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      Is Free Testosterone Concentration a Prognostic Factor of Survival in Chronic Renal Failure (CRF)?

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          Abstract

          Background

          Lowered testosterone level in CRF patients is associated with elevated risk of death due to cardiovascular reasons, and is influenced by many factors, including acid-base balance disorders. Aims: evaluation of testosterone concentration (TT) and free testosterone concentration (fT) in pre-dialysis and dialysis patients; assessment of TT and fT relationships with biochemical parameters; evaluation of prognostic importance of TT and fT in predicting patient survival.

          Material/Methods

          4 groups of men: 14 – on hemodialysis (HD), 13 – on peritoneal dialysis (PD), 9 – with chronic renal failure (CRF) and 8 – healthy (CG), aged 56±17, 53±15, 68±12, 43±10 years, respectively. TT and biochemical parameters were measured; fT was calculated.

          Results

          The lowest TT and fT were observed in HD and CRF, the highest – in CG (p=0.035 for TT; p=0.007 for fT). fT in CRF and CG were different (p=0.031). TT and age was associated in HD (p=0.026). Age and fT was strongly associated in PD (p<0.001). After adjustment for age, TT was negatively associated with BMI (p=0.013) and fT was positively associated with HCO3 level (p=0.007). fT was lower in those who died during 5 years of observation than in survivors (p=0.009). We have found that, opposite to TT, fT appeared to be a better predictor of 5-year survival than age. After combining pH and HCO3 levels into a single variable – no acidosis, acidosis with HCO3 normal serum level, acidosis with low concentrations of HCO3 and adjustment for age and the study group – a trend toward the lowest values of free testosterone in decompensated acidosis was observed (p trend=0.027). Such a trend was not seen for testosterone concentrations (p trend=0.107).

          Conclusions

          Total and free testosterone levels were lower in HD and pre-dialysis than in healthy patients. Free testosterone level may predict long-term survival better than age. Total and free testosterone levels are lower in metabolic acidosis and total and free testosterone levels were positively associated with HCO3 level.

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          Low serum testosterone and mortality in older men.

          Gail Laughlin, Elizabeth Barrett-Connor, Jaclyn Bergstrom (2008)
          Declining testosterone levels in elderly men are thought to underlie many of the symptoms and diseases of aging; however, studies demonstrating associations of low testosterone with clinical outcomes are few. The objective of the study was to examine the association of endogenous testosterone levels with mortality in older community-dwelling men. This was a prospective, population-based study of 794 men, aged 50-91 (median 73.6) yr who had serum testosterone measurements at baseline (1984-1987) and were followed for mortality through July 2004. All-cause mortality by serum testosterone level was measured. During an average 11.8-yr follow-up, 538 deaths occurred. Men whose total testosterone levels were in the lowest quartile (<241 ng/dl) were 40% [hazards ratio (HR) 1.40; 95% confidence interval (CI) 1.14-1.71] more likely to die than those with higher levels, independent of age, adiposity, and lifestyle. Additional adjustment for health status markers, lipids, lipoproteins, blood pressure, glycemia, adipocytokines, and estradiol levels had minimal effect on results. The low testosterone-mortality association was also independent of the metabolic syndrome, diabetes, and prevalent cardiovascular disease but was attenuated by adjustment for IL-6 and C-reactive protein. In cause-specific analyses, low testosterone predicted increased risk of cardiovascular (HR 1.38; 95% CI 1.02-1.85) and respiratory disease (HR 2.29; 95% CI 1.25-4.20) mortality but was not significantly related to cancer death (HR 1.34; 95% CI 0.89-2.00). Results were similar for bioavailable testosterone. Testosterone insufficiency in older men is associated with increased risk of death over the following 20 yr, independent of multiple risk factors and several preexisting health conditions.
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            Association of serum bicarbonate with risk of renal and cardiovascular outcomes in CKD: a report from the Chronic Renal Insufficiency Cohort (CRIC) study.

