Antibody-mediated rejection in pediatric kidney transplant recipients: A report from the Pediatric Nephrology Research Consortium.

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.

Nocturnal blood pressure dipping, blood pressure variability, and cognitive function in early and middle-aged adults.

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.

Late-Onset Hyponatremia in Premature Infants.

Late-onset hyponatremia (LOH) frequently affects premature infants 2 or more weeks of age due to inadequate sodium intake and excessive kidney loss. Late-onset hyponatremia typically occurs in infants who are physiologically stable and is defined as serum sodium of 132 mEq/L or less or between 133 and 135 mEq/L if receiving sodium supplementation. Recent evidence suggests that spot urine sodium levels may improve the recognition of LOH, as low levels of excreted urine reflect a total body sodium deficit and negative balance. Untreated LOH may result in poor somatic growth, neurodevelopmental delay, higher incidence of bronchopulmonary dysplasia, and more severe retinopathy of prematurity. The primary prevention of LOH is to maintain serum sodium between 135 and 145 mEq/L; however, there are currently no formal protocols guiding sodium supplementation. The purpose of this article is to present on overview of LOH pathophysiology and its effect on somatic growth, neurodevelopment outcomes, and other related sequelae. We further discuss general management strategies and describe a protocol for sodium supplementation that is presently undergoing an evaluation for effectiveness.

Dual diagnosis of autosomal dominant polycystic kidney disease and sickle cell disease in a teenage male.

BACKGROUND: Sickle cell disease (SCD) and autosomal dominant polycystic kidney disease (ADPKD) are relatively common genetic conditions with considerable overlap in clinical presentation. In addition to similarities between the signs and symptoms in sickle cell nephropathy and ADPKD, more than half of SCD patients have kidney cysts. The co-occurrence of these two diseases has not been previously reported in the literature. CASE DIAGNOSIS/TREATMENT: A 16-year-old Black male with SCD had bilateral kidney enlargement and multiple simple cysts on ultrasound. Although kidney cysts are significantly more common in individuals affected with SCD, genetic testing with a broad kidney gene panel was performed to explore the possible presence of another underlying genetic cause of his cysts, in addition to SCD. A dual diagnosis of SCD and ADPKD was made following the identification of two copies of the common pathogenic sickle cell HBB variant (c.20A > T, p.Glu7Val) and a pathogenic missense variant in PKD1 (c.8311G > A, p.Glu2771Lys). CONCLUSIONS: SCD and ADPKD differ in pathophysiological mechanisms and treatment regimens. As such, it will be paramount for this teenager to be closely monitored for signs of diminished kidney function and to be co-managed as he transitions to adult care to ensure proper treatment and management. Early identification of individuals with both SCD and a co-occurring condition is crucial to ensuring proper clinical management. Furthermore, identifying and reporting additional patients with SCD and ADPKD dual diagnoses will help us to understand the co-occurring disease course and optimal treatments.

Blunted rest-activity circadian rhythm increases the risk of all-cause, cardiovascular disease and cancer mortality in US adults.

To examine whether rest-activity circadian rhythm parameters can predict all-cause, cardiovascular disease and cancer mortality in a general adult population of the US. We further compared the mortality predictive performance of these parameters with that of traditional risk factors. This study included 7,252 adults from US National Health and Nutrition Examination Surveys (NHANES) 2011-2014, who had wrist accelerometer data obtained at baseline and follow-up status linked to the National Death Index records (2011-2019). During a median of 81 months (interquartile range, 69-94 months) of follow-up, 674 (9.3%) deaths occurred. There were inverse associations between relative amplitude (RA) and all-cause mortality, cardiovascular disease and cancer mortality with increased quartiles RA associated with lower mortality risk (all P < 0.05). The Hazard Ratios ranged from 0.61 to 0.79. Furthermore, RA outperformed all the tested traditional predictors of all-cause mortality with the exception of age. This study suggests that participants with blunted rest-activity circadian rhythms had a higher risk of all-cause, cardiovascular disease and cancer mortality. Future studies will be needed to test whether interventions that regulate rest-activity circadian activity rhythms will improve health outcomes.

Transient enalapril attenuates the reduction in glomerular filtration rate in prenatally programmed rats.

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.