Humoral immunity of BBIBP-CorV (Sinopharm) in kidney transplant recipients: Is it time to revise vaccination strategies.

BACKGROUND: The mortality of coronavirus disease 2019 (COVID-19) is high in transplant patients, and effective vaccination is aimed to reduce severe disease and mortality. METHODS: We conducted a cross-sectional study to evaluate humoral and cellular response to two 4-µg doses of BBIBP-CorV vaccine in 100 kidney transplant recipients, using anti-spike IgG, total anti-receptor-binding domain, neutralizing antibody (Ab) level (enzyme-linked immunoassay), and interferon-gamma release assay (IGRA). RESULTS: Seroconversion was evaluated 85.84 ± 30.72 days after the second dose. Note that, 58% of all and 43.05% of infection-naïve participants have developed at least one of the tested antibodies. IGRA was positive in 30.7% of tested transplant recipients. Sixty percent of the participants had either humoral or cellular responses to COVID-19. Only age was independently linked to seropositivity of any degree after vaccination (p < .05). COVID-naïve patients older than 60 years developed significantly less neutralizing Abs. (p = .011). Six patients developed mild COVID infection more than a month after the second dose of the vaccine (54.5 ± 20.8 days). No vaccine-related adverse effects were reported, except self-limited mild to moderate fever and injection site pain. CONCLUSION: BBIBP-CorV vaccine can be used safely in kidney transplant recipients, although impaired cellular and humoral immunity necessitate adjustments in vaccination strategies, like higher (8-µg doses), fourth booster dose, or boost with different platform vaccine.

Agreement between the results of tuberculin skin test and Interferon-Gamma Release Assays in renal transplant candidates.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Low rate of COVID-19 pneumonia in kidney transplant recipients-A battle between infection and immune response?

BACKGROUND: With COVID-19 pandemic, concerns about kidney transplant recipients are rising. However, the incidence, clinical course, outcome, and predictive factors of disease severity are obscured. METHODS: We describe clinical and laboratory manifestations, radiologic findings, clinical course, and finally outcome of kidney transplant recipients with COVID-19 pneumonia. RESULTS: Of 2493 kidney transplant recipients under follow-up in our clinic, 19 cases (4 cases diagnosed based on radiologic findings) were admitted. The mean age of patients was 47.6 ± 12.4 years, and the mean time from transplantation was 115.6 ± 70.3 months. Lymphopenia and eosinopenia were 84.2% and 78.9%, respectively. Nine patients did not survive the hospital course. History of acute rejection during the past 12 months, diabetes, higher N/L ratio, lower platelet count, elevated N/L x CRP, higher levels of LDH, positive D-dimer, higher troponin, and prolonged PT were associated with mortality. Among patients with positive COVID-19 test, history of acute rejection, low platelet count, and positive D-dimer were associated with poor outcome. Treatment with cyclosporine was associated with better clinical outcome. CONCLUSIONS: Low rate of admission in transplant recipients specially in the very first years of transplantation might be due to protective effects of immunosuppressive agents against cytokine storm or modification of immunity function. We suggest evaluation of T-cell number, function, and cytokine profile as a guide to manage COVID-19 mainly in patients with higher risk of mortality.

The appropriate dose of thymoglobulin induction therapy in kidney transplantation.

BACKGROUND: Thymoglobulin is used effectively as an induction agent in kidney transplantation, but there is no consensus on the optimal dose. In order to delineate the safest effective dose, an open-labeled randomized clinical trial was designed. METHODS: In this study, 90 adult kidney transplant recipients (KTR) were randomized before transplantation in three groups to receive thymoglobulin: Arm A (4.5 mg/kg in 3 days), Arm B (4.5 mg/kg single bolus dose), and Arm C (6 mg/kg in 3 days). Renal function, infections, and rate of readmissions were evaluated during the first post transplantation year. RESULTS: Ninety adult kidney recipients were enrolled (51% deceased donor). No significant statistical difference was found in acute rejection episodes or type of rejection between these groups, although patients in Arm A showed more severe histopathologic changes according to Banff 2013 criteria, in renal biopsies (P=.03). At the first month after transplantation serum Cr was lower (P=.001) and GFR was higher (P=.04) in Arm A, but there was no significant difference among the three groups at 3, 6, and 12 months post-transplant. CONCLUSION: Although all regimens showed the same efficacy regarding the rate of rejection episodes, 3-day 4.5 mg/kg Thymoglobulin had significantly fewer complications.

