Protective Effects of L-Carnitine Against Delayed Graft Function in Kidney Transplant Recipients: A Pilot, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

OBJECTIVE: Delayed graft function (DGF) is an early complication after deceased donor kidney transplantation with significant adverse effects on graft outcomes. Ischemia-reperfusion injury during transplantation is a major cause of DGF. Tissue concentrations of carnitine, an antioxidant and regulator of cellular energy supply, decrease in the kidney following ischemia-reperfusion insult. Based on promising animal data, this study evaluated the possible protective effect of L-carnitine against DGF. DESIGN: This study is a pilot, randomized, double-blind, placebo-controlled clinical trial that was conducted on kidney transplantation patients in kidney transplant ward of Imam Khomeini hospital complex affiliated to Tehran University of Medical Sciences, Tehran, Iran. SUBJECTS: Patients older than 14 years old undergoing their first kidney transplantation from a deceased donor were evaluated for eligibility to take part in this study. Fifty-six patients were randomly assigned to L-carnitine or placebo groups. INTERVENTION: During this trial, 3 g of oral L-carnitine or placebo was administered in 3 divided doses each day for 4 consecutive days starting the day before kidney transplantation (i.e., days -1, 0, 1, and 2). MAIN OUTCOME MEASURE: The need for dialysis within the first week after transplantation, serum creatinine and urine output were assessed daily. After hospital discharge, patients were followed for 3 months regarding organ function. RESULTS: DGF incidence did not differ between the L-carnitine and placebo groups (18.51% vs. 23.8%, respectively; P = .68). Total allograft failure within 3 months after kidney transplantation happened in 6 patients in the placebo and 1 patient in the L-carnitine group (P = .05). CONCLUSION: This study showed no protective effects of oral L-carnitine supplementation against DGF occurrence recipients; however, 3-month graft loss was lower in the L-carnitine supplemented group.

Effects of omega-3 fatty acids on depression and quality of life in maintenance hemodialysis patients.

Depression and health-related quality of life (HRQoL) are closely interrelated among hemodialysis (HD) patients and associated with negative impacts on patients' clinical outcomes. Considering previous reports on clinical benefits of omega-3 fatty acids in major depression and HRQoL in other patient populations, this study examined effects of omega-3 fatty acids on depression and HRQoL in chronic HD patients. In this randomized placebo-controlled trial, 40 adult patients with a Beck Depression Inventory (BDI) score of ≥16 and HD vintage of at least 3 months were randomized to ingest 6 soft-gel capsules of either omega-3 fatty acids (180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid in each capsule) or corresponding placebo, daily for 4 months. At baseline and after 4 months, 2 questionnaires of BDI and the Medical Outcome Study 36-Item Short-Form Health Survey were completed by each patient. Although baseline BDI score was comparable between the 2 groups, it was significantly lower in the omega-3 group compared with the placebo group at the end of the study (P = 0.008). Except for mental health, social functioning, and general health, other domains of HRQoL showed significant improvement in the omega-3 group compared with the placebo group at month 4 of the study (P < 0.05 for all). Regression analysis revealed that ameliorated BDI score by omega-3 treatment had considerable role in the improvement of overall HRQoL score, physical and mental component dimensions, and score of physical functioning, role-physical, and bodily pain. Supplemental use of omega-3 fatty acids in HD patients with depressive symptoms seems to be efficacious in improving depressive symptoms and HRQoL.

The effect of omega-3 fatty acids on depressive symptoms and inflammatory markers in maintenance hemodialysis patients: a randomized, placebo-controlled clinical trial.

PURPOSE: This study was designed to investigate the effects of omega-3 fatty acids on depression and chronic inflammation in hemodialysis patients. METHOD: Fifty-four maintenance hemodialysis patients were randomized to ingest two omega-3 (each containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid) or placebo capsules, three times daily for 4 months. MAIN OUTCOME MEASURES: Beck Depression Inventory (BDI) score and serum levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and at the end of the study. RESULTS: Omega-3 supplement lowered BDI score significantly after 4 months of intervention. Among pro- and anti-inflammatory mediators, only serum ferritin level and IL-10 to IL-6 ratio showed significant changes in favor of omega-3 supplement during the study. In linear regression model adjusted for baseline values, omega-3 treatment was a significant predictor of reduced serum CRP, ferritin, and iPTH levels, and increased IL-10 to IL-6 ratio. No significant association was found between the anti-inflammatory and anti-depressant effects of omega-3 supplement. CONCLUSIONS: Supplemental use of omega-3 fatty acids decreases depressive symptoms in hemodialysis patients apart from their anti-inflammatory effects.

