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Precision Prevention and Care in Chronic Kidney Disease

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A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: closed (15 June 2023) | Viewed by 31015

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Special Issue Editors

Dr. Ming-Yen Lin

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Guest Editor

Department of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Interests: chronic kidney disease prevention and care; causal inference; multi-sate model

Dr. Daw-Yang Hwang

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Guest Editor

National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan
Interests: disease-causing genes of human diseases; autosomal dominant polycystic kidney disease

Dr. Yihuang Kang

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Guest Editor

Department of Information and Management, National Sun Yat-Sen University, Kaohsiung 804, Taiwan
Interests: temporal data mining; health informatics; machine learning; interactive machine learning

Special Issue Information

Dear Colleagues,

Over ten percent of the world's population, or nearly 850 million people, suffer from chronic kidney disease (CKD). Many complex determinants contribute to it, and some of them may be appropriately avoided. Early CKD is usually asymptomatic, but could be detected by urinary screening. Care is the key to prolong disease progression in late CKD. However, appropriate CKD care depends on underlying diseases and complication controls. In the past decade, personalized data has been well produced and recorded. A wonderful time to assist in the development of care plans for different people who are at risk of or are suffering from CKD’s threats is coming. In this Special Issue, I would like to sincerely invite you to contribute your relevant articles on optimizing CKD prevention and care.

Dr. Ming-Yen Lin
Dr. Daw-Yang Hwang
Dr. Yihuang Kang
Guest Editors

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Keywords

chronic kidney disease
precision screening
precision prevention
precision care
precision prescription
mobile medicine
machine learning

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Published Papers (10 papers)

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Research

13 pages, 1923 KiB

Open AccessArticle

Expression of Angiopoetin-Like Protein-4 and Kidney Injury Molecule-1 as Preliminary Diagnostic Markers for Diabetes-Related Kidney Disease: A Single Center-Based Cross-Sectional Study

by Gulnaz Bano, Mohammad Tarique Imam, Ram Bajpai, Ghada Alem, Varun Kumar Kashyap, Anwar Habib and Abul Kalam Najmi

J. Pers. Med. 2023, 13(4), 577; https://doi.org/10.3390/jpm13040577 - 24 Mar 2023

Cited by 2 | Viewed by 1702

Abstract

The purpose of the study was to examine the urinary levels of kidney injury molecule-1 (KIM-1) and angiopoietin-like protein-4 (ANGPTL-4) in individuals with diabetic kidney disease (DKD) and their association with established DKD diagnostic markers such as albuminuria and estimated glomerular filtration rate (eGFR). Levels of ANGPTL-4 and KIM-1 were estimated in urine samples. A total of 135 participants were recruited into three groups: 45 diabetes type 2 patients in the control group and 90 DKD patients in two disease groups. Concentrations of ANGPTL-4 and KIM-1 were conclusively related to the urinary albumin–creatinine ratio (UACR). Also, the levels of both ANGPTL-4 and KIM-1 were negatively associated with the eGFR. Multivariable Poisson regression analysis showed that urinary ANGPTL-4 (PR: 3.40; 95% CI: 2.32 to 4.98; p < 0.001) and KIM-1 (PR: 1.25; 95% CI: 1.14 to 1.38; p < 0.001) were prevalent in DKD patients. Receiver operating characteristic (ROC) analysis of urinary ANGPTL-4 and KIM-1 in the combined form resulted in an area under curve (AUC) of 0.967 (95%CI: 0.932–1.000; p < 0.0001) in the microalbuminuria group and 1 (95%CI: 1.000–1.000; p < 0.0001) in the macroalbuminuria group. The association of urinary levels of ANGPTL-4 and KIM-1 with UACR and eGFR and significant prevalence in the diabetic kidney disease population illustrates the diagnostic potential of these biomarkers. Full article

(This article belongs to the Special Issue Precision Prevention and Care in Chronic Kidney Disease)

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14 pages, 300 KiB

Open AccessArticle

The Association between Iron Deficiency and Renal Outcomes Is Modified by Sex and Anemia in Patients with Chronic Kidney Disease Stage 1–4

by Pei-Hua Yu, Yu-Lin Chao, I-Ching Kuo, Sheng-Wen Niu, Yi-Wen Chiu, Jer-Ming Chang and Chi-Chih Hung