Tacrolimus Intrapatient Variability on Graft Outcomes in Adherent Renal Transplantation Patients: A Cross-Sectional Study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. DOI: 10.52547/ijkd.7815.

Investigating the role of uric acid and uric acid-to-creatinine ratio as a predictive factor of chronic obstructive pulmonary disease exacerbation in 2019.

INTRODUCTION: Serum uric acid has been suggested as an independent marker of oxidative metabolism in chronic obstructive pulmonary disease (COPD), a disease with significant social, health, and economic burden. Therefore, we aimed to investigate the role of this factor in COPD exacerbation. METHODS: We investigated 20- to 70-year-old patients who were admitted due to COPD exacerbation (acute phase) or presented to the pulmonary clinic for follow-up (non-acute phase). Correlation of uric acid and uric acid-to-creatinine ratio (UCR) with multiple factors and their predictive performance for more exacerbations and acute phase of COPD was investigated (receiver operating characteristic [ROC] analysis). RESULTS: Overall, 63 patients were enrolled in this study, of whom 79.4% were men. Acute-phase group encompassed 79.4% of the population with a greater rate of heavy smoking and average exacerbation in a year (p-value = 0.009 and <0.001). The mean of uric acid and UCR was 5.6 (SD, 2.35) and 4.4 (SD, 1.9) in the total population, respectively, and were significantly higher in the acute phase and patients with frequent exacerbations (FE ≥ 3 exacerbations a year), p-value <0.05. The area under the curve (AUC) of ROC analysis showed a high performance of uric acid and UCR for predicting acute phase (0.84 [95%CI, 0.73-0.96] and 0.86 [0.74-0.98]), FE (0.72 [0.60-0.85] and 0.75 [0.63-0.87]), and FE among acute-phase patients (AUC, 0.63 [0.46-0.79] and 0.66 [0.50-0.81], respectively). CONCLUSION: Uric acid and UCR could be invaluable predictors of frequent exacerbation and the acute phase of COPD. Therefore, they might be applicable in evaluating the severity and progress of the disease.

Measured GFR in Donor Selection, to Do or Not to Do? That is the Question.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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%.  DOI: 10.52547/ijkd.7271.

Immunogenicity and Safety of SpikoGen, an Adjuvanted Recombinant SARS-CoV-2 Spike Protein, as a Heterologous Third Booster Dose in Kidney Transplant Patients: A Single-arm Clinical Trial.

PURPOSE: Studies have found that immunocompromised patients have suboptimal responses to COVID-19 vaccines, leading to approval of a need for booster doses in this population. SpikoGen® is a subunit recombinant spike protein vaccine combined with Advax-CpG55.2™ adjuvant to protect against COVID-19. Previous clinical trials found this vaccine to be tolerable, immunogenic, and efficacious in reducing the risk of COVID-19, including severe disease. However, the effects of this vaccine have not been assessed in immunocompromised patients. This study sought to assess the immunogenicity and safety of the SpikoGen vaccine as a third booster dose in patients undergoing kidney transplant who were receiving immunosuppressive therapy and had received their primary vaccination based on an inactivated whole virus platform (Sinopharm). METHODS: This single-arm trial was performed with 43 patients undergoing kidney transplant. The participants received a single booster dose of the SpikoGen vaccine 1 to 3 months after primary vaccination with 2 doses of the Sinopharm vaccine. Immunogenicity assessments were performed at baseline and 30 days after the booster dose. The primary outcomes were seroconversion rates of anti-S1 and surrogate virus neutralizing antibodies. Safety outcomes included the incidence of solicited and unsolicited adverse events in the 7 days and 1 month after the booster dose, respectively. FINDINGS: The SpikoGen vaccine induced positive humoral and cellular responses 30 days after the booster dose in those patients who were seropositive or seronegative after 2 primary doses of the Sinopharm vaccine. Thirty days after the SpikoGen vaccine booster, seroconversion rates were 35.29% (95% CI, 19.75%-53.51%) to anti-S1 and 29.41% (95% CI, 13.27%-46.57%) to surrogate neutralizing antibodies. The most common local and systemic reported solicited adverse events were injection site pain and fatigue, which were largely mild and transient. No serious adverse events were reported. IMPLICATIONS: A single booster dose of SpikoGen vaccine given 1 to 3 months after primary vaccination with 2 doses of Sinopharm vaccine induced positive humoral and cellular immune responses in immunosuppressed patients undergoing renal transplant, thereby achieving spike antibody levels predictive of protection. This study was performed as a single-center study, and it will be important for future large multicenter studies to extend these results to other immunocompromised patient groups.