Effects of oral supplementation with omega-3 fatty acids on nutritional state and inflammatory markers in maintenance hemodialysis patients.

OBJECTIVE: The objective was to determine the effects of omega-3 supplementation on nutritional state and inflammatory markers of hemodialysis patients. DESIGN AND METHODS: This was a randomized, placebo-controlled trial. Adult patients undergoing maintenance hemodialysis were included. Patients with malignancy, pregnancy, concurrent inflammatory or infectious diseases, or concomitant use of any medication affecting inflammation status were excluded. The omega-3 group received 6 soft-gel capsules of fish oil (180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid in each) daily for 4 months, and the placebo group received corresponding paraffin oil capsules.Nutrition indices including body mass index; mid-arm muscle circumference; serum concentrations of albumin, prealbumin, and transferrin; and serum levels of inflammatory/anti-inflammatory markers including interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, C-reactive protein, ferritin, parathyroid hormone, and ratios of IL-10 to TNF-α and IL-10 to IL-6 were measured before and after 4 months of intervention. RESULTS: Twenty patients in the placebo and 25 patients in the omega-3 group completed the study. There were no significant changes in nutritional markers between the omega-3 and placebo groups after 4 months of intervention. Regression analysis adjusting post-treatment values of nutrition markers for baseline values, omega-3 treatment, and patients' baseline demographic and clinical data revealed that omega-3 treatment was a significant independent predictor of increased serum prealbumin level (182.53; 95% confidence interval 21.14, 511.18; P = .11). Although slight reduction of inflammatory state was observed in the omega-3 group, no significant differences were evident in the mean changes of inflammatory and anti-inflammatory markers between the 2 groups with the exception of serum ferritin level and the IL-10 to IL-6 ratio, which significantly changed in favor of omega-3 supplementation (P < .001 and P = .003, respectively). CONCLUSIONS: Omega-3 supplementation in hemodialysis patients produced a slight attenuation in systemic inflammation without any remarkable effects on nutritional markers.

Potential effects of omega-3 fatty acids on anemia and inflammatory markers in maintenance hemodialysis patients.

BACKGROUND: Anemia is a common complication among hemodialysis (HD) patients. Although intravenous iron and erythropoiesis-stimulating agents revolutionized anemia treatment, about 10% of HD patients show suboptimal response to these agents. Systemic inflammation and increased serum hepcidin level may contribute to this hyporesponsiveness. Considering the anti-inflammatory properties of omega-3 fatty acids, this study aimed to evaluate potential role of these fatty acids in improving anemia and inflammation of chronic HD patients. METHODS: In this randomized, placebo-controlled trial, 54 adult patients with HD duration of at least 3 months were randomized to ingest 1800 mg of either omega-3 fatty acids or matching placebo per day for 4 months. Anemia parameters including blood hemoglobin, serum iron, transferrin saturation (TSAT), erythropoietin resistance index, and required dose of intravenous iron and erythropoietin, and serum concentrations of inflammatory/anti-inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, C-reactive protein (CRP), hepcidin, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and after 4 months of the intervention. RESULTS: 45 subjects (25 in the omega-3 and 20 in the placebo group) completed the study. No significant changes were observed in blood hemoglobin, serum iron, TSAT, and required dose of intravenous iron in either within or between group comparisons. Additionally, erythropoietin resistance index as well as required dose of intravenous erythropoietin showed no significant change in the omega-3 group compared to the placebo group. Although a relative alleviation in inflammatory state appeared in the omega-3 group, the mean differences of inflammatory and anti-inflammatory markers between the two groups did not reach statistically significant level except for IL-10-to-IL-6 ratio and serum ferritin level which showed significant changes in favor of omega-3 treatment (P <0.001 and P = 0.003, respectively). CONCLUSION: Omega-3 fatty acids relatively improved systemic inflammation of chronic HD patients without any prominent benefits on anemia. However, future well-designed studies on larger number of patients may determine utility of omega-3 fatty acids in HD patients with respect to inflammation and anemia.

