Antihypertensive agents: a long way to safe drug prescribing in children.

Recently updated clinical guidelines have highlighted the gaps in our understanding and management of pediatric hypertension. With increased recognition and diagnosis of pediatric hypertension, the use of antihypertensive agents is also likely to increase. Drug selection to treat hypertension in the pediatric patient population remains challenging. This is primarily due to a lack of large, well-designed pediatric safety and efficacy trials, limited understanding of pharmacokinetics in children, and unknown risk of prolonged exposure to antihypertensive therapies. With newer legislation providing financial incentives for conducting clinical trials in children, along with publication of pediatric-focused guidelines, literature available for antihypertensive agents in pediatrics has increased over the last 20 years. The objective of this article is to review the literature for safety and efficacy of commonly prescribed antihypertensive agents in pediatrics. Thus far, the most data to support use in children was found for angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), and calcium channel blockers (CCB). Several gaps were noted in the literature, particularly for beta blockers, vasodilators, and the long-term safety profile of antihypertensive agents in children. Further clinical trials are needed to guide safe and effective prescribing in the pediatric population.

Responsiveness of the PROMIS® measures to changes in disease status among pediatric nephrotic syndrome patients: a Midwest pediatric nephrology consortium study.

BACKGROUND: Nephrotic syndrome represents a condition in pediatric nephrology typified by a relapsing and remitting course, proteinuria and the presence of edema. The PROMIS measures have previously been studied and validated in cross-sectional studies of children with nephrotic syndrome. This study was designed to longitudinally validate the PROMIS measures in pediatric nephrotic syndrome. METHODS: One hundred twenty seven children with nephrotic syndrome between the ages of 8 and 17 years participated in this prospective cohort study. Patients completed a baseline assessment while their nephrotic syndrome was active, a follow-up assessment at the time of their first complete proteinuria remission or study month 3 if no remission occurred, and a final assessment at study month 12. Participants completed six PROMIS measures (Mobility, Fatigue, Pain Interference, Depressive Symptoms, Anxiety, and Peer Relationships), the PedsQL version 4.0, and two global assessment of change items. RESULTS: Disease status was classified at each assessment: nephrotic syndrome active in 100% at baseline, 33% at month 3, and 46% at month 12. The PROMIS domains of Mobility, Fatigue, Pain Interference, Depressive Symptoms, and Anxiety each showed a significant overall improvement over time (p < 0.001). When the PROMIS measures were compared to the patients' global assessment of change, the domains of Mobility, Fatigue, Pain Interference, and Anxiety consistently changed in an expected fashion. With the exception of Pain Interference, change in PROMIS domain scores did not correlate with changes in disease activity. PROMIS domain scores were moderately correlated with analogous PedsQL domain scores. CONCLUSION: This study demonstrates that the PROMIS Mobility, Fatigue, Pain Interference, and Anxiety domains are sensitive to self-reported changes in disease and overall health status over time in children with nephrotic syndrome. The lack of significant anchoring to clinically defined nephrotic syndrome disease active and remission status may highlight an opportunity to improve the measurement of HRQOL in children with nephrotic syndrome through the development of a nephrotic syndrome disease-specific HRQOL measure.

Gut microbiome and kidney disease: a bidirectional relationship.

Recent technological advances and efforts, including powerful metagenomic and metatranscriptomic analyses, have led to a tremendous growth in our understanding of microbial communities. Changes in microbial abundance or composition of human microbial communities impact human health or disease state. However, explorations into the mechanisms underlying host-microbe interactions in health and disease are still in their infancy. Although changes in the gut microbiota have been described in patients with kidney disease, the relationships between pathogenesis, mechanisms of disease progression, and the gut microbiome are still evolving. Here, we review changes in the host-microbiome symbiotic relationship in an attempt to explore the bidirectional relationship in which alterations in the microbiome affect kidney disease progression and how kidney disease may disrupt a balanced microbiome. We also discuss potential targeted interventions that may help re-establish this symbiosis and propose more effective ways to deploy traditional treatments in patients with kidney disease.

Incidence, risk factors, and outcomes of opportunistic infections in pediatric renal transplant recipients.

