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The interaction between fluid status and angiopoietin-2 in adverse renal outcomes of chronic kidney disease.

ABSTRACT: BACKGROUND:Fluid overload is not only the characteristic but also an important complication in chronic kidney disease (CKD) patients. Angiopoietin-2 (Angpt2) disturbs endothelium and vessel permeability, which may induce fluid overload. The aim of this study is to examine the interaction between fluid status and Angpt2 in adverse renal outcomes of CKD. METHODS:This cohort study enrolled 290 patients with CKD stages 3-5 from January 2011 to December 2011 and followed up until December 2015. Fluid status was presented as overhydration (OH) value measured by body composition monitor, while OH>1.1L was defined as fluid overload. Renal outcomes were defined as commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate < -5 ml/min/1.73 m2/y). RESULTS:During a mean follow-up of 38.6±18.3 months, 125 (43.1%) patients progressed to commencing dialysis and 99(34.7%) patients presented rapid renal function decline. All patients were stratified by OH of 1.1L and the median of circulating Angpt2. These patients with both OH>1.1L and high circulating Angpt2 were more likely to reach commencing dialysis compared to other groups. The risks for commencing dialysis and rapid renal function decline were significantly higher in patients with OH>1.1L and high circulating Angpt2 level compared to those with OH?1.1L and low circulating Angpt2 (2.14, 1.21-3.78, P = 0.009; 4.96, 1.45-16.97, P = 0.01). There was a significant interaction between OH level and circulating Angpt2 in entering dialysis (P-interaction = 0.02). CONCLUSIONS:Fluid overload and Angpt2 might have a synergistic effect on adverse renal outcomes in CKD patients.

SUBMITTER: Tsai YC

PROVIDER: S-EPMC5363828 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The interaction between fluid status and angiopoietin-2 in adverse renal outcomes of chronic kidney disease.

Tsai Yi-Chun YC Chiu Yi-Wen YW Kuo Hung-Tien HT Lee Jia-Jung JJ Lee Su-Chu SC Chen Tzu-Hui TH Lin Ming-Yen MY Hwang Shang-Jyh SJ Kuo Mei-Chuan MC Hsu Ya-Ling YL Chen Hung-Chun HC

PloS one 20170323 3

<h4>Background</h4>Fluid overload is not only the characteristic but also an important complication in chronic kidney disease (CKD) patients. Angiopoietin-2 (Angpt2) disturbs endothelium and vessel permeability, which may induce fluid overload. The aim of this study is to examine the interaction between fluid status and Angpt2 in adverse renal outcomes of CKD.<h4>Methods</h4>This cohort study enrolled 290 patients with CKD stages 3-5 from January 2011 to December 2011 and followed up until Decem ...[more]

