Pediatric en bloc kidney transplant from donors <15 kg: An excellent approach to expand the pediatric deceased donor pool.

INTRODUCTION: Most kidneys from small pediatric donors are transplanted to adult recipients because of the perceived risk of surgical complications and graft thrombosis. In this study, we aim to demonstrate our favorable outcomes in transplanting pediatric kidneys from donors <15 k into pediatric recipients. METHODS: This study retrospectively analyzes the outcomes of seven pediatric recipients of en block kidney transplants from pediatric donors weighing <15 kg performed at King Fahad Specialist Hospital-Dammam from December 2014 to January 2018. Baseline characteristics of donors and recipients were collected. The incidences of surgical complication, immediate, and intermediate graft function were the primary outcomes. RESULTS: The study included seven recipients monitored for a mean duration of 6.86 ± 1.35. Donors' and recipients' mean weights were 7.4 ± 3.2 kg and 20.7 ± 9.2 kg, respectively. Ureteric stricture occurred in one patient. There was a substantial improvement of 1-year estimated glomerular filtration rate (eGFR) compared to the 1-week mark (106.7 ± 26.38 mL/min. 1.73 m2 vs. 63.7 ± 22.92 mL/min/1.73 m2, p = .0069). The observed improvement in renal function persisted at the 5-year mark and during the last follow-up, with eGFR of 70.3 ± 40.7 mL/min/1.73 m2, and 79.8 ± 30.8 mL/min/1.73 m2, respectively. There was also increase of 27.9% in the size of the en bloc kidney observed at the 6 months. CONCLUSION: In a specialized transplant center with highly skilled surgeons, the utilization of en bloc kidney transplant from donors weighing less than 15 kg is an effective strategy for expanding the donor pool and ensuring favorable graft outcomes.

The humoral immune response to the BNT 162B2 vaccine in pediatrics on renal replacement therapy.

INTRODUCTION: Since the start of the COVID-19 pandemic, data published on the immunogenicity of the SARS-CoV-2 BNT 162B2 vaccine in pediatric patients receiving renal replacement therapy are scant. Our primary objective is to study this population's humoral immune response to the COVID-19 vaccine. METHODS: Pediatric kidney transplant recipients (PKTRs) and hemodialysis recipients (HR) at our center who received two doses of the SARS-CoV-2 BNT 162B2 vaccine were included. Transplant and HR who had PCR-positive COVID-19 infections during the study, regardless of their vaccine status, were also included. SARS-CoV-2 anti-spike protein (S1/S2) IgG was measured after the second dose of the vaccine and after any PCR-positive COVID-19 infection as routine clinical practice. Data on demographics, induction, maintenance immunosuppressants, type of transplant, and posttransplant or dialysis duration were included. RESULTS: Of the 61 patients included, 19 were dialysis recipients who received two doses of vaccine without subsequent infection (HV), and 42 were kidney transplant recipients. All dialysis patients and 33 (78.6%) transplant recipients received two doses of the SARS-CoV-2 BNT 162b2 vaccine. A total of 33.3% (11/33) of the transplant recipients who received vaccination developed COVID-19 infection (KTH) at a median time of 13 days after the second dose of vaccine. Nine transplant patients had pure COVID-19 infection without vaccination (KTI). The seroconversion rate in the HV group was 94.7% (18/19) compared to 50% (11/22) in the kidney transplant vaccine recipients who did not develop subsequent COVID-19 infection (KTV) (p < .001). The median S1/S2 IgG titers for the HV group were 400 AU/mL versus 15 AU/mL in the KTV group (p < .0001). There was no significant difference in the duration of the test from the second dose of the vaccine between HV and KTV (55 vs. 33.5 days, p = .095). The KTH had higher titers than KTV group (370 vs. 15 p < .0001). The median duration of the test after vaccination in the vaccine group and those with hybrid immunity was similar (35 vs. 33.5 days, p = .2).There were no clear predictors for seroconversion in the PKTRs. Natural infection alone was as good as the vaccine in eliciting humoral immune response. CONCLUSION: The humoral immune response to two doses of the SARS-CoV-2 BNT 162B2 vaccine in PKTRs without subsequent COVID-19 infection is suboptimal compared to that in hemodialysis recipients and in PKTRs with hybrid immunity from both infection and vaccination.