OIs present significant risks to patients following solid organ transplantation. The purpose of this study was to identify risk factors for the development of OIs after kidney transplantation in pediatric patients and to evaluate the impact of OIs on outcomes in this patient population. A single-center retrospective longitudinal cohort analysis including pediatric patients 21 yr of age or younger transplanted from July 1999 to June 2013 at an academic medical center was conducted. Patients were excluded if they received multi-organ transplant. A total of 175 patients were included in the study. Patients who developed OIs were more likely to be female and younger at the time of transplant. A six-factor risk model for OI development was developed. Death, disease recurrence, and PTLD development were similar between groups but trended toward increased incidence in the OI group. Incidence of rejection was significantly higher in the OI group (p = 0.04). Patients who developed OIs had several important risk factors, including younger age, EBV-negative serostatus, CMV donor (+)/recipient (-), biopsy-proven acute rejection, ANC <1000, MMF dose >500 mg/m(2), and any infection. Incidence of rejection was higher in the OI group, but rate of graft loss was not statistically different.

Vitamin D in incident nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND: Cross-sectional studies of children with prevalent nephrotic syndrome (NS) have shown 25-vitamin D (25(OH)D) deficiency rates of 20-100 %. Information on 25(OH)D status in incident patients or following remission is limited. This study aimed to assess 25(OH)D status of incident idiopathic NS children at presentation and longitudinally with short-term observation. METHODS: Multicenter longitudinal study of children (2-18 years old) from 14 centers across the Midwest Pediatric Nephrology Consortium with incident idiopathic NS. 25(OH)D levels were assessed at diagnosis and 3 months later. RESULTS: Sixty-one children, median age 5 (3, 11) years, completed baseline visit and 51 completed second visit labs. All 61 (100 %) had 25(OH)D < 20 ng/ml at diagnosis. Twenty-seven (53 %) had 25(OH)D < 20 ng/ml at follow-up. Fourteen (28 %) children were steroid resistant. Univariate analysis showed that children prescribed vitamin D supplements were less likely to have 25(OH)D deficiency at follow-up (OR 0.2, 95 % CI 0.04, 0.6). Steroid response, age, and season did not predict 25(OH)D deficiency. Multivariable linear regression modeling showed higher 25(OH)D levels at follow-up by 13.2 ng/ml (SE 4.6, p < 0.01) in children supplemented with vitamin D. CONCLUSIONS: In this incident idiopathic NS cohort, all children at diagnosis had 25(OH)D deficiency and the majority continued to have a deficiency at 2-4 months. Supplemental vitamin D decreased the odds of 25(OH)D deficiency at follow-up, supporting a role for supplementation in incident NS.

Closing the gap in hypertension control between younger and older adults: National Health and Nutrition Examination Survey (NHANES) 1988 to 2010.

BACKGROUND: Joint National Committee goal blood pressure for all adults was <140/<90 mm Hg or lower from 1984 to 2013. Adults aged ≥60 years (older) have mainly isolated systolic hypertension, with major trials attaining systolic blood pressure <150 but not <140 mm Hg. The main objective was to assess changes in hypertension control to <140/<90 mm Hg in younger (aged <60 years) and older adults and <150/<90 mm Hg in the latter. METHODS AND RESULTS: National Health and Nutrition Examination Surveys (NHANES) 1988 to 1994, 1999 to 2004, and 2005 to 2010 were analyzed in adults aged ≥18 years. From 1988 to 1994 to 2005 to 2010, hypertension control to <140/<90 mm Hg improved in older (31.6% to 53.1%; P<0.001) and younger (45.7% to 55.9%; P<0.001) patients. The age gap in control declined from 14.1% (P<0.01) in 1988 to 1994 to 2.8% (P=0.13) in 2005 to 2010. Better hypertension control reflected increased percentages of older (55.6% to 77.5%) and younger (34.6% to 54.7%) patients on treatment and treated older (45.7% to 64.9%) and younger (56.8% to 73.4%) patients controlled (all P<0.001). Control to <150/<90 mm Hg rose from 48.8% to 69.9% in older adults. Antihypertensive medication number and percentages on ≥3 medications increased in both age groups but increased more in older patients (P<0.01). Blood pressure control was higher in both age groups with ≥2 healthcare visits per year and on statin therapy. CONCLUSIONS: The age gap in hypertension control to <140/<90 mm Hg was virtually eliminated in 2005 to 2010 as clinicians intensified therapy, especially in older patients in whom isolated systolic hypertension predominates, controlling 70% to <150/<90 mm Hg. More frequent healthcare visits and the use of statin therapy may improve hypertension control in all adults.