Nighttime Blood Pressure Abnormalities in Iranian CKD Patients: Necessity to Perform Ambulatory Blood Pressure Monitoring.

INTRODUCTION: Ambulatory blood pressure monitoring (ABPM) is a valuable tool for detecting abnormalities in nighttime blood pressure (BP), including non-dipping and nighttime hypertension. These abnormalities are independent predictors of a poor prognosis in patients with chronic kidney disease (CKD). The aim of our study  was to analyze ABPM data and evaluate nighttime BP abnormalities in an Iranian CKD population. METHODS: This cross-sectional study was conducted on sixty two patients at stages III and IV of CKD who were referred to a nephrology clinic in Tehran, Iran. The patients were classified as either dippers (19.4%) or non-dippers (80.6%), as well as nighttime normotensives (38.7%) or hypertensives (61.3%), based on ABPM  data and in accordance with 2023 ESC/ESH guidelines. We compared demographic data, estimated glomerular filtration rate (eGFR), and daytime BP levels among these groups. RESULTS: The mean age of patients was 56.34 years, with 61.1% of them being male. Daytime pulse pressure was significantly greater in non-dippers compared to dippers (52.67 vs. 44 mmHg, P = .02). We found a significant correlation between the extent of BP dipping and eGFR (R = 0.281, P = .02). Systolic and diastolic daytime BP levels were significantly higher in individuals with nighttime hypertension. Diabetic patients were more likely to be non-dippers and have nighttime hypertension. After adjusting for age, diabetes mellitus, and daytime pulse pressure in a multivariable model, we determined that eGFR independently predicted the  extent of BP dipping. CONCLUSION: Our results showed that both non-dipping and nighttime hypertension are highly prevalent in CKD patients, but they have distinct contributing factors. The eGFR was identified as an independent predictor of BP dipping, whereas nighttime BP levels were primarily determined by daytime BP levels. DOI: 10.52547/ijkd.7559.

Transcriptomic analysis of human cytomegalovirus to survey the indirect effects on renal transplant recipients.

Post-transplant human cytomegalovirus (HCMV) viremia has been linked to adverse "indirect effects" among transplant patients. HCMV-created immunomodulatory mechanisms could be associated with the indirect effects. OBJECTIVE: In the present study, the RNA-Seq whole transcriptome of renal transplant (RT) patients was analyzed to seek the underlying pathobiologic pathways associated with the long-term indirect effects of HCMV. METHODS: To investigate the activated biological pathways in HCMV infection, total RNA was extracted from PBMCs of 2 RT patients with active HCMV and 2 RT patients without infection and then were sequenced using RNA-Seq. The resulted raw data were analyzed by conventional RNA-Seq software to determine the Differentially Expressed Genes (DEGs). Afterward, Gene Ontology (GO) and pathway enrichment analyses were conducted to determine the enriched pathways and biological processes by DEGs. Eventually, the relative expressions of some significant genes were validated in the twenty external RT patients. RESULT: The analysis of RNA-Seq data related to RT patients with HCMV active viremia led to the identification of 140 up-regulated and 100 down-regulated DEGs. KEGG pathway analysis revealed the enrichment of DEGs in IL18 signaling, AGE-RAGE signaling pathway in diabetic complications, signaling by GPCR, Platelet activation, signaling and aggregation, Estrogen signaling pathway and signaling by Wnt due to HCMV infection. The expression levels of six genes involved in enriched pathways including F3, PTX3, ADRA2B, GNG11, GP9, HBEGF were then verified using RT-qPCR. The results were in consistent with RNA-Seq resultsoutcomes. CONCLUSION: This study specifies some pathobiological pathways which are activated in HCMV active infection and could be linked to the adverse indirect effects caused by HCMV infection in transplant patients.

