scholarly journals Identification of Potential Biomarkers of Chronic Kidney Disease in Individuals with Diabetes: Protocol for a Cross-sectional Observational Study

10.2196/16277 ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. e16277
Author(s):  
Ashani R Lecamwasam ◽  
Mohammadreza Mohebbi ◽  
Elif I Ekinci ◽  
Karen M Dwyer ◽  
Richard Saffery

Background The importance of identifying people with diabetes and progressive kidney dysfunction relates to the excess morbidity and mortality of this group. Rates of cardiovascular disease are much higher in people with both diabetes and kidney dysfunction than in those with only one of these conditions. By the time these people are identified in current clinical practice, proteinuria and renal dysfunction are already established, limiting the effectiveness of therapeutic interventions. The identification of an epigenetic or blood metabolite signature or gut microbiome profile may identify those with diabetes at risk of progressive chronic kidney disease, in turn providing targeted intervention to improve patient outcomes. Objective This study aims to identify potential biomarkers in people with diabetes and chronic kidney disease (CKD) associated with progressive renal injury and to distinguish between stages of chronic kidney disease. Three sources of biomarkers will be explored, including DNA methylation profiles in blood lymphocytes, the metabolomic profile of blood-derived plasma and urine, and the gut microbiome. Methods The cross-sectional study recruited 121 people with diabetes and varying stages (stages 1-5) of chronic kidney disease. Single-point data collection included blood, urine, and fecal samples in addition to clinical data such as anthropometric measurements and biochemical parameters. Additional information obtained from medical records included patient demographics, medical comorbidities, and medications. Results Data collection commenced in January 2018 and was completed in June 2018. At the time of submission, 121 patients had been recruited, and 119 samples remained after quality control. There were 83 participants in the early diabetes-associated CKD group with a mean estimated glomerular filtration rate (eGFR) of 61.2 mL/min/1.73 m2 (early CKD group consisting of stage 1, 2, and 3a CKD), and 36 participants in the late diabetic CKD group with a mean eGFR of 23.9 mL/min/1.73 m2 (late CKD group, consisting of stage 3b, 4, and 5), P<.001. We have successfully obtained DNA for methylation and microbiome analyses using the biospecimens collected via this protocol and are currently analyzing these results together with the metabolome of this cohort of individuals with diabetic CKD. Conclusions Recent advances have improved our understanding of the epigenome, metabolomics, and the influence of the gut microbiome on the incidence of diseases such as cancers, particularly those related to environmental exposures. However, there is a paucity of literature surrounding these influencers in renal disease. This study will provide insight into the fundamental understanding of the pathophysiology of CKD in individuals with diabetes, especially in novel areas such as epigenetics, metabolomics, and the kidney-gut axis. International Registered Report Identifier (IRRID) DERR1-10.2196/16277

2019 ◽  
Author(s):  
Ashani R Lecamwasam ◽  
Mohammadreza Mohebbi ◽  
Elif I Ekinci ◽  
Karen M Dwyer ◽  
Richard Saffery

BACKGROUND The importance of identifying people with diabetes and progressive kidney dysfunction relates to the excess morbidity and mortality of this group. Rates of cardiovascular disease are much higher in people with both diabetes and kidney dysfunction than in those with only one of these conditions. By the time these people are identified in current clinical practice, proteinuria and renal dysfunction are already established, limiting the effectiveness of therapeutic interventions. The identification of an epigenetic or blood metabolite signature or gut microbiome profile may identify those with diabetes at risk of progressive chronic kidney disease, in turn providing targeted intervention to improve patient outcomes. OBJECTIVE This study aims to identify potential biomarkers in people with diabetes and chronic kidney disease (CKD) associated with progressive renal injury and to distinguish between stages of chronic kidney disease. Three sources of biomarkers will be explored, including DNA methylation profiles in blood lymphocytes, the metabolomic profile of blood-derived plasma and urine, and the gut microbiome. METHODS The cross-sectional study recruited 121 people with diabetes and varying stages (stages 1-5) of chronic kidney disease. Single-point data collection included blood, urine, and fecal samples in addition to clinical data such as anthropometric measurements and biochemical parameters. Additional information obtained from medical records included patient demographics, medical comorbidities, and medications. RESULTS Data collection commenced in January 2018 and was completed in June 2018. At the time of submission, 121 patients had been recruited, and 119 samples remained after quality control. There were 83 participants in the early diabetes-associated CKD group with a mean estimated glomerular filtration rate (eGFR) of 61.2 mL/min/1.73 m2 (early CKD group consisting of stage 1, 2, and 3a CKD), and 36 participants in the late diabetic CKD group with a mean eGFR of 23.9 mL/min/1.73 m2 (late CKD group, consisting of stage 3b, 4, and 5), <i>P</i><.001. We have successfully obtained DNA for methylation and microbiome analyses using the biospecimens collected via this protocol and are currently analyzing these results together with the metabolome of this cohort of individuals with diabetic CKD. CONCLUSIONS Recent advances have improved our understanding of the epigenome, metabolomics, and the influence of the gut microbiome on the incidence of diseases such as cancers, particularly those related to environmental exposures. However, there is a paucity of literature surrounding these influencers in renal disease. This study will provide insight into the fundamental understanding of the pathophysiology of CKD in individuals with diabetes, especially in novel areas such as epigenetics, metabolomics, and the kidney-gut axis. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/16277


