Chan, Winnie

Background The concepts that obesity is merely a consequence of overeating, and that metabolic health then reflects obesity, may be insufficient and potentially flawed. The role of fructose intake and metabolic endotoxemia has gained attention recently, but data in kidney transplantation are lacking. This study evaluated the risk factors for metabolic syndrome (MS), its components, and other associated markers in kidney transplant recipients (KTRs), focusing particularly on fructose intake and systemic endotoxemia. Methods This cross-sectional observational study enrolled 128 KTRs longer than 1 year posttransplantation. Clinical, biochemical, anthropometric, and questionnaire assessments were undertaken. Results Obesity (body mass index, ≥30 kg/m2) and MS (International Diabetes Federation Definition) were found in 36.7% and 50% of KTRs, respectively. Both increased fructose intake (P = 0.01) and endotoxin level (P = 0.02) were independently associated with MS; and higher fructose intake was independently associated with obesity (P < 0.001). Specifically, increased fructose intake was associated with the central obesity (P = 0.01) and hyperglycemia (P < 0.001) criteria of MS, whereas higher endotoxin level was associated with the hypertriglyceridemia (P = 0.003) and low HDL cholesterol concentration (P = 0.002) criteria of MS. Neither saturated fat nor total caloric intakes were independently associated with obesity and MS; and neither obesity nor central obesity were independently associated with the dyslipidemia and hyperglycemia criteria of MS. Principal component analysis demonstrated relationships between higher levels of endotoxin, soluble endothelial selectin, triglycerides, and insulin resistance (r > 0.6), as well as relationships between increased fructose intake, inflammation, and blood glucose (r > 0.6). Conclusions Dietary modifications through decreasing fructose intake and addressing systemic endotoxemia are plausible targets for improving metabolic health of KTRs.

Renal disease variability in autosomal dominant polycystic kidney disease (ADPKD) is strongly influenced by the gene locus ( PKD1 versus PKD2 ). Recent studies identified nontruncating PKD1 mutations in approximately 30% of patients who underwent comprehensive mutation screening, but the clinical significance of these mutations is not well defined. We examined the genotype-renal function correlation in a prospective cohort of 220 unrelated ADPKD families ascertained through probands with serum creatinine ≤1.4 mg/dl at recruitment. We screened these families for PKD1 and PKD2 mutations and reviewed the clinical outcomes of the probands and affected family members. Height–adjusted total kidney volume (htTKV) was obtained in 161 affected subjects. Multivariate Cox proportional hazard modeling for renal and patient survival was performed in 707 affected probands and family members. Overall, we identified pathogenic mutations in 84.5% of our families, in which the prevalence of PKD1 truncating, PKD1 in–frame insertion/deletion, PKD1 nontruncating, and PKD2 mutations was 38.3%, 4.3%, 27.1%, and 30.3%, respectively. Compared with patients with PKD1 truncating mutations, patients with PKD1 in–frame insertion/deletion, PKD1 nontruncating, or PKD2 mutations have smaller htTKV and reduced risks (hazard ratio [95% confidence interval]) of ESRD (0.35 [0.14 to 0.91], 0.10 [0.05 to 0.18], and 0.03 [0.01 to 0.05], respectively) and death (0.31 [0.11 to 0.87], 0.20 [0.11 to 0.38], and 0.18 [0.11 to 0.31], respectively). Refined genotype-renal disease correlation coupled with targeted next generation sequencing of PKD1 and PKD2 may provide useful clinical prognostication for ADPKD.