J. Pers. Med. 2023, 13(3), 521; https://doi.org/10.3390/jpm13030521 - 14 Mar 2023

Viewed by 2450

Abstract

Iron deficiency is prevalent in women and patients with chronic kidney disease (CKD). Iron deficiency is not only related to anemia but contributes to adverse consequences for the kidney as well. Whether iron status is associated with renal outcomes after considering sex and anemia in patients with CKD stage 1–4 is unclear. Thus, we investigated the association of iron or iron saturation with renal outcomes in a CKD cohort. During a follow-up of 8.2 years, 781 (31.2%) patients met the composite renal outcome of renal replacement therapy and a 50% decline in renal function. In linear regression, iron was associated with sex, hemoglobin (Hb), and nutritional markers. In a fully adjusted Cox regression model, the male patients with normal iron had a significantly decreased risk of renal outcomes (hazard ratio (HR) 0.718; 95% confidence interval (CI) 0.579 to 0.889), but the female patients did not exhibit this association. The non-anemic patients (Hb ≥ 11 g/dL) had a decreased risk of renal outcomes (HR 0.715; 95% CI 0.568 to 0.898), but the anemic patients did not. In the sensitivity analysis, transferrin saturation (TSAT) showed similar results. When comparing iron and TSAT, both indicators showed similar prognostic values. In conclusion, iron deficiency, indicated by either iron or iron saturation, was associated with poor renal outcomes in the male or non-anemic patients with CKD stage 1–4. Full article

(This article belongs to the Special Issue Precision Prevention and Care in Chronic Kidney Disease)

10 pages, 914 KiB

Open AccessArticle

Association between Serum Soluble Urokinase-Type Plasminogen Activator Receptor Level and Arterial Stiffness in Chronic Hemodialysis Patients

by Wei-Chen Lin, Tsung-Jui Wu, Chih-Hsien Wang, Yi-Jen Hsieh and Bang-Gee Hsu

J. Pers. Med. 2023, 13(3), 470; https://doi.org/10.3390/jpm13030470 - 4 Mar 2023

Cited by 3 | Viewed by 1491

Abstract

Cardiovascular diseases (CVDs) remain a significant cause of death in hemodialysis (HD) patients. To explore their associations, we examine the role of soluble urokinase-type plasminogen activator receptor (suPAR) in arterial stiffness in chronic HD patients. From June to August 2020, we recruited 135 chronic HD patients. The arterial stiffness group included patients with a carotid–femoral pulse-wave velocity (cfPWV) of >10 m/s. Fifty-five HD patients (40.7%) were in the arterial stiffness group. They had a higher prevalence of diabetes (p = 0.001) and hypertension (p = 0.039), were older (p = 0.007) and had higher aortic systolic blood pressure (p = 0.034), brachial systolic blood pressure (p = 0.025), glucose (p = 0.019), C-reactive protein (p = 0.039), and AIx75 (p = 0.003) and suPAR (p < 0.001) levels than the control group. After we performed multivariable logistic regression analysis, except age and glucose, serum suPAR (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.48–2.70, p < 0.001) was independently associated with arterial stiffness in chronic HD patients. In the multivariable linear regression analysis, suPAR positively correlated with cfPWV (β = 0.475, p < 0.001) and could serve as a biomarker for arterial stiffness development in patients undergoing HD. Full article

(This article belongs to the Special Issue Precision Prevention and Care in Chronic Kidney Disease)

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12 pages, 1093 KiB

Open AccessEditor’s ChoiceArticle

Plasma Interleukin-6 Level Predicts the Risk of Arteriovenous Fistula Dysfunction in Patients Undergoing Maintenance Hemodialysis

by Jihyun Baek, Hyeyeon Lee, Taeyoung Yang, So-Young Lee, Yang Gyun Kim, Jin Sug Kim, ShinYoung Ahn, Kipyo Kim, Seok Hui Kang, Min-Jeong Lee, Dong-Young Lee, Hye Yun Jeong and Yu Ho Lee

J. Pers. Med. 2023, 13(1), 151; https://doi.org/10.3390/jpm13010151 - 12 Jan 2023

Cited by 4 | Viewed by 2037

Abstract

Systemic inflammation has been proposed as a relevant factor of vascular remodeling and dysfunction. We aimed to identify circulating inflammatory biomarkers that could predict future arteriovenous fistula (AVF) dysfunction in patients undergoing hemodialysis. A total of 282 hemodialysis patients were enrolled in this prospective multicenter cohort study. Plasma cytokine levels were measured at the time of data collection. The primary outcome was the occurrence of AVF stenosis and/or thrombosis requiring percutaneous transluminal angioplasty or surgery within the first year of enrollment. AVF dysfunction occurred in 38 (13.5%) patients during the study period. Plasma interleukin-6 (IL-6) levels were significantly higher in patients with AVF dysfunction than those without. Diabetes mellitus, low systolic blood pressure, and statin use were also associated with AVF dysfunction. The cumulative event rate of AVF dysfunction was the highest in IL-6 tertile 3 (p = 0.05), and patients in tertile 3 were independently associated with an increased risk of AVF dysfunction after multivariable adjustments (adjusted hazard ratio = 3.06, p = 0.015). In conclusion, circulating IL-6 levels are positively associated with the occurrence of incident AVF dysfunction in hemodialysis patients. Our data suggest that IL-6 may help clinicians identify those at high risk of impending AVF failure. Full article