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Irina Lousa ◽  
Maria João Valente ◽  
Susana Rocha ◽  
Sofia D. Viana ◽  
Inês Preguiça ◽  
...  

Abstract Background and Aims The conventionally used biomarkers for chronic kidney disease (CKD) diagnosis are not very sensitive for early diagnosis. Their values become clinically significant only when kidney damage is advanced, and a substantial filtration capacity has been lost. The reliance on these biomarkers may result in a long-time lapse in diagnosis, compromising the earlier use of successful therapeutic interventions to prevent CKD progression and reduce the risk of other common comorbidities. The study of earlier and more sensitive biomarkers for CKD diagnosis is an important medical need. Potentially new biomarkers reflecting different pathophysiological processes underlying CKD, such as changes in renal function, tubulointerstitial injury, inflammation and fibrosis, have been proposed. The use of a panel of biomarkers is likely to be synergetic in detecting CKD, since there are several different mechanisms by which CKD can initiate. Our aim was to identify markers of renal damage/dysfunction and evaluate their sensitivity for CKD detection, in patients at the earlier stages of the disease, stages 1 and 2. Method This study included 32 healthy controls and 29 CKD patients at stages 1 and 2, categorized according to the KDIGO guidelines, using the CKD-EPI equation based on serum creatinine to estimate the glomerular filtration rate (GFR). Causes of CKD in the studied patients were diabetes mellitus (n = 19), polycystic kidney disease (n = 1) and of unknown cause (n = 7) or other (n = 2). Circulating levels of creatinine and β-trace protein (BTP), as markers of renal function; interleukin 6 (IL-6), as a marker of inflammation; tissue inhibitor metalloproteinase 1 (TIMP 1), as a marker of tubulointerstitial injury; pro B-type natriuretic peptide (proBNP), as a marker of cardio-renal dysfunction; and cell-free DNA (cfDNA), as a marker of cellular damage, were evaluated. Results Compared to controls, we found significantly higher values of all studied markers in CKD patients (stage 1 and stage 2): BTP, TIMP-1, IL-6, pro-BNP, and cfDNA. In CKD patients, GFR was negatively correlated with circulating levels of pro-BNP (r = -0.610, P = 0.004, n = 20) and cfDNA (r = -0.408, P = 0.028, n = 29); and, microalbuminuria was positively correlated with circulating levels of BTP (r = 0.465, P = 0.013, n = 28). The biomarker cfDNA was positively correlated with TIMP-1 (r = 0.445, P = 0.16, n = 29) , a marker of tubulointerstitial injury, and with IL-6 (r = 0.670, P &lt; 0.001, n = 29), a marker of inflammation. All patients presented at least two of the studied biomarkers with higher values than the median value presented by controls. Of all studied biomarkers, BTP was the one that was most altered in patients (86.2% presented higher values than the highest value presented by controls). Conclusion Our results suggest that the studied biomarkers are sensitive to the primary response to renal injury, being significantly elevated in the earlier stages of CKD, particularly BTP. Pro-BNP and cfDNA correlate well with disease severity assessed by GFR. The use of a panel comprising several biomarkers, related with different pathophysiological mechanisms underlying CKD initiation and progression, may increase the potential to detect patients at risk, when compared with the evaluation of each biomarker alone. Further validation for the use of these new potential biomarkers requires larger studies with standardized analytical methodologies. Acknowledgments: This work was supported by Applied Molecular Biosciences Unit (UCIBIO) and financed by FEDER COMPETE2020 funds UIDB/04378/2020 and UIDP/04539/2020 (CIBB); by POCI-01-0145-FEDER-007440; by FCT doctoral grant SFRH/BD/145939/2019; by funds from Portugal Regional Coordination and Development Commissions (Norte-01-0145-FEDER-000024).