Alteration in body water compartments following intermittent fasting in Ramadan.

Concerning the health outcomes of intermittent fasting in Ramadan, loss of fat-free mass (FFM) and changes in the content of body water are of paramount importance. In this study, we aimed to assess the concomitant alterations in body water compartment and composition following Ramadan fasting in healthy individuals. We conducted an open-label cohort with longitudinal follow-up, involving 73 healthy medical staff who planned to fast for at least 20 consecutive days during Ramadan. The primary outcomes of the cohort were changes in parameters related to body composition and water content, which were measured using bioelectrical impedance analysis by InBody S10 (InBody, Seoul, South Korea). Based on the results, the participants' weight decreased significantly by approximately 1,030 g after the fasting period (p < 0.001). There was a significant reduction in the fat mass of an average 828 g (p < 0.001), which accounted for more than 80% of the weight loss. The decline in FFM was not significant (190 g; p = 0.234). The amount of total body water (TBW) and extracellular water (ECW) did not change, while intracellular water (ICW) decreased significantly by about 160 mL (p = 0.027). A strong correlation was observed between the reduction of phase angle and the increase in ECW/TBW ratio (R = -0.71, p < 0.001). Overall, our findings revealed a minimal amount of weight loss after Ramadan fasting, which was mainly due to the loss of fat mass. The parallel decrease in ICW and phase angle indicated impaired cell membrane integrity, with subsequent movement of water from the intracellular to the extracellular compartment.

Frequency of CD39+, LAG3+, and CTLA4+ Regulatory T Cells in Two Different Immunosuppressive Protocols in Renal Allograft Recipients (Sirolimus vs Mycophenolate mofetil): A Cohort Report.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: it seems that both treatment regimen protocols with a low dose ATG induction therapy may be clinically applicable in kidney transplant recipients.

Discordance Between Using Estimated and Measured Glomerular Filtration Rate for Drug Dosing in Kidney Transplant Recipients.

INTRODUCTION: Estimating glomerular filtration rate (eGFR) using different formulas is common clinical practice for evaluating kidney function and drug dosing. But, the performance of available eGFR equations is questionable during early days after kidney transplantation. METHODS: This study compared the performance of three common eGFR equations (Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) in relation with measured GFR (mGFR) using clearance of Tc-99m-diethylenetriaminepentaacetic acid, 7 to 10 days post kidney transplantation. Agreement of mGFR and different eGFR equations in the staging of kidney function and dosing of 8 common antimicrobials were assessed. RESULT: Thirty kidney and 5 simultaneous pancreas-kidney transplant recipients were included. CG applying total body weight (CGTBW) had the lowest bias (-12 mL/min/ 1.73 m2) and the highest percentage of estimation within 30% of mGFR (71.4%). MDRD showed the best precision (13.14 mL/min/ 1.73m2) and linear correlation with mGFR. CKD-EPI and MDRD acted better than CG for staging the level of kidney function. CGTBW had the lowest discordance rate with mGFR for antimicrobials dosing (33.6%). Discordance rates of drug dosing between mGFR and eGFR formulas were greater for drugs that have higher dosing levels such as (val)-ganciclovir (≥ 54.3%). CONCLUSION: Until developing more accurate methods for estimating kidney function during first 1 to 2 weeks after kidney transplantation, CGTBW method is suggested for drug dose adjustment and MDRD or CKD-EPI equation for the staging of kidney function in these patients, keeping in mind that these formulas underestimate the level of kidney function in new transplant recipients.

The effect of aerobic and resistance exercise training on the health related quality of life, physical function, and muscle strength among hemodialysis patients with Type 2 diabetes.

