disorders would be the important lesion. Nevertheless, the clues from the clinical data, such as biochemistry examination, serological examination, and radiological studies are quite indirect and limited. It is no doubt that pathological examination of kidney will supply the direct evidence. There is a requirement for greater understanding of image processing techniques for renal diagnosis to optimize treatment and patient care. METHODS: This study aims to systematically review the literature on publications that has been used image processing methods on pathological microscopic image for renal diagnosis. RESULTS: Nine included studies revealed image analysis techniques for the diagnosis of renal abnormalities on pathological microscopic image, renal image studies are clustered as follows: Glomeruli Segmentation and analysis of the Glomerular basement membrane (55/55%), Blood vessels and tubules classification and detection (22/22%) and The Grading of renal cell carcinomas (22/22%). CONCLUSIONS: A medical image analysis method should provide an auto-adaptive and no external-human action dependency. In addition, since medical systems should have special characteristics such as high accuracy and reliability then clinical validation is highly recommended. New high-quality studies based on Moore neighborhood contour tracking method for glomeruli segmentation and using powerful texture analysis techniques such as the local binary pattern are recommended.

Future of the Renal Biopsy: Time to Change the Conventional Modality Using Nanotechnology.

At the present time, imaging guided renal biopsy is used to provide diagnoses in most types of primary and secondary renal diseases. It has been claimed that renal biopsy can provide a link between diagnosis of renal disease and its pathological conditions. However, sometimes there is a considerable mismatch between patient renal outcome and pathological findings in renal biopsy. This is the time to address some new diagnostic methods to resolve the insufficiency of conventional percutaneous guided renal biopsy. Nanotechnology is still in its infancy in renal imaging; however, it seems that it is the next step in renal biopsy, providing solutions to the limitations of conventional modalities.

The effectiveness of systemic antibiotic therapy with and without ethanol-locked solution in the treatment of hemodialysis-related catheter infection.

Bacterial overgrowth in the inner layer of the catheter as a biofilm is highly encountered in routine medical care, and it may occur in a few days after inserting a catheter as an access in hemodialysis (HD) patients. Catheter-induced bacteremia is often due to the development of biofilms. Locking catheters with antimicrobial agents is an effective way of reducing the risk of catheter-related infection. In a controlled, randomized clinical trial, 64 chronic HD patients (32 men and 32 women with a mean age of 57.5 ± 15.6 years) were divided into case and control groups, with 32 patients in each group. The case group received systemic antibiotic and a lock of catheters with 60% ethanol and the control group received only systemic antibiotic. The results were evaluated after three weeks of treatment. The success rate of clearing infection in group A (29 patients) and group B (18 patients) was 90.6% and 56.2%, respectively (P = 0.002). We conclude that the significant difference in the success rate of clearing catheter infection in HD patients is due to the use of 60% ethanol-lock along with antibiotic therapy, and suggest this for routine use.