Coronavirus disease 2019 vaccine in pediatric post-kidney transplantation.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of persons worldwide. Many vaccines have been developed; however, their efficacy in pediatric solid organ transplant recipients is yet to be determined. METHODS: This is a prospective observational, non-interventional single-center study on the safety and efficacy of a COVID-19 vaccine (BNT162b2) in pediatric kidney transplant recipients. The primary aim of this study was to evaluate immunogenicity according to SARS-CoV-2-specific neutralizing antibody titer after two vaccine doses. The secondary aims were to investigate the safety of the vaccines, solicited local and systemic adverse reactions, incidence of COVID-19 post-vaccination, and effects on transplant graft function. Baseline investigations were conducted on pediatric renal transplant recipients, and recruited participants were advised to have the Comirnaty® mRNA vaccine according to protocol. RESULTS: A total of 48 patients (male, n = 31, 64.6%; female, n = 17, 35.4%), median age 14 [12-16] years were included, and all received two doses of the vaccine. The vaccine had a favorable safety and side-effect profile. The S-antibody titer of all patients ranged between .4 and 2,500 U/ml and was > 50 U/ml in 89% of the patients. No difference in the measured antibody immune response was noted between infected and uninfected children. No major side effects were reported. CONCLUSION: The vaccine had a favorable safety profile in 12- to 15-year-old kidney transplant recipients, producing a greater measured antibody response than that in older transplant recipients.

Comparison of the safety and immunogenicity of the BNT-162b2 vaccine and the ChAdOx1 vaccine for solid organ transplant recipients: a prospective study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resulting disease, coronavirus disease 2019 (COVID-19), has spread to millions of people worldwide. Preliminary data from organ transplant recipients have shown reduced seroconversion rates after the administration of different SARS-CoV-2 vaccination platforms. However, it is unknown whether different vaccination platforms provide different levels of protection against SARS-CoV-2. To answer this question, we prospectively studied 431 kidney and liver transplant recipients (kidney: n = 230; liver: n = 201) who received either the ChAdOx1 vaccine (n = 148) or the BNT-162b2 vaccine (n = 283) and underwent an assessment of immunoglobulin M/immunoglobulin G spike antibody levels. The primary objective of the study is to directly compare the efficacy of two different vaccine platforms in solid organ transplant recipients by measuring of immunoglobulin G (IgG) antibodies against the RBD of the spike protein (anti-RBD) two weeks after first and second doses. Our secondary endpoints were solicited specific local or systemic adverse events within 7 days after the receipt of each dose of the vaccine. There was no difference in the primary outcome between the two vaccine platforms in patients who received two vaccine doses. Unresponsiveness was mainly linked to diabetes. The rate of response after the first dose among younger older patients was significantly larger; however, after the second dose this difference did not persist (p = 0.079). Side effects were similar to those that were observed during the pivotal trials.

Diagnostic potential of interferon-gamma release assay to detect latent tuberculosis infection in kidney transplant recipients.

BACKGROUND: Latent tuberculosis (TB) infection (LTBI) is screened by using clinical assessment, tuberculin skin test (TST), chest radiography, and recently by interferon-gamma release assays (IGRA). The objective of this study was to evaluate the diagnostic potential of QuantiFERON® -TB Gold In-Tube test (QFT) for diagnosing LTBI in patients planned for kidney transplantation. METHODS: All adult patients with end-stage renal disease, evaluated for kidney transplantation in a referral center from August 2008 till May 2013, were enrolled, after consenting in a prospective, observational, non-interventional study. LTBI diagnosis was conducted by TST, chest x-ray, and clinical assessment, followed by IGRA by QFT. RESULTS: Overall, 278 patients were enrolled and kidney transplantation was performed in 173 patients. Contributed follow-up was 836.5 patient-years, and TB-free transplant duration was 478.5 patient-years. By standard methods, LTBI was diagnosed in 14 patients. Peri-transplant chemoprophylaxis was given to 53 patients, which included recipients of organs from all deceased donors and living donors with LTBI. QFT was positive in 70 patients, negative in 200 patients, and indeterminate in 8 patients. The agreement between LTBI diagnosis using standard methods and IGRA by QFT was poor (kappa: 0.089+0.046, P-value=.017). Twenty-seven of the QFT-positive patients were transplanted and only one was given isoniazid preventive therapy. None of the transplant recipients developed TB after a median follow-up of 25 months (range 2-58 months, mean 27 months). CONCLUSIONS: The agreement of the QFT with standard diagnosis of LTBI in kidney transplant recipients was poor.

