An inverse association between serum vitamin D levels with the presence and severity of impaired nerve conduction velocity and large fiber peripheral neuropathy in diabetic subjects.

Diabetic neuropathy (DN) is the most common complication of diabetes mellitus (DM) and also the major cause of morbidity and mortality in diabetic patients. There have been recent speculations that circulating 25-hydroxyvitamin D (25(OH)-D) could be involved in DN development and progression. This study explored the association between serum 25(OH)-D and DN in diabetic subjects by performing strict matching of possible confounders. Overall, 33 diabetic subjects with DN and 29 controls matched in terms of age, sex, BMI, height and disease duration entered this study. Nerve conduction velocity (NCV) was performed to determine the existence and severity of large fiber neuropathy. 25(OH)-D had significantly lower value in DN group (21.2 ± 11.5 vs. 13.5 ± 5.1 ng/mL, P = 0.001). None of the other observed variables showed a significant association with existence and severity of DN. After adjustment for all studied variables, serum vitamin D had an independent and inverse association with both DN presence and severity, as each 1 ng/mL increase in serum 25(OH)-D was correlated with 2.2 and 3.4 % decrease in the presence and severity of NCV impairment, respectively. While adjusted for demographic variables, comorbidities and treatment of DM, our results imply that decreased levels of circulating 25(OH)-D may contribute to increased risk of large fiber neuropathy in type 2 diabetic subjects.

Expression of Programmed Cell Death 1 and Helios Genes Correlates With rs872071A>G and rs12203592C>T Single-Nucleotide Polymorphisms of InterferonRegulatory Factor 4 in Patients with T-Cell-Mediated Rejection of Renal Allograft.

OBJECTIVES: Acute T-cell-mediated rejection of the renal allograft is a serious posttransplant challenge that requires administration of high-dose immunosuppressive drugs with considerable side effects; therefore, specific targeting of T-cell responses may improve both prevention and treatment of T-cell-mediated rejection. A potential candidate for this purpose is interferon regulatory factor 4 because of its implication in differentiation and function of T cells. Our aim was to evaluate the frequency of the rs872071A>G and rs12203592C>T single-nucleotide polymorphisms of the interferon regulatory factor 4 gene and association of these 2 polymorphisms with the gene expression of programmed cell death 1 and Helios in patients with T-cell-mediated rejection versus stable recipients. MATERIALS AND METHODS: Sixty recipients with T-cell- mediated rejection and 60 age-matched and sex-matched stable recipients were recruited. Two single-nucleotide polymorphisms of interferon regulatory factor 4 gene, as well as the expression of programmed cell death 1 and Helios genes in peripheral blood mononuclear cells, were investigated with real-time polymerase chain reaction. RESULTS: Programmed cell death 1 gene expression was reduced in patients with T-cell-mediated rejection versus stable recipients (P = .03). The frequency of rs872071A>G and rs12203592C>T single-nucleotide polymorphisms showed no significant difference between groups. Presence of the rs12203592C>T single-nucleotide polymorphism was directly correlated with the expression of programmed cell death 1 gene (P = .049), and rs872071A>G positivity was directly correlated with Helios gene expression (P = .008), which suggests an inhibitory role for interferon regulatory factor 4 on programmed cell death 1 and Helios molecules. CONCLUSIONS: Programmed cell death 1 gene expression was lower in patients with T-cell-mediated rejection versus stable recipients. Low-expressing singlenucleotide polymorphisms of interferon regulatory factor 4 could enhance the downstream gene expression of programmed cell death 1 and Helios immunoregulatory molecules. Therefore, specific inhibition of interferon regulatory factor 4 may promote tolerance induction in the allograft.

Vitamin C and kidney transplantation: Nutritional status, potential efficacy, safety, and interactions.

BACKGROUND AND AIM: There are several observational and interventional studies regarding the advantages of sufficient serum levels of vitamin C and the evaluation of the effects of vitamin C supplementation post kidney transplantation. These studies have been put together to investigate the role of vitamin C post-kidney transplantation and make suggestions for designing future studies based on the use of vitamin C supplements or nutritional interventions among these patients. METHODS: This narrative review was done by searching in the Embase, PubMed, and SCOPUS databases. RESULTS: The results are presented in several sections as follows; nutritional status, potential protective effects, safety concerns, and medications/laboratory tests interactions of vitamin C. CONCLUSIONS: Kidney transplant recipients are prone to vitamin C deficiency, which is related to higher mortality based on several long-term observational studies. Vitamin C supplementation improves endothelial function and creatinine clearance. Vitamin C is considered as a safe supplement, however, side effects such as kidney stones, pro-oxidant effect, hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, impact on lymphocytic activity, acid-base disturbance, and increased sodium load following its administration have been reported. Interaction of vitamin C and cyclosporine is the most important interaction with post-renal transplant medications. Vitamin C also interferes with creatinine assay using Jaffe and enzymatic methods.

