The frequency of peripheral PD-1+ TCD4+ cells is reversely associated with serum creatinine levels in recipients of kidney allografts.

The long-term survival of solid organ allografts remains a challenge for organ transplantation systems worldwide. T-cell exhaustion has been supposed to be associated with immunologic tolerance in transplantation and might reflect the immunologic status in recipients. The aim of the present study was to compare the TCD4+ cells of kidney transplant recipients with high and low serum creatinine levels for their expressions of PD-1 and TIGIT as two well-known exhaustion markers. Blood samples were taken from 20 kidney allograft recipients with serum creatinine levels above 2 mg/dL and 20 recipients with creatinine levels below 2 mg/dL. The percentages of PD-1+ CD4+ and TIGIT+ CD4+ cells were analyzed along with the evaluation of TNF-α, IFN-γ, and IL-10 release from peripheral blood mononuclear cells (PBMCs). The patients with serum creatinine levels below 2 mg/dL demonstrated a higher frequency of PD-1+ CD4+ T-cells (p = 0.003) along with lower TNF-α secretion from PBMCs (p = 0.028). The frequency of PD-1 + CD4+ T-cells was reversely correlated with the serum creatinine levels in recipients of kidney allografts (r = 0.59, p < 0.001). Besides, the MFI of TIGIT on TCD4+ cells demonstrated a trend for higher expression in patients with serum creatinine levels below 2 mg/dL (p = 0.070). The expression of PD-1+ on CD4+ T-cells demonstrated a potential for estimation of the immunologic status of the host in interaction with alloantigens. The exhaustion markers could be regarded as potential diagnostic indicators for the evaluation of immunologic tolerance in renal transplantation.

Post-COVID-19 syndrome mimicking cholangiocarcinoma: A case report.

Key Clinical Message: The differential diagnosis of post-COVID-19 syndrome is important in patients with symptoms of biliary obstruction. This patient had severe COVID-19 who underwent ERCP and mimicked cholangiocarcinoma. Abstract: Patients with severe coronavirus disease 2019 (COVID-19) manifest liver injuries with pathological changes because of lowered blood oxygen saturation, cardiac malfunction, hepatotoxic drugs during treatment, and cellular injury. This paper reports a patient with a history of severe COVID-19 who mimics cholangiocarcinoma after undergoing endoscopic retrograde cholangiopancreatography (ERCP). It was shown that differential diagnosis of post-COVID-19 syndrome is greatly important mostly in patients with symptoms of biliary obstruction.

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.

Dysregulation of immunity in COVID-19 and SLE.

The immune response plays a crucial role in preventing diseases, such as infections. There are two types of immune responses, specific and innate immunity, each of which consists of two components: cellular immunity and humoral immunity. Dysfunction in any immune system component increases the risk of developing certain diseases. Systemic lupus erythematosus (SLE), an autoimmune disease in the human body, develops an immune response against its own components. In these patients, due to underlying immune system disorders and receipt of immunosuppressive drugs, the susceptibility to infections is higher than in the general population and is the single largest cause of mortality in this group. COVID-19 infection, which first appeared in late 2019, has caused several concerns in patients with SLE. However, there is no strong proof of additional risk of developing COVID-19 in patients with SLE, and in some cases, studies have shown less severity of the disease in these individuals. This review paper discusses the immune disorders in SLE and COVID-19.

The Association of Sleep Quality and Vitamin D Levels in Hemodialysis Patients.

BACKGROUND: To date, hemodialysis (HD) is the most common therapy for chronic kidney disease (CKD) patients. However, it causes different complications such as sleep disorders. Sleep regulation is connected to vitamin D; hence, its deficiency might influence the quality and duration of sleep. This study is aimed at evaluating the correlation of sleep quality and vitamin D levels in 80 HD patients. METHODS: This cross-sectional study was performed on 80 hemodialysis patients admitted to 29 Bahman hospitals in Tabriz, Iran. Before beginning of dialysis, serum 25 (OH) D levels were assessed among patients and the sleep patterns and sleep quality of patients were accurately calculated by the Pittsburgh sleep quality index (PSQI) standard questionnaire. RESULTS: Our results showed that 22 HD patients (27.5%) had severe sleep disorders. In addition, it was found that serum levels of vitamin D had significant correlation with sleep quality (r = -0.341, p = 0.002) in general, even after adjusting confounding factors such as calcium (Ca), phosphate (P), and parathyroid hormone (PTH) level. In poor sleepers (PSQI ≤ 5), a negative correlation was observed between the levels of vitamin D and PSQI score (r = -0.397, p = 0.004). PSQI scores in the normal range of PTH (r = -0.377, p = 0.006) and in >600 pg/ml of PTH (r = -0.675, p = 0.011) had a correlation with vitamin D levels. The level of vitamin D was the single independent predictor of sleep efficiency (ß coefficient = -0.386, p = 0.001). CONCLUSION: The present project reported that the positive effect of vitamin D is associated with sleep disorder in HD patients. In future studies, normal levels of Ca and P should be considered along with normal vitamin D levels among the included patients.

