Metabolic syndrome: a fata morgana? Bakker, Stephan J. L.; Gansevoort, Ron T.; de Zeeuw, Dick
Nephrology, dialysis, transplantation,
01/2007, Letnik:
22, Številka:
1
Journal Article
Abstract Common polymorphisms of the Cholestryl Ester Transfer Protein ( CETP ) gene may predict lower risk of cognitive decline. We investigated the association of cognitive function with CETP ...genotype in a population-based cohort of 4135 persons aged 35–82 years. Cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0 points; best score, 175 points) and CETP I405V and Taq1B genotypes were determined by polymerase chain reaction. RFFT score was not associated with I405V genotype in persons aged 35–64 years. Remarkably, beyond age 65, homozygous valine carriers had higher RFFT scores than heterozygous carriers and noncarriers: RFFT (SD), 52 (21), 49 (18), and 47 (17) points, respectively ( p = 0.005). There also was a statistically significant interaction between I405V genotype and age. Beyond age 65, the difference between homozygous valine carriers and noncarriers increased by 0.11 point per year ( p = 0.005). RFFT score was not associated with Taq1B genotype. In conclusion, CETP I405V valine homozygosity was associated with better cognitive function in persons aged 65 years or older.
Background
Previous studies using conventional cTnI assays reported conflicting results on the evolution of cTnI levels during hemodialysis. The determinants and prognostic significance of changes in ...cTnI during hemodialysis are presently unknown. The aim of this prospective study was to characterize the determinants and prognostic significance of intra-dialysis changes in cTnI using a sensitive assay.
Methods
cTnI was measured before and after hemodialysis with a sensitive assay in 90 chronic patients without acute cardiac symptoms. Multivariable regression analyses were used to identify factors that were associated with intra-dialysis rise in cTnI. The prognostic effect of an intra-dialysis rise in cTnI during a 52-month follow-up was evaluated using Cox regression models. The primary and secondary endpoint was the incidence of major adverse cardiovascular events and all-cause mortality, respectively.
Results
Pre-dialysis cTnI was elevated in 31 patients (34 %). cTnI increased significantly during dialysis and this had a trend to be associated with longer dialysis vintage. A greater intra-dialysis rise in cTnI was associated with a significantly higher incidence of cardiovascular events, also after correction for age, gender, dialysis vintage, residual diuresis, previous cardiovascular events, and pre-dialysis cTnI levels (HR per 10 ng/L rise in cTnI: 1.21; CI 1.06–1.38;
p
0.005).
Conclusion
TnI levels rise significantly during hemodialysis and a greater intra-dialysis rise in cTnI is associated with an increased incidence of cardiovascular events. These findings suggest that hemodialysis has an acute deleterious effect on the heart. An intra-dialysis rise in cTnI may help identify patients who are susceptible to the hemodynamic stress of hemodialysis.
Chronic low-grade inflammation is involved in chronic transplant dysfunction after renal transplantation. Procalcitonin (PCT), known to reflect microbial inflammation, may also reflect ongoing ...noninfectious chronic low-grade inflammation in organ parenchyma, including transplanted kidneys. We aimed to compare predictive performance of plasma PCT for development of graft failure in renal transplant recipients (RTR) with that of high-sensitivity C-reactive protein (hsCRP), an established marker of systemic chronic low-grade inflammation.
We included 575 RTR with functioning grafts for more than or equal to 1 year at a median (interquartile range) time of 6.1 (2.9-11.7) years posttransplant. PCT was determined using an ultrasensitive immunoluminometric assay and hsCRP using high-sensitivity enzyme-linked immunosorbent assay.
Median (interquartile range) plasma PCT and hsCRP concentrations were 0.023 (0.017-0.036) ng/mL and 2.1 (0.8-4.9) mg/L, respectively. After a median (interquartile range) of 5.2 (4.5-5.7) years of follow-up, incidence of graft failure was 0.5%, 2.6%, and 18.5% according to increasing PCT tertiles (P<0.001 by log-rank test). Area under the curve of receiver operating characteristic analysis of PCT for prediction of graft failure was significantly higher than that of hsCRP (0.84 vs. 0.56, P<0.001). After adjustment for potential confounders, PCT remained an independent predictor of graft failure (hazard ratio=2.3 95% confidence interval 1.4-3.7 per doubling PCT, P=0.0004), whereas this was not the case for hsCRP.
We identified plasma PCT as a strong and an independent predictor of graft failure in RTR. These data suggest that PCT in RTR reflects ongoing inflammation in parenchyma of transplanted kidneys. Further studies are required to investigate whether PCT could be of use as an early biomarker for chronic transplant dysfunction.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and variable renal function decline that frequently leads to end-stage renal failure. With the ...advent of renoprotective treatment, there is renewed interest in noninvasive biomarkers to help identify patients at risk of rapid disease progression at early stages. Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor–binding protein 7 (IGFBP7) have been validated as early markers of acute kidney injury. Because these markers are associated with tubular damage, we studied the performance of both markers in a cohort with chronic tubular pathology. We investigated whether these biomarkers may be useful to evaluate disease severity in ADPKD.
In a cross-sectional analysis, we measured TIMP-2 and IGFBP7 in stored spot urine samples of patients with ADPKD with various stages of chronic kidney disease (CKD) and healthy controls by enzyme-linked immunosorbent assay. Renal function was estimated using the CKD–Epidemiology Collaboration equation. Patients were stratified according to the Kidney Disease Outcomes Quality Initiative classification for CKD. In a subset of patients, total kidney volume (TKV; using magnetic resonance imaging MRI) was measured.
In 296 patients with ADPKD (45.5 ± 11.5 years, 51.0% female, serum creatinine 106 85–147 μmol/l), urine levels of TIMP-2 and IGFBP7 were not increased or tended to be lower as compared with 71 healthy controls (46.5 ± 18.5 years, 72.6% female). The levels did not differ across CKD stages, which remained so after correcting for urine creatinine or osmolality, and for age, sex, and urine protein in multivariable analyses.
Urinary levels of TIMP-2 and IGFBP7 were not higher in patients with ADPKD, and did not correlate with disease severity.
Summary Background Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a ...meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. Methods In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders. Findings The analysis included 105 872 participants (730 577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1 128 310 participants (4 732 110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1·73 m2 and 105 mL/min/1·73 m2 and increased at lower eGFRs. Compared with eGFR 95 mL/min/1·73 m2 , adjusted HRs for all-cause mortality were 1·18 (95% CI 1·05–1·32) for eGFR 60 mL/min/1·73 m2 , 1·57 (1·39–1·78) for 45 mL/min/1·73 m2 , and 3·14 (2·39–4·13) for 15 mL/min/1·73 m2 . ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0·6 mg/mmol, adjusted HRs for all-cause mortality were 1·20 (1·15–1·26) for ACR 1·1 mg/mmol, 1·63 (1·50–1·77) for 3·4 mg/mmol, and 2·22 (1·97–2·51) for 33·9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements. Interpretation eGFR less than 60 mL/min/1·73 m2 and ACR 1·1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease. Funding Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.
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