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.

Comparing IRF-4 Gene Expression Between Acute T cell- Mediated Rejection and Stable Renal Transplant Recipients.

INTRODUCTION: Renal transplant rejection is one of the clinical challenges, which usually requires administration of immunosuppressive drugs causing serious side effects. Therefore, invention of effective and specific therapeutics is necessary to control undesired immune responses particularly T-cell reactions to allograft. Interferon Regulatory Factor-4 (IRF-4) due to its implication on T cells differentiation and function might be targeted to treat T cell-mediated cellular rejection (TCMR). The aim of this study was to investigate the association between IRF-4 gene expression and acute TCMR, as well as to examine the correlation between IRF-4 gene expression and cellular expression of Programmed cell death-1 (PD-1) and Helios molecules. METHODS: Peripheral blood samples were obtained from 30 patients with biopsy proven acute TCMR and 30 stable recipients. IRF-4 gene expression was quantified using RT-PCR, and cellular expression of PD-1 and Helios were evaluated with flowcytometry. RESULTS: IRF-4 gene expression was significantly increased in acute TCMR patients compared with stable recipients (P < .05). Helios protein expression was slightly decreased in TCMR group but this was not statistically significant. There was a negative correlation between IRF-4 gene expression and PD-1 as well as Helios frequency in the whole studied population. CONCLUSION: IRF-4 expression increases in acute TCMR which might also lead to a diminished expression of downstream immunoregulatory molecules such as PD-1 and Helios. Therefore, specific inhibition of IRF-4 may be helpful in managing acute TCMR.

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.

Non-Hodgkin lymphoma with primary involvement of skeletal muscle.

Non-Hodgkin lymphoma usually presents with generalized lymphadenopathy, but it can also involve any part of the human body. Lymphomatous involvement of muscles is a rare presentation and has been reported to occur in only 1.1% in non-Hodgkin lymphoma. Here we, present a 32 year-old Iranian man with primary involvement of spleen, bone, bone marrow and muscle, mimicking soft tissue sarcoma; core needle biopsy of the gluteal muscle showed diffuse large B cell lymphoma.

A salty cause of cough in a 24-year-old man.

With improvement in the diagnosis and treatment of cystic fibrosis cases in recent years, the survival of these cases has been increased. On the other hand, an increasing number of cases are presented during adulthood. Here we report a 24-year-old man with a history of productive cough, bilateral paranasal sinusitis and polyps, and recurrent abdominal pain. Thoracic computed tomography revealed a bilateral scattered tree in bud pattern and some bronchiectatic changes. Semen analysis showed azoospermia. A sweat chloride test was >60 mEq/l in two occasions.

Serum visfatin is associated with type 2 diabetes mellitus independent of insulin resistance and obesity.

OBJECTIVE: The aim of this study was to evaluate the association of serum visfatin, adiponectin and leptin with 2 diabetes mellitus (T2DM) in the context of the role of obesity or insulin resistance, which is not well understood. METHODS: A total of 76 newly-diagnosed T2DM patients and 76 healthy control subjects, matched for age, body mass index (BMI) and sex ratio, were enrolled. Anthropometric parameters, glycemic and lipid profile, insulin resistance (measured by homeostasis model assessment of insulin resistance index [HOMA-IR]), leptin, adiponectin, and visfatin were assessed. RESULTS: On the contrary to adiponectin, serum leptin and visfatin levels were higher in T2DM patients compared with controls (10.07 ± 4.5, 15.87 ± 16.4, and 5.49 ± 2.4 vs. 12.22 ± 4.9 µg/ml, 8.5 ± 7.8 ng/ml and 3.58 ± 2.2 ng/ml, respectively, P<0.01). Waist circumference and BMI were correlated with leptin and adiponectin but not with visfatin. Leptin, adiponectin and visfatin all were associated with T2DM following adjusting for obesity measures. After controlling for HOMA-IR, visfatin remained as an independent predictor of T2DM (odds ratio=1.32, P<0.05). In a multiple regression analysis to determine visfatin only triglycerides and fasting glucose remained in the model (P<0.05). CONCLUSION: Elevation of visfatin in T2DM is independent of obesity and insulin resistance and is mainly determined by fasting glucose and triglycerides.