Dietary intakes of fiber and magnesium and incidence of metabolic syndrome in first year after renal transplantation.

OBJECTIVE: Considering the high prevalence of metabolic syndrome (MetS) and the associated cardiovascular disease mortality after renal transplant, and considering that the lack of prospective studies regarding the role of fiber and magnesium in MetS prevention after transplant precludes definitive recommendations, we prospectively evaluated the potential role of fiber and magnesium intake in the incidence of MetS at 1 year after renal transplantation. DESIGN: This was a prospective cohort study. SETTING, PARTICIPANTS, AND MEASUREMENTS: We included 160 recipients of kidney transplant (100 men and 60 women) aged over 18 years who were free of MetS or diabetes at time of transplant, and followed these patients for 1 year. METHODS: The usual dietary intakes were assessed with a Willett-format 168-item food-frequency questionnaire. We defined MetS according to modified Adult Treatment Panel III guidelines. We categorized participants by tertiles of dietary fiber and magnesium. To determine associations of fiber and magnesium intake with MetS incidence 1 year posttransplant, we used multivariable logistic regression. RESULTS: After controlling for potential confounders, including baseline body mass index and energy intake, subjects within the highest tertile of fiber intake had a lower odds ratio for incident MetS (odds ratio, 0.41; 95% confidence interval, 0.08 to 0.99; P < .05 for trend) than those in the lowest tertile. There was no significant overall association between magnesium intake and MetS. CONCLUSIONS: These findings support current dietary recommendations to increase intakes of fiber-rich foods as a primary preventive approach against MetS and cardiovascular disease, which are very prevalent after renal transplant.

COVID-19 Rapid Guideline in Kidney Transplant Recipients.

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.

Omega-3 in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis, Effects on Inflammatory Markers and Lipid Profile.

INTRODUCTION: CKD is one of the most prevalent entities associated with high morbidity and mortality. Most of the patients with renal diseases, particularly patients undergoing dialysis, suffer from cardiovascular disease and it is necessary to employ appropriate strategies to prevent and manage this complication. The aim of this study was to evaluate the anti-inflammatory effects of omega-3 in patients undergoing CAPD. METHODS: Nineteen CAPD patients with certain inclusion and exclusion criteria enrolled in this study. Omega-3 capsules with a dose of 1 g/d up to three months, were administrated. Some inflammatory markers such as ESR, CRP, HS-CRP, IL-6, MDA, and homocysteine were measured in three phases. In addition, lipid profile including triglyceride, cholesterol, LDL, and HDL were measured. RESULTS: Results of this study showed that CRP, HS-CRP, and homocysteine levels increased insignificantly (P > .05) whereas, MDA level was increased significantly (P < .05). ESR and IL-6 levels both decreased but did not show any statistically significance (P > .05). Results of lipid profile also suggested that none of the lipid levels changed significantly (P > .05). CONCLUSION: It is necessary to design large trials in order to understand clear effects of omega-3 on inflammatory markers in PD patients. In addition, the results of this current pilot study should be interpreted with caution.

Adding Colchicine to the Antiretroviral Medication - Lopinavir/Ritonavir (Kaletra) in Hospitalized Patients with Non-Severe Covid-19 Pneumonia: A Structured Summary of a Study Protocol for a Randomized Controlled Trial.

