Circadian rhythm of water and solute excretion in nocturnal enuresis HYPOTHESIS: Several circadian rhythms of the kidney play a role in the pathogenesis of enuresis DESIGN & OUTCOMES:

Background The association of hyperthyroidism with renal disease is very rare and the importance of timely clinical recognition cannot be overemphasized. Case presentation An 11-year-old girl presented with gastrointestinal symptoms while hypertension, edema and abdominal pain were noticed on clinical examination. Laboratory investigation revealed: hemoglobin 9.4 (11.5-15.5) g/dL, total white cell count 16 (4.5-12)×109/L, platelets 247 (150-450)×109/L, C-reactive protein (CRP) 31.8 (<5) mg/L, blood urea nitrogen (BUN) 126 (13-43) mg/dL, creatinine 0.98 (0.53-0.79) mg/dL, albumin 25 (35-52) g/dL, complement factor C3 0.7 (0.9-1.8) g/L, complement factor C4 0.1 (0.1-0.4) g/L, tri-iodothyronine 6.5 (2.5-5.2) pg/mL, free thyroxine 2.4 (1-1.7) ng/dL, thyroid stimulating hormone (TSH) <0.02 (0.5-4.3) mU/L. Urinalysis showed nephrotic range proteinuria. Renal function deteriorated necessitating hemodialysis (HD). A renal biopsy revealed an immune complex-mediated membranoproliferative glomerulonephritis (MPGN). Elevated thyroid hormones and suppressed TSH levels with elevated thyroperoxidase antibodies and thyroid stimulating immunoglobulins confirmed the diagnosis of Graves' disease. Corticosteroids were commenced and eventually thiamazole was added with gradual improvement of renal function, cessation of HD and discharge from the hospital. Conclusions Graves' disease complicated by MPGN is extremely rare, but can cause life-threatening complications.

Diarrhea-associated hemolytic uremic syndrome (HUS) is usually associated with shigatoxin-producing Escherichia coli or shigella infections. We report 2 cases of HUS, respectively, caused by salmonella and Campylobacter jejuni infections. None of these bacteria produce shigatoxins, and the underlying mechanism of HUS development remains unknown. In streptococcus pneumoniae-associated HUS, bacterial neuraminidase cleaves neuraminic acid and causes exposure of Thomsen-Friedenreich cryptantigen on the cell surface of, for example, erythrocytes, which induces an inflammatory response caused by binding of preformed IgM. Both campylobacter and salmonella bacteria also produce neuraminidase, and HUS development could be explained by a similar mechanism.

Background: Lisinopril, an angiotensin-converting enzyme inhibitor (ACEi), is a frequently prescribed antihypertensive drug in the pediatric population, while being used off-label under the age of 6 years in the US and for all pediatric patients globally. The SAFEPEDRUG project (IWT-130033) investigated lisinopril pharmacokinetics in hypertensive pediatric patients corresponding with the day-to-day clinical population. Methods: The dose-escalation pilot study included 13 children with primary and secondary hypertension who received oral lisinopril once daily in the morning; doses ranged from 0.05mg.kg-1 to 0.2 mg.kg-1. Patients were aged between 1.9 and 17.9 years (median 13.5 years) and weight ranged between 9.62 and 97.2kg (median 53.2kg). All data were analyzed using Monolix version 2020R1 (Lixoft®, France) and R version 3.6.2. Results: A one-compartment model with 1st order absorption and 1st order elimination optimally describes the data. Parameter estimates of ka (0.077h-1 [9.6%], typical value [relative standard error]), V/F (32.9L 70.g-1 [37%]) and CL/F (23.1L h-1 .70kg-1[8.5%]) show good predictive ability. Significant covariate effects include total body weight on elimination clearance, and distribution volume and estimated glomerular filtration rate (eGFR) on elimination clearance. The effects of eGFR on the elimination clearance are optimally described by a power law parameterization centered around 105 mL.min.1.73m2. The effects of body weight were implemented using fixed allometric exponents centered around an adult weight of 70kg. Conclusion: Lisinopril dose and regimen adjustments for pediatric patients should include eGFR on top of weight adjustments. An expanded model characterizing the pharmacodynamic effect is required to identify the optimal dose and dosing regimen.