The Clinical Manifestations and Disease Burden of Cystinosis in Saudi Arabia: A Single-Tertiary Center Experience.

BACKGROUND: There is a lack of regional and local evidence that describes the nature of cystinosis, a multiorgan accumulation of cystine, and its extent of organ damage. Therefore, this study aimed to determine the outcomes of cystinosis in patients who were followed up at a large tertiary care hospital. METHODS: Medical records of patients with cystinosis were retrospectively reviewed. Patients' baseline demographics, lab values, medications, comorbidities, and complications were collected and described. Univariable and multivariable logistics regression models were constructed to control for confounders and build prediction models. RESULTS: In our cohort of 39 patients, the mean age was 13.8±9.9 years. Approximately 56.4% of the patients had stunted growth, and the mortality rate was 25.6%. Regarding complications, the majority of patients developed myopathy (79.5%), end-stage renal disease (ESRD) (74.4%), and hypothyroidism (71.8%). Age (odds ratio=1.14, 95% confidence interval (95% CI): 1.012, 1.285) and stunted growth (odds ratio=6.62, 95% CI: 1.024, 42.835) were found to be predictors of renal replacement therapy and renal transplantation, respectively (p<0.047). CONCLUSION: This study on cystinosis patients reveals a high incidence of renal complications, with a significant mortality rate and common complications such as myopathy and ESRD. Age was found to be an independent risk factor for renal replacement therapy, while stunted growth predicted the need for transplantation. These findings underscore the urgency for early diagnosis, comprehensive treatment, and careful monitoring in managing cystinosis effectively.

Safety and efficacy of peginterferon-α2a plus ribavirin treatment in renal transplant recipients with chronic hepatitis C.

BACKGROUND & AIMS: Interferon (IFN)-based therapy in chronic hepatitis C virus (HCV)-infected renal transplant (RT) recipients has been associated with a high risk of acute allograft rejection (AAR) and poor efficacy. We assessed the safety and efficacy of PegIFNα-2a and ribavirin (RBV) combination therapy in HCV-infected RT recipients. METHODS: Thirty-two adult RT recipients of >12-month duration, infected with HCV genotypes 1 (62.5%) and 4 (37.5%), and significant fibrosis (Metavir ≥ F2) were recruited in an open-label trial with PegIFNα-2a 135-180 µg/week, plus RBV 200-1200 mg/day for 48 weeks, based on the estimated glomerular filtration rate. Safety assessments were performed weekly for 4 weeks, 2-weekly for 8 weeks, and 6-weekly for 36 weeks. Study end points were sustained virologic response (SVR) or development of AAR. Allograft biopsies were performed for 20% increase in creatinine from pretreatment levels, or optionally at week 12 on surveillance protocol. Renal safety was compared with matched untreated historical controls (n=31). RESULTS: None of the treated patients showed AAR when biopsied for raised creatinine (12.5%) or during surveillance (37.5%), with incremental and sustained creatinine increases occurring in 6.3% of treated patients and 16.1% of untreated controls (p=0.148), by week 72 assessment. Mean pretreatment and end-of-assessment creatinine in treated patients remained similar (106.8 ± 32.0 vs. 113.4 ± 62.8, respectively; p=0.140), while levels increased significantly in the controls (106.6 ± 35.6 vs. 142.5 ± 93.0, respectively; p=0.013). Rapid, early virologic response (EVR) and SVR occurred in 12.5%, 56.3%, and 37.5% of cases, respectively. SVR was similar in both genotypes (p=1.000). PegIFN and RBV dose reductions were required in 34.4% and 78.1%, respectively; discontinuation was required in 12.5%. Binary logistic regression identified only EVR (OR, 20.4; 95% CI: 2.2-192.6; p=0.008) as an independent predictor of SVR. CONCLUSIONS: PegIFN/RBV therapy is not associated with AAR in RT recipients at low risk for rejection but has modest efficacy in the treatment of HCV.