OBJECTIVES: Colchicine is a well-known drug, which has been used for years to treat a wide range of rheumatic and inflammatory disorders. It helps break the cycle of inflammation through diverse mechanisms including reducing Intereukin-6, Interleukin-8, Tumour Necrosis Factor-alpha besides controlling oxidative stress pathways which all are important and pathologic components in the clinical course and outcome of patients infected with COVID-19. This study aims to assess the anti-inflammatory effects of colchicine in non-severe hospitalized COVID-19 patients. TRIAL DESIGN: Prospective, randomized (1:1 ratio), double blind study with parallel group design. PARTICIPANTS: Hospitalized patients with positive nasopharyngeal swab for COVID-19 infection (RT -PCR) and lung Computed tomography scan involvement compatible with COVID-19 pneumonia. The patients are not severely hypoxic, do not need intubation or invasive oxygenation. EXCLUSION CRITERIA: known hypersensitivity to colchicine; known hepatic failure; estimated glomerular filtration rate (eGFR)<30 ml/min/1.73m2 (by the CKD-EPI Creatinine Equation for Glomerular Filtration Rate (GFR) which estimates GFR based on serum creatinine. ; kidney transplant recipients, using Digoxin, QTc >450 msec. Participants will be recruited from inpatients at Labbafinejad Meidcal Center , Tehran, Iran. INTERVENTION AND COMPARATOR: Eligible enrolled patients will be randomized into two groups. Group A will receive the antiretroviral Lopinavir/Ritonavir (Kaletra) while group B will receive Lopinavir/Ritonavir (Kaletra) + Colchicine 1.5 mg loading then 0.5 mg twice daily orally. All patients in both groups will receive the same amounts of essential minerals, vitamins as antioxidants, and antibiotics. Patients of both groups will be treated under optimal treatment based on the CDC and WHO guidelines and national consensus proposed in Iran including the same dosages of Lopinavir/Ritonavir, antibiotics, trace elements and antioxidants while only in group-B patients Colchicine will be added on top of this protocol. MAIN OUTCOMES: Primary: Time for clinical improvement and lung CT score changes 14 days after treatment. Secondary: 14 days after treatment - C-Reactive Protein test x Neutrophil to Lymphocyte Ratio , Interleukin-6, malondialdehyde (MDA) levels reduction - Percentage of patients who require supplemental Oxygen - Mean hospital stay length RANDOMISATION: Patients will be allocated to each group (ratio 1:1) by using an online randomization tool: http://www.graphpad.com/quickcalcs/index.cfm BLINDING (MASKING): This will be a double-blind study in which participants and those assessing the final outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Regarding the pandemic crisis and our center capacity to hospitalize confirmed COVID-19 patients, a total of 80 patients was found to be logical to be randomized into two groups of 40- patients. TRIAL STATUS: Recruitment is ongoing. Recruitment began on 20/03/2020 and the date by which the recruitment is anticipated to be completed is 30/05/2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04360980, registered 24/04/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Mediterranean diets are associated with a lower incidence of metabolic syndrome one year following renal transplantation.

Considering the high prevalence of metabolic syndrome and its association with cardiovascular mortality, we prospectively evaluated the role of diet in the incidence of metabolic syndrome in renal transplant recipients. Our prospective cohort of 160 adult renal allograft recipients was followed for 1 year and had no existing metabolic syndrome or diabetes mellitus. Routine dietary intakes were assessed with food-frequency questionnaires, and metabolic syndrome was defined according to the Adult Treatment Panel III guidelines. We identified 3 major patterns by factor analysis, consisting of those recipients predominantly consuming fats and sugars, those predominantly consuming whole grain, and the Mediterranean diet. When analyzed by multivariable logistic regression and after controlling for potential confounders, subjects in the highest tertile of scores for the Mediterranean diet had a significantly lower odds of metabolic syndrome than those in the lowest tertile. Subjects in the highest tertile of scores for consuming fats and sugars had significantly greater odds of metabolic syndrome compared with those in the lowest tertile. Our study shows that the Mediterranean dietary pattern is associated with a reduced risk of metabolic syndrome in renal transplant recipients.

