Serum bicarbonate is associated with kidney outcomes in autosomal dominant polycystic kidney disease

BACKGROUND: Metabolic acidosis accelerates progression of chronic kidney disease, but whether this is also true for autosomal dominant polycystic kidney disease (ADPKD) is unknown. METHODS: Patients with ADPKD from the DIPAK (Developing Interventions to halt Progression of ADPKD) trial were included [n = 296, estimated glomerular filtration rate (eGFR) 50 ± 11 mL/min/1.73 m(2), 2.5 years follow-up]. Outcomes were worsening kidney function (30% decrease in eGFR or kidney failure), annual eGFR change and height-adjusted total kidney and liver volumes (htTKV and htTLV). Cox and linear regressions were adjusted for prognostic markers for ADPKD [Mayo image class and predicting renal outcomes in ADPKD (PROPKD) scores] and acid–base parameters (urinary ammonium excretion). RESULTS: Patients in the lowest tertile of baseline serum bicarbonate (23.1 ± 1.6 mmol/L) had a significantly greater risk of worsening kidney function [hazard ratio = 2.95, 95% confidence interval (CI) 1.21–7.19] compared with patients in the highest tertile (serum bicarbonate 29.0 ± 1.3 mmol/L). Each mmol/L decrease in serum bicarbonate increased the risk of worsening kidney function by 21% in the fully adjusted model (hazard ratio = 1.21, 95% CI 1.06–1.37). Each mmol/L decrease of serum bicarbonate was also associated with further eGFR decline (−0.12 mL/min/1.73 m(2)/year, 95% CI −0.20 to −0.03). Serum bicarbonate was not associated with changes in htTKV or htTLV growth. CONCLUSIONS: In patients with ADPKD, a lower serum bicarbonate within the normal range predicts worse kidney outcomes independent of established prognostic factors for ADPKD and independent of urine ammonium excretion. Serum bicarbonate may add to prognostic models and should be explored as a treatment target in ADPKD

The time-dependent rearrangement of the epithelial basement membrane in human skin wounds

In 62 human skin wounds (surgical wounds, stab wounds and lacerations after surgical treatment) we analyzed the immunohistochemical localization of collagen IV in the epithelial basement membrane. In 27 of these wounds the distribution of collagen VII, which represents a specific component of the basement membrane of stratified epithelia, was also analyzed. We were able to demonstrate a virtually identical co-distribution of both collagen IV and VII in the wound area with no significant time-dependent differences in the appearance of both collagen types. Fragments of the epithelial basement membrane could be detected in the wound area from as early as 4 days after wounding and after 8 days a complete restitution of the epithelial basement membrane was observed. In all cases with a wound age of more than 21 days the basement membrane was completely reformed over the former lesional area. The period between 8 and 21 days after wounding was characterized by a wide variability ranging from complete restitution to deposition of basement membrane fragments or total lack of the epidermal basement membrane

Primary School Pupils:Unequal GMC Developmental Pathways in a Single School Year

Gross motor coordination (GMC) is essential for the development of specific motor skills and long-term participation in physical activities and sports. Group analysis reveals that, on average, children develop these skills gradually; however, how individuals develop GMC is less clear. The main aim of this study is to increase the understanding of developmental patterns within one school year, and whether children’s grade, gender, or baseline GMC proficiency are associated with these developmental patterns. In total, 2594 Dutch children aged 6–12 years performed the modified Körper Koordinations Test für Kinder (KTK3+) twice in one school year (autumn and spring). The KTK3+ includes four subtests: walking backwards, moving sideways, jumping sideways, and eye-hand coordination (EHC) test. On average, children developed significantly on all subtests (p < 0.001). At baseline, children in higher grades scored significantly higher than children in lower grades, and children in grades 5 and 6 (age 9 and 10 years) showed most development (raw scores on average, p < 0.001). Boys outperformed girls on EHC across all grades, whereas girls outperformed boys on walking backwards. Nevertheless, both boys and girls developed similarly. Children with lower scores at baseline developed more quickly across all grades. Noteworthy is that 12.1–24% (depending on the test item) of the children scored lower in the spring than in the autumn tests. On average, children develop their GMC; however, we report large differences in their individual trajectories and note that a substantial number did not show a positive GMC development. Further research should examine GMC development with more possible influencing factors as well as over a longer time span to better understand differences in children’s GMC development. This may result in more individualized programs in PE lessons, enabling children to optimally develop their GMC, and better use of GMC assessment tools to monitor children’s development