Severe delayed graft function in a living-related kidney transplant recipient due to combination of alloimmunity, autoimmunity, and heterologous immunity: A case report.

BACKGROUND: Delayed graft function is a manifestation of acute kidney injury unique to transplantation usually related to donor ischemia or recipient immunological causes. Ischemia also considered the most important trigger for innate immunity activation and production of non-HLA antibodies. While ischemia is inevitable after deceased donor transplantation, this complication is rare after living transplantation. Heterologous Immunity commonly used to describe the activation of T cells recognizing specific pathogen-related antigens as well unrelated antigens is common post-viral infection. In transplant-setting induction of heterologous immunity that cross-react with HLA-antigens and subsequent reactivation of memory T cells can lead to allograft rejection. METHODS: Here we describe a non-sensitized child with ESRD secondary to lupus nephritis and recent history of COVID-19 infection who experienced 17 days of anuria after first kidney living transplantation from her young HLA-haploidentical uncle donor. Graft histology showed acute cellular rejection, evidence of mild antibody-mediated rejection and vascular wall necrosis in some arterioles suggesting possibility of intraoperative graft ischemia. Both pre- and post-transplant sera showed very high level of several non-HLA antibodies. RESULTS: The patient was treated for cellular and antibody-mediated rejection while maintained on hemodialysis before her graft function started to improve on day seventeen post transplantation. CONCLUSION: The cellular rejection likely trigged by ischemia that activated T-cells-mediated immunity. The high level of non- HLA-antibodies further aggravated the damage and the rapid onset of rejection may be partly related to memory T-cell activation induced by heterologous immunity.

HLA Sensitization in the Era of COVID-19: Single-Center Experience.

It is well known that several viral infections are capable of triggering the formation of HLA antibodies; however, an association between SARS-CoV-2 and the development of anti-HLA antibodies is not yet confirmed. In this study, we compared the prevalence of HLA antibody before and after COVID-19 infection in a cohort of 3 groups included 58 healthy nonsensitized employees (HNEs), 130 kidney transplant recipients (KTRs), and 62 kidney transplant candidates. There were no significant changes observed in HLA class I antibodies in any of the groups, but evaluation of antibodies to HLA class II revealed a significant change in the KTR group (P = .0184) after acquiring COVID-19 infection and in the HNE group (P = .0043) when compared to the reported prevalence in a similar population. Although we observed the emergence of convalescent de novo donor-specific antibodies in 2 patients, we did not encounter any rejection episodes in the KTR group. Finally, the results of flow cytometry crossmatch in the HNE group were not consistent with the state of antibodies. In conclusion, COVID-19 infection has the potential to produce class II antibodies but with little effect on preexisting sensitization. These antibodies are likely to be transient and not necessarily causing positive crossmatch with the corresponding antigens at the proper mean fluorescent intensity and therefore should not affect access to transplantation. There is a need for further evaluation to ascertain the genuineness of these antibodies and their exact effect on transplant readiness and outcomes.

Durability of Antibody Responses to SARS-CoV-2 Infection and Its Relationship to Disease Severity Assessed Using a Commercially Available Assay.

Background: Assessing the humoral immune response to SARS-CoV-2 is crucial for inferring protective immunity from reinfection and for assessing vaccine efficacy. Data regarding the durability and sustainability of SARS-CoV-2 antibodies are conflicting. In this study, we aimed to determine the seroconversion rate of SARS-CoV-2 infection in a cohort of reverse-transcriptase polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections and the antibody dynamics, durability, and the correlation of antibody titers with disease severity using the commercially available SARS-CoV-2 anti-spike (S1/S2) protein. Methods: A total of 342 subjects with PCR-confirmed COVID-19 were enrolled. A total of 395 samples were collected at different time points (0-204) after the onset of symptoms or from the day of positive PCR in asymptomatic patients. Demographics, clinical presentation and the date of PCR were collected. All samples were tested using the automated commercial chemiluminescent system (DiaSorin SARS-CoV-2 S1/S2 IgG) on the LIAISONXL® platform (LIAISON). Results: The seroconversion rate for samples collected 14 days after the onset of infection was much higher than that for samples collected before 14 days (79.4% vs. 39.4%). The rate of seroconversion in symptomatic participants (62.1%) was similar to that of asymptomatic participants (56.1%) (p = 0.496). The IgG titer distribution was also similar across both groups (p = 0.142), with a median IgG level of 27.86 AU/ml (3.8-85.5) and 15 AU/ml (3.8-58.85) in symptomatic and asymptomatic participants, respectively. However, IgG titers were significantly higher in ICU patients, with a median of 104 AU/ml (3.8-179) compared to 34 AU/ml (3.8-70) in the non-ICU participants (p < 0.0001). Furthermore, the median time to seroconversion occurred significantly faster in ICU patients than in non-ICU participants (19 versus 47 days) (P < 0.0001). IgG titers were also higher in subjects ≥50 years compared to those <50 years (p < 0.009), male compared to female (p < 0.054) and non-Saudi compared to Saudi (p < 0.003). Approximately 74% of all samples tested beyond 120 days were positive. Conclusion: Antibodies can persist in circulation for longer than 4 months after COVID-19 infection. The majority of patients with COVID-19 mounted humoral immune responses to SARS-CoV-2 infection that strongly correlated with disease severity, older age and male gender. However, the population of individuals who tested negative should be further evaluated.

