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Chronic Kidney Disease: Clinical Challenges and Management

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (20 March 2026) | Viewed by 14386

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Dr. Shuzo Kobayashi

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Guest Editor

Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, Kamakura, Japan
Interests: vascular biology; cardiovascular disease; hemodialysis; kidney disease; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

Dr. Takayasu Ohtake

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Guest Editor

Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, Kamakura, Japan
Interests: kidney disease; regenerative medicine; hemodialysis; vascular biology; cardiovascular disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) is a devastating disease which progresses to end-stage renal disease (ESRD) and has a large impact on prognosis in CKD patients via concomitant atherosclerotic cardiovascular diseases, malnutrition, inflammation, malignancy, etc. Previous large clinical trials have shown that drugs, including angiotensin converting enzyme inhibitors (ACEi), angiotensin type Ⅱ receptor blockers (ARBs), SGLT2 inhibitors, and mineral corticoid receptor antagonists (MRAs), retard the progression of CKD. However, the results are still not optimal, leading to an increase in dialysis patients worldwide. Although interventional treatment could retard the progression of CKD, improvement in kidney function (reverse kidney dysfunction), as the final goal, has not been fully achieved. Regenerative cell therapies or exosome therapies using several cell sources are emerging as new potential strategies. However, there are still challenges for human CKD.

Based on the abovementioned background, we introduce this Special Issue, entitled “Chronic Kidney Disease: Clinical Challenges and Management”, in the Journal of Clinical Medicine. As Guest Editors of this Special Issue, we invite submissions focused on treatment approaches (even if challenging and/or small clinical trials), observational research, and trials conducted by specialists in the fields of nursing, nutrition, rehabilitation, pharmacies, and multidisciplinary team approaches for CKD and comorbid diseases.

Dr. Shuzo Kobayashi
Dr. Takayasu Ohtake
Guest Editors

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Keywords

chronic kidney disease
clinical trial
end-stage renal disease
kidney dysfunction
management
challenge

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Published Papers (7 papers)

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14 pages, 2983 KB

Open AccessArticle

Predicting Lifetime Risk of Kidney Failure Using Age and a Single eGFR Measurement

by Ryo Enoki, Mariko Miyazaki, Enyu Imai, Tetsuhiro Tanaka and Koji Okamoto

J. Clin. Med. 2026, 15(7), 2653; https://doi.org/10.3390/jcm15072653 - 31 Mar 2026

Viewed by 772

Abstract

Background: The prognosis of chronic kidney disease (CKD) typically requires longitudinal estimated glomerular filtration rate (eGFR) data, making risk stratification difficult at initial consultation. Furthermore, eGFR-based clinical decisions often overlook the critical factor of patient age. This study aimed to establish a simplified predictive model for progressive CKD and quantify the impact of clinical interventions. Methods: Utilizing a historical dataset (1988–2003) from the pre-renin-angiotensin system inhibitor (RASi) and pre-sodium-glucose cotransporter 2 inhibitor (SGLT2i) era, we developed heatmaps to predict the probability of reaching eGFR < 30 mL/min/1.73 m² by age 80 years. The model also estimated the risk reduction from smoking cessation and pharmacological therapies. The predictive performance for age + eGFR was assessed using standard calibration and discrimination metrics, and clinical utility was evaluated using decision curve analysis across a range of threshold probabilities. Risk reclassification analyses compared age +eGFR-based categories with conventional eGFR-based stratification. Results: Regarding the risk of eGFR < 30 mL/min/1.73 m² by age 80 years, simulations confirmed a correlation between age and eGFR. At age 40 years, an eGFR of ~57 mL/min/1.73 m² indicated a 50% probability of progressing to CKD stage 4 by age 80 years. This threshold decreases to 53 and 48 mL/min/1.73 m² at 50 and 60 years of age, respectively. Calibration and discrimination analyses demonstrated acceptable agreement between predicted and observed risks. Decision curve analysis showed that an age + eGFR threshold of approximately 115 primarily provided a net benefit at lower threshold probabilities, supporting intensified surveillance strategies, whereas an age +eGFR of 100 showed a positive net benefit across a broader range of thresholds, comparable to the conventional eGFR < 45 mL/min/1.73 m² criterion. While proteinuria markedly increased risk, smoking cessation provided a 9.4–11.2% risk reduction. Combined RASi and SGLT2i treatment showed the greatest impact, reducing progression probability by 31.2–40.0% (e.g., reducing a 50.0% baseline risk to 32.1% in 40-year-old men). Conclusions: The age + eGFR rule represents a simple, clinically interpretable heuristic for age-adjusted risk stratification based on a single eGFR measurement and may offer potential clinical utility for guiding surveillance intensity and consideration of earlier intervention strategies. However, external validation is required before clinical application. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Clinical Challenges and Management)

