Background Phthalates are associated with increased blood pressure in children. Large exposures to di-(2-ethylhexyl) phthalate (DEHP) among premature infants have been a cause for concern. Methods We conducted a prospective observational cohort study to determine if DEHP exposures are related to systolic blood pressure (SBP) in premature infants, and if this exposure is associated with activation of the mineralocorticoid receptor (MR). Infants were monitored longitudinally for 8 months from birth. Those who developed idiopathic hypertension were compared with normotensive infants for DEHP exposures. Appearance of urinary metabolites after exposure was documented. Linear regression evaluated the relationship between DEHP exposures and SBP index and whether urinary cortisol/cortisone ratio (a surrogate marker for 11β-HSD2 activity) mediated those relationships. Urinary exosomes were quantified for sodium transporter/channel expression and interrogated against SBP index. Results Eighteen patients met the study criteria, nine developed transient idiopathic hypertension at a postmenstrual age of 40.6 ± 3.4 weeks. The presence of urinary DEHP metabolites was associated with prior IV and respiratory tubing DEHP exposures ( p < 0.05). Both IV and respiratory DEHP exposures were greater in hypertensive infants ( p < 0.05). SBP index was related to DEHP exposure from IV fluid ( p = 0.018), but not respiratory DEHP. Urinary cortisol/cortisone ratio was related to IV DEHP and SBP index ( p < 0.05). Sodium transporter/channel expression was also related to SBP index ( p < 0.05). Conclusions Increased blood pressure and hypertension in premature infants are associated with postnatal DEHP exposure. The mechanism of action appears to be activation of the MR through inhibition of 11β-HSD2. Electronic supplementary material The online version of this article (10.1007/s00467-019-04244-4) contains supplementary material, which is available to authorized users.

IntroductionThe Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients.MethodsPatients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment.ResultsA total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001).ConclusionThis report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.

While increased risk of cardiovascular disease (CVD) in patients with hyperlipidemia, chronic kidney disease (CKD), or end-stage renal disease (ESRD) is well documented, transient hyperlipidemia or intermittent renal disease as a consequence of relapsing nephrotic syndrome (NS) has not been studied. To investigate this enigma, 62 patients, between 25 and 53 years of age, who had steroid-responsive/dependent NS during childhood, were identified from the records of the Division of Pediatric Nephrology at Yale School of Medicine. Forty patients were located and contacted to ascertain symptoms or occurrences of CVD via a telephone interview. At the time of follow-up, 23-46 years after cessation of NS, none of these patients had ESRD or CKD. Three patients had experienced a myocardial infarction (MI): a 32-year-old male with a family history of CVD; a 41-year-old male with a history of heavy smoking, hypertension, diabetes mellitus, and elevated cholesterol; a 31-year-old male after a cocaine overdose. The occurrence of events (8%) and mortality from CVD (none) in this cohort of patients is comparable to patients of a similar age in the general population and is lower than that of patients of the same age who are on dialysis. The data suggest that relapsing NS during childhood does not place patients at increased risk for CVD mortality or morbidity compared with the general population. Consequently, it would appear that factors related to persistent proteinuria or renal insufficiency, rather than transient proteinuria and renal disease, contribute to the CVD documented in patients with CKD or ESRD.

Simple multicystic dysplastic kidney (MCDK) disease, defined as unilateral MCDK without other genitourinary tract involvement, portends an excellent prognosis. Nevertheless, its long-term management remains undefined. This study aims to provide subspecialty discharge recommendations for these patients. We identified eighty patients with simple MCDK disease by renal ultrasound between 1996 and 2006. Their charts were reviewed for growth of the contralateral kidney, involution of the MCDK, and incidence of complications, specifically hypertension, chronic renal insufficiency (CRI), urinary tract infection (UTI), and malignancy. Mean follow-up was 5 years. At approximately 1 year, 59% of unaffected kidneys were hypertrophied (>or=95th percentile for age/height) and 100% were >50th percentile. With continued follow-up, 80.3% of unaffected kidneys were hypertrophied. Likewise, at 1 year, 71.2% of MCDKs assessed were either involuting or had disappeared; on further follow-up, this increased to 89.6%. No patient had hypertension, CRI, or malignancy. Four patients (5%) developed nonrecurrent UTIs, none leading to renal scarring or growth impairment. These data suggest that subspecialty follow-up may be discontinued once contralateral hypertrophy and ipsilateral involution occur, assuming that the patient has not experienced hypertension, CRI, or UTI. These criteria are often met by 1 year of age, which would preclude repeated visits, uncomfortable investigations, and unnecessary costs.

Fifty-eight consecutive paediatric recipients of 65 renal transplants were prospectively studied for up to 72 months for evidence of cytomegalovirus (CMV) infection. Blood, urine and saliva were screened for CMV pre transplant and then weekly for the first 6 weeks, and monthly thereafter, by conventional cell culture and by detection of early antigen fluorescent foci. Donor CMV serostatus was available in 51 cases. All patients received triple therapy as immunosuppression and none had CMV prophylaxis. Twenty-six episodes of CMV infection (40% of transplants) and 10 of CMV disease (15%) were identified. Donor CMV seropositivity, regardless of recipient CMV serostatus, was significantly associated with CMV infection (P = 0.04). First CMV excretion was significantly earlier in patients who subsequently became symptomatic than in those who did not (P = 0.04), and a positive blood culture was significantly associated with CMV disease (P = 0.04). We found no association between extra anti-rejection treatment or recipient's age and CMV infection or disease. CMV disease had no influence on renal function as assessed by glomerular filtration rate at 6, 12 and 24 months post transplant, nor on graft loss. CMV disease was fatal in 1 patient. We conclude that trials of CMV prophylactic agents are indicated, particularly in recipients of CMV seropositive grafts. A positive blood culture should lead to consideration of anti-CMV therapy.