INTRODUCTION: Diabetic patients who undergo hemodialysis commonly suffer from reduction of both exercise capacity and muscle strength. These factors may have a negative effect on health related quality of life (HRQoL) and physical function. We investigated the effect of aerobic and resistance exercise training on the HRQoL, physical function, and muscle strength among hemodialysis patients with Type 2 diabetes. METHODS: Twenty-eight diabetic patients who were on hemodialysis in the Milad Hospital (Tehran, Iran) were recruited for the study. Subjects were randomized into control (n = 13) and exercise training groups (n = 15). The exercise training group performed combined aerobic and resistance exercise training at moderate intensity (11-15/20 on the Borg scale) during hemodialysis treatment, 3 times a week for 8 weeks. The primary outcomes consisted of physical function measured by a 6-min walk test (6MWT), HR-QoL measured by the Short Form Health Survey (SF-36), and lower limb muscle strength measured using a hand-held Digital Dynamometer. RESULTS: The 6MWT distance increased significantly in the exercise training group (36%). Bilateral hip flexor strength (right, 24.5%; left, 30.4%) and abductor strength (right, 27.6%; left, 25.2%) decreased significantly in the non-exercising control group but no significant change was found in the exercise group (P > 0.05). There were no significant changes in any of the 8 generic subscales of HR-QoL neither in the exercise training group nor controls following an 8- week study. CONCLUSIONS: 8 weeks of combined aerobic-resistance exercise training among diabetic hemodialysis patients seem to be effective in improvement of physical function and lower limb muscle strength.

Comparison of Oral and Intravenous N-acetyl Cysteine in Preventing Contrast Nephropathy.

INTRODUCTION: Despite high rates of morbidity and mortality in patients with contrast-induced nephropathy (CIN), there is no consensus regarding prevention of this well-known complication of contrast media use. One agent that has been widely used in this regard is N-acetyl cysteine (NAC). Nevertheless, its efficacy is still controversial. The aim of this study was to assess the efficacy of NAC, both in the oral and intravenous forms, for the prevention of CIN. METHODS: This study is a double-blind randomized placebo controlled clinical trial. We randomized 434 adult patients with chronic kidney disease (constant serum creatinine ≥1.5 mg/dL) who were candidates for coronary angiography/plasty. The patients were categorized into three groups. One group received 1,200 mg NAC intravenously half an hour before the procedure and oral placebo starting 3 days before angiography. The second group received oral NAC 600 mg twice daily for 3 days, starting the day before the intervention and intravenous placebo half an hour before intervention. The third group received both oral and intravenous placebo. CIN was defined as a 25% relative increase in serum creatinine from baseline value, 48 h after use of contrast medium. RESULTS: Of the 434 patients, 149 received intravenous NAC, 145 received oral NAC, and the remaining 140 received placebo. The incidence of CIN in the three groups was 6.1%, 7.6%, and 10.8%, respectively (p = 0.34). CONCLUSION: In patients with chronic kidney disease, neither intravenous nor oral NAC is superior to placebo for preventing CIN.

Association Between Pre-Transplant Magnesemia and Post-Transplant Dysglycemia in Kidney Transplant Recipients.

BACKGROUND: Serum magnesium (Mg) status in kidney transplant recipients has been a center of attention in the past few years. Current evidence suggests an association between pre-transplant hypomagnesemia and post-transplant hyperglycemia. OBJECTIVE: The purpose of this study was to assess the associations of pre-transplant magnesemia with blood glucose disturbances within 6 months post-kidney transplantation. METHODS: In this retrospective cohort, 89 first-time kidney transplant recipients with 6 months of follow-up were included. None of the participants had a positive history of rejection, pre-transplant history of diabetes mellitus or fasting plasma glucose ≥ 100 mg/dL. RESULTS: Post-transplant diabetes mellitus (PTDM) and impaired fasting glucose (IFG) 6 months post-transplant was found in 7.9% and 41.6% of the study group, respectively. The mean pre-transplant serum Mg level was 1.92 ± 0.30 mg/dL in the study population (n = 89), and it was significantly lower in IFG (n = 37) and IFG/PTDM (n = 44) groups compared to normoglycemic (n = 45) recipients (1.83 ± 0.31 mg/dL vs. 2.00 ± 0.27 mg/dL, P = 0.008, and 1.84 ± 0.31 mg/dL vs. 2.00 ± 0.27 mg/dL, P = 0.012, respectively). Patients with serum Mg less than 1.9 mg/dL were nearly 2.6 times more likely to develop IFG or IFG/PTDM within 6 months post-transplant (P = 0.044 and P = 0.040, respectively). CONCLUSIONS: Pre-transplant hypomagnesemia may be considered a risk factor for developing post-transplant glycemic disturbances, and patients with lower pre-transplant Mg concentration could be at a higher risk for developing IFG.