PMID: 28333979

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Project description:BACKGROUND:In studies including the general population, the presence of non-malignant monoclonal gammopathy (MG) can be causally associated with kidney damage and shorter survival. We assessed whether the presence of an MG is associated with a higher risk of kidney failure or death in individuals with chronic kidney disease (CKD). METHODS AND FINDINGS:Data were used from 3 prospective cohorts of individuals with CKD (not on dialysis or with a kidney transplant): (1) Renal Impairment in Secondary Care (RIISC, Queen Elizabeth Hospital and Heartlands Hospital, Birmingham, UK, N = 878), (2) Salford Kidney Study (SKS, Salford Royal Hospital, Salford, UK, N = 861), and (3) Renal Risk in Derby (RRID, Derby, UK, N = 1,739). Participants were excluded if they had multiple myeloma or any other B cell lymphoproliferative disorder with end-organ damage. Median age was 71.0 years, 50.6% were male, median estimated glomerular filtration rate was 42.3 ml/min/1.73 m2, and median urine albumin-to-creatinine ratio was 3.4 mg/mmol. All non-malignant MG was identified in the baseline serum of participants of RIISC. Further, light chain MG (LC-MG) was identified and studied in participants of RIISC, SKS, and RRID. Participants were followed up for kidney failure (defined as the initiation of dialysis or kidney transplantation) and death. Associations with the risk of kidney failure were estimated by competing-risks regression (handling death as a competing risk), and associations with death were estimated by Cox proportional hazards regression. In total, 102 (11.6%) of the 878 RIISC participants had an MG. During a median follow-up time of 74.0 months, there were 327 kidney failure events and 202 deaths. The presence of MG was not associated with risk of kidney failure (univariable subhazard ratio [SHR] 0.97 [95% CI 0.68 to 1.38], P = 0.85; multivariable SHR 1.16 [95% CI 0.80 to 1.69], P = 0.43), and although there was a higher risk of death in univariable analysis (hazard ratio [HR] 2.13 [95% CI 1.49 to 3.02], P < 0.001), this was not significant in multivariable analysis (HR 1.37 [95% CI 0.93 to 2.00], P = 0.11). Fifty-five (1.6%) of the 3,478 participants from all 3 studies had LC-MG. During a median follow-up time of 62.5 months, 564 of the 3,478 participants progressed to kidney failure, and 803 died. LC-MG was not associated with risk of kidney failure (univariable SHR 1.07 [95% CI 0.58 to 1.96], P = 0.82; multivariable SHR 1.42 [95% CI 0.78 to 2.57], P = 0.26). There was a higher risk of death in those with LC-MG in the univariable model (HR 2.51 [95% CI 1.59 to 3.96], P < 0.001), but not in the multivariable model (HR 1.49 [95% CI 0.93 to 2.39], P = 0.10). An important limitation of this work was that only LC-MG, rather than any MG, could be identified in participants from SKS and RRID. CONCLUSIONS:The prevalence of MG was higher in this CKD cohort than that reported in the general population. However, the presence of an MG was not independently associated with a significantly higher risk of kidney failure or, unlike in the general population, risk of death.

Project description:BACKGROUND: Excess extracellular volume is a major clinical problem in patients with chronic kidney disease (CKD). However, whether the extracellular volume status is associated with disease progression is unclear. We investigated the association between the extracellular volume status and renal outcomes. METHODS: We performed a retrospective cohort study of 149 patients with CKD who underwent bioelectrical impedance analysis (BIA) from 2005 to 2009. Patients were categorized according to tertiles of extracellular volume status. The extracellular volume status was assessed by examining the ratio of extracellular water measured by BIA (ECWBIA) to the total body water calculated using the Watson formula (TBWWatson). The main outcomes were adverse renal outcomes as defined by a decline of ?50% from the baseline glomerular filtration rate or initiation of renal replacement therapy. RESULTS: A higher %ECWBIA/TBWWatson ratio tended to be associated with older age, male sex, diabetes mellitus, resistant hypertension, lower renal function, lower serum albumin levels, higher proteinuria levels, and a higher frequency of furosemide use. In the multivariate analysis, proteinuria remained independently associated with the %ECWBIA/TBWWatson ratio. Both the intracellular and extracellular water volumes decreased with age (correlation between ICW and age, r=-0.30, P<0.001; correlation between ECW and age, r=-0.17, P=0.03). Consequently, the %ECWBIA in the body fluid composition increased with age. During a median follow-up of 4.9 years, patients in the highest tertile of the %ECWBIA/TBWWatson ratio were at greater risk of adverse renal outcomes (16.6 per 100.0 patient years) than were those in the lowest tertile (8.1 per 100.0 patient years) or second tertile (5.6 per 100.0 patient years) (log-rank P=0.005). After adjustment for covariates, the %ECWBIA/TBWWatson ratio was significantly associated with adverse renal outcomes (hazard ratio, 1.21; 95 % confidence interval, 1.10-1.34; P<0.001). CONCLUSIONS: The ECWBIA/TBWWatson ratio was independently associated with adverse renal outcomes. Proteinuria was independently associated with the extracellular volume status. The balance between ICW and ECW changes with age in that the percentage of ECW content in the body fluid composition increases. Elderly patients with CKD may thus be susceptible to volume overload.

Dataset Information

The interaction between fluid status and angiopoietin-2 in adverse renal outcomes of chronic kidney disease.

Publications

The interaction between fluid status and angiopoietin-2 in adverse renal outcomes of chronic kidney disease.

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