Renin Angiotensin System Blocker Fetopathy: A Midwest Pediatric Nephrology Consortium Report.

OBJECTIVES: Fetuses continue to be exposed to renin angiotensin system (RAS) blockers despite their known teratogenicity and a black box warning. We hypothesized that fetopathy from in utero exposure to RAS blockers has a broader spectrum of clinical manifestations than described previously and that there are a variety of clinical scenarios leading to such exposures. STUDY DESIGN: This was a retrospective study performed through the Midwest Pediatric Nephrology Consortium. Cases of RAS blocker fetopathy were identified, with determination of renal and extrarenal manifestations, timing of exposure, and the explanation for the fetal exposure. RESULTS: Twenty-four cases were identified. RAS blocker exposure after the first trimester was associated with more severe renal manifestations. Chronic dialysis or kidney transplantation was required in 8 of 17 (47%) patients with RAS blocker exposure after the first trimester and 0 of 7 patients with exposure restricted to the first trimester (P = .05). Extrarenal manifestations, some not previously noted in the literature, included central nervous system anomalies (cystic encephalomalacia, cortical blindness, sensorineural hearing loss, arachnoid cysts) and pulmonary complications (pneumothorax, pneumomediastinum). RAS blocker exposure usually was secondary to absent or poor prenatal care or undiagnosed pregnancy. CONCLUSION: RAS blocker fetopathy continues to be a cause of considerable morbidity, with more severe renal manifestations associated with exposure after the first trimester. A variety of significant extrarenal manifestations occur in these patients. Clinicians should emphasize the risk of fetopathy when prescribing RAS blockers to women of childbearing age.

The impact of disease duration on quality of life in children with nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND: The Patient Reported Outcomes Measurement Information System (PROMIS) II is a prospective study that evaluates patient reported outcomes in pediatric chronic diseases as a measure of health-related quality of life (HRQOL). We have evaluated the influence of disease duration on HRQOL and, for the first time, compared the findings of the PROMIS measures to those of the PedsQL™ 4.0 Generic Scales (PedsQL) from the PROMIS II nephrotic syndrome (NS) longitudinal cohort. METHODS: This was a prospective study in which 127 children (age range 8-17 years) with active NS from 14 centers were enrolled. Children with active NS defined as the presence of nephrotic range proteinuria (>2+ urinalysis and edema or urine protein/creatinine ratio >2 g/g) were eligible. Comparisons were made between children with prevalent (N = 67) and incident (N = 60) disease at the study enrollment visit. RESULTS: The PROMIS scores were worse in prevalent patients in the domains of peer relationship (p = 0.01) and pain interference (p < 0.01). The PedsQL showed worse scores in prevalent patients for social functioning (p < 0.01) and school functioning (p = 0.03). Multivariable analyses showed that prevalent patients had worse scores in PROMIS pain interference (p = 0.02) and PedsQL social functioning (p < 0.01). CONCLUSION: The PROMIS measures detected a significant impact of disease duration on HRQOL in children, such that peer relationships were worse and pain interfered with daily life to a greater degree among those with longer disease duration. These findings were in agreement with those for similar domains in the PedsQL legacy instrument.

Therapy of acute hypertension in hospitalized children and adolescents.

Acute hypertension (HTN) in hospitalized children and adolescents occurs relatively frequently, and in some cases, if not recognized and treated promptly, it can lead to hypertensive crisis with potentially significant morbidity and mortality. In contrast to adults, where acute HTN is most likely due to uncontrolled primary HTN, children and adolescents with acute HTN are more likely to have secondary HTN. This review will briefly cover evaluation of acute HTN and various age-specific etiologies of secondary HTN and provide more in-depth discussion on treatment targets, potential risks of acute HTN therapy, and available pediatric data on intravenous and oral antihypertensive agents, and it proposes treatment schema including unique therapy of specific secondary HTN scenarios.

