The enterohepatic circulation of bile salts is an important physiological route to recycle bile salts and ensure intestinal absorption of dietary lipids. The Na 1 -taurocholate cotransporting polypeptide SLC10A1 (NTCP) plays a key role in this process as the major transporter of conjugated bile salts from the plasma compartment into the hepatocyte. Here we present the first patient with NTCP deficiency, who was clinically characterized by mild hypotonia, growth retardation, and delayed motor milestones. Total bile salts in plasma were extremely elevated (up to 1,500 lM, ref. <16.3) but there were no clinical signs of cholestatic jaundice, pruritis, or liver dysfunction. Bile salt synthesis and intestinal bile salt signaling were not affected, as evidenced by normal plasma 7a-hydroxy-4-cholesten-3-one (C4) and FGF19 levels. Importantly, the presence of secondary bile salts in the circulation suggested residual enterohepatic cycling of bile salts. Sequencing of the SLC10A1 gene revealed a single homozygous nonsynonymous point mutation in the coding sequence of the gene, resulting in an arginine to histidine substitution at position 252. Functional studies showed that this mutation resulted in a markedly reduced uptake activity of taurocholic acid. Immunofluorescence studies and surface biotinylation experiments demonstrated that the mutant protein is virtually absent from the plasma membrane. Conclusion: We describe the identification of NTCP deficiency as a new inborn error of metabolism with a relatively mild clinical phenotype. The identification of NTCP deficiency confirms that this transporter is the main import system for conjugated bile salts into the liver but also indicates that auxiliary transporters are able to sustain the enterohepatic cycle in its absence. (HEPATOLOGY 2015;61:260-267)

Background Screening for chronic kidney disease is a challenge in community and primary care settings, even in high-income countries. We developed an artificial intelligence deep learning algorithm (DLA) to detect chronic kidney disease from retinal images, which could add to existing chronic kidney disease screening strategies. MethodsWe used data from three population-based, multiethnic, cross-sectional studies in Singapore and China. The Singapore Epidemiology of Eye Diseases study (SEED, patients aged ≥40 years) was used to develop (5188 patients) and validate (1297 patients) the DLA. External testing was done on two independent datasets: the Singapore Prospective Study Program (SP2, 3735 patients aged ≥25 years) and the Beijing Eye Study (BES, 1538 patients aged ≥40 years). Chronic kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min per 1•73m². Three models were trained: 1) image DLA; 2) risk factors (RF) including age, sex, ethnicity, diabetes, and hypertension; and 3) hybrid DLA combining image and RF. Model performances were evaluated using the area under the receiver operating characteristic curve (AUC). Findings In the SEED validation dataset, the AUC was 0•911 for image DLA (95% CI 0•886 -0•936), 0•916 for RF (0•891-0•941), and 0•938 for hybrid DLA (0•917-0•959). Corresponding estimates in the SP2 testing dataset were 0•733 for image DLA (95% CI 0•696-0•770), 0•829 for RF (0•797-0•861), and 0•810 for hybrid DLA (0•776-0•844); and in the BES testing dataset estimates were 0•835 for image DLA (0•767-0•903), 0•887 for RF (0•828-0•946), and 0•858 for hybrid DLA (0•794-0•922). AUC estimates were similar in subgroups of people with diabetes (image DLA 0•889 [95% CI 0•850-0•928], RF 0•899 [0•862-0•936], hybrid 0•925 [0•893-0•957]) and hypertension (image DLA 0•889 [95% CI 0•860-0•918], RF 0•889 [0•860-0•918], hybrid 0•918 [0•893-0•943]).Interpretation A retinal image DLA shows good performance for estimating chronic kidney disease, underlying the feasibility of using retinal photography as an adjunctive or opportunistic screening tool for chronic kidney disease in community populations.

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In multi-ethnic Asian adults, lower eGFR and higher albuminuria were independently associated with incident CVD and all-cause mortality. These findings extend previously reported similar associations in Western populations to Asians and emphasize the need for early detection of CKD and intervention to prevent adverse outcomes.

