Jonas Esche

Higher glucocorticoid secretion in the physiological range is associated with lower bone strength at the proximal radius in healthy children: importance of protein intake adjustment.

Whether higher production of glucocorticoids (GCs) within the physiological range may already be affecting bone status in healthy children is unknown. Because dietary protein intake affects both bone and GCs, we examined the association of urinary measures of glucocorticoid status and cortical bone in healthy non‐obese children, after particularly controlling for protein intake. Proximal forearm bone parameters were measured by peripheral quantitative computed tomography (pQCT). Subjects studied (n = 175, 87 males, aged 6 to 18 years) had two 24‐hour urine samples collected: the first sample at 1 year before bone measurement, and the second sample at the time of bone measurement. Major urinary GC metabolites were measured by mass spectrometry and summed to assess daily adrenal GC secretion (∑C21). Urinary free cortisol (UFF) and cortisone (UFE) were summed to assess potentially bioactive free GCs (UFF + UFE). After controlling for several covariates and especially urinary nitrogen (the biomarker of protein intake) cortisol secretion ∑C21 was inversely associated with all analyzed pQCT measures of bone quality. ∑C21 also predicted a higher endosteal and lower periosteal circumference, explaining both a smaller cortical area and (together with lower BMD) a lower strength‐strain‐index (SSI). UFF + UFE, UFE itself, and a urinary metabolite‐estimate of 11beta‐hydroxysteroid dehydrogenase type1 (11beta‐HSD1) activity showed corresponding reciprocal associations (p < 0.05) with BMD and bone mineral content, but not with SSI and bone geometry variables. In conclusion, higher GC levels, even within the physiological range, appear to exert negative influences on bone modeling and remodeling already during growth. Our physiological data also suggest a relevant role of cortisone as the direct source for intracrine‐generated cortisol by bone cell 11beta‐HSD1.

Seizure Outcomes in Patients With Surgically Treated Cerebral Arteriovenous Malformations.

BACKGROUND Epilepsy is the second most common symptom in cerebral arteriovenous malformation (AVM) patients. The consecutive reduction of life quality is a clinically underrated problem because treatment usually focuses on the prevention of intracerebral hemorrhage. OBJECTIVE To evaluate postoperative seizure outcome with the aim of more accurate counseling for postoperative seizure outcome. METHODS From 1985 to 2012, 293 patients with an AVM were surgically treated by J.S. One hundred twenty-six patients with preoperative seizures or epilepsy could be identified; 103 of 126 had a follow-up of at least 12 months and were included in the analysis. The different epilepsy subtypes were categorized (sporadic seizures, chronic epilepsy, drug-resistant epilepsy [DRE]). Preoperative workup and surgical technique were evaluated. Seizure outcome was analyzed by using International League Against Epilepsy classification. RESULTS Sporadic seizures were identified in 41% of patients (chronic epilepsy and DRE were identified in 36% and 23%, respectively). Detailed preoperative epileptological workup was done in 13%. Seizure freedom was achieved in 77% (79% at 5 years, 84% at 10 years). Outcome was significantly poorer in DRE cases. More extensive resection was performed in 11 cases with longstanding symptoms (>24 months) and resulted in better seizure outcome as well as the short duration of preoperative seizure history. CONCLUSION Patients presenting with AVM-associated epilepsy have a favorable seizure outcome after surgical treatment. Long-standing epilepsy and the progress into DRE markedly deteriorate the chances to obtain seizure freedom and should be considered an early factor in establishing the indication for AVM removal.

Diet‐independent relevance of serum uric acid for blood pressure in a representative population sample

A direct relationship between serum uric acid and blood pressure (BP) has been reported, but the possible confounding impact of diet on this association is unclear. The authors performed a cross‐sectional analysis in the representative German Health Interview and Examination Survey for Adults (n=6788, aged 18–79 years). In adjusted regression models considering dietary factors, each 1‐mg/dL higher uric acid value was associated with a 1.10‐mm Hg (P=.0002) and a 0.60‐mm Hg (P=.04) higher systolic BP among participants younger than 50 years and participants 50 years and older, respectively. For diastolic BP, uric acid was a significant predictor (β=0.71 mm Hg, P=.0001) among participants younger than 50 years and for participants 50 years and older without antihypertensive treatment. Adjusted odds ratios of hypertension for participants with hyperuricemia were broadly similar in younger (odds ratio, 1.71; P=.02) and older (odds ratio, 1.81; P=.0003) participants. Uric acid is a significant predictor of systolic BP and hypertension prevalence in the general adult population in Germany independently of several known dietary BP influences.

