Transthyretin Predicts Cardiovascular Outcome in Hemodialysis Patients With Type 2 Diabetes

Henze, Andrea; Espe, Katharina M.; Wanner, Christoph; Krane, Vera; Raila, Jens; Hocher, Berthold; Schweigert, Florian J.; Drechsler, Christiane

doi:10.2337/dc12-0455

Cited by 8 publications

(8 citation statements)

References 36 publications

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“…Several studies have suggested the use of serum prealbumin as a better surrogate of nutritional status and cardiovascular outcome and a predictor of mortality in patients with maintenance HD [5] , [7] , [16] , [18] . The cumulative survival of HD patients with prealbumin > 30 mg/dL was significantly better than that of patients with prealbumin < 30 mg/dL [12] , [14] .…”

Section: Discussionmentioning

confidence: 99%

Low prealbumin levels are independently associated with higher mortality in patients on peritoneal dialysis

Lee

Cho

Kwon

et al. 2016

Kidney Research and Clinical Practice

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BackgroundPrealbumin, a sensitive marker for protein–energy status, is also known as an independent risk factor for mortality in hemodialysis patients. We investigated the impact of prealbumin on survival in incident peritoneal dialysis (PD) patients.MethodsIn total, 136 incident PD patients (mean age, 53.0 ± 15.8 years) between 2002 and 2007 were enrolled in the study. Laboratory data, dialysis adequacy, and nutritional parameters were assessed 3 months after PD initiation. Patients were classified into 2 groups according to prealbumin level: high prealbumin (≥ 40 mg/dL) and low prealbumin (< 40 mg/dL).ResultsThe patients in the low-prealbumin group were older and had more comorbidities such as diabetes and cardiovascular diseases compared with the patients in the high-prealbumin group. Mean subjective global assessment scores were lower, and the high-sensitivity C-reactive protein levels were higher in the low-prealbumin group. Serum creatinine, albumin, and transferrin levels; percent lean body mass; and normalized protein catabolic rate were positively associated, whereas subjective global assessment scores and high-sensitivity C-reactive protein levels were negatively associated with prealbumin concentration. During the median follow-up of 49 months, patients in the lower prealbumin group had a higher mortality rate. Multivariate analysis revealed that prealbumin < 40 mg/dL (hazard ratio, 2.30; 95% confidence interval, 1.14–4.64) was an independent risk factor for mortality. In receiver operating characteristic curves, the area under the curve of prealbumin for mortality was the largest among the parameters.ConclusionPrealbumin levels were an independent and sensitive predictor for mortality in incident PD patients, showing a good correlation with nutritional and inflammatory markers.

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Section: Discussionmentioning

confidence: 99%

Low prealbumin levels are independently associated with higher mortality in patients on peritoneal dialysis

Lee

Cho

Kwon

et al. 2016

Kidney Research and Clinical Practice

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“…Prealbumin, a marker for protein malnutrition, has been advocated as a useful marker for predicting gastric surgery complications, cardiovascular outcome, and mortality in diabetic hemodialysis patients [ 10 , 11 ]. To our knowledge, there is no available study on the patterns or prognostic value of prealbumin levels in patients with DKA and DK.…”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, we aimed to evaluate changes in prealbumin levels and their diagnostic value in reflecting the severity of hyperglycemic emergencies. It should be stressed that previous studies only provided limited information and did not characterize the correlation with hyperglycemic crises [ 5 , 10 , 11 ]. The current study was performed due to limitations of the existing data in the literature.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Hyperglycemic Emergencies on the Kidney and Liver

Feng

Jiang

et al. 2013

Journal of Diabetes Research

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Studies on the alterations of liver and kidney function parameters in patients with diabetic ketoacidosis (DKA) and diabetic ketosis (DK) were limited. Participants with DKA, DK, non-DK, and healthy controls were enrolled in the current study. Parameters of liver and kidney function were measured and evaluated. The patients with DKA had higher levels of plasma glucose, hemoglobin A1c (HbA1c), uric acid, and creatinine but lower levels of transferases and protein compared with the other three groups (P < 0.05 for all). The patients with DK had higher levels of plasma glucose and HbA1c but lower levels of glutamyl transpeptidase and protein compared with the non-DK and control groups (P < 0.05). Prealbumin levels were significantly reduced in the severe DKA patients compared with the mild/moderate DKA patients. Serum prealbumin levels were correlated with albumin levels (r = 0.401, P = 0.010), HCO3 (r = 0.350, P = 0.027), and arterial pH (r = 0.597, P < 0.001) in the DKA patients. A diagnostic analysis showed that lower prealbumin levels significantly reflected the presence of hyperglycemic emergencies (P < 0.001). Liver and kidney function parameters deteriorated, especially in DKA. Prealbumin levels can be of value in detecting the presence of hyperglycemic crisis. This clinical trial is registered with ChiCTR-OCH-12003077.

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“… 16 − 18 The TTR tetramer concentration in human plasma varies from ≈3.4 to 5 μM. 19 , 20 Following rate-limiting tetramer dissociation and partial monomer denaturation, TTR can aggregate via a downhill polymerization mechanism to form fibrillar cross-β-sheet, or amyloid, deposits, as well as a spectrum of structurally diverse aggregates. 12 , 21 − 24 Dissociation of TTR tetramers begins by dimer separation along the weaker dimer–dimer interface comprising the thyroxine binding sites (Figure 1 A).…”

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confidence: 99%

Quantification of Transthyretin Kinetic Stability in Human Plasma Using Subunit Exchange

Rappley¹,

Monteiro²,

Novais³

et al. 2014

Biochemistry

101

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The transthyretin (TTR) amyloidoses are a group of degenerative diseases caused by TTR aggregation, requiring rate-limiting tetramer dissociation. Kinetic stabilization of TTR, by preferential binding of a drug to the native tetramer over the dissociative transition state, dramatically slows the progression of familial amyloid polyneuropathy. An established method for quantifying the kinetic stability of recombinant TTR tetramers in buffer is subunit exchange, in which tagged TTR homotetramers are added to untagged homotetramers at equal concentrations to measure the rate at which the subunits exchange. Herein, we report a subunit exchange method for quantifying the kinetic stability of endogenous TTR in human plasma. The subunit exchange reaction is initiated by the addition of a substoichiometric quantity of FLAG-tagged TTR homotetramers to endogenous TTR in plasma. Aliquots of the subunit exchange reaction, taken as a function of time, are then added to an excess of a fluorogenic small molecule, which immediately arrests further subunit exchange. After binding, the small molecule reacts with the TTR tetramers, rendering them fluorescent and detectable in human plasma after subsequent ion exchange chromatography. The ability to report on the extent of TTR kinetic stabilization resulting from treatment with oral tafamidis is important, especially for selection of the appropriate dose for patients carrying rare mutations. This method could also serve as a surrogate biomarker for the prediction of the clinical outcome. Subunit exchange was used to quantify the stabilization of WT TTR from senile systemic amyloidosis patients currently being treated with tafamidis (20 mg orally, once daily). TTR kinetic stability correlated with the tafamidis plasma concentration.

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Transthyretin Predicts Cardiovascular Outcome in Hemodialysis Patients With Type 2 Diabetes

Cited by 8 publications

References 36 publications

Low prealbumin levels are independently associated with higher mortality in patients on peritoneal dialysis

Low prealbumin levels are independently associated with higher mortality in patients on peritoneal dialysis

The Impact of Hyperglycemic Emergencies on the Kidney and Liver

Quantification of Transthyretin Kinetic Stability in Human Plasma Using Subunit Exchange

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