Search

Background: Adult kidney transplant recipients (KTRs) fully vaccinated against COVID‐19 have substantial morbidity and mortality related to SARS‐CoV‐2 infection compared with the general population. However, little is known regarding the safety and efficacy of the COVID‐19 vaccination series in pediatric KTRs. Methods: A multicenter, retrospective observational study was performed across nine pediatric transplantation centers. Eligible KTRs fully vaccinated against COVID‐19 were enrolled and data were collected pertaining to SARS‐CoV‐2 infection incidence and severity, graft outcomes and post‐vaccination safety profile, as well as overall patient survival. Results: A total of 247 patients were included in this investigation with a median age at transplantation of 11 years (IQR 5–15). SARS‐CoV‐2 infection was observed in 30/110 (27.27%) of fully vaccinated patients, tested post‐transplant, within the defined follow‐up period. Of these patients, 6/30 (18.18%) required hospitalization and 3/30 (12.12%) required reduction in immunosuppression, with no reported deaths. De novo donor‐specific antibodies (DSAs) were found in 8/86 (9.30%) of DSA‐tested patients with two experiencing rejection and subsequent graft loss. The overall incidence of rejection and graft loss among the total cohort was 11/247 (4.45%) and 6/247 (3.64%), respectively. A 100% patient survival was observed. Conclusions: Observationally, infectious outcomes of SARS‐CoV‐2 in fully vaccinated pediatric KTRs are excellent, with a low incidence of infection requiring hospitalization and no associated deaths. Though de novo DSAs were observed, there was minimal graft rejection and graft loss reported in the total cohort. [ABSTRACT FROM AUTHOR]

Background: Antibody‐mediated rejection (AMR) is a major cause of kidney allograft loss. There is a paucity of large‐scale pediatric‐specific data regarding AMR treatment outcomes. Methods: Data were obtained from 14 centers within the Pediatric Nephrology Research Consortium. Kidney transplant recipients aged 1–18 years at transplant with biopsy‐proven AMR between 2009 and 2019 and at least 12 months of follow‐up were included. The primary outcome was graft failure or an eGFR <20 mL/min/1.73 m2 at 12 months following AMR treatment. AMR treatment choice, histopathology, and DSA class were also examined. Results: We reviewed 123 AMR episodes. Median age at diagnosis was 15 years at a median 22 months post‐transplant. The primary outcome developed in 27.6%. eGFR <30 m/min/1.73 m2 at AMR diagnosis was associated with a 5.6‐fold higher risk of reaching the composite outcome. There were no significant differences in outcome by treatment modality. Histopathology scores and DSA class at time of AMR diagnosis were not significantly associated with the primary outcome. Conclusions: In this large cohort of pediatric kidney transplant recipients with AMR, nearly one‐third of patients experienced graft failure or significant graft dysfunction within 12 months of diagnosis. Poor graft function at time of diagnosis was associated with higher odds of graft failure. [ABSTRACT FROM AUTHOR]

Higher nighttime blood pressure (BP), less BP dipping, and higher BP variability have been linked with worse cognitive function in the elderly. The goal of this study is to explore whether this relationship already exists in early and middle adulthood. We further examined whether ethnic differences between African Americans and European Americans in BP parameters can explain ethnic differences in cognitive function. 24‐h ambulatory BP monitoring and cognitive function were obtained from 390 participants (average age: 37.2 years with a range of 25–50; 54.9% African Americans; 63.6% females). We observed that higher nighttime BP, decreased dipping, and higher variability were significantly associated with lower scores on the Picture Sequence Memory Test. Significant negative associations between variability and overall composite scores were also observed. No significant associations between average 24‐h or daytime BP and cognitive function were observed. Ethnic differences in nighttime diastolic pressures and dipping can explain 6.81% to 10.8% of the ethnicity difference in the score of the Picture Sequence Memory Test (ps <.05). This study suggests that the associations of nighttime BP, dipping, and variability with cognitive function already exist in young and middle‐aged adults. Ethnic differences in nighttime BP and dipping can at least partially explain ethnic differences in cognitive function. The stronger association of these parameters with cognitive function than daytime or average BP in this age range raises the importance of using ambulatory BP monitoring for more precise detection of abnormal BP patterns in young adulthood. [ABSTRACT FROM AUTHOR]