Association Between CYP3A5 Genetic Polymorphisms with Tacrolimus Dose Requirement and Allograft Outcomes in Iranian Kidney Transplant Recipients.

INTRODUCTION: Tacrolimus is the cornerstone of immunosuppressive therapy in organ transplantation with variable inter-individual pharmacokinetics. This study assessed the relationship between CYP3A5/3A4 polymorphisms and tacrolimus dose requirement as well as 6-month transplant outcomes in Iranian kidney transplant recipients. METHODS: In this prospective study, 110 adult kidney transplant recipients treated with tacrolimus were genotyped for the presence of common SNPs: rs776746: A > G (CYP3A5*3). Patients who carried at least one CYP3A5*1 allele were known as CYP3A5 expressers while those who were CYP3A5*3/*3 homozygotes were classified as CYP3A5 non-expressers. RESULTS: The daily tacrolimus dose was significantly higher and tacrolimus dose adjusted trough levels (C/D ratio) was significantly lower in CYP3A5 expressers compared with non-expressers (P < .05). Although the incidence of clinically suggested acute allograft rejection was significantly higher (OR = 0.365 [95% CI: 0.14 - 0.93]; P < .05) and median time to first acute rejection was sooner among CYP3A5 expressers compared with non-expressers (12.17 vs. 26.83 days, P < .05); however, estimated glomerular filtration rate, incidence of biopsy proven acute rejection and delayed graft function and 6-month patients' and grafts' survival did not differ between the two groups. CONCLUSION: CYP3A5 genetic polymorphism is significantly associated with required tacrolimus dose. After achieving desired tacrolimus blood level, although some transplant outcomes such as the incidence of clinically suggested acute rejection and time to first rejection were different between CYP3A5 expressers and non-expressers, however, other clinical outcomes did not differ between groups. Therefore, it is not the time to routinely assess kidney transplant recipients for CYP3A5 genetic polymorphism before transplantation.

Development of a Simple Risk Score Model to Predict Renal Artery Stenosis.

BACKGROUND/AIMS: Renal artery stenosis (RAS) is a known cause of secondary hypertension and renal failure. Although renal artery angiography is the gold standard for diagnosing RAS, a simple method to estimate if patients will develop RAS is required. The aim of this retrospective study was to develop a simple risk score to predict significant RAS. METHODS: Four thousand one hundred seventy-seven patients who underwent renal angiography between 2002 and 2016 at Tehran Heart Center were included. Significant RAS was defined as narrowing of the renal artery by at least 70%. Multiple predictors of the RAS were determined using multivariable logistic regression with a backward elimination method. The scoring system obtained from the final model was presented as nomogram. The possible nonlinear effect of continuous variables was evaluated using restricted cubic splines. Overfitting of the final model was assessed applying the tenfold cross-validation method. Model performance was checked using calibration plot as well as Hosmer-Lemeshow goodness of fit test, and area under the receiver operating characteristics (ROC) curve. RESULTS: The prevalence of RAS was 14.1%. Female sex (OR [95% CI]: 1.53 [1.26-1.85]), hypertension (OR [95% CI]: 1.38 [1.08-1.77]), estimated glomerular filtration rate (OR [95% CI]: 0.98 [0.97-0.98]), body mass index (OR [95% CI]: 0.97 [0.95-0.99]), and age (OR [95% CI]: 1.01 [1.00-1.02]) were determined as the multiple predictors of RAS. The area under the ROC curve of the final predictive model was 0.702 (95% CI: 0.679-0.725). CONCLUSION: This model assesses the risk of RAS using available information. This model can be used for both clinical and research purposes.

Comparing the Effect of Immediate versus Delayed Initiation of Tacrolimus on Delayed Graft Function in Kidney Transplant Recipients: A Randomized Open-label Clinical Trial.

