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.

Early post-operative acute kidney injury after cardiac transplantation: Incidence and predictive factors.

BACKGROUND: Heart transplantation, as a therapeutic option for patients with advanced heart failure, possesses a high rate of morbidity and mortality. One of the complications associated with this procedure is the development of postoperative acute kidney injury (AKI) MATERIAL AND METHODS: We aimed to evaluate the incidence of early postoperative AKI and the need for continuous renal replacement therapy (RRT) after heart transplantation. Data of 126 patients who underwent heart transplantation from January 2015 to November 2019 were collected. Statistical analysis was performed to identify the predictors of postoperative AKI. RESULTS: Out of 126 patients, 74 (58.7 %) developed AKI and 13 (10%) required RRT after transplant. Independent predictors of AKI are shown to be factors associated with surgical procedures such as graft ischemic time as were previous cardiac operation, administered Voluven (starch) dose > 400 ml, and transfusion of more than four blood units. CONCLUSION: Our findings suggest that modifiable factors exist that can affect the risk of developing AKI following heart transplantation.

Possible association of vitamin D status with lung involvement and outcome in patients with COVID-19: a retrospective study.

PURPOSE: Vitamin D deficiency has been reported as a key factor in the development of infectious diseases such as respiratory tract infections and inflammatory processes like acute respiratory distress syndrome. However, the impact of vitamin D on the severity and outcome of COVID-19 is still not fully known. Herein, we aimed to evaluate the prognostic role of serum vitamin D concentration on the extent of lung involvement and final outcome in patients with COVID-19. METHODS: Seventy-three subjects with confirmed diagnosis of COVID-19 were investigated in this study. The patients had been admitted to our academic hospital from February 28, 2020 to April 19, 2020. Demographic and clinical data, serum 25(OH)D levels, and findings of initial chest computed tomography were recorded. Linear and binary logistic regression, cox regression and ROC curve tests were used for statistical analysis. RESULTS: The mean age of patients was 55.18 ± 14.98 years old; 46.4% were male. Mean serum 25(OH)D concentration was significantly lower in the deceased (13.83 ± 12.53 ng/ mL compared with discharged patients (38.41 ± 18.51 ng/mL) (P < 0.001). Higher levels of 25(OH)D were associated with significantly less extent of total lung involvement (ß = - 0.10, P = 0.004). In addition, vitamin D deficiency [25(OH) D < 25 ng/mL] was associated with a significant increase in the risk of mortality (hazard ratio = 4.15, P = 0.04). CONCLUSION: This study suggests that serum vitamin D status might provide useful information regarding the clinical course, extent of lung involvement and outcome of patients with COVID-19. However, further studies with larger sample size are needed to confirm these findings.

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.

Relationship Between Malnutrition Inflammation Score and Dietary Fat Quality Indices with Cardiovascular Diseases in Hemodialysis Patients.

INTRODUCTIONS: Malnutrition-inflammation-atherosclerosis is an independent risk factor and the most significant cause of death in dialysis patients, accounting for about 50% of deaths in the population. Moreover, the high incidence of cardiovascular-induced mortality in patients with end-stage kidney disease cannot be fully attributed to cardiovascular (CVD) risk factors only. Studies suggest that risk factors such as oxidative stress, inflammation, bone disorders, vascular stiffness, and energy protein loss are closely related to CVD and its associated mortality in these patients. Moreover, dietary fat is a crucial factor in CVD. This study focused on determining the relationship between malnutrition-inflammation and fat quality indicators among CKD patients. METHODS: This study was conducted on 121 hemodialysis patients aged 20 to 80 years in a teaching hospital affiliated to Hashminejad kidney center in Tehran, Iran during 2020 to 2021. Data on general characteristics and anthropometric indices were collected. The malnutrition-inflammation score was assessed by using MIS and DMS questionnaires and dietary intake was measured by a 24-hour recall questionnaire. RESULTS: Out of 121 hemodialysis patients participating in the study, 57.3% were male and 42.7% were female. Anthropometric demographic characteristics showed no significant difference among diverse groups with heart disease (P > .05). There was no significant relationship between malnutrition-inflammation and heart disease indices in hemodialysis patients (P > .05). Furthermore, there was no correlation between the dietary fat quality index and heart disease (P > .05). CONCLUSION: In this study, there was no significant relationship between the malnutrition-inflammation index and the dietary fat quality index with cardiac disease in hemodialysis patients. Further studies are needed to have a tangible conclusion.  DOI: 10.52547/ijkd.7280.