Outcomes of Kidney Transplantation in Older Recipients.

BACKGROUND Access to kidney transplantation is limited for elderly patients with end-stage renal disease (ESRD), who often die while on the waiting list or receive kidneys from marginal deceased donors. In our transplantation center, most donated kidneys were from younger living relatives, in whom donations to elderly outcomes were not previously studied. In this study, we aimed to determine the short- and long-term outcomes of patients aged ³65 years to justify the use of kidneys from younger donors in older recipients. We also compared the outcomes between those who received kidneys from living donors (LDs) and deceased donors (DDs). MATERIAL AND METHODS We analyzed the patients' demographic data and the 1-, 5-, and 10-year patient and graft survival rates of patients aged ≥65 years who received kidney transplants between January 2005 and December 2020. RESULTS Among 158 patients, 136 received kidneys from LD and 22 from DD. The mean age was 69 years old. In this cohort, the most common cause of ESRD was diabetes. The graft survival rates were 99%, 96%, and 94% after 1, 5, and 10 years, respectively. Patient survival was 94%, 83%, and 61% after 1, 5, and 10 years, respectively. Delayed graft function rates, 1-year patient survival, and 5- and 10-year graft survival rates were lower in the DD group. Ischemic heart disease and transplantation from DD were independent risk factors for mortality. CONCLUSIONS Our study demonstrated reasonably good patient and graft survival rates in older patients. Outcomes were better in patients who received kidneys from LD.

Mpox Perceptions and Vaccine Advocacy among the Healthcare Workers of Solid Organ Transplant Centers: A Multicenter, Cross-Sectional Survey in Saudi Arabia.

BACKGROUND: In response to the global Mpox outbreaks, this survey aimed to assess the knowledge, perceptions, and advocacy of Mpox vaccines among solid organ transplant healthcare workers (HCWs) in Saudi Arabia. METHODS: A cross-sectional survey was conducted among solid organ transplant HCWs in Saudi Arabia from 15 August to 5 September 2022. A total of 199 responses were received from participants primarily working in the kidney (54.8%) and liver (14.6%) transplant units. RESULTS: The survey found that most participants were aware of the 2022 Mpox outbreak, but the majority were more concerned about COVID-19 than Mpox. While the majority of participants thought laboratory personnel and HCWs in direct contact with Mpox patients should receive the vaccine, less than 60% believed that all HCWs should be vaccinated. Additionally, over half of the participants lacked knowledge of animal-human transmission of the virus. CONCLUSION: The results highlight the need for increased education on Mpox among transplant HCWs in Saudi Arabia, particularly regarding the virus's transmission dynamics and vaccines. This education is crucial to improve HCWs' understanding of this emerging disease, especially given their vulnerability during the COVID-19 pandemic.

Awareness, Attitudes, and Willingness: A Cross-Sectional Study of Organ Donation in Saudi Arabia.