The efficacy and safety of intravenous hydralazine for the treatment of hypertension in the hospitalized child.

BACKGROUND: Intravenous (IV) hydralazine is frequently used for the treatment of elevated blood pressure (BP) in hospitalized children. Its safety and efficacy have not been examined. METHODS: This is a retrospective chart review of IV hydralazine use in hospitalized children (birth to 17 years) over a 3-year period. Demographic data and data on adverse effects (AE), BP, and heart rate (HR) prior to and after each first dose were collected. RESULTS: The patient cohort comprised 110 children admitted to the hospital during the study period, of whom 77 received the recommended dose. Mean age of the children was 8.5 ± 5.4 years; 33 % were male, and 32.5 % were white. Pre-dose systolic and diastolic BP indexes were 1.3 and 1.2, respectively. The median reduction in systolic and diastolic BP was 8.5 and 11.5 %, respectively. Sixteen (21 %) children achieved a 25 % reduction in systolic or diastolic BP, and BP increased in 30 % of patients; 10 % of children had a BP of <95th percentile for age, sex, and height after one dose. Seven (9 %) children had a documented AE. HR increased by a median of 3.5 %. In the multivariable models examining percentage change in systolic and diastolic BP, male gender was significantly associated with a change in systolic BP. CONCLUSIONS: In hospitalized children, IV hydralazine was well tolerated, BP response was variable, and 21 % of the patients achieved a ≥25 % reduction of systolic or diastolic BP. Further studies are needed to compare the safety and efficacy of IV hydralazine to other short-acting antihypertensive agents.

Decreased heart rate variability is associated with increased transcranial Doppler velocities in children with sickle cell disease.

OBJECTIVE: To explore the relationship between 24-hour blood pressure (BP) variability, heart rate (HR) variability, and transcranial Doppler velocity (TCDV) in a cohort of pediatric sickle cell disease (SCD) patients. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective study of 11 children aged 8-18 years with SCD who previously underwent 24-hour ambulatory BP monitoring and TCDV measurements. INTERVENTIONS: Medical records were reviewed for TCDV and 24-hour ABP data. TCDV in the right and left middle cerebral artery were examined, and the highest velocity was recorded. HR and BP standard deviations were used as markers of variability. The relationships between daytime, nighttime, and 24-hour blood pressures and heart rate variability were determined. RESULTS: Mean age, body mass index and hemoglobin levels were 11.2 ± 3.0 years, 18.7 ± 3.4 kg/m2, and 9.1 ± 1.7 g/dL, respectively. Median transcranial Doppler velocity was 136cm/s (125-142). Decreased day, night, and 24-hour heart rate variability were significantly associated with increased transcranial Doppler velocity (R = -.69, P = .02; R = -.82 P =.002; R = -.66, P = .03, respectively). BP variability did not correlate with TCDV. Nighttime BP indexes were higher than daytime. CONCLUSIONS: In this small cohort, decreased heart rate variability assessed by the standard deviation of HR was associated with increased transcranial Doppler velocities in children with SCD. No correlation between measurements of BP variability and TCDV was found. Our study provides new information on heart rate and blood pressure variability and TCDV; a surrogate marker of stroke risk in sickle cell disease. Larger multicenter studies are needed to confirm our findings.

Masked hypertension is prevalent in children with sickle cell disease: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND: The prevalence of hypertension and abnormal blood pressure (BP) patterns on 24-h ambulatory BP monitoring (ABPM) remains unknown in children with sickle cell disease (SCD). METHODS: Thirty-eight asymptomatic children with sickle cell disease (SCD) (12 HbSS receiving routine care, 13 HbSC, and 13 HbSS receiving chronic transfusion therapy) underwent 24-h ABPM. Average clinic BP, demographic and biochemical characteristics were collected. RESULTS: Median age was 13 years (range 11-16), body mass index (BMI) 19.1 kg/m(2) (range 18.2-21.1), and 50% were male. Seventeen subjects (43.6%) had ambulatory hypertension, while 4 (10.3%) were hypertensive based on their clinic BP. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) dip were 8.3 ± 5.9% and 14.7 ± 7.6% respectively. Twenty-three subjects (59%) had impaired SBP dipping, 7 (18%) had impaired DBP dipping, and 5 (13%) had reversed dipping. Clinic and ABP classification were modestly correlated (rho = 0.38, P = 0.02). CONCLUSION: Abnormalities in ABP measurements and patterns in children with SCD are prevalent and require more attention from heath care providers. ABPM is a valuable tool in identifying masked hypertension and abnormalities in circadian BP.