2021 ◽  
Vol 11 (11) ◽  
pp. 1118
Author(s):  
Tessa Gryp ◽  
Karoline Faust ◽  
Wim Van Biesen ◽  
Geert R. B. Huys ◽  
Francis Verbeke ◽  
...  

Chronic kidney disease (CKD) is characterized by the accumulation of uremic toxins which exert deleterious effects on various organ systems. Several of these uremic toxins originate from the bacterial metabolization of aromatic amino acids in the colon. This study assessed whether the gut microbial composition varies among patients in different stages of CKD. Uremic metabolites were quantified by UPLC/fluorescence detection and microbial profiling by 16S rRNA amplicon sequencing. Gut microbial profiles of CKD patients were compared among stages 1–2, stage 3 and stages 4–5. Although a substantial inter-individual difference in abundance of the top 15 genera was observed, no significant difference was observed between groups. Bristol stool scale (BSS) correlated negatively with p-cresyl sulfate and hippuric acid levels, irrespective of the intake of laxatives. Butyricicoccus, a genus with butyrate-generating properties, was decreased in abundance in advanced stages of CKD compared to the earlier stages (p = 0.043). In conclusion, in this cross-sectional study no gradual differences in the gut microbial profile over the different stages of CKD were observed. However, the decrease in the abundance of Butyricicoccus genus with loss of kidney function stresses the need for more in-depth functional exploration of the gut microbiome in CKD patients not on dialysis.


2021 ◽  
Author(s):  
Kailash Nagar ◽  
Arpita Vaidya ◽  
Khushabu Patel

ABSTRACTIntroductionChronic kidney disease is considered as a public health problem worldwide [1]. It is defined by kidney tissue injury with or without a decrease in glomerular filtration rate and /or a decrease in kidney function over a period of three or more months. When the glomerular filtration rate [GFR] is below 15ml./min./1.73m2, the patient is in the terminal stage or dialysis, requiring renal replacement therapy [RRT], dialysis or transplant as alternative treatments. Renal failure is the inability of the kidney to excrete wastes, concentrate urine, and conserve electrolytes. Renal failure is precipitated from a variety of etiological factors. It is treatable but not curable, which means that the patient needs a long term therapies or transplantation [2].The overall prevalence of depression, anxiety and stress in this study found to be 22.9%, 19.2%, and 28.2%, respectively. Forty nine (13.84%) respondents had mild depression twenty eight (7.91%) has moderate depression[2].Depression and anxiety are frequent comorbid disorders among chronic kidney disease (CKD) patients, with estimated prevalence of approximately 25% in this population, [3] and are associated with worse outcomes, such as progression to end-stage renal disease (ESRD) and mortality [4,5,6,7]. The transition from predialysis management to renal replacement therapy (RRT) is a stressful event in the course of CKD, leading to challenges and decisions that might increase their susceptibility to anxiety, mood disorders or even exacerbate psychological issues that already exist [8].AimsThe researcher aim to assess the level of depression, anxiety and stress among chronic kidney disease patient in selected hospital of Nadiad City, Gujarat. The research wants to explore the actual psychological status of the patients who were suffering from chronic illness like CKD, because due to long term suffering from the illness disturbed the everyone mind and cause various psychological changes in the body. Hence research want to assess what kind of changes take place due to chronic kidney diseases.ObjectivesTo assess the level of depression among CKD patients at selected hospital, Nadiad.To assess the level of anxiety among CKD patients at selected hospital, Nadiad.To assess the level of stress among the CKD patients at selected hospital, Nadiad.MethodologyDesign and SettingDescriptive cross sectional survey research design was adopted for the study and non-probability purposive sampling method was used to drawn samples from the participants. For the data collection researcher has used modified The DASS-42 is a 42 item self-report scale designed to measure the negative emotional states of depression, anxiety and stress, it is a standardized tool.Prior to data collection written setting permission obtain from the head of the hospital as well prior inform consent form was obtain from the study participants, the objectives and methods of the study were appropriately explain to the samples. For data collection researcher has select MPUH kidney hospital situated Nadiad City. The total sample size was 30 chronic kidney disease patients.The research data collection tool consist of following Section I Demographic variables of the CKD patients section II DASS 42 questionnaire self rating scale.Statistical AnalysisDescriptive statistics applied where, data were analyzed by using SPSS software, and Frequency, percentage, tables etc. were used to represent the statistical data in the tables and graph and figure.ResultThe majority of participants (30%) were 41-50 years, sample (36.67%) belong age group of above 50 years, majority 56.67% were Male, (43.33%) were graduate, (67%) Having 5000-10000 Monthly Income, (60%) were living in Joint family, (56.67%) were belong to 0-3 years, (23.33%) were belong above 9 years if illness. Duration of hospitalization (80%) 0-15 days.Prevalence rate of depression, anxiety and stress among Chronic Kidney Disease the most of patient have 50%, had moderate symptoms of depression, anxiety and stress, 30% had mild and only 20% have severe symptoms of depression, anxiety and stress which was measured by DASS self rating scale.ConclusionsThe currents study ended to assess the prevalence rate of the depression, anxiety and stress among Chronic Kidney Disease patients, the study result concluded that the majority (50%) of Patients having moderate level of depression, anxiety and stress. The people in age group 41-50 or above 50 are having higher rate of depression, anxiety, and stress during chronic kidney disease.