Incidence of hyperkalemic RTA in pediatric post-renal transplant patients and the role of fludrocortisone.

BACKGROUND: One of the most common forms of post-transplant tubulopathy is hyperkalemic (RTA). The true incidence of hyperkalemic RTA in pediatric patients has not yet been studied. (CNIs) remain mostly blamed. Most cases are managed with sodium bicarbonate and potassium binding resins. Few studies have addressed the role of fludrocortisone in managing such patients. This study aimed to assess the efficacy and safety of fludrocortisone in the treatment of post-transplant hyperkalemic RTA. METHOD: This is a retrospective cohort study of all pediatric (aged ≤16 years) post-kidney transplant patients who were followed up in KFSH-D, Saudi Arabia from January 2015 until September 2019. A total of 136 pediatric post-renal transplant patients were reviewed, of these, 39 patients who were commenced on fludrocortisone post-transplant treatment and were followed up for at least 6 months after fludrocortisone initiation were included in this study. RESULTS: The incidence of hyperkalemic RTA in our center was 60.6%. The medication requirements decreased significantly after fludrocortisone initiation. The median sodium bicarbonate dose decreased from 1.2 mEq/kg/day (range, 0.0-4.7) prior to fludrocortisone treatment to 0.0 mEq/kg/day (range, 0.0-4.3) at 6-month follow-up (p < .001). Similarly, the median (SPS) dose decreased from 1.2 g/kg/day (range, 0.0-4.0) before fludrocortisone treatment to 0.0 g/kg/day (range, 0.0-3.6) (p < .001) at 6-month follow-up. The initial mean potassium level 5.17 mmol/L ± 0.61SD dropped to 4.60 mmol/L ± 0.46SD at 6-month follow-up (p < .001). The initial mean serum bicarbonate level 22.31 mmol/L ± 3.67SD increased to 24.5 mmol/L ± 2.8SD at 6-month follow-up (p < .01). No effect on systolic and diastolic blood pressure was observed during follow-up. CONCLUSION: Hyperkalemic RTA incidence was high in our cohort. Fludrocortisone is safe and effective drug in the treatment of post-kidney transplant hyperkalemic RTA.

Detection of SARS-CoV-2 antibodies in pediatric kidney transplant patients.

BACKGROUND: The seroprevalence of SARS-CoV-2 infection has been studied in immunocompetent children. However, data in the pediatric kidney transplant population (PKT) are lacking. METHODS: Using two commercial immunoassays that measured IgG antibodies against SARS-CoV-2 spike protein and IgG against the nucleocapsid (N) protein, we screened 72 PKT recipients who attended the outpatient clinic for routine blood work. The majority of patients with positive serology underwent an additional serology test at least once during subsequent clinical follow-up. Patients were confirmed to have SARS-CoV-2 infection if they had two positive tests. RESULTS: Eight patients out of the 72 screened (11.1%) had positive results for SARS-CoV-2 IgG antibodies in both serological tests. Of those who tested positive, 4 had positive SARS-CoV-2 PCR results before screening. All patients were asymptomatic or had a history of mild symptoms. All tested patients had persistently positive antibodies at a median follow-up time of 75 days (IQR, 44.5, 86.5 days). One patient had a positive PCR test at 75 days and a positive serology test at 120 days post infection. CONCLUSION: The seroprevalence of SARS-CoV-2 was relatively high (11.1%) in our population. Although all patients were asymptomatic or mildly symptomatic, they mounted a strong humoral immune response that persisted for a few months despite being on triple immunosuppressants. These findings have positive implications regarding vaccination efficacy in this group.