Rituximab in post-transplant pediatric recurrent focal segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) recurs in 20-40 % of allografts. Plasmapheresis (TPE) has been one of the mainstays of treatment with variable results. Rituximab (RTX), a monoclonal antibody to the protein CD20, is being used for treatment of recurrent FSGS (recFSGS) but pediatric experience is limited. METHODS: We conducted a retrospective review of eight patients with recFSGS, treated with RTX (1-4 doses) after having minimal response to TPE. Complete response was defined as a decrease in urine protein creatinine ratio (Up/c) to less than 0.2 and partial response was a decrease in Up/c ratio by 50 % of baseline and in the sub-nephrotic range (U p/c <2). RESULTS: Complete response was seen in two of eight patients, and partial response was seen in four of eight patients. Two patients had no response. At last follow-up, all the partial responders had sub-nephrotic range proteinuria (Up/c ratios ranging from 0.29 to 1.6). Delayed response, up to 9 months post-RTX, was also seen in some of the patients. Significant complications such as rituximab-associated lung injury (RALI), acute tubular necrosis, and central nervous system(CNS) malignancy were also observed in our case series. CONCLUSIONS: Rituximab can be used with caution as a treatment for recFSGS. Efficacy is variable from none to complete response. Even partial reduction in proteinuria is of benefit in prolonging the life of the allograft. Long-term, multicenter studies are needed to prove its sustained efficacy in those who respond and to monitor for serious adverse effects.

Serum uric acid in U.S. adolescents: distribution and relationship to demographic characteristics and cardiovascular risk factors.

BACKGROUND: Despite being associated with multiple disease processes and cardiovascular outcomes, uric acid (UA) reference ranges for adolescents are lacking. We sought to describe the distribution of UA and its relationship to demographic, clinical, socioeconomic, and dietary factors among U.S. adolescents. METHODS: A nationally representative subsample of 1,912 adolescents aged 13-18 years in NHANES 2005-2008 representing 19,888,299 adolescents was used for this study. Percentiles of the distribution of UA were estimated using quantile regression. Linear regression models examined the association of UA and demographic, socioeconomic, and dietary factors. RESULTS: Mean UA level was 5.14 ± 1.45 mg/dl. Mean UA increased with increasing age and was higher in non-Hispanic white race, male sex, higher body mass index (BMI) Z-score, and with higher systolic blood pressure. In fully adjusted linear regression models, sex, age, race, and BMI were independent determinants of higher UA. CONCLUSIONS: This study defines serum UA reference ranges for adolescents. Also, it reveals some intriguing relationships between UA and demographic and clinical characteristics that warrant further studies to examine the pathophysiological role of UA in different disease processes.

Potentiation of vincristine toxicity with concomitant fluconazole prophylaxis in children with acute lymphoblastic leukemia.

Use of azole antifungals as prophylaxis is becoming an increasingly common practice in acute lymphoblastic leukemia (ALL). Limited literature in adults heightened the awareness of possible increased vincristine (VCR) toxicity in patients receiving concomitant azole therapy. This is due to inhibition of cytochrome P450 3A4, which may increase overall exposure to VCR, resulting in dose reductions or omissions. The primary objective of this study was to determine whether the use of fluconazole prophylaxis increases vincristine toxicity in children with ALL. The authors retrospectively evaluated children with ALL between January 2004 and December 2009. Patients were subdivided into 2 groups based on whether or not they received fluconazole prophylaxis during induction therapy. Data were collected for up to 3 months following the completion of induction therapy. Thirty-one patients were included for analysis. There was no significant difference in gender, race, steroid use, gastrointestinal (GI) toxicity, VCR dose modification, and the rate of fungal or bacterial infections between these 2 groups. Only advanced age is an independent predictor of neuropathy. Patients receiving fluconazole were 4.5 times more likely to experience neuropathy than those not receiving azole; however, this was not statistically significant. The authors report an increased incidence of VCR toxicity in patients with ALL receiving concomitant fluconazole prophylaxis. Judicious use of azole antifungals is warranted in children with ALL.