OBJECTIVE: Delayed graft function (DGF) is an early complication after kidney transplantation with negative impact on allograft outcomes. This study assessed the effect of delayed initiation of tacrolimus as a nephrotoxic drug, on DGF occurrence and allograft function. METHODS: This randomized, open-label clinical trial was conducted on kidney transplant recipients with the age of at least 14 years who underwent the first kidney transplantation from deceased or living donor. Patients were randomly allocated to immediate (n = 26) or delayed tacrolimus (n = 27) groups. All patients received thymoglobulin as induction therapy and similar maintenance immunosuppression including tacrolimus, mycophenolate, and prednisolone with the difference in the time of initiation of tacrolimus either on the day of transplantation (immediate tacrolimus group) or day 3 after transplant (delayed tacrolimus group). FINDINGS: DGF incidence (46.15% vs. 37.04%; P = 0.501) and duration (9.75 ± 6.41 vs. 8.6 ± 6.16 days; P = 0.675) were not different between the immediate and delayed tacrolimus groups. Estimated creatinine clearance using Cockcroft-Gault equation (63.14 ± 18.81 vs. 58.19 ± 19.42 mL/min in immediate and delayed tacrolimus groups respectively; P = 0.373) and estimated acute rejection-free survival were also comparable between the groups over the 3 months of follow-up. Compared with the immediate group, the delayed tacrolimus group showed higher estimated 3-month grafts' survival (100% vs. 84.27%; P = 0.072). CONCLUSION: Delayed initiation of tacrolimus after kidney transplantation under the umbrella of thymoglobulin induction did not result in either lower incidence or duration of DGF or improved the level of graft function in kidney transplant recipients but non-statistically significant increased 3-month grafts' survival.

Cytopenia Occurrence in Kidney Transplant Recipients Within Early Post-transplant Period.

OBJECTIVE: This study assessed incidence, severity, and time to occurrence of drug-induced leukopenia/thrombocytopenia within 1st month after kidney transplantation. METHODS: This cross-sectional study was conducted on newly kidney transplant recipients from two hospitals, Iran. Patients with thrombocytopenia due to acute antibody-mediated rejection were excluded from the study. Demographic, clinical, and laboratory data of patients within the 1st month after transplantation were collected. FINDINGS: Of 213 patients, 14.1% and 66.2% experienced leukopenia and thrombocytopenia, respectively. Cytopenia happened more commonly among patients with thymoglobulin-containing regimen (for leukopenia: 24.6% vs. 0%, P < 0.001; for thrombocytopenia 84.4% vs. 41.8%, P < 0.001). Most leukopenia patients experienced Grades 1 and 2 of leukopenia (46.6% and 40% of patients). Most thrombocytopenic patients showed Grade 1 of thrombocytopenia (78.7%). Cumulative dose of thymoglobulin did not differ between patients with and without leukopenia (5.57 ± 1.13 vs. 5.9 ± 1.96 mg/kg; P = 0.613) or with and without thrombocytopenia (5.87 ± 1.86 vs. 5.56 ± 1.38 mg/kg; P = 0.29). Cytopenia were more common among recipients from deceased compared with from living donors (91.3% vs. 8.7% for leukopenia patients, P = 0.001; 69.9% vs. 33.1% for thrombocytopenia, P = 0.02). More patients with kidney from deceased donors received thymoglobulin in their immunosuppressive regimen (82% vs. 37%; P < 0.001). The median time to leukopenia and thrombocytopenia were 3 days and 1 day, respectively. CONCLUSION: Among immunosuppressive and prophylactic antimicrobial agents, thymoglobulin is more related to cytopenia; therefore, thymoglobulin dose reduction is recommended as the first intervention to manage cytopenia without need for reduction of its cumulative dose. The higher prevalence of cytopenia among recipients from deceased donors may be related to the higher use of thymoglobulin in these patients.

Rituximab-Related Late-Onset Neutropenia in Kidney Transplant Recipients Treated for Antibody-Mediated Acute Rejection.