(This article belongs to the Special Issue Precision Prevention and Care in Chronic Kidney Disease)

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9 pages, 245 KiB

Open AccessArticle

Factors Influencing Self-Management Behaviors among Hemodialysis Patients

by Li-Ching Ma, Yueh-Min Liu, Yen-Chung Lin, Chia-Te Liao, Kuo-Chin Hung, Remy Chen, Kuo-Cheng Lu, Kuei-Fang Ho and Cai-Mei Zheng

J. Pers. Med. 2022, 12(11), 1816; https://doi.org/10.3390/jpm12111816 - 2 Nov 2022

Cited by 9 | Viewed by 3294

Abstract

Aim: To investigate the factors affecting hemodialysis patients’ self-management ability at a dialysis center in Taiwan. Background: Taiwan has the highest incidence and prevalence of end-stage kidney disease (ESKD) in the world. Over 90% of patients with ESKD receiving hemodialysis (HD) and self-management behaviors are critical among these patients. Failure to adhere to self-managed care increases the cost of medical care and the risk of morbidity and mortality. Methods: In this cross-sectional study, a total of 150 HD patients were observed for their self-management behaviors and the factors influencing these behaviors including education level, comorbid conditions, biochemical analysis, depression, and social support, etc., were analyzed. Results: Self-management behaviors in HD patients were significantly impaired in the presence of diabetes mellitus, hypertension, anemia, hypoalbuminemia, and depression. The major predictor of patients’ self-management was depression, explaining 14.8% of the total variance. Further addition of social support, hypertension, and diabetes mellitus into the regression model increased the total explained variance to 28.6%. Of the various domains of self-management, the partnership domain received the highest score, whereas emotional processing received the lowest score. Conclusions: This study found the important factors influencing self-management behaviors; through this acknowledgement and early correction of these factors, we hope to improve HD patients’ individual life quality and further decrease their morbidity and mortality. Full article

(This article belongs to the Special Issue Precision Prevention and Care in Chronic Kidney Disease)

13 pages, 8647 KiB

Open AccessArticle

The Effect of Statin on Anemia in Patients with Chronic Kidney Disease and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis

by Meng-Hsu Tsai, Fu-You Su, Hao-Yun Chang, Po-Cheng Su, Li-Yun Chiu, Michal Nowicki, Chih-Chin Kao and Yen-Chung Lin

J. Pers. Med. 2022, 12(7), 1175; https://doi.org/10.3390/jpm12071175 - 19 Jul 2022

Cited by 2 | Viewed by 3432

Abstract

Although erythropoietin-stimulating agents are effective in treating anemia in patients with end-stage kidney disease (ESKD) undergoing hemodialysis, some ESKD patients, especially those with inflammation, continue to suffer from anemia. Statin, an inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase with lipid-lowering effects, may have a pleiotropic effect in reducing inflammation, and thus increase hemoglobin (Hb) level. We searched the PubMed, Embase, and Cochrane databases for relevant studies. The population of interest comprised advanced chronic kidney disease (CKD) patients and ESKD patients receiving hemodialysis with statin treatment. The included study designs were randomized control trial/cohort study/pre-post observational study, and outcomes of interest were Hb, erythropoietin resistance index (ERI) and ferritin. PRISMA 2020 guidelines were followed, and risk of bias (RoB) was assessed using the RoB 2.0 tool in randomized controlled trials, and the Newcastle-Ottawa scale (NOS) in cohort studies. We eventually included ten studies (5258 participants), comprising three randomized controlled trials and seven cohort studies. Overall, Hb increased by 0.84 g/dL (95% confidence interval [CI]: −0.02 to 1.70) in all groups using statins, including single-arm cohorts, and by 0.72 g/dL (95% CI: −0.02 to 1.46) in studies with placebo control. Hb levels were higher in the study group than in the control group, with a mean difference of 0.18 g/dL (95% CI: 0.04–0.32) at baseline and 1.0 g/dL (95% CI: 0.13–1.87) at the endpoint. Ferritin increased by 9.97 ng/mL (95% CI: −5.36 to 25.29) in the study group and decreased by 34.01 ng/mL (95% CI: −148.16 to 80.14) in the control group; ferritin fluctuation was higher in the control group. In conclusion, statin may improve renal anemia in ESKD patients receiving hemodialysis and regular erythropoietin-stimulating agents. Future studies with more rigorous methodology and larger sample size study should be performed to confirm this beneficial effect. Full article