Characterization of the Urinary Metagenome and Virome in Healthy Children.

Recent advances in next-generation sequencing and metagenomic studies have provided insights into the microbial profile of different body sites. However, research on the microbial composition of urine is limited, particularly in children. The goal of this study was to optimize and develop reproducible metagenome and virome protocols using a small volume of urine samples collected from healthy children. We collected midstream urine specimens from 40 healthy children. Using the metagenomics shotgun approach, we tested various protocols. Different microbial roots such as Archaea, Bacteria, Eukaryota, and Viruses were successfully identified using our optimized urine protocol. Our data reflected much variation in the microbial fingerprints of children. Girls had significantly higher levels of Firmicutes, whereas boys had significantly higher levels of Actinobacteria. The genus Anaerococcus dominated the urinary bacteriome of healthy girls, with a significant increase in Anaerococcus prevotii, Anaerococcus vaginalis, and Veillonella parvula (p-value < 0.001) when compared with that of boys. An increased relative abundance of Xylanimonas and Arthrobacter, with a significantly high abundance of Arthrobacter sp. FB24 (p-value 0.0028) and Arthrobacter aurescences (p-value 0.015), was observed in boys. The urinary mycobiome showed a significant rise in the genus Malassezia and Malassezia globose fungus (p-value 0.009) in girls, whereas genus Saccharomyces (p-value 0.009) was significantly high in boys. The beta diversity of the urinary mycobiome was found to differ between different age groups. Boys had significantly more Mastadenovirus and Human mastadenovirus-A in their urinary virome than girls. With increasing age, we noticed an increase in the relative abundance of the order Caudovirales. Our optimized protocols allowed us to identify the unique microbes for each sex by using an adequate volume of urine (3−10 mL) to screen for the bacteriome, mycobiome, and virome profiles in the urine of healthy children. To the best of our knowledge, this is the first study to characterize the metagenomics profiles of urine in a healthy pediatric population.

Relationships between renin, aldosterone, and 24-hour ambulatory blood pressure in obese adolescents.

Renin-angiotensin system (RAS) activation and abnormalities of ambulatory blood pressure (ABP) are present in obesity, but relationships between components of the RAS and ABP have not been defined in the young. Anthropometric measurements and 24-h ABP were obtained on 30 obese adolescents with and without type 2 diabetes mellitus. Plasma renin activity (PRA), aldosterone, and other cardiovascular risk factors were measured. Median PRA levels were 2.5 [interquartile range (IQR), 1.7-4.1] ng/mL/h and were higher in the diabetic subjects compared with the nondiabetics. Females had significantly higher PRA than males 3.2 (IQR, 2-4.8) versus 1.8 (IQR, 1.1-2.9) ng/mL/h (p = 0.04) and were more obese. BMI Z score and PRA were significantly correlated (rho = 0.46, p < 0.001). PRA inversely correlated with 24-h systolic ABP (rho = -0.46, p = 0.02) and strongly with 24-h pulse pressure (rho = -0.61, p = 0.001). Aldosterone levels were also correlated with 24-h pulse pressure (rho = -0.46, p = 0.02). In multivariate models, lower PRA was independently associated with 24-h systolic blood pressure. In this study, PRA was positively correlated with BMI, but the relationships between components of the RAS and ABP were inverse. Further studies are needed to define the pathophysiologic relationship between RAS components and blood pressure regulation in obese youth.

The Human Microbiome in Chronic Kidney Disease: A Double-Edged Sword.