Background: Neutropenia is common in the first year after pediatric kidney transplant and is associated with an increased risk of infection, allograft loss, and death. Granulocyte colony‐stimulating factor (G‐CSF) increases neutrophil production, but its use in pediatric solid organ transplant recipients remains largely undescribed. Methods: We performed a multicenter retrospective cohort study of children with neutropenia within the first 180 days after kidney transplant. Multivariable linear regression and Poisson regression were used to assess duration of neutropenia and incidence of hospitalization, infection, and rejection. Results: Of 341 neutropenic patients, 83 received G‐CSF during their first episode of neutropenia. Median dose of G‐CSF was 5 mcg/kg for 3 (IQR 2–7) doses. G‐CSF use was associated with transplant center, induction immunosuppression, steroid‐free maintenance immunosuppression, hospitalization, and decreases in mycophenolate mofetil, valganciclovir, and trimethoprim–sulfamethoxazole dosing. Absolute neutrophil count nadir was also significantly lower among those treated with G‐CSF. G‐CSF use was not associated with a shorter duration of neutropenia (p =.313) and was associated with a higher rate of neutropenia relapse (p =.002) in adjusted analysis. G‐CSF use was associated with a decreased risk of hospitalization (aIRR 0.25 (95%CI 0.12–0.53) p <.001) but there was no association with incidence of bacterial infection or rejection within 90 days of neutropenic episode. Conclusion: G‐CSF use for neutropenia in pediatric kidney transplant recipients did not shorten the overall duration of neutropenia but was associated with lower risk of hospitalization. Prospective studies are needed to determine which patients may benefit from G‐CSF treatment. [ABSTRACT FROM AUTHOR]

Prenatal programming results in an increase in blood pressure in adult offspring. We have shown that compared to control adult offspring whose mothers were fed a 20% protein diet, programmed adults whose mothers were fed a 6% protein diet during the last half of pregnancy have an increase in renal sympathetic nerve activity and urinary angiotensinogen/creatinine levels. We hypothesized that the increase in urinary angiotensinogen was mediated by renal sympathetic nerve activity in programmed rats. In this study performed in 3 month old rats, renal denervation resulted in normalization of blood pressure in the 6% programmed group (150 ± 3 Hg in 6% sham vs. 121 ± 4 Hg in 6% denervated, P < 0.001), and a reduction in blood pressure in the 20% group (126 ± 2 Hg 20% sham vs. 113 ± 4 Hg 20% denervated ( P < 0.05). We confirm that the intrarenal renin-angiotensin system assessed by urinary angiotensinogen/creatinine is upregulated in offspring of rats fed a 6% protein diet rats compared to 20% controls. To determine if sympathetic nerve activity was mediating the increase in urinary angiotensinogen in programmed rats, we compared denervated to sham-operated control and programmed rats. Renal denervation had no effect on urinary angiotensinogen/creatinine ratio in the 20% group and no effect on the increased urinary angiotensinogen/creatinine ratio found in programmed rats. This study demonstrates that the increase in urinary angiotensinogen in programmed rats is not mediated by renal sympathetic nerve activity. [ABSTRACT FROM AUTHOR]

A maternal low-protein diet has been shown to program hypertension and a reduction in glomerular filtration rate in adult offspring. This study examined the effect of continuous administration of enalapril in the drinking water and transient administration of enalapril administered from 21 to 42 days of age on blood pressure and glomerular filtration rate (GFR) in male rats whose mothers were fed a 20% protein diet (control) or a 6% protein diet (programmed) during the last half of pregnancy. After birth all rats were fed a 20% protein diet. Programmed rats (maternal 6% protein diet) were hypertensive at 15 months of age compared to control rats and both continuous and transient administration of enalapril had no effect on blood pressure on control offspring, but normalized the blood pressure of programmed offspring. GFR was 3.2 ± 0.1 mL/min in the control group and 1.7 ± 0.1 mL/min in the programmed rats at 17 months of age (P < 0.001). The GFR was 3.0 ± 0.1 mL/min in the control and 2.7 ± 0.1 mL/min in the programmed group that received continuous enalapril in their drinking water showing that enalapril can prevent the decrease in GFR in programmed rats. Transient administration of enalapril had no effect on GFR in the control group (3.2 ± 0.1 mL/min) and prevented the decrease in GFR in the programmed group (2.9 ± 0.1 mL/min). In conclusion, transient exposure to enalapril for 3 weeks after weaning can prevent the hypertension and decrease in GFR in prenatal programmed rats. [ABSTRACT FROM AUTHOR]