The Impact of Intravenous Iron Supplementation on Hematinic Parameters and Erythropoietin Requirements in Hemodialysis Patients.

INTRODUCTION: Anemia is one of the most common complications of chronic kidney disease (CKD). As a result of the side effects of high doses of recombinant human erythropoietin (rhEPO) and the differences in the standard dose of the injectable iron, this study aimed to evaluate the effect of high and low intravenous iron supplementation on hematinic parameters and EPO requirements in patients under hemodialysis. METHODS: This multicenter, randomized, double-blind clinical trial was conducted on 60 patients with CKD admitted to Sina and 29 Bahman hospitals in Tabriz, Iran in 2019-2020 to undergo hemodialysis. In the two studied groups, low (100 mg/week) and high (400 mg/week) doses of iron were administered and subjects were followed up for 6 months. The incidence of acute myocardial ischemia, stroke, and mortality during 6 months was recorded. RESULTS: The required rhEPO dosage (mg/week) to maintain hemoglobin levels between 10 and 12 g/dL in the high-dose iron group was significantly decreased during the follow-up period (52,129.03 ± 23,810 vs. 45,760 ± 20,978.71, P ≤ 0.028). Transferrin saturation (TSAT) index had a significant upward trend after iron injection and significant correlations with the serum levels of Fe (r ≥ 0.353, P ≤ 0.007), ferritin (r ≥ 0.315, P ≤ 0.016), and total iron binding capacity (r ≥ 0.219, P < 0.050) during the follow-up period in the studied groups. CONCLUSION: High-dose intravenous iron (400 mg/week) can reduce the mean dose of rhEPO requirements and increase the TSAT index over a period of 6 months in hemodialysis patients. High-dose IV iron administration can decrease cardiovascular events in hemodialysis patients with iron deficiency anemia.

Current status of COVID-19 among hemodialysis patients in the East Azerbaijan Province of Iran.

INTRODUCTION: Management of vulnerable patients during the COVID-19 pandemic requires careful precautions. Hemodialysis patients constitute a large group of at-risk patients that not only suffer from a compromised immune system but also are at a higher risk due to frequent admission to healthcare units. Therefore, a better understanding on the pathogenesis and possible risk factors of COVID-19 in hemodialysis patients is of high importance. METHODS: A total of 670 maintained hemodialysis patients from all dialysis units of the East Azerbaijan Province of Iran, including 44 COVID-19 patients were included in the present study. Possible associations between the backgrounds of patients and the incidence of COVID-19 were assessed. Also, hemodialysis patients with COVID-19 were compared to 211 nonhemodialysis COVID-19 patients. FINDINGS: Chronic glomerulonephritis patients and those with blood group A demonstrated a higher incidence of COVID-19. On the other hand, patients with blood group AB+ and those with hypertension etiology of kidney failure demonstrated a lower incidence of COVID-19. Hemodialysis patients with COVID-19 had higher counts of polymorphonuclears (PMNs) in their peripheral blood compared to other COVID-19 patients. DISCUSSION: A better comprehension on the risk factors associated with COVID-19 in hemodialysis patients can improve our understanding on the pathogenesis of COVID-19 in different situations and help the enhancement of current therapeutics for COVID-19 in hemodialysis patients.

Dysregulated levels of glycogen synthase kinase-3ß (GSK-3ß) and miR-135 in peripheral blood samples of cases with nephrotic syndrome.