Effects of short-term atorvastatin use in patients with calcium stones: A randomized placebo-controlled clinical trial.

Purpose: A few experimental and observational studies have reported that atorvastatin prevents calcium oxalate stone formation. Our study is the first to investigate the effect of atorvastatin on 24-hour urinary metabolites, urinary malondialdehyde (U-MDA) (an oxidative stress marker) and urinary neutrophil gelatinase-associated lipocalin (U-NGAL) (a renal tubular injury marker) in patients with calcium stones and hyperoxaluria. Materials and Methods: This randomized, double-blind, placebo-controlled, parallel-group clinical trial included 32 adults with recurrent calcium stone formation and hyperoxaluria. All participants received a 3-month course of either atorvastatin (20 mg/d) or placebo of an identical shape. Both groups received the usual nutritional care based on the European Association of Urology guidelines. Results: Twenty-eight participants completed the study. Serum levels of total and low-density lipoprotein cholesterol decreased in the atorvastatin group, and these changes were significantly different between groups (p<0.001). No statistically significant differences were observed between intergroup changes of the 24-hour urinary metabolite analysis, the U-MDA to creatinine ratio and the U-NGAL to creatinine ratio. Conclusions: Atorvastatin administration at a dose of 20 mg/d for 3 months did not affect 24-hour urinary metabolite, U-MDA and U-NGAL levels in recurrent calcium stone formers. However, this study could not disprove the preventive role of atorvastatin in kidney stone formation. Future studies should consider a larger sample size, longer follow-up, different drug doses, and measurements of multiple biomarkers of oxidative stress and tubular injury.

Invasive fungal infections following renal transplantation: a review of 2410 recipients.

BACKGROUND: Organ transplant recipients, on long-term graft preserving immunosuppressive therapy, are at increased risk for life threatening opportunistic fungal infections. MATERIAL/METHODS: In order to evaluate the incidence of invasive fungal infections (IFIs) and to identify the most common fungal pathogens, we conducted a retrospective study on 2410 ESRD cases undergone living kidney transplantation in three transplant centers between 1998 and 2008. RESULTS: IFIs developed in 21 recipients (0.87%), 17 male and 4 female. Their immunosuppression was cyclosporine based. The mean age of patients was 48+/-10 (ranged from 32 to 67) years. Diagnosis was made by radiological findings, positive blood or bronchoalveolar lavage (BAL) cultures and tissue biopsies. Mucormycosis was the most common cause of IFIs in population studied (n=11), followed by disseminated candidiasis (n=4), aspergillosis (n=3), nocardiasis (n=2) and histoplasmosis (n=1). Pulmonary involvement was dominant (47.6%). The treatment was successful in only 10 patients and the rest died. CONCLUSIONS: In our large series of kidney transplant recipients, mucormycosis was found to be the most common cause of invasive fungal infection. Prompt diagnosis and treatment are necessary to avoid the life threatening complications and may greatly improve prognosis.

Contrast-induced Nephropathy: Essentials and Concerns.

The administration of radiocontrast media may lead to kidney injury, known as contrast-induced nephropathy, which is reversible in most cases, but its development may be associated with adverse outcomes. This review article provides recommendations for the prevention of contrast nephropathy.

C3 Glomerulonephritis With Multiple Mutations in Complement Factor H.

Complement C3 glomerulopathy refers to a disease process in which abnormal control of complement activation or degradation results in predominant C3 fragment deposition within the glomerulus and causes glomerular damage. Abnormal control of the complement alternative pathway is a well-established risk factor for the occurrence of C3 glomerulonephritis. It is the first reported case in Iran with multiple mutations in complement factor H, with one of these mutations we have expected in hemolytic uremic syndrome rather than C3 glomerulopathy Genetic analysis showed that the molecular abnormalities of factor H led to complement factor H malfunction that were polymorphous and not restricted to the C-terminal domains of the protein.

Effect of Lactobacillus Rhamnosus on serum uremic toxins (phenol and P-Cresol) in hemodialysis patients: A double blind randomized clinical trial.