Practice of Childhood Nephrotic Syndrome Management amongPediatric Nephrologists in the GCC Countries.

Childhood nephrotic syndrome (NS) management is greatly variable among pediatric nephrologists worldwide. We aimed to evaluate if this variability exists among pediatric nephrologists in the gulf countries and whether certain training programs influence this variability. A web-based multiple-choice survey of 35 NS management questions distributed to certified pediatric nephrologists working in the Gulf countries. Amongst 92 invitees, the response rate was 67%. The majority (73%) were older than 50 years and male (58%). Sixty percent trained in North America and 41% had >10 years of experience. Sixty-three percent use a 12- week corticosteroids regimen for the initial treatment of childhood NS and only 10% never consider long-term small alternate dose corticosteroids therapy to sustain remission before commencing a corticosteroids-sparing agent for frequently relapsing or corticosteroids-dependent NS. Mycophenolate mofetil was the drug of choice for frequently relapsing and corticosteroids dependent NS in 51% and 58% of the participants, respectively, whereas calcineurin inhibitors were preferred by the vast majority (95%) of the participants for corticosteroids-resistant childhood NS. Regarding rituximab treatment, almost half of the participants (48%) give two doses of rituximab one to two weeks apart and 61% do not give another course of rituximab until the child relapse. Fellowship training site and the duration of the clinical experience did not seem to influence certain management of childhood NS. As shown in North American studies, great variability in the management of childhood NS does exist in the Gulf countries. The country of fellowship training and the experience did not seem to contribute to this variability.

Silent disease and loss of taste and smell are common manifestations of SARS-COV-2 infection in a quarantine facility: Saudi Arabia.

OBJECTIVES: In this study, we aimed to study the clinical presentations, and viral clearance of SARS-COV-2 positive quarantined individuals. DESIGN: Cross-sectional study. SETTING: Governmental- designated facility in the eastern province, Saudi Arabia. PARTICIPANTS: 128 laboratory-confirmed COVID-19 quarantined individuals who had a history of travel abroad in the last 14 days before the quarantine or were in direct contact with laboratory-confirmed cases. The study was from March 18th-till April 16th. PRIMARY AND SECONDARY MEASURES: The clinical presentation, prevalence of asymptomatic carriers among SARS-COV-2 positive quarantined subjects, and the difference between virus clearance among symptomatic and asymptomatic individuals. RESULTS: Sixty-nine of the 128 residents (54%) were completely asymptomatic until the end of the study. The remaining 59 residents (46%) had only mild symptoms. The most common symptom was a sudden loss of smell and taste, accounting for 47.5%. The median time to virus clearance was significantly different between the two groups. Symptomatic residents cleared the virus at a median of 17 days (95% CI, 12.4-21.6) from the first positive PCR vs. 11days (95% CI, 8.7-13.3) in the asymptomatic group (P = 0.011). False-negative test results occurred in 18.8% of the total residents and false-positive results in 3%. CONCLUSION: The prevalence of asymptomatic carriers among quarantined travelers and those identified by contact tracing is high in our study. Therefore, testing, tracing, and isolating travelers and contacts of laboratory-confirmed cases, regardless of symptoms, were very effective measures for early disease identification and containment. Loss of taste and smell were the most common presentations in our mild symptomatic residents and should be used as a screening tool for COVID-19. The persistent positive PCR beyond 14 days observed in the mild symptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control.

Induction prednisone dosing for childhood nephrotic syndrome: how low should we go?