BACKGROUND: Organ transplantation is inherently dependent on the availability of organ donors. There is a noticeable paucity of literature addressing the rates of organ donation registration and the awareness of Islamic regulations (Fatwa) regarding organ donation within Saudi Arabia. Our study aimed to evaluate the level of organ donation registration, awareness of Islamic regulations, and knowledge of the Saudi Center for Organ Transplantation (SCOT) within the Saudi society. METHODS: We conducted a cross-sectional survey from 30 March to 9 April 2023. This survey aimed to assess the awareness of Islamic (Fatwa) guidance on organ donation, the role of SCOT, and the rate of organ donation registration facilitated through the Tawakkalna app, the official health passport application in Saudi Arabia. RESULTS: Out of 2329 respondents, 21% had registered as potential deceased organ donors, despite 87% acknowledging the importance of organ donation. Awareness of the Islamic Fatwa regarding organ donation was reported by 54.7% of respondents, and 37% recognized the Fatwa's acceptance of brain death criteria. The likelihood of registration as organ donors was higher among Saudi citizens under 45 years of age, females, healthcare workers (HCWs), individuals with higher education, relatives of patients awaiting organ donations, those informed about the Islamic Fatwas, and those willing to donate organs to friends. Conversely, being over the age of 25, Saudi nationality, employment as an HCW, awareness of SCOT, and prior organ donation registration were predictive of a heightened awareness of Islamic Fatwas. However, perceiving the importance of organ donation correlated with a lower awareness of the Fatwas. Significant positive correlations were found between awareness of SCOT, awareness of Fatwas, and registration for organ donation. CONCLUSIONS: While the Saudi population exhibits a high regard for the importance of organ donation, this recognition is not adequately translated into registration rates. The discrepancy may be attributable to limited awareness of SCOT and the relevant Islamic Fatwas. It is imperative to initiate organ donation awareness campaigns that focus on religious authorization to boost organ donation rates and rectify prevalent misconceptions.

Coronavirus Disease-19: Disease Severity and Outcomes of Solid Organ Transplant Recipients: Different Spectrums of Disease in Different Populations?

BACKGROUND: Coronavirus disease-19 (COVID-19) is associated with significant mortality. The elderly, patients with comorbidities, and solid organ transplant (SOT) recipients are particularly at risk. We observed a low incidence of severe disease in our population and aimed to determine the outcomes of COVID-19 (disease severity/intensive care unit [ICU] admissions/mortality) in SOT recipients. METHODS: All SOT recipients diagnosed with COVID-19 were included. Their demographic and clinical data were recorded from the hospital electronic system. Patients were assigned to 1 of 4 stages of disease severity: stage A = asymptomatic, stage B = mild, stage C = moderate, and stage D = severe. RESULTS: Of the 3052 SOT recipients, 67 were diagnosed with COVID-19. The mean age was 52 years, and 69% were male. There were approximately 25% patients in stage A, 28% in stage B, 34% in stage C, and 12% in stage D. Patients in stages C and D were older than those in stage A (P = 0.04) or stage B (P = 0.03). Lactic dehydrogenase (P < 0.01) and D-dimer (P < 0.01) levels were higher across the stages. Approximately 70% of patients were admitted for a median duration of 9 days and the median follow-up was 35 days. Acute kidney injury occurred in 19% of patients, and 45% required supplementary oxygen. The symptomatic patients were treated with Hydroxychloroquine (83%), Azithromycin (89%), and Tocilizumab (23%). Around 15% of patients were admitted to ICU and 2 patients have died. CONCLUSIONS: Most SOT recipients developed mild to moderate COVID-19 infection; few required ICU admission and 2 patients have died. Remaining patients have recovered and have been discharged from the hospital.

Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial.

BACKGROUND: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. AIMS: To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. METHODS: Prospective, randomized, double blind, non-inferiority, controlled clinical trial EXPECTED OUTCOMES: 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. SECONDARY OUTCOMES: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) TRIAL REGISTRATION: The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.

Severe hyponatremia after donor nephrectomy.