BACKGROUND: Uremic toxins such as p-cresol and phenol are suggested to be associated with higher mortality in hemodialysis patients. The aim of this study was to investigate the effects of probiotics on some serum uremic toxin levels in hemodialysis patients. METHODS: Patients undergoing hemodialysis in a university dialysis center were enrolled in this randomized controlled double blind clinical trial. The patients received probiotic (Lactobacillus Rhamnosus) for duration of 4 weeks. All data were presented as the mean ± SD. Statistical analyses were performed by SPSS statistical software. Paired t-test was used to compare pre- and post-treatment p-cresol levels. P values less than .05 were considered statistically significant. RESULTS: A total of 42 hemodialysis patients (32 male and 10 female) were enrolled in this study. The mean ± SD age of the patients in Lactobacillus Rhamnosus and placebo groups were 57.05 ± 13.96 and 59.67 ± 15.04 years, respectively. Values of uremic toxins before treatment did not differ statistically between groups but they were significantly lower in Lactobacillus Rhamnosus group compared with placebo group (P < .05). Total Phenol and p-cresol levels were associated with sodium, energy, carbohydrate, fat and protein intake and fiber consumption, accompanying by hemodialysis hours per week in linear regression analyses. CONCLUSIONS: This study demonstrated that probiotics could be a promising target in hemodialysis patients with the capability of decreasing serum phenolic uremic toxins in this population. TRIAL REGISTRATION: IRCT20154182017N21 Date:09/12/2016.

New Insights Into Pathophysiology, Diagnosis, and Treatment of Renovascular Hypertension.

Renovascular disease includes renal artery stenosis, renovascular hypertension, and azotemic renovascular disease (ischemic nephropathy). Renovascular hypertension is defined as an elevated blood pressure caused by renal hypoperfusion, usually resulting from anatomic stenosis of the renal artery and activation of the renin-angiotensin system. It accounts for 1% to 2 % of all cases of hypertension in the general population and 5.8 % of secondary hypertension, but it plays a major role in treatable causes of hypertension in the young individuals. Although renovascular stenosis is a common and progressive disease in patients with atherosclerosis, it is a relatively uncommon cause of hypertension in patients with mild hypertension. In contrast, renal artery stenosis is more frequent in certain high-risk populations. Early diagnosis of renovascular hypertension and timely implementation of appropriate therapeutic procedures ensures optimum control of blood pressure, prevents ischemic nephropathy progression, and prevents the development of cardiovascular morbidity and mortality in the hypertensive patient population. As with most complex disorders, management decisions must be highly individualized for patients with renovascular disease. It is essential to consider renal arterial disease as one aspect of atherosclerotic disease.

Incidence of Ganciclovir Resistance in CMV-positive Renal Transplant Recipients and its Association with UL97 Gene Mutations.

Human cytomegalovirus (CMV) remains the most common infection affecting organ transplant recipients. Despite advances in the prophylaxis and acute treatment of CMV, it remains an important pathogen affecting the short- and long-term clinical outcome of solid organ transplant recipient. The emergence of CMV resistance in a patient reduces the clinical efficacy of antiviral therapy, complicates therapeutic and clinical management decisions, and in some cases results in loss of the allograft and/or death of the patient. Common mechanisms of CMV resistance to ganciclovir have been described chiefly with the UL97 mutations. Here we evaluate Incidence of ganciclovir resistance in 144 CMV-positive renal transplant recipients and its association with UL97 gene mutations. Active CMV infection was monitored by viral DNA quantification in whole blood, and CMV resistance was assessed by UL97 gene sequencing. Six mutations in six patients were detected. Three patients (2.6%) of 112 patients with history of ganciclovir (GCV) treatment had clinical resistance with single UL97 mutations at loci known to be related to resistance (including mutations at codon 594, codon 460, and codon 520). three patients who were anti-CMV drug naïve had single UL97 mutations (D605E) without clinical resistance. Our results confirm and extend our earlier findings on the specific mutations in the UL97 phosphotransferase gene in loci that have established role in ganciclovir resistance and also indicate that clinical ganciclovir resistance due to UL97 gene mutations is an issue in subjects with history of with ganciclovir treatment. D605E mutations remains a controversial issue that needs further investigations.