OBJECTIVES: Kidney transplant is a new area for use of rituximab, which is being used to treat acute antibody-mediated rejection or as an induction agent in ABO- or HLA-incompatible grafts. We report on late-onset neutropenia in rituximab-treated kidney transplant recipients with antibody-mediated rejection. MATERIALS AND METHODS: This observational prospective study was performed on kidney transplant recipients with clinically suspicious or biopsy-proven antibody-mediated rejection treated with plasmapheresis plus intravenous immunoglobulin with (cases) or without (controls) rituximab. RESULTS: Compared with none of the controls, 4 of 6 patients (66.7%) in the rituximab-treated group experienced late-onset neutropenia 35 to 93 days after the last dose of rituximab. The course of neutropenia was complicated by endocarditis in 1 patient, resulting in his death just because of a lack of valvular surgery. CONCLUSIONS: Increased use of rituximab to treat antibody-mediated rejection among kidney transplant recipients requires attention to its late-onset adverse event, neutropenia. Although asymptomatic in some patients, kidney transplant recipients treated concomitantly with plasmapheresis and mycophenolate mofetil are predisposed to hypogammaglobulinemia, and monitoring of patients for infections is required.

Fibroblast Growth Factor 23 in Postrenal Transplant: An Often Forgotten Hormone.

Fibroblast growth factor 23 is likely to be the most important regulator of phosphate homeostasis, which mediates its functions through fibroblast growth factor receptors and the coreceptor Klotho. In addition to reducing expression of the sodium-phosphate cotransporters NPT2a and NPT2c in the proximal tubules, fibroblast growth factor 23 inhibits renal 1α-hydroxylase and stimulates 24-hydroxylase and appears to reduce parathyroid hormone secretion in short-term studies. Fibroblast growth factor 23 synthesis and secretion by osteocytes and osteoblasts are upregulated through 1,25-dihydroxyvitamin D3 and through an increased dietary phosphate intake. Recent studies have indicated that a low-protein diet and calcium deficiency reduce circulating fibroblast growth factor 23 levels, but magnesium deficiency increases fibroblast growth factor levels. Drugs such as phosphate binders, bisphosphonate, and estrogens have various effects on circulating fibroblast growth factor 23 levels. The high cardiovascular disease event rates and mortality associated with elevated levels of this hormone may be due to various effects on the cardiovascular system, including left ventricular hypertrophy, arterial stiffness, vascular calcifications, endothelial dysfunction, and increased levels of inflammatory markers. In addition, elevated levels of this hormone may contribute to mineral bone metabolism disorders and to patient and allograft survival after renal transplant. Here, we discuss the effects of fibroblast growth factor 23 on adverse renal, bone, and cardiovascular outcomes after kidney transplant.

Potential Effects of Omega-3 Fatty Acids on Insulin Resistance and Lipid Profile in Maintenance Hemodialysis Patients: a Randomized Placebo-Controlled Trial.

INTRODUCTION: Insulin resistance (IR), a risk factor for cardiovascular disease and all-cause mortality, is prevalent among maintenance hemodialysis patients. Effects of omega-3 fatty acids on IR in hemodialysis patients have not been well understood. This study aimed to determine the effects of omega-3 fatty acids on IR and serum lipids of hemodialysis patients. MATERIALS AND METHODS: Fifty-four adult patients on hemodialysis were randomly assigned to receive either 1800 mg of omega-3 fatty acids or placebo daily for 4 months. Serum concentrations of glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, insulin, leptin, and adiponectin were measured at baseline and after 4 months of the intervention. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance and 2 adipokine-based measures of IR, including the leptin-adiponectin ratio and homeostasis model assessment corrected by adiponectin. RESULTS: Mean differences of serum C-reactive protein, insulin, leptin, and adiponectin concentrations did not show significant difference between the two groups following 4 months of intervention. Fasting serum glucose and low-density lipoprotein cholesterol were not significantly influenced by omega-3 supplementation, either. Serum triglyceride, total cholesterol, and high-density lipoprotein cholesterol levels significantly decreased in the omega-3 group (P = .02, P = .03, and P < .001, respectively). None of the indirect indexes of IR showed significant changes at the end of the study in either the omega-3 or placebo group. CONCLUSIONS: Supplemental use of omega-3 fatty acids showed some beneficial effects on lipid profile of hemodialysis patients without any improvement in IR.