BACKGROUND: Historically, children with nephrotic syndrome (NS) across British Columbia (BC), Canada have been cared for without formal standardization of induction prednisone dosing. We hypothesized that local historical practice variation in induction dosing was wide and that children treated with lower doses had worse relapsing outcomes. METHODS: This retrospective cohort study included 92 NS patients from BC Children's Hospital (1990-2010). We excluded secondary causes of NS, age < 1 year at diagnosis, steroid resistance, and incomplete induction due to early relapse. We explored cumulative induction dose and defined dosing quartiles. Relapsing outcomes above and below each quartile threshold were compared including total relapses in 2 years, time to first relapse, and proportions developing frequently relapsing NS (FRNS) or starting a steroid-sparing agent (SSA). RESULTS: Cumulative prednisone was widely distributed with approximated median, 1st, and 3rd quartile doses of 2500, 2000, and 3000 mg/m2 respectively. Doses ≤ 2000 mg/m2 showed significantly higher relapses (4.2 vs 2.7), shorter time to first relapse (61 vs 175 days), and higher SSA use (36 vs 14%) compared to higher doses. Doses ≤ 2500 mg/m2 also showed significantly more relapses (3.9 vs 2.2), quicker first relapse (79 vs 208 days), and higher FRNS (37 vs 17%) and SSA use (28 vs 11%). Relapsing outcomes lacked statistical difference in ≤ 3000 vs > 3000 mg/m2 doses. CONCLUSIONS: Results strongly justify our development of a standardized, province-wide NS clinical pathway to reduce practice variation and minimize under-treatment. The lowest induction prednisone dosing threshold to minimize future relapsing risks is likely between 2000 and 2500 mg/m2. Further prospective studies are warranted.

Indications for kidney biopsy in idiopathic childhood nephrotic syndrome.

BACKGROUND: Most cases of childhood nephrotic syndrome (NS) are due to minimal change disease (MCD), while a minority of children have focal segmental glomerulosclerosis (FSGS) and an unfavorable clinical course, requiring a kidney biopsy to confirm diagnosis. We hypothesized that clinical characteristics at diagnosis and initial response to corticosteroid treatment accurately predict FSGS and can be used to guide consistent practice in the indications for kidney biopsy. METHODS: This was a case control study (1990-2012). Inclusion criteria included age 1-17 years, meeting the diagnostic criteria for NS, and having biopsy-proven FSGS or MCD. Clinical characteristics at diagnosis included age, kidney function [estimated glomerular filtration rate (eGFR)], hypertension, hematuria, nephritis (reduced eGFR, hematuria, hypertension), and response to steroids. RESULTS: From a total of 169 children who underwent kidney biopsy for NS we included 65 children with MCD and 22 with FSGS for analysis. There were no significant between-group differences in age, sex, or eGFR at the time of diagnosis. The FSGS group had a higher proportion of hypertension (40 vs. 15%; p = 0.02), hematuria (80 vs. 47%; p = 0.01), and nephritis (22 vs. 2%; p = 0.004) and was more likely to be steroid resistant after 6 weeks of treatment than the MCD group (67 vs. 19%; p < 0.001). As predictors of FSGS, hematuria had a high sensitivity of 0.80 [95% confidence interval (CI) 0.56-0.93] and low specificity of 0.53 (95% CI 0.39-0.66), nephritis had a low sensitivity of 0.22 (95% CI 0.07-0.48) and high specificity of 0.98 (95% CI 0.88-0.99), and steroid resistance had a low sensitivity of 0.67 (95% CI 0.43-0.85) and high specificity of 0.81 (95% CI 0.68-0.90). The combination of steroid resistance after 6 weeks of therapy and/or nephritis at diagnosis yielded the optimal sensitivity and specificity at 0.80 (95% CI 0.56-0.93) and 0.75 (95% CI 0.60-0.86), respectively, confirmed by the highest receiver operator characteristic area under the curve of 0.77. CONCLUSION: Steroid resistance after 6 weeks of therapy and/or nephritis at initial presentation is an accurate predictor of FSGS in children with NS and will be used as the indication for kidney biopsy in our newly developed clinical pathway. This approach will maximize the yield of diagnostic FSGS biopsies while minimizing the number of unnecessary MCD biopsies.

First case of pneumonia caused by Cupriavidus pauculus in an infant in the Gulf Cooperation Council.

Cupriavidus pauculus is an emerging organism causing infections in immunocompromised and immunocompetent patients. We report a C.pauculus pneumonia case susceptible to cefepime in an infant with end-stage renal failure. To our knowledge, this is the first case report of C. pauculus causing respiratory infections in the Gulf Cooperation Council.