Living kidney donation is safe and established but can lead to short- and long-term complications. Hyponatremia is the most common disorder of body fluid and electrolyte balance in clinical practice, associated with increased morbidity, mortality, and the length of hospital stay. A correct diagnosis of the etiology of hyponatremia is critical, both to determine correct management and prognosis. Here, we present a case of a severe hyponatremia following left- sided donor nephrectomy with a physical examination suggestive of mild hypovolemia. Laboratory tests revealed high urine osmolality and sodium concentration mimicking syndrome of inappropriate antidiuretic hormone secretion (SIADH), in the setting of abnormally blunted response to Synacthen. The patient responded well to hydrocortisone replacement. Differentiating between primary adrenal insufficiency and SIADH as a cause of severe hyponatremia was the key to successfully treating this patient. Hyponatremia following donor nephrectomy is unusual and could be explained in this case by hypocortisolism.

Successful Treatment With Abatacept in Recurrent Focal Segmental Glomerulosclerosis After Kidney Transplant.

Primary focal segmental glomerulosclerosis recurrence occurs in 10% to 50% of recipients after kidney transplant and may affect both children and adults. Treatment after recurrence with plasma exchange and immunosuppression is quite variable and challenging, and those who do not respond usually progress to allograft failure. Podocyte injury and B7-1 expression and subsequently its blockade (abatacept) have been reported to be associated with complete remission of proteinuria in 4 patients with focal segmental glomerulosclerosis recurrence after kidney transplantation and in 1 patient with focal segmental glomerulosclerosis in native kidney. Here, we report our experience of successfully treating 3 consecutive patients with focal segmental glomerulosclerosis recurrence after kidney transplant with abatacept, which induced proteinuria remission.

ABO incompatible kidney transplantation: the Saudi experience.

Although the outcomes of ABO-incompatible (ABOi) kidney transplant recipients are quite favorable, these patients are at increased risk of early antibody-mediated rejection (AMR) and graft loss. Some studies have also shown high mortality in the ABOi group mainly due to increased risk of infections. The AMR rates have been reported anywhere from <10% to >50% in the literature. The outcomes of the ABOi kidney transplants in the Saudi population are not known. In this study, we aimed to determine the graft and patient survival in ABOi kidney transplant recipients in the Saudi population. We included all adult patients who underwent ABOi transplantation between 2007 and 2016. All patients received rituximab, therapeutic plasma exchange, thymoglobulin, intravenous antibiotics, and intravenous immunoglobulin. The maintenance immunosuppression was prednisone, mycophenolate mofetil, and tacrolimus. The data were collected from a prospectively maintained database. A total of 77 patients were included in the study. The most common blood group mismatch was A to O (44.2%), followed by B to O (26.0%) and A to B (16.9%). In the 1st year, 17% of patients developed acute cellular rejection and AMR occurred in 7.8% of patients. Two patients were diagnosed with BK nephropathy. In the 1st year, urinary tract infection occurred in 25 (32.5%) patients. No patient was diagnosed severe viral or fungal infection. In the 1st year, four grafts were lost (graft survival of 94.8%); all grafts were lost within two weeks, three due to AMR and one due to technical reason. One year patient survival was 100%. In this study of ABOi kidney transplant recipients, we observed low risks of infectious complications with excellent patient and graft survival. Our immunosuppressive protocol can be considered safe.

Ramadan Fasting in Kidney Transplant Recipients: A Single-Centre Retrospective Study.