Chronic kidney disease (CKD) is an increasing global health burden. Current treatments for CKD include therapeutics to target factors that contribute to CKD progression, including renin-angiotensin-aldosterone system inhibitors, and drugs to control blood pressure and proteinuria control. Recently, associations between chronic disease processes and the human microbiota and its metabolites have been demonstrated. Dysbiosis-a change in the microbial diversity-has been observed in patients with CKD. The relationship between CKD and dysbiosis is bidirectional; gut-derived metabolites and toxins affect the progression of CKD, and the uremic milieu affects the microbiota. The accumulation of microbial metabolites and toxins is linked to the loss of kidney functions and increased mortality risk, yet renoprotective metabolites such as short-chain fatty acids and bile acids help restore kidney functions and increase the survival rate in CKD patients. Specific dietary interventions to alter the gut microbiome could improve clinical outcomes in patients with CKD. Low-protein and high-fiber diets increase the abundance of bacteria that produce short-chain fatty acids and anti-inflammatory bacteria. Fluctuations in the urinary microbiome are linked to increased susceptibility to infection and antibiotic resistance. In this review, we describe the potential role of the gut, urinary and blood microbiome in CKD pathophysiology and assess the feasibility of modulating the gut microbiota as a therapeutic tool for treating CKD.

Case Report: Recurring Peritonitis and Dialysis Failure in a Toddler on Peritoneal Dialysis.

We report a case of a 2-year-old-boy with end stage renal disease (ESRD) secondary to posterior urethral valves (PUV) on peritoneal dialysis (PD). Our patient developed multiple episodes of peritonitis, refractory anemia and feeding intolerance over a 12-month-period. He was treated with multiple courses of intraperitoneal antibiotics. Despite being on high-calorie formula, he was slowly thriving. The feeding intolerance was attributed to past history of prematurity, gastro-esophageal reflux disease and ESRD co-morbidities. He had anemia resistant to erythrocyte stimulating agents and iron supplementation. His family received re-training and mastered the PD techniques. They reported no breach of the aseptic techniques. His workup which included multiple AP abdominal XR-plain films were read as unremarkable and showed the gastrostomy tube (GT) and the PD catheter in good position. He completed his antibiotic courses as prescribed after each peritonitis episode, peritoneal fluid cultures repeated after each treatment completion showed no growth. During the last peritonitis episode, our patient developed ultrafiltration failure. A cross-table abdominal XR was obtained to evaluate the peritoneal catheter position and showed an intra-abdominal foreign body. During surgery, a needle was laparoscopically removed from the ileum and the PD catheter was replaced. Subsequently, our patient's feeding intolerance and resistant anemia resolved. Finally PD was successfully resumed.

Bifidobacterium reduction is associated with high blood pressure in children with type 1 diabetes mellitus.

Children with Type 1 diabetes mellitus (T1DM) have an elevated risk of abnormal blood pressure (BP) measurements and patterns. Both hypertension and T1DM are well-known risk factors for cardiovascular disease and kidney failure. The human microbiome has been linked to both diabetes and hypertension, but the relationship between the gut microbiome and BP in children with T1DM is not well-understood. In this cross-sectional study, we examined the relationship between resting office BP and gut microbiota composition, diversity, and richness in children with T1DM and healthy controls. We recruited 29 pediatric subjects and divided them into three groups: healthy controls (HC, n = 5), T1DM with normal BP (T1DM-Normo, n = 17), and T1DM with elevated BP (T1DM-HBP, n = 7). We measured the BP, dietary and clinical parameters for each subject. We collected fecal samples to perform the 16s rDNA sequencing and to measure the short-chain fatty acids (SCFAs) level. The microbiome downstream analysis included the relative abundance of microbiota, alpha and beta diversity, microbial markers using Linear Discriminant effect size analysis (LEfSe), potential gut microbial metabolic pathways using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) and metabolic pathways validation using Statistical Inference of Associations between Microbial Communities And host phenotype (SIAMCAT) machine learning toolbox. Our study results showed that T1DM-HBP group had distinct gut microbial composition (at multiple taxonomic levels) and reduced diversity (richness and abundance) compared with T1DM-Normo and HC groups. Children with T1DM-HBP showed a significant reduction of Bifidobacterium levels (especially B. adolescentis, B. bifidum, and B. longum) compared to the T1DM-Normo group. We also observed unique gut-microbial metabolic pathways, such as elevated lipopolysaccharide synthesis and glutathione metabolism in children with T1DM-HBP compared to T1DM-Normo children. We can conclude that the reduction in the abundance of genus Bifidobacterium could play a significant role in elevating the BP in pediatric T1DM subjects. More studies are needed to corroborate our findings and further explore the potential contributing mechanisms we describe.