Analyzing stage and duration of Anglo-Chinese business-to-business relationships

This is the post-print version of the final paper published in Industrial Marketing Management. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2010 Elsevier B.V.The manuscript reports on a study aimed at analyzing a series of relational variables derived from the Western industrial buyer–seller relationship and Chinese guanxi literature. The findings based on data collected from over 200 Taiwanese trading firms reveal that buyer's perceptions of organizational trust, communication, cooperation, social bonding and the saving of face are higher in Anglo-Chinese relationships that venture beyond the short-term. It is also found that cooperation, social bonding and performance are greater in those b2b relationships surveyed that are relatively more mature than in emerging states. The findings also reveal that relationship duration and stage have a significant moderating effect on various Inter-organizational and Interpersonal–Outcome relationships. Several managerial implications are extracted to help Western firms better manage their international relations, as well as help new exporting firms penetrate such well-established guanxi networks

Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study

Introduction and Aims: The DIPAK-1 Study investigates the reno- and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several episodes of hepatic cyst infection, all during lanreotide treatment. We describe these events and provide a review of the literature. Methods: The DIPAK-1 Study is an ongoing investigator-driven, randomized, controlled, open-label multicenter trial. Patients (ADPKD, ages 18–60 years, estimated glomerular filtration rate 30–60 mL/min/1.73 m2) were randomized 1:1 to receive lanreotide 120 mg subcutaneously every 28 days or standard care during 120 weeks. Hepatic cyst infection was diagnosed by local physicians. Results: We included 309 ADPKD patients of which seven (median age 53 years [interquartile range: 48–55], 71% female, median estimated glomerular filtration rate 42 mL/min/1.73 m2 [interquartile range: 41–58]) developed eight episodes of hepatic cyst infection during 342 patient-years of lanreotide use (0.23 cases per 10 patient-years). These events were limited to patients receiving lanreotide (p < 0.001 vs. standard care). Baseline characteristics were similar between subjects who did or did not develop a hepatic cyst infection during lanreotide use, except for a history of hepatic cyst infection (29 vs. 0.7%, p < 0.001). Previous studies with somatostatin analogs reported cyst infections, but did not identify a causal relationship. Conclusions: These data suggest an increased risk for hepatic cyst infection during use of somatostatin analogs, especially in ADPKD patients with a history of hepatic cyst infection. The main results are still awaited to fully appreciate the risk–benefit ratio. ClinicalTrials.gov identifier: NCT 01616927

Yield of diagnostic tests in unexplained renal hypophosphatemia: A case series

Background: Isolated renal hypophosphatemia may be inherited or acquired. An increasing number of patients with unexplained renal hypophosphatemia is being referred to our clinics, but the optimal diagnostic work-up is not known. Therefore, the aim of this study was to assess the diagnostic yield in these patients. Methods: We retrospectively evaluated all patients who were referred because of unexplained isolated renal hypophosphatemia to two academic tertiary referral centers in The Netherlands in the period of 2013-2017. Results: We evaluated 17 patients. In five female patients renal hypophosphatemia could be attributed to the use of oral contraceptives. The other 12 patients had a median age of 48 years (10 males). There were no other signs of tubulopathy and none of the patients used drugs known to be associated with hypophosphatemia. FGF23 levels were above normal (> 125 RU/ml) in 2/12 patients. Genetic testing, performed in all patients, did not identify a mutation in genes known to be associated with renal phosphate wasting. A scan with a radiolabeled somatostatin analogue was performed in 8 patients. In one patient, with an FGF23 level of 110 RU/ml, an increased uptake of the somatostatin analog was observed due to tumor induced o