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13 pages, 236 KB

Open AccessArticle

Verification of the Utility of Urinary L-FABP as a Predictor of Impaired Renal Function Based on Its Relationship with Changes in Renal Function

by Yuichi Kato and Takeshi Sugaya

J. Clin. Med. 2026, 15(6), 2243; https://doi.org/10.3390/jcm15062243 - 16 Mar 2026

Viewed by 410

Abstract

Background: In patients with diabetes or hypertension, if appropriate intervention is not initiated early in the course of kidney disease, not only does the risk of progressing to end-stage renal failure increase, but mortality associated with vascular complications also rises as the disease progresses; therefore, there is an urgent need to develop urinary biomarkers that enable early diagnosis and prediction of disease progression. Methods: This two-year prospective observational study involved 185 outpatients. Patients were classified into two groups based on their baseline urinary L-FABP levels relative to the reference value of 8.4 μg/g·Cr at the start of the study. The rate of eGFR decline during the observation period was evaluated. Results: The results showed an interaction (synergistic effect) between urinary L-FABP and time in patients with diabetes or hypertension who had an eGFR of at least 60 mL/min/1.732 m²/kg/1.732 m². Patients with high urinary L-FABP levels (>8.4 μg/g·Cr) exhibited a notably faster eGFR decline compared with those with low levels (≤8.4 μg/g·Cr). This finding suggests the potential of urinary L-FABP as a predictor of renal function decline; we evaluated this utility using the area under the ROC curve (AUC) and logistic regression analysis. The results indicate that urinary L-FABP holds potential as a predictor of renal function decline in diabetic or hypertensive patients with preserved eGFR. Conclusions: Among the analysis groups in which the validation was conducted, it was demonstrated that urinary L-FABP holds potential as a predictor of renal function decline in patients with diabetes or hypertension who have a maintained eGFR. Given that urinary L-FABP is thought to reflect tubulointerstitial damage associated with renal microcirculatory impairment, its future utility as a urinary biomarker for the early diagnosis and prognosis of chronic kidney disease (CKD) is anticipated. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Clinical Challenges and Management)

17 pages, 988 KB

Open AccessArticle

Exploring the Associations Between Inflammatory Biomarkers, Survival, and Cardiovascular Events in Hemodialysis Patients and the Interrelationship with Nutritional Parameters—The Experience of a Single Transylvanian Dialysis Center

by Crina Claudia Rusu, Ina Kacso, Diana Moldovan, Alina Potra, Dacian Tirinescu, Maria Ticala, Yuriy Maslyennikov, Alexandra Urs and Cosmina Ioana Bondor

J. Clin. Med. 2025, 14(4), 1139; https://doi.org/10.3390/jcm14041139 - 10 Feb 2025

Cited by 5 | Viewed by 2557

Abstract

Background/Objectives: In hemodialysis (HD), inflammatory biomarkers are discussed as prognostic markers for survival and cardiovascular events (CVEs). The results of the studies are not uniform and there are particularities related to population groups and comorbidities. In addition, it is known that inflammation determines protein malnutrition and less about the effect of adipose tissue on inflammation in HD. This study investigates the relationship between inflammatory molecules and nutritional biomarkers, and CVE and survival in HD patients. Methods: We included, in an observational, longitudinal study, 65 patients with chronic HD (53 without diabetes and 22 smokers), with a mean age of 60.1 ± 12.4 years. High-sensitivity C-reactive protein (hs-CRP), interleukin 1 beta, tumor necrosis factor alpha (TNF-alpha), interleukin 6, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), soluble CD163 (sCD163), and fibroblast growth factor 21 were determined. We recorded survival and cardiovascular events for 60 months. Univariate and multivariate analyses were performed. Results: Hs-CRP was significantly associated with survival (p = 0.014) in the total group. In smokers and former smokers, TNF-α lower than 368.34 pg/mL was associated with better survival. In multivariate analysis, hs-CRP was correlated with adipose tissue biomarkers (p = 0.006), and sCD163 was correlated with total and LDL cholesterol (p = 0.002). In addition, in univariate analysis, sTWEAK was correlated with serum albumin (p = 0.026, r = −0.30). In conclusion, in HD patients, hs-CRP was significantly associated with survival, and low TNF-alpha values in smokers and former smokers were linked to better survival. Hs-CRP was also correlated with adipose tissue biomarkers, CD163 was correlated with total and LDL cholesterol, and albumin was inversely associated with sTWEAK. The relation between inflammatory molecules and adipose tissue biomarkers was less identified in HD patients until now. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Clinical Challenges and Management)