(This article belongs to the Special Issue Precision Prevention and Care in Chronic Kidney Disease)

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16 pages, 1564 KiB

Open AccessArticle

Effectiveness of a Nutritional Mobile Application for Management of Hyperphosphatemia in Patients on Hemodialysis: A Multicenter Open-Label Randomized Clinical Trial

by Lee-Fang Teong, Ban-Hock Khor, Hi-Ming Ng, Sharmela Sahathevan, Kristo Radion Purba, Sreelakshmi Sankara Narayanan, Abdul Halim Abdul Gafor, Bak-Leong Goh, Boon-Cheak Bee, Rosnawati Yahya, Sunita Bavanandan, Zaimi Wahab, Sadanah Aqashiah Mazlan, Karuthan Chinna, Zaki Morad, Zulfitri Azuan Mat Daud and Tilakavati Karupaiah

J. Pers. Med. 2022, 12(6), 961; https://doi.org/10.3390/jpm12060961 - 12 Jun 2022

Cited by 4 | Viewed by 2897

Abstract

This study aims to determine the effectiveness of a phosphate mobile app (PMA), MyKidneyDiet-Phosphate Tracker ©2019, on hemodialysis (HD) patients with hyperphosphatemia. A multicenter, open-label, randomized controlled trial design allowed randomization of patients with hyperphosphatemia to either the usual care group (UG; receiving a single dietitian-led session with an education booklet) or the PMA group (PG). Thirty-three patients in each intervention group completed the 12-week study. Post-intervention, serum phosphorus levels were reduced in both groups (PG: −0.25 ± 0.42 mmol/L, p = 0.001; UG: −0.23 ± 0.33 mmol/L, p < 0.001) without any treatment difference (p > 0.05). Patients in both groups increased their phosphate knowledge (PG: 2.18 ± 3.40, p = 0.001; UG: 2.50 ± 4.50, p = 0.003), without any treatment difference (p > 0.05). Dietary phosphorus intake of both groups was reduced (PG: −188.1 ± 161.3 mg/d, p < 0.001; UG: −266.0 ± 193.3 mg/d, p < 0.001), without any treatment difference (p > 0.05). The serum calcium levels of patients in the UG group increased significantly (0.09 ± 0.20 mmol/L, p = 0.013) but not for the PG group (−0.03 ± 0.13 mmol/L, p = 0.386), and the treatment difference was significant (p = 0.007). As per phosphate binder adherence, both groups reported a significant increase in Morisky Medication Adherence Scale scores (PG: 1.1 ± 1.2, p < 0.001; UGa: 0.8 ± 1.5, p = 0.007), without any treatment difference (p > 0.05). HD patients with hyperphosphatemia using the PMA achieved reductions in serum phosphorus levels and dietary phosphorus intakes along with improved phosphate knowledge and phosphate binder adherence that were not significantly different from a one-off dietitian intervention. However, binder dose adjustment with meal phosphate content facilitated by the PMA allowed stability of corrected calcium levels, which was not attained by UC patients whose binder dose was fixed. Full article

(This article belongs to the Special Issue Precision Prevention and Care in Chronic Kidney Disease)

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11 pages, 1428 KiB

Open AccessArticle

Kidney Function Change and All-Cause Mortality in Denosumab Users with and without Chronic Kidney Disease

by Ping-Hsun Wu, Ming-Yen Lin, Teng-Hui Huang, Tien-Ching Lee, Sung-Yen Lin, Chung-Hwan Chen, Mei-Chuan Kuo, Yi-Wen Chiu, Jer-Ming Chang and Shang-Jyh Hwang

J. Pers. Med. 2022, 12(2), 185; https://doi.org/10.3390/jpm12020185 - 31 Jan 2022

Cited by 5 | Viewed by 4569

Abstract

Denosumab is approved for osteoporosis treatment in subjects with and without chronic kidney disease (CKD). Confirmation is required for its safety, treatment adherence, renal function effect, and mortality in patients with CKD. A retrospective cohort study was conducted to compare new users of denosumab in terms of their two-year drug adherence in all participants (overall cohort) and CKD participants (CKD subcohort), which was defined as baseline estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m². The eGFR was calculated using the 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. We defined high adherence (HA) users as receiving three or four doses and low adherence (LA) users as receiving one or two doses. All-cause mortality was analyzed using Kaplan–Meier curves and Cox regression models. In total, there were 1142 subjects in the overall cohort and 500 subjects in the CKD subcohort. HA users had better renal function status at baseline than LD users in the overall cohort. A decline in renal function was only observed among LD users in the overall cohort. In the CKD subcohort, no baseline renal function difference or renal function decline was demonstrated. The all-cause mortality rate of HA users was lower than LA users in both the overall cohort and CKD. A randomized control trial is warranted to target this unique population to confirm our observations. Full article