            Jing Chen, Claudia Lora, Jing Chen … (2013)
            The purpose of this study is to evaluate serum bicarbonate level as a risk factor for renal outcomes, cardiovascular events, and mortality in patients with chronic kidney disease (CKD). Observational cohort study. 3,939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 and December 2008. Serum bicarbonate level. Renal outcomes, defined as end-stage renal disease (either initiation of dialysis therapy or kidney transplantation) or 50% reduction in estimated glomerular filtration rate (eGFR); atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease); congestive heart failure events; and death. Time to event. Mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m(2), and median serum bicarbonate level was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, 332 experienced an atherosclerotic event, and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal end point was 3% lower per 1-mEq/L increase in serum bicarbonate level (HR, 0.97; 95% CI, 0.94-0.99; P = 0.01). The association was stronger for participants with eGFR >45 mL/min/1.73 m(2) (HR, 0.91; 95% CI, 0.85-0.97; P = 0.004). The risk of heart failure increased by 14% (HR, 1.14; 95% CI, 1.03-1.26; P = 0.02) per 1-mEq/L increase in serum bicarbonate level over 24 mEq/L. Serum bicarbonate level was not associated independently with atherosclerotic events (HR, 0.99; 95% CI, 0.95-1.03; P = 0.6) and all-cause mortality (HR, 0.98; 95% CI, 0.95-1.02; P = 0.3). Single measurement of sodium bicarbonate. In a cohort of participants with CKD, low serum bicarbonate level was an independent risk factor for kidney disease progression, particularly for participants with preserved kidney function. The risk of heart failure was higher at the upper extreme of serum bicarbonate levels. There was no association between serum bicarbonate level and all-cause mortality or atherosclerotic events. Copyright © 2013 National Kidney Foundation, Inc. All rights reserved.
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              Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD.

              Judy Anderson, Kamyar Kalantar-Zadeh, Csaba P. Kovesdy (2009)
              Metabolic acidosis, usually manifested by low serum bicarbonate level, is common in chronic kidney disease (CKD) and appears to be associated with higher mortality in dialysis patients. It is not known whether a similar association is present in patients with non-dialysis-dependent CKD (NDD-CKD). We used multivariable-adjusted Cox models to examine the association between baseline and time-variable serum bicarbonate (measured as total CO2) with the outcomes of all-cause mortality and the composite of pre-dialysis mortality or end-stage renal disease in 1240 male patients with moderate and advanced NDD-CKD. Serum bicarbonate showed a significant U-shaped association with all-cause mortality, with the highest mortality rate observed in patients with baseline serum bicarbonate levels or =22 mmol/L: 1.33 (1.05-1.69), P = 0.02] and the lowest mortality observed in patients with baseline serum bicarbonate of 26-29 mmol/L. The associations between lower serum bicarbonate level and mortality were more accentuated in subgroups of patients with better nutritional status and lower inflammation. Both lower and higher serum bicarbonates are associated with increased all-cause mortality in patients with moderate and advanced NDD-CKD. Clinical trials are needed to determine if therapeutic interventions aimed at optimizing serum bicarbonate can result in improved outcomes in this population.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Med Sci Monit
                Journal ID (iso-abbrev): Med. Sci. Monit
                Journal ID (publisher-id): Medical Science Monitor
                Title: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                Publisher: International Scientific Literature, Inc.
                ISSN (Print): 1234-1010
                ISSN (Electronic): 1643-3750
                Publication date Collection: 2015
                Publication date (Electronic): 07 November 2015
                Volume: 21
                Pages: 3401-3408
                Affiliations
                [1 ]Department of Internal Medicine, Nephrology and Dialysotherapy, Military Institute of Medicine, Warsaw, Poland
                [2 ]Department of Nephrology, Dialysotherapy and Internal Medicine, Medical University of Warsaw, Poland
                [3 ]Department of Epidemiology and Biostatistics, National Research Institute of Mother and Child, Warsaw, Poland
                [4 ]Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland
                Author notes
                Corresponding Author: Longin Niemczyk, e-mail: lniemczyk@ 123456wum.edu.pl
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                Publisher ID: 894146
                DOI: 10.12659/MSM.894146
                PMC ID: 4642367
                PubMed ID: 26546587
                SO-VID: 74cf2735-45ae-4b49-91f7-50cd30924459
                Copyright © © Med Sci Monit, 2015
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License

                History
                Date received : 18 March 2015
                Date accepted : 06 July 2015
                Categories
                Subject: Clinical Research

                Keywords: acidosis,kidney failure, chronic,quality of life,survival analysis,testosterone
                Data availability:
                Keywords: acidosis, kidney failure, chronic, quality of life, survival analysis, testosterone

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