BACKGROUND: Glycogen synthase kinase-3 (GSK-3ß) is a serine/threonine kinase with multifunctions in various physiological procedures. Aberrant level of GSK-3ß in kidney cells has a harmful role in podocyte injury. METHODS: In this article, the expression levels of GSK-3ß and one of its upstream regulators, miR-135a-5p, were measured in peripheral blood mononuclear cells (PBMCs) of cases with the most common types of nephrotic syndrome (NS); focal segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis (MGN). In so doing, fifty-two cases along with twenty-four healthy controls were included based on the strict criteria. RESULTS: Levels of GSK-3ß mRNA and miR-135 were measured with quantitative real-time PCR. There were statistically significant increases in GSK-3ß expression level in NS (P = 0.001), MGN (P = 0.002), and FSGS (P = 0.015) groups compared to the control group. Dysregulated levels of miR-135a-5p in PBMCs was not significant between the studied groups. Moreover, a significant decrease was observed in the expression level of miR-135a-5p in the plasma of patients with NS (P = 0.020), MGN (P = 0.040), and FSGS (P = 0.046) compared to the control group. ROC curve analysis approved a diagnostic power of GSK-3ß in discriminating patients from healthy controls (AUC: 0.72, P = 0.002) with high sensitivity and specificity. CONCLUSIONS: Dysregulated levels of GSK-3ß and its regulator miR-135a may participate in the pathogenesis of NS with different etiology. Therefore, more research is needed for understanding the relationship between them.

Detection and Management of Common Medication Errors in Internal Medicine Wards: Impact on Medication Costs and Patient Care.

Purpose: Medication errors (MEs) are a leading cause of morbidity and mortality, yet they have remained as confusing and underappreciated concept. The complex pharmacotherapy in hospitalized patients necessitates continued report and surveillance of MEs as well as persistent pharmaceutical care. This study evaluated the frequency, types, clinical significance, and costs of MEs in internal medicine wards. Methods: In this 8-month prospective and cross-sectional study, an attending clinical pharmacist visited the patients during each physician's ward round at the morning. All MEs including prescription, transcription, and administration errors were detected, recorded, and subsequently appropriate corrective interventions were proposed during these rounds. The changes in the medications' cost after implementing clinical pharmacist's interventions were compared to the calculated medications' cost, assuming that the MEs would not have been detected by clinical pharmacist and continued up to discharge time of the patients. Results: 89% of the patients experienced at least one ME during their hospitalization. A mean of 2.6 errors per patient or 0.2 errors per ordered medication occurred in this study. More than 70% of MEs happened at the prescription stage by treating physicians. The most prevalent prescription errors were inappropriate drug selection, unauthorized drugs and untreated indication. The highest MEs occurred on cardiovascular agents followed by antibiotics, and vitamins, minerals, and electrolytes. The net effect of clinical pharmacist's contributions in medication therapy management was to decline medications' costs by 33.9%. Conclusion: The role of clinical pharmacy services in detection, prevention and reducing the cost of MEs is of paramount importance to internal medicine wards.

Therapeutic Effects of Omega-3 Fatty Acids on Chronic Kidney Disease-Associated Pruritus: a Literature Review.

Uremic pruritus remains one of the most tormenting, frequent and potentially disabling problem in chronic kidney disease (CKD) patients. However, an area of substantial etiological interest with relation to uremic pruritus is the essential fatty acids deficiency. So we performed a literature review to elucidate the efficacy of omega-3 fatty acids on uremic pruritus. This review evaluated all of the studies published in English language, focusing on the clinical effects of omega-3 fatty acids on uremic pruritus. The literature review was conducted in December 2015 and carried out by searching Scopus, Medline, Cochrane central register of controlled trials, and Cochrane database of systematic reviews. The search terms were "kidney injury", "kidney failure", "chronic kidney disease", "end-stage renal disease", "dialysis", "hemodialysis", "peritoneal dialysis", "pruritus", "itch", "skin problems", "fish oil", "omega 3", "n-3 fatty acids", "polyunsaturated fatty acids", "docosahexaenoic acid", and "eicosapentaenoic acid". Four small studies investigating potential benefits of omega-3 fatty acids on symptoms of uremic pruritus were found. Among them, three small randomized controlled trials have shown a significant improvement in pruritus symptoms (evaluated by a standard questionnaire) in CKD patients who took omega-3 supplement compared to omega-6, omega-9, and placebo supplementation. Despite numerous limitations of the studies, it is worth noting that even minor reduction in itching symptoms may be clinically significant for CKD patients. Therefore, and considering multiple health benefits of omega-3 fatty acids in advanced CKD and negligible risk profile, omega-3 intake can wisely be applied to CKD patients with uremic pruritus.