(This article belongs to the Special Issue Precision Prevention and Care in Chronic Kidney Disease)

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11 pages, 551 KiB

Open AccessArticle

A Low-Protein Diet with a Renal-Specific Oral Nutrition Supplement Helps Maintain Nutritional Status in Patients with Advanced Chronic Kidney Disease

by Owen J. Kelly, Meng-Chuan Huang, Hsin-Yin Liao, Chih-Ching Lin, Tsui-Yin Tung, Rhoda Wen-Yi Cheng, Michael Yao-Hsien Wang, Menaka Yalawar and Shang-Jyh Hwang

J. Pers. Med. 2021, 11(12), 1360; https://doi.org/10.3390/jpm11121360 - 14 Dec 2021

Cited by 7 | Viewed by 4578

Abstract

A low-protein diet (LPD) is recommended to patients with non-dialysis advanced chronic kidney disease (CKD) for delaying renal function decline. However, this approach potentially prevents an adequate calorie and micronutrient intake. We examined the influence of an LPD including a renal-specific oral nutrition supplement (RONS) on the nutrition status of patients with stage 3b–5 CKD. This multicenter, open-label study prospectively enrolled patients over 18 years of age, with an estimated glomerular filtration rate (eGFR) between 10 and 45 mL/min/1.73 m², serum albumin ≥3.0 g/dL, and body mass index ≤30 kg/m². All participants implemented the LPD with one serving of RONS daily for 6 months. Daily energy intake, nutrition status, renal function, and quality of life were assessed before and after the intervention. Of 53 enrolled patients, 35 (66.0%) completed the study. We found that RONS use increased patients’ energy intake and maintained their serum albumin, nutritional status, and quality of life. Body weight and handgrip strength increased significantly at 6 months after enrollment (p = 0.0357); eGFR slightly decreased at 3 and 6 months after enrollment, suggesting that patients’ residual renal function was preserved. Our findings support the conclusion that patients with non-dialysis advanced CKD may benefit from additional RONS besides their regular diet. Patients with advanced CKD receiving RONS might achieve better nutrition and delay renal function decline. Full article

(This article belongs to the Special Issue Precision Prevention and Care in Chronic Kidney Disease)

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15 pages, 1380 KiB

Open AccessArticle

U-Shaped Association between Waist-to-Hip Ratio and All-Cause Mortality in Stage 3–5 Chronic Kidney Disease Patients with Body Mass Index Paradox

by Feng-Ching Shen, Yi-Wen Chiu, Mei-Chuan Kuo, Ming-Yen Lin, Jia-Jung Lee, Shang-Jyh Hwang, Jer-Ming Chang, Chi-Chih Hung and Hung-Chun Chen

J. Pers. Med. 2021, 11(12), 1355; https://doi.org/10.3390/jpm11121355 - 13 Dec 2021

Cited by 12 | Viewed by 2913

Abstract

The obesity paradox, referring to the association of high body mass index (BMI) with low all-cause mortality risk, is found in patients with chronic kidney disease (CKD). Central obesity is associated with metabolic syndrome and may have better prognostic value than BMI for all-cause mortality. Whether central obesity is associated with all-cause mortality in cases of obesity paradox in CKD patients remains unknown. We included 3262 patients with stage 3–5 CKD, grouped into five quintiles (Q1–5) by waist-to-hip ratio (WHR). Low WHR and BMI were associated with malnutrition and inflammation. In Cox regression, high BMI was not associated with all-cause mortality, but BMI < 22.5 kg/m² increased the mortality risk. A U-shaped association between central obesity and all-cause mortality was found: WHR Q1, Q4, and Q5 had higher risk for all-cause mortality. The hazard ratio (95% confidence interval) of WHR Q5 and Q1 for all-cause mortality was 1.39 (1.03–1.87) and 1.53 (1.13–2.05) in male and 1.42 (1.02–1.99) and 1.28 (0.88–1.85) in female, respectively. Waist-to-height ratio and conicity index showed similar results. Low WHR or low BMI and high WHR, but not high BMI, are associated with all-cause mortality in advanced CKD. Full article

(This article belongs to the Special Issue Precision Prevention and Care in Chronic Kidney Disease)

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