Dietary Acid Load and Potassium Intake Associate with Blood Pressure and Hypertension Prevalence in a Representative Sample of the German Adult Population

Diets rich in fruits and vegetables, like the Dietary Approaches to Stop Hypertension (DASH)-diet, are usually characterized by high potassium intake and reduced dietary acid load, and have been shown to reduce blood pressure (BP). However, the relevance of potential renal acid load (PRAL) for BP has not been compared with the relevance to BP of urinary biomarker (K-urine)- and dietary food frequency questionnaire (K-FFQ)-based estimates of potassium intake in a general adult population sample. For 6788 participants (aged 18–79 years) of the representative German Health-Interview and Examination Survey for Adults (DEGS1), associations of PRAL, K-urine, and K-FFQ with BP and hypertension prevalence were cross-sectionally examined in multivariable linear and logistic regression models. PRAL was significantly associated with higher systolic BP (p = 0.0002) and higher hypertension prevalence (Odds ratio [OR] high vs. low PRAL = 1.45, p = 0.0004) in models adjusted for age, sex, body mass index (BMI), estimated sodium intake, kidney function, relevant medication, and further important covariates. Higher estimates of K-FFQ and K-urine were related to lower systolic BP (p = 0.04 and p < 0.0001) and lower hypertension prevalence (OR = 0.82, p = 0.04 and OR = 0.77, p = 0.02) as well as a lower diastolic BP (p = 0.03 and p = 0.0003). Our results show, for the first time in a comparative analysis of a large representative population sample, significant relationships of BP and hypertension prevalence with questionnaire- and biomarker-based estimates of potassium intake and with an estimate of dietary acid load.

Dietary Potential Renal Acid Load Is Positively Associated with Serum Uric Acid and Odds of Hyperuricemia in the German Adult Population

Background Initial interventional data indicate that a reduction in dietary acid load (e.g., by an increased consumption of alkalizing fruit and vegetables) can increase renal uric acid excretion and decrease serum uric acid (SUA). Objective Against this background, we examined the association between dietary potential renal acid load (PRAL) and SUA in a representative population sample. Methods Cross-sectional analyses were performed in 6894 participants (aged 18-79 y) of the German Health Interview and Examination Survey for Adults (DEGS1). Dietary intake was assessed with a food-frequency questionnaire. Nutritive acid load and the intake of uric acid equivalents (UAEs) were characterized by assigning PRAL and UAE values to reported food consumption. In multiple linear regression models, the associations of PRAL, UAEs, and relevant food groups with SUA were analyzed. Multiple logistic regressions were used to calculate ORs for hyperuricemia comparing lower and upper tertiles of the predictors. Results After adjustment for relevant confounders, PRAL (P = 0.003), alcohol (P < 0.0001), and UAE (P = 0.03) intakes were positively associated with SUA, whereas the intake of dairy products and fruit and vegetables was inversely associated (both P < 0.0001). Subgroup analyses among participants without interacting medication use confirmed these results. In addition, participants with lower PRAL had lower odds for hyperuricemia (OR: 0.60; 95% CI: 0.43, 0.83). Conclusions Apart from observing known dietary influences on SUA, we found in this population-based, cross-sectional study in adults that low PRAL may represent a potentially SUA-reducing dietary pattern. This highlights dietary alkalization as a possible nonpharmacologic option to influence elevated SUA concentrations.

Response to: Relationship between serum uric acid and blood pressure by adjusting dietary factors

To the Editor: We read with interest the letter in response to our recently published work.1 We thank Dr Kawada for his comments on our analyses of uric acid as a potentially dietindependent influencing factor of blood pressure (BP) in the German adult population. We are fully in line with Dr. Kawada that multiple factors, including exercise, sleep, and especially diet are related to BP. For this reason, we performed comprehensive data analyses using different statistical models to examine whether uric acid per se, independently of many of the known determinants, is relevant for BPvariation. Despite this extensive adjustment, explained model variation remained below 0.3, as has been indicated by Dr Kawada. Similar or even lower R2values, for example in the recent study of Lee et al2 on the association of uric acid and BP in Korean adults, underline that research is still needed with respect to further determinants of human BP. In this regard, Dr Kawada particularly mentioned our different sensitivityand subgroupanalyses performed to specifically check robustness of the uric acid/BP relationship under various conditions, and he points out the “advantage of elucidating the dietindependent relationship.” We again thank Dr Kawada for this appraisal. Finally, we also agree with his view that the causal mechanism relating uric acid and BP needs to be further explored in more depth. CONFLICT OF INTEREST

Prospective relation of adolescent citrate excretion and net acid excretion capacity with blood pressure in young adulthood

Experimental data and observational studies in adults suggest that even subtle changes in acid-base balance, indicative of a higher systemic proton load, are related to higher blood pressure (BP) levels and an increased hypertension risk. However, these associations have not been investigated during growth. The kidney is the central organ in regulating excretion of nonvolatile acids, and renal citrate excretion has been shown to be a sensitive, noninvasive marker of changes in systemic acid balance. We thus analyzed the prospective relation of 24-h citrate excretion, as well as net acid excretion capacity (NAEC; a noninvasive indicator of the renal ability to excrete protons), during adolescence (boys: 10-15 yr; girls: 9-14 yr) with BP levels in young adulthood (18-30 yr) in 374 healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. In linear-regression analyses adjusted for age, sex, 24-h urinary excretions of sodium and potassium, as well as further relevant confounders, a 1-mmol/1.73 m2/day higher adolescent citrate excretion was related to 1.2 mmHg lower systolic BP ( P = 0.02) but not to diastolic BP ( P = 0.6). A 10-mEq higher NAEC during adolescence was related to 1.7 mmHg lower systolic BP in young men, but this association was statistically nonsignificant ( P = 0.07) after multivariable adjustment. Additional adjustment for adult body mass index did not alter these findings. To conclude, subtle changes in systemic acid-base balance during adolescence are already indicative for later BP. Potential sex differences in these associations should be investigated in further studies.