2018 ◽  
Vol 5 (2) ◽  
pp. 56-63
Author(s):  
Abdul Wakhid ◽  
Estri Linda Wijayanti ◽  
Liyanovitasari Liyanovitasari

Background: Self efficacy can optimize the quality of life of clients who undergo the healing process due to chronic diseases. Individuals with higher self-efficacy move their personal and social resources proactively to maintain and improve the quality and length of their lives so that they experience a better quality of life. Objectives: the purpose of this study was to find the correlation between self efficacy and quality of life of patients with chronic kidney disease who undergo hemodialysis at RSUD Semarang Regency. Metode: This type of research was descriptive correlation with cross sectional approach. The samples in this study more 76 people with total sampling technique. The data collection tool for self efficacy was measured by General Self-Efficacy scale, for quality of life with WHOQoL-BREF. Statistical test used Kolmogorov-smirnov. Result: The result showed that self efficacy in patients with chronic kidney disease was mostly in moderate category (53,9%), quality of life in patients with chronic kidney disease was mostly in good category (68,4%). There was a correlation between self efficacy and quality of life of patients with chronic kidney disease who undergo hemodialysis at RSUD Semarang Regency, the result obtained p-value of 0.000 <α (0,05). Suggestion: Patients with chronic kidney disease can maintain good quality of life by helping to generate positive self-esteem and high self efficacy.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Hirotaka Ochiai ◽  
Takako Shirasawa ◽  
Takahiko Yoshimoto ◽  
Satsue Nagahama ◽  
Akihiro Watanabe ◽  
...  

Abstract Background Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to ALT ratio (AST/ALT ratio) have been shown to be related to non-alcoholic fatty liver disease or insulin resistance, which was associated with chronic kidney disease (CKD). However, it is unclear whether ALT and AST/ALT ratio are associated with CKD. In this study, we examined the relationship of ALT and AST/ALT ratio to CKD among middle-aged females in Japan. Methods The present study included 29,133 women aged 40 to 64 years who had an annual health checkup in Japan during April 2013 to March 2014. Venous blood samples were collected to measure ALT, AST, gamma-glutamyltransferase (GGT), and creatinine levels. In accordance with previous studies, ALT > 40 U/L and GGT > 50 U/L were determined as elevated, AST/ALT ratio < 1 was regarded as low, and CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 and/or proteinuria. Logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for CKD. Results “Elevated ALT and elevated GGT” and “elevated ALT and non-elevated GGT” significantly increased the OR for CKD when compared with “non-elevated ALT and non-elevated GGT” (OR: 2.56, 95% CI: 2.10–3.12 and OR: 2.24, 95% CI: 1.81–2.77). Compared with “AST/ALT ratio ≥ 1 and non-elevated GGT”, “AST/ALT ratio < 1 and elevated GGT” and “AST/ALT ratio < 1 and non-elevated GGT” significantly increased the OR for CKD (OR: 2.73, 95% CI: 2.36–3.15 and OR: 1.68, 95% CI: 1.52–1.87). These findings still remained after adjustment for confounders. Conclusions Elevated ALT was associated with CKD regardless of GGT elevation. Moreover, low AST/ALT ratio was also associated with CKD independent of GGT elevation.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2453
Author(s):  
Ana M Pinto ◽  
Helen L MacLaughlin ◽  
Wendy L Hall