SIBO is common among postgastrectomy patients. It appears to be associated with postprandial intestinal symptoms and might aggravate late hypoglycemia. SIBO could be a new therapeutic target for managing intestinal symptoms in postgastrectomy patients.

BackgroundAdiponectin and leptin, two of the key cytokines secreted by adipocytes, have been shown to be associated with cardiovascular disease. However, the association of these adipocytokines with chronic kidney disease (CKD) is not clear. We examined the association of serum adiponectin, leptin levels and leptin to adiponectin ratio (LAR) with CKD in a population-based sample of Asian adults.MethodsWe conducted a case-control study (450 CKD cases and 920 controls matched for age, sex and ethnicity) involving Chinese and Indian adults aged 40–80 years who participated in the Singapore Epidemiology of Eye Diseases Study (2007–2011). CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73m2 from serum creatinine. Serum adiponectin and leptin levels were measured using commercially available ELISA. Odds ratio of CKD associated with elevated adiponectin and leptin levels were estimated using logistic regression models adjusted for age, gender, ethnicity, education, smoking, body mass index, diabetes, blood pressure, total and HDL cholesterol.ResultsCKD cases had higher levels of leptin (mean [SD] 9.7 [11.5] vs.16.9 [20.2] ng/mL, p<0.0001) and adiponectin (10.4 [7.4] vs. 9.2 [4.2], p = 0.001) compared to controls. In multi-variable models, compared to those in the lowest quartile, the OR (95% confidence interval) of CKD among those in the highest quartile were: 6.46 (3.84, 10.88), 1.94 (1.32–2.85) and 2.88 (1.78–4.64) for leptin, adiponectin and LAR. Similar associations were also observed when adiponectin and leptin were analyzed as continuous variables. This positive association of serum adiponectin, leptin and LAR with CKD was consistently present in subgroups of gender, ethnicity, diabetes, hypertension and overweight status (all P-interaction >0.1).ConclusionsHigher levels of serum adiponectin, leptin and LAR were positively associated with CKD independent of traditional risk factors in this Asian population.

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Background. Hypophosphatemia in critically ill patients may be exacerbated by renal replacement therapy (RRT). We aimed to identify risk factors and adverse outcomes associated with hypophosphatemia in intensive care patients treated with RRT for acute kidney injury (AKI). Methods. This was a secondary analysis of data from a single-center prospective cohort study of medical and surgical intensive care patients with RRT for AKI between 18 December 2010 and 3 April 2013. Demographic, comorbidity, laboratory and RRT data were retrieved from patient case notes and electronic medical records. Outcomes assessed were hypophosphatemia (serum phosphate <0.94 mmol/L) during RRT, intensive care unit (ICU) mortality, and duration of mechanical ventilation and vasopressor support. Results. Among 96 patients who received acute RRT, 25 (26.0%) developed hypophosphatemia. On multivariate logistic regression, serum phosphate at RRT initiation [adjusted odds ratio (OR) 0.29, 95% confidence interval (CI) (0.09, 0.91), P = 0.03] was independently associated with hypophosphatemia during acute RRT. Patients with hypophosphatemia during RRT required longer ventilatory support [median 12 (interquartile range: 8, 17) days versus 5 (3, 9) days, P < 0.001] and vasopressor support [5 (4, 15) days versus 2 (2, 6) days, P = 0.003] compared with those without hypophosphatemia but there was no significant difference in ICU mortality [5 patients (20.0%) versus 24 patients (33.8%), P = 0.20]. Hypophosphatemia during RRT was independently associated with prolonged mechanical ventilation (≥7 days) [adjusted OR 14.0, 95% CI (1.37, 143.90), P = 0.03]. Conclusion. Hypophosphatemia is common during acute RRT for critically ill patients and was associated with adverse clinical outcomes.