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11 pages, 554 KB

Open AccessArticle

Asymmetric Dimethylarginine (ADMA) as a Novel Risk Factor for Progression of Coronary Artery Calcification in Patients with Chronic Kidney Disease

by Shuzo Kobayashi, Takayasu Ohtake, Yasuhiro Mochida, Kunihiro Ishioka, Machiko Oka, Kyoko Maesato, Hidekazu Moriya and Sumi Hidaka

J. Clin. Med. 2025, 14(4), 1051; https://doi.org/10.3390/jcm14041051 - 7 Feb 2025

Cited by 6 | Viewed by 1579

Abstract

Background: Vascular calcification (VC) is a characteristic feature of atherosclerosis in patients with chronic kidney disease (CKD), and coronary artery calcification (CAC) significantly impacts future cardiovascular events and mortality. Although factors associated with CAC are well reported, only a few studies have evaluated the factors associated with the progression of CAC in pre-dialysis patients with CKD. Methods: We quantitatively evaluated CAC progression using the CAC score (CACS) measured using 16-row multi-detector computed tomography and assessed associated factors in 74 patients with CKD. Results: The median annual increase in CACS was 23.7 (IQR 2.0–73.0). CAC progression was associated with serum phosphate and plasma asymmetric dimethylarginine (ADMA) levels, an endogenous inhibitor of nitric-oxide synthase and a marker of endothelial dysfunction and atherosclerosis, in univariate analysis. Multivariate analysis revealed that ADMA is an independent risk factor for CAC progression in patients with CKD. The annual change in CACS was significantly different between patients with ADMA values <0.51 and those with ADMA values >0.51 (p < 0.05). Elevated ADMA levels were also significantly associated with estimated glomerular filtration rate (eGFR) decline in the univariate analysis. Conclusions: ADMA is a novel risk factor for CAC progression in patients with CKD. Vascular endothelial cell dysfunction, represented by elevated ADMA levels, may contribute to the progression of vascular calcification in patients with pre-dialysis CKD. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Clinical Challenges and Management)

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10 pages, 197 KB

Open AccessArticle

Public Unawareness of Renal Function: A Questionnaire Survey at a Health Promotion Seminar

by Yukinori Aimiya, Sho Hasegawa, Mikio Sakakibara, Midori Hasegawa, Naotake Tsuboi, Naoki Nakagawa and Shigeki Yamada

J. Clin. Med. 2025, 14(3), 664; https://doi.org/10.3390/jcm14030664 - 21 Jan 2025

Viewed by 1634

Abstract

Background: Progression of chronic kidney disease (CKD) increases the risk of complications such as cardiovascular disease; however, knowledge regarding renal function in the general population is low. We aimed to determine factors necessitating CKD education in the general population. Methods: Participants for a health promotion seminar were recruited via the Sugiura Memorial Foundation website and Sugi Pharmacy stores. Those who agreed to participate in the seminar were included in the questionnaire survey after a health seminar. Results: Out of 1548 participants, 1050 answered all questionnaire items, resulting in a valid response rate of 67.83%. Multivariable analysis revealed that sex (OR = 0.611), pharmacy consultations (OR = 0.661), receiving a blood test within 1 year (OR = 0.268), awareness of blood pressure (OR = 0.038), and knowledge of blood glucose level (OR = 0.099) were factors for unawareness of renal function. Conclusions: This study suggests that female individuals unaware of their blood pressure or glucose levels, those who have not had a blood test within 1 year, and those who have not sought health consultations need education on renal function. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Clinical Challenges and Management)

11 pages, 1153 KB

Open AccessArticle

The Association Between the Perception of Exercise Benefits and Barriers and Exercise Self-Efficacy During the Induction Phase of Dialysis in Patients with End-Stