Dent disease presenting with nyctalopia and electroretinographic correlates of vitamin A deficiency.

Purpose: To report a unique case of Dent Disease presenting with nyctalopia associated with vitamin A deficiency and abnormal electroretinogram findings without prior systemic symptomatology. Observations: A 16-year-old male presented with a several month history of nyctalopia and peripheral vision deficits. Central visual acuity, anterior and posterior segment examinations, and macular optical coherence tomography were unremarkable. Electroretinogram (ERG) testing revealed a rod-cone dystrophic pattern, with further workup demonstrating serum vitamin A deficiency (VAD). Laboratory evaluation revealed renal dysfunction and proteinuria with a significantly elevated urinary retinol-binding protein (RBP). Kidney biopsy showed glomerular and tubular disease.Genetic screening for inherited renal disease was performed identifying a hemizygous pathogenic variant c.2152C>T (p.Arg718*) in the Chloride Voltage-Gated Channel 5 (CLCN5) gene, confirming the diagnosis of X-linked Dent Disease. Following vitamin A supplementation, our patient reported resolution of nyctalopia and reversal of abnormal ERG findings were demonstrated. Conclusions and Importance: To our knowledge, this is the first case in the literature describing Dent disease solely presenting with ophthalmic symptoms of nyctalopia and abnormal electroretinogram findings that later reversed with vitamin A repletion. This case stresses the importance for clinicians to consider renal tubular disorders in the differential for VAD.

Acute kidney injury requiring kidney replacement therapy in childhood lupus nephritis: a cohort study of the Pediatric Nephrology Research Consortium and Childhood Arthritis and Rheumatology Research Alliance.

BACKGROUND: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited. METHODS: A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure. RESULTS: Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe (> 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score > 4 on kidney biopsy were associated with kidney failure. CONCLUSIONS: Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Role of Growth Hormone in Chronic Kidney Disease.

Growth hormone (GH) has become a critical therapy for treating growth delay and failure in pediatric chronic kidney disease. Recombinant human GH treatment is safe and significantly improves height and height velocity in these growing patients and improved growth outcomes are associated with decreased morbidity and mortality as well as improved quality of life. However, the utility of recombinant human GH in adults with chronic kidney disease and end-stage renal disease for optimization of body habitus and reducing frailty remains uncertain. Semin Nephrol 41:x-xx © 2021 Elsevier Inc. All rights reserved.

Proteinuria and nocturnal blood pressure dipping in hypertensive children and adolescents.

BACKGROUND: The absence of nocturnal blood pressure dipping is associated with adverse cardiovascular outcomes in adults, and proteinuria is a risk factor for non-dipping in this population. Risk factors for non-dipping in children are largely unknown. METHODS: We retrospectively identified patients aged 5-19 years who underwent 24-h ambulatory blood pressure monitoring (ABPM) from August 2018 to January 2019 and had a spot urine protein-to-creatinine ratio (PCR) within 1 year of their ABPM. Dipping was defined as ≥10% reduction in systolic and diastolic blood pressure from day to night. Multivariable logistic and linear regression models evaluated the association of proteinuria with non-dipping. RESULTS: Among 77 children identified, 27 (35.1%) were non-dippers. Each two-fold higher urine PCR was associated with 38% higher odds of non-dipping, after adjusting for body mass index (BMI). Higher urine PCR was also associated with a lower diastolic dipping percentage by 1.33 (95% confidence interval 0.31-2.34), after adjusting for BMI, age, and estimated glomerular filtration rate. CONCLUSIONS: Limitations of this study include its retrospective design and the time lapse between urine PCR and ABPM. Proteinuria appears to be associated with blood pressure non-dipping in children. This finding needs to be confirmed in prospective studies. IMPACT: Our study demonstrates the association of proteinuria with non-dipping of blood pressure in children. This association has been explored in adults, but to our knowledge, this is the first time it is evaluated in children referred for evaluation of elevated blood pressure. Non-dipping is a modifiable risk factor for kidney function decline and cardiovascular disease in adulthood, and thus early identification in children is important. The association between proteinuria and non-dipping in children will allow us to more readily identify those at risk, with a future focus on interventions to modify blood pressure dipping patterns.

Respiratory illness among Gulf War and Gulf War era veterans who use the Department of Veterans Affairs for healthcare.

BACKGROUND: Veterans of the 1990-1991 Gulf War were exposed to a variety of toxic substances during their service that included several airborne hazards, but only a few small studies have assessed respiratory outcomes in Gulf War veterans. This paper presents population prevalence estimates and prevalence ratios of respiratory disease among Gulf War and Gulf War Era veterans who use VA healthcare. METHODS: A total of 360,909 Gulf War deployed veterans and 323,638 Gulf War Era non-deployed veterans were included in the analysis. Ten-year period prevalence rates (PRs) for fifteen respiratory diseases were calculated for Gulf War and Gulf War Era veterans and period prevalence ratios comparing Gulf War veterans to Gulf War Era veterans were calculated. RESULTS: The five respiratory conditions with the highest prevalence per 100,000 veterans across both Gulf War deployed and Gulf War Era non-deployed veterans (respectively) were: allergic rhinitis (8,400 and 8,041), chronic obstructive pulmonary disease (4,763 and 4,795), asthma (4,685 and 4,477), chronic airway obstruction (3,983 and 4,059), and chronic sinusitis (2,863 and 2,672). The adjusted PRs showed a small, but significantly increased, elevation in Gulf War-deployed compared to Gulf War Era non-deployed veterans for chronic bronchitis (PR 1.19; 95% CI 1.10, 1.28), emphysema (PR 1.11; 95% CI 1.01, 1.21), chronic airway obstruction (PR 1.09; 95% CI 1.07, 1.12), and chronic obstructive pulmonary disease (PR 1.09; 1.07, 1.11). DISCUSSION: Gulf War veterans should continue to be monitored in the future to better evaluate the potential long-term consequences on respiratory health.

Cachexia/Protein energy wasting syndrome in CKD: Causation and treatment.

Cachexia is a multifactorial syndrome defined by significant body weight loss, fat and muscle mass reduction, and increased protein catabolism. Protein energy wasting (PEW) is characterized as a syndrome of adverse changes in nutrition and body composition being highly prevalent in patients with CKD, especially in those undergoing dialysis, and it is associated with high morbidity and mortality in this population. Multiple mechanisms are involved in the genesis of these adverse nutritional changes in CKD patients. There is no obvious distinction between PEW and cachexia from a pathophysiologic standpoint and should be considered as part of the spectrum of the same nutritional disorder in CKD with similar management approaches for prevention and treatment based on current understanding. A plethora of factors can affect the nutritional status of CKD patients requiring a combination of therapeutic approaches to prevent or reverse protein and energy depletion. At present, there is no effective pharmacologic intervention that prevents or attenuates muscle atrophy in catabolic conditions like CKD. Prevention and treatment of uremic muscle wasting involve optimal nutritional support, correction of acidosis, and physical exercise. There has been emerging consistent evidence that active treatment, perhaps by combining nutritional interventions and resistance exercise, may be able to improve but not totally reverse or prevent the supervening muscle wasting and weakness. Active research into more direct pharmacological treatment based on basic mechanistic research is much needed for this unmet medical need in patients with CKD.

Therapeutic plasma exchange for the treatment of pediatric renal diseases in 2013.

Therapeutic plasma exchange is an extracorporeal treatment modality that removes systemic circulating pathologic factors or replaces absent plasma components and plays a role in many nephrologic conditions. It presents a number of technical challenges in the pediatric population but has become an increasingly common practice in pediatric nephrology over the past several decades. While prospective evidence is often lacking, our increased understanding of the molecular pathogenesis underlying many pediatric renal diseases provides sound reasoning for the use of plasma exchange in treating these conditions. This review will present the currently accepted indications for plasma exchange in children, the technical aspects of the procedure and its potential complications.

Influence of urine creatinine concentrations on the relation of albumin-creatinine ratio with cardiovascular disease events: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Higher urine albumin-creatinine ratio (ACR) is associated with cardiovascular disease (CVD) events, an association that is stronger than that between spot urine albumin on its own and CVD. Urine creatinine excretion is correlated with muscle mass, and low muscle mass also is associated with CVD. Whether low urine creatinine concentration in the denominator of the ACR contributes to the association of ACR with CVD is uncertain. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 6,770 community-living individuals without CVD. PREDICTORS: Spot urine albumin concentration, the reciprocal of the urine creatinine concentration (1/UCr), and ACR. OUTCOME: Incident CVD events. RESULTS: During a mean of 7.1 years of follow-up, 281 CVD events occurred. Geometric mean values for spot urine creatinine concentration, urine albumin concentration, and ACR were 95 ± 2 (SD) mg/dL, 0.7 ± 3.7 mg/dL, and 7.0 ± 3.1 mg/g. Urine creatinine concentration was lower in older, female, and low-weight individuals. Adjusted HRs per 2-fold higher increment in each urinary measure with CVD events were similar (1/UCr: 1.07 [95% CI, 0.94-1.22]; urine albumin concentration: 1.08 [95% CI, 1.01-1.14]; and ACR: 1.11 [95% CI, 1.04-1.18]). ACR ≥10 mg/g was associated more strongly with CVD events in individuals with low weight (HR for lowest vs highest tertile: 4.34 vs 1.97; P for interaction = 0.006). Low weight also modified the association of urine albumin concentration with CVD (P for interaction = 0.06), but 1/UCr did not (P for interaction = 0.9). LIMITATIONS: We lacked 24-hour urine data. CONCLUSIONS: Although ACR is associated more strongly with CVD events in persons with low body weight, this association is not driven by differences in spot urine creatinine concentration. Overall, the associations of ACR with CVD events appear to be driven primarily by urine albumin concentration and less by urine creatinine concentration.

Influence of urine creatinine on the relationship between the albumin-to-creatinine ratio and cardiovascular events.

BACKGROUND AND OBJECTIVES: In the albumin-to-creatinine ratio (spot-ACR), urine creatinine corrects for tonicity but also reflects muscle mass. Low muscle mass is associated with cardiovascular disease (CVD). We hypothesized that the spot-ACR would be higher in women, lower-weight persons, and older individuals, independent of timed urine albumin excretion (24hr-UAE), and accordingly, that spot-ACR would be more strongly associated with CVD events than 24hr-UAE in these subgroups. DESIGN, SETTING, PARTICIPANTS, & METHODS: 2627 PREVEND (Prevention of Renal and Vascular End-stage Disease) participants with 24hr-UAE <30 mg/d were followed for CVD events for 11 years. Cox regression evaluated associations of spot-ACR and 24hr-UAE with CVD events by sex, weight, and age. RESULTS: Female sex (26%), lower weight (2% per 5 kg), and older age (4% per 5 years) were associated with higher spot-ACR independent of 24hr-UAE (P<0.001). Spot urine albumin concentration (hazard ratio [HR], 1.26 per ln-SD higher) and 1/spot urine creatinine concentration (HR, 1.16 per ln-SD higher) were associated with CVD events. Spot-ACR was more strongly associated with CVD events than either component of the ratio (HR, 1.41 per ln-SD higher). Associations of spot-ACR ≥10 mg/g versus less (HR, 2.33) and 24hr-UAE ≥10 mg/d versus less (HR, 2.09) with CVD events were similar, and there were no significant differences across subgroups (P for interactions >0.06). CONCLUSIONS: In community-living individuals with 24hr-UAE <30 mg/d, spot-ACR is higher in women, older persons, and lower-weight persons, independent of 24hr-UAE. Low spot urine creatinine is associated with CVD risk, but high urine albumin is a stronger determinant of the association of spot-ACR with CVD than is low urine creatinine.