BACKGROUND: Fasting during the lunar month of Ramadan is mandatory to all healthy adult Muslims. Renal transplant recipients are often worried about the impact of fluid and electrolyte deprivation during fasting on the function of their allograft. We aimed to examine the effect of fasting Ramadan on the graft function in renal transplant recipients. METHODS: This retrospective cohort study included patients who underwent kidney transplantation in our tertiary referral center. Baseline pre-Ramadan estimated glomerular filtration rate (eGFR), mean arterial pressure (MAP), and urinary protein excretion were compared to those during and after Ramadan within and between the fasting and non-fasting groups. RESULTS: The study population included 280 kidney transplant recipients who chose to fast during the Ramadan month (June-July 2014) and 285 recipients who did not fast. In the fasting group, baseline eGFR did not change from that during or post-Ramadan (72.6 ± 23.7 versus 72.3 ± 24.5 mL/min/1.73 m2, P = 0.53; and 72.6 ± 23.7 versus 72 ± 23.2 mL/min/1.73 m2, P = 0.14, respectively). Compared to baseline, there were no significant differences between the fasting and the non-fasting groups in terms of mean percent changes in eGFR, MAP, and urinary protein excretion. CONCLUSION: Fasting during the month of Ramadan did not have significant adverse effects on renal allograft function.

Vascular access types in patients starting hemodialysis after failed kidney transplant: does close nephrology follow-up matter?

BACKGROUND: Native arteriovenous fistulae (AVFs) are preferred while central venous catheters (CVCs) are least suitable vascular access (VA) in patients requiring hemodialysis (HD). Unfortunately, around 80% of patients start HD with CVCs. Late referral to nephrologist is thought to be a factor responsible for this. We retrospectively analyzed the types of VA at HD initiation in renal transplant recipients followed by nephrologists with failed transplant. If early referral to nephrologist improves AVF use, these patients should have higher prevalence of AVF at HD initiation. METHODS: All patients who failed their kidney transplants from January 2002 to April 2013 were included in the study. Data regarding planning of VA by nephrologist, documented discussion about renal replacement therapy (RRT), estimated glomerular filtration rate (eGFR) at 6 months and last clinic visit before HD initiation, time of VA referral, and subsequent VA at dialysis initiation were gathered and analyzed. RESULTS: Eighty-three patients failed their transplants during study period. Data were inaccessible in six patients. Eleven patients started peritoneal dialysis (PD) while 66 started HD. Thirty-two had previous functioning VA while 34 needed VA. There were 11/34 patients (32%) with eGFR <15 mL/min at six months while 21/34 (61%) had eGFR <15 mL/min at last clinic visit before HD initiation. Only 11/34 (32%) had documented RRT discussion, 8/34 (24%) had VA referral, and 7/34 (21%) had vein mapping. A total of 30/34 (88.3%) started HD with CVC while 4/34 (11.3%) started HD with AVF (p<0.0001). CONCLUSIONS: Early referral to nephrologist by itself may not improve VA care amongst patient with end-stage renal disease.

New-onset diabetes after kidney transplantation: Incidence, risk factors, and outcomes.

Many patients develop new-onset diabetes after kidney transplantation (NODAT). Its incidence and epidemiology are unknown in the Saudi population. We aimed to study the incidence, epidemiology, and outcomes of kidney transplant recipients who developed NODAT. This is a retrospective study of all adults who received kidney transplant between January 2003 and December 2009. NODAT was defined according to the criteria outlined in the 2003 International Consensus guidelines. A total of 500 patients were included in this study, 54% were male patients. One hundred thirty-six patients (27%) developed diabetes (NODAT group). In the univariate analysis, patients were older in the NODAT group (P <0.001), were of higher weight (P = 0.006), and had positive family history of diabetes (P = 0.002). Similarly, more patients in this group had impaired glucose tolerance before transplant (P = 0.01) and history of hepatitis C infection (P = 0.005). In the multivariate analysis, older age [odds ratio (OR) 1.06], family history of diabetes (OR 1.09), hepatitis C infection (OR 1.92), and impaired fasting glucose (OR 1.79) were significant risk factors for the development of NODAT. Mortality was 6% in the NODAT group and 0.5% in the non-diabetic group had died (P <0.001). Graft survival was not different between the groups (P = 0.35). In conclusion, there is a significant risk of developing diabetes after renal transplantation. Patients are at higher risk if they are older, have a family history of diabetes, pre-transplant impaired fasting/random glucose, and hepatitis C virus infection.