Low heart rate variability (HRV) is independently associated with increased risk of sudden cardiac death (SCD) and all cardiac death in haemodialysis patients. Long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) may exert anti-arrhythmic effects. This study aimed to investigate relationships between dialysis, sleep and 24 h HRV and LC n-3 PUFA status in patients who have recently commenced haemodialysis. A cross-sectional study was conducted in adults aged 40–80 with chronic kidney disease (CKD) stage 5 (n = 45, mean age 58, SD 9, 20 females and 25 males, 39% with type 2 diabetes). Pre-dialysis blood samples were taken to measure erythrocyte and plasma fatty acid composition (wt % fatty acids). Mean erythrocyte omega-3 index was not associated with HRV following adjustment for age, BMI and use of β-blocker medication. Higher ratios of erythrocyte eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) were associated with lower 24 h vagally-mediated beat-to-beat HRV parameters. Higher plasma EPA and docosapentaenoic acid (DPAn-3) were also associated with lower sleep-time and 24 h beat-to-beat variability. In contrast, higher plasma EPA was significantly related to higher overall and longer phase components of 24 h HRV. Further investigation is required to investigate whether patients commencing haemodialysis may have compromised conversion of EPA to DHA, which may impair vagally-mediated regulation of cardiac autonomic function, increasing risk of SCD.


2020 ◽  
Vol 22 (1) ◽  
pp. 43
Author(s):  
Irina Lousa ◽  
Flávio Reis ◽  
Idalina Beirão ◽  
Rui Alves ◽  
Luís Belo ◽  
...  

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and the mortality rate continues to be unacceptably high. The biomarkers currently used in clinical practice are considered relevant when there is already significant renal impairment compromising the early use of potentially successful therapeutic interventions. More sensitive and specific biomarkers to detect CKD earlier on and improve patients’ prognoses are an important unmet medical need. The aim of this review is to summarize the recent literature on new promising early CKD biomarkers of renal function, tubular lesions, endothelial dysfunction and inflammation, and on the auspicious findings from metabolomic studies in this field. Most of the studied biomarkers require further validation in large studies and in a broad range of populations in order to be implemented into routine CKD management. A panel of biomarkers, including earlier biomarkers of renal damage, seems to be a reasonable approach to be applied in clinical practice to allow earlier diagnosis and better disease characterization based on the underlying etiologic process.


Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 19
Author(s):  
Ashani Lecamwasam ◽  
Tiffanie M. Nelson ◽  
Leni Rivera ◽  
Elif I. Ekinci ◽  
Richard Saffery ◽  
...  

(1) Background: Individuals with diabetes and chronic kidney disease display gut dysbiosis when compared to healthy controls. However, it is unknown whether there is a change in dysbiosis across the stages of diabetic chronic kidney disease. We investigated a cross-sectional study of patients with early and late diabetes associated chronic kidney disease to identify possible microbial differences between these two groups and across each of the stages of diabetic chronic kidney disease. (2) Methods: This cross-sectional study recruited 95 adults. DNA extracted from collected stool samples were used for 16S rRNA sequencing to identify the bacterial community in the gut. (3) Results: The phylum Firmicutes was the most abundant and its mean relative abundance was similar in the early and late chronic kidney disease group, 45.99 ± 0.58% and 49.39 ± 0.55%, respectively. The mean relative abundance for family Bacteroidaceae, was also similar in the early and late group, 29.15 ± 2.02% and 29.16 ± 1.70%, respectively. The lower abundance of Prevotellaceae remained similar across both the early 3.87 ± 1.66% and late 3.36 ± 0.98% diabetic chronic kidney disease groups. (4) Conclusions: The data arising from our cohort of individuals with diabetes associated chronic kidney disease show a predominance of phyla Firmicutes and Bacteroidetes. The families Ruminococcaceae and Bacteroidaceae represent the highest abundance, while the beneficial Prevotellaceae family were reduced in abundance. The most interesting observation is that the relative abundance of these gut microbes does not change across the early and late stages of diabetic chronic kidney disease, suggesting that this is an early event in the development of diabetes associated chronic kidney disease. We hypothesise that the dysbiotic microbiome acquired during the early stages of diabetic chronic kidney disease remains relatively stable and is only one of many risk factors that influence progressive kidney dysfunction.


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