Clinical outcomes of kidney recipients with COVID-19 (COVID-19 in kidney recipients).

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused significant mortality since late 2019. Patients undergoing kidney transplantation (KT) are prone to COVID-19 due to immunosuppressive drug use and various comorbidities such as hypertension and diabetes. METHODS: One hundred thirty-three KT recipients with COVID-19 were included in this retrospective cohort study. Hospital mortality was considered a primary outcome, while acute kidney injury (AKI) was considered a secondary outcome. Demographic information, maintenance immunosuppression, medical history, laboratory information, and echocardiographic and electrocardiography results of patients were recorded. Patients were also followed for 2 months post-discharge for post-COVID-19 symptoms, readmission, and transplant function. RESULTS: Regarding the primary outcome of the 133 patients, 13 died and 120 survived. The deceased patients were significantly older (median age, 64 vs. 50.5 years; p = 0.04) and had a significantly higher median serum creatinine level (p = 0.002) and lower median glomerular filtration rate (p = 0.010) than patients who survived. The incidence of AKI was 47.3%, more common in deceased patients (p = 0.038) than in patients who survived. Troponin levels were significantly higher in deceased patients and those with AKI (p = 0.0004 and p = 0.039, respectively) than in patients who survived and those without AKI. A multivariable Cox regression analysis revealed that older age (adjusted hazard ratio, 1.13; 95% confidence interval, 1.01-1.27) and AKI (adjusted hazard ratio, 3.43; 95% confidence interval, 1.34-8.79) were associated with in-hospital mortality. CONCLUSION: In conclusion, kidney recipients with COVID-19 had a higher mortality rate than the general population, with a higher prevalence in older individuals and those who experienced AKI during hospitalization than in patients who survived and those without AKI.

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.

The relationship between CT value and clinical outcomes in renal patients with COVID-19.

PURPOSE: Concomitant kidney diseases raise the mortality rate due to the SARS-CoV-2 virus as an independent factor. Although a qualitative PCR test's result is sufficient for diagnosis, Cycle threshold value may present relevant information to the physicians in providing faster treatment in patients with chronic conditions, including kidney diseases, to prevent morbidity and subsequent mortality. Thus, the present study was conducted to determine the relationship between the Cycle threshold value and clinical outcomes in renal patients with the coronavirus 2019. METHODS: This retrospective study was conducted on renal patients with the coronavirus 2019 infection admitted to Labbafinejad Hospital in Tehran, the capital of Iran, within a period of one year, from late February 2020 to February 2021. Data were collected per the prepared checklist. Cycle threshold values were measured by performing PCR on nasopharynx and oropharynx swab samples of patients. RESULTS: According to the adjusted analysis, having high viral load increased the odds of in-hospital mortality (aOR = 11.65, 95% CI 3.93-34.54), ICU admission (aOR = 5.49, 95% CI 2.16-13.97), and invasive ventilation (aOR = 7.18, 95% CI 2.61-19.74). Having high viral load also increased the odds of O2 therapy (aOR = 3.08, 95% CI 0.79-12.01), although the difference was not statistically significant (P = 0.105). CONCLUSION: Cycle threshold value was a significant predictor of mortality in renal patients. Nevertheless, further studies are required on how to render optimal use of the Cycle threshold value, given that the quality of the test sample and the different groups of patients under study affect the effectiveness of this marker in predicting disease severity.

The relationship between T-cell infiltration in biopsy proven acute T-cell mediated rejection with allograft function and response to therapy: A retrospective study.

AIM: To evaluate the degree of CD3, CD20, Th17, and Tregs infiltration in kidney biopsy of the patients with acute cellular rejection and the possible relation with graft outcome. MATERIALS AND METHODS: In this retrospective study, fifty patients with Acute T Cell-Mediated Rejection (ATCMR) were enrolled. Previous and one year clinical follow-up data were collected. The kidney specimens were evaluated for infiltration of CD3, CD20, FOXP3, and Th17 with IHC. According to the serum creatinine level in one-year follow-up of the patients after rejection therapy and function of the transplanted organ from the day admitted into the hospital, they were respectively categorized in Stable graft function versus impaired graft function; appropriate response to treatment versus failure to response. RESULTS: Treg (P = 0.96) and Th17 (P = 0.24) cells were more in the unstable group than the stable group, but the difference wasn't significant. On the other hand, the FOXP3/Th17 ratio was higher in the stable group (P = 0.22). Moreover Treg (P = 0.1) and Th17 (P = 0.15) were higher in failure to response group, but FOXP3/Th17 was higher in proper response group (P = 0.8). CONCLUSION: From the results, it can be concluded that TH17 infiltration has a more significant effect on graft outcome and response to rejection therapy.

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.

Prognostic Value of Blood Pressure Responsiveness in Hemodialysis for Cardiovascular Mortality, Development of A New Predictive Equation.

INTRODUCTION: Cardiovascular disease is considered as the main cause of mortality and morbidity in HD-patients and AS is a fundamental cause. This study was conducted to investigate whether intradialytic BP changes can use as a surrogate clinical marker. METHODS: Fifty-one patients on maintenance hemodialysis, for at least 12 hours per week, were included in a prospective cohort study. Intradialytic BP was measured using validated automated device. PWV was performed to assess Augmentation Index (AIx) as marker of arterial stiffness. All measurements were repeated in alive individuals after 5 years of follow-up. Patients with 5% reduction of intradialytic BP were considered as HD-responsive and Several statistical analyses were employed based on responsiveness to HD. RESULTS: After 5-year follow-up the findings demonstrated BP response to HD was an important and independent determinant of mortality (P < .05). Augmentation index (AIx) (P < .05), heart rate (P < .05), and calcium phosphate product (P < .05) as well as log PTH (P < .05) were significantly different between two responsive and non-responsive to HD. Pearson's Correlation studies revealed a significant relationship between the BP response to HD and heart rate (r = 0.4, P < .05), LVEF (r = -0.4, P < .05) and PTH (r = -0.3, P < .05). BP response to HD and log-PTH remained significant even after age and gender adjustment (P < .05). CONCLUSION: BP-response to HD can use as a clinical and surrogate marker of AS which is significantly associated with mortality and LVEF. Arterial stiffness and intradialytic BP can predict the changes in Ejection Fraction (EF). DOI: 10.52547/ijkd.6810.

Continuous Renal Replacement Therapy with Low Dose Systemic Heparin in Liver Transplant Recipients.

INTRODUCTION: Continuous renal replacement therapy (CRRT) is an effective dialysis method in critically ill patients. Citrate and heparin are commonly used as anticoagulants to prevent premature circuit clotting. The aim of this study was to evaluate the safety and efficacy of using low dose systemic heparin while on CRRT in liver transplant recipients. METHODS: We retrospectively evaluated and analyzed data from 29 liver transplant recipients undergoing CRRT in the postoperative course in this cross-sectional study. Numerous variables were recorded, such as coagulation parameters, duration of intensive care unit (ICU) stay, duration of dialysis, heparin dose, circuit life span, and anticoagulant complications. RESULTS: Out of 29 recipients, there were 16 (55%) female and 13 (45%) male. All participants underwent whole organ liver transplantation with a median age of 45 years. Overall, 98 successful dialysis sessions were recorded in this study with a mean circuit life span of 36 hours. Mean ± SD duration of CRRT for each recipient was 4.8 ± 3.1 days. The median total dose of heparin used for each recipient was 25,000 units , and the median dose of heparin per-day for each recipient was about 3,300 units. There were no episodes of anticoagulant-related bleeding complications. Thirteen (13.2%) episodes of premature circuit clotting occurred. We found a significant association between the first dose and total dose of heparin usage with first postoperative INR and PTT level (P < .05, P < .05, P < .001, and P < .05). CONCLUSION: In liver transplant recipients, low dose heparin during CRRT for patency of circuit is well tolerated.

Biomarkers in Primary Membranous Nephropathy, A Guide to Precision Medicine.

Membranous nephropathy (MN) as one of the most common glomerulonephritis still relies on an invasive procedure of kidney biopsy for precise recognition. Over the recent past years noninvasive methods using wide range of biomarkers have been developed in order to diagnose and estimating the final prognosis of MN. Plasma, urine and tissue are readily accessible specimens for identification of these biomarkers. In order to utilize a single biomarker or a panel of them for detection of a specific entity, many factors should taking into consideration like the accuracy, precision, and validity, accompanying with being available and cost effective. This review is focused on recently developed biomarkers and their application on the diagnosis besides determining the prognosis of MN. The clinical utilities and limitations of each biomarker are discussed in details.

Perspective of 20 Years Hemodialysis Registry in Iran, on the Road to Progress.

End-stage renal disease (ESRD) is a foremost health issue with major consequences in various parts of the world. In Iran, the prevalence/incidence of ESRD has increased during the past decades. The economic burden of ESRD treatment on patients, their families, and the whole healthcare system is huge as well. Hence ESRD is considered emerging public health problem in developing countries, including Iran, requiring short- and longterm changes in healthcare policies. Developing a national registry system for dialysis patients in Iran now enables us to summarize certain clinical characteristics of these patients and compares the present situation with the late 1990s when dialysis services just began to expand in the country. In this paper, the authors provide information regarding the process of establishing dialysis registry in Iran along with the report of the output of such a registry. Focusing on such an important measure in the whole country of around along with the data that it has produced is a gateway to further progress.

Time-Varying Covariates and Risk Factors for Graft Loss in Kidney Transplantation.

OBJECTIVES: The present study was designed to evaluate the factors involved in long-term graft survival in recipients of kidney transplantation. MATERIALS AND METHODS: We reviewed 755 Iranian adult recipients who underwent kidney transplantation at Shahid Labbafinejad Medical Center in Tehran, Iran. Patients were followed for 5 years after transplantation. The primary outcome was the time between transplantation and graft loss. Using Cox regression, we studied the effect of time-independent variables (recipients' age and sex, donors' age, and type of donor), time-dependent covariates (body mass index [BMI], systolic blood pressure, diastolic blood pressure, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels, proteinuria and serum creatinine level), and immunosuppressive drugs on graft loss 60 months after transplantation. The results are presented as the hazard ratio (HR) with 95% confidence intervals. RESULTS: Result from Cox proportional hazards model showed that the HR of graft loss was 1.62 (95% CI: 1.03-2.54) in cadaveric donor compared with living donor kidney recipients. The HR of graft loss for recipient age was 1.02 (95% CI: 1.002-1.030). Moreover, according to obtained results, the risk of losing functional transplant increased for each mg/dL rise in serum creatinine at least 9% and at most 40%. Our results also showed that 1 unit increase of BMI has at least a 2% and at most a 15% decremented effect on the hazard ratio of graft loss. CONCLUSIONS: Having lower levels of creatinine and receiving a kidney from a younger living donor were associated with a decreased risk of graft loss. Graft loss is more likely to occur in patients with lower BMI.

A Noninvasive Urine Metabolome Panel as Potential Biomarkers for Diagnosis of T Cell-Mediated Renal Transplant Rejection.

Acute T cell-mediated rejection (TCMR) is a major complication after renal transplantation. TCMR diagnosis is very challenging and currently depends on invasive renal biopsy and nonspecific markers such as serum creatinine. A noninvasive metabolomics panel could allow early diagnosis and improved accuracy and specificity. We report, in this study, on urine metabolome changes in renal transplant recipients diagnosed with TCMR, with a view to future metabolomics-based diagnostics in transplant medicine. We performed urine metabolomic analyses in three study groups: (1) 7 kidney transplant recipients with acute TCMR, (2) 15 kidney transplant recipients without rejection but with impaired kidney function, and (3) 6 kidney transplant recipients with stable renal function, using 1H-nuclear magnetic resonance. Multivariate modeling of metabolites suggested a diagnostic panel where the diagnostic accuracy of each metabolite was calculated by receiver operating characteristic curve analysis. The impaired metabolic pathways associated with TCMR were identified by pathway analysis. In all, a panel of nine differential metabolites encompassing nicotinamide adenine dinucleotide, 1-methylnicotinamide, cholesterol sulfate, gamma-aminobutyric acid (GABA), nicotinic acid, nicotinamide adenine dinucleotide phosphate, proline, spermidine, and alpha-hydroxyhippuric acid were identified as novel potential metabolite biomarkers of TCMR. Proline, spermidine, and GABA had the highest area under the curve (>0.7) and were overrepresented in the TCMR group. Nicotinate and nicotinamide metabolism was the most important pathway in TCMR. These findings call for clinical validation in larger study samples and suggest that urinary metabolomics warrants future consideration as a noninvasive research tool for TCMR diagnostic innovation.

Nephrologist, Pulmonologist Connection: From Bench to Bedside, Mini Review.

Whether working in intensive care unit or not as nephrologists we are all facing complicated cases with different sign and symptoms. Among them is a category of patients presenting with concomitant respiratory and kidney failure called pulmonary renal syndrome, which needs mutual connection between nephrologist and pulmonologist closely for the best decision-making. Although this is not a common entity, still associated with high rate of morbidity and mortality involving diffuse alveolar hemorrhage and glomerulonephritis. Understanding the updates in the field of management would benefit both the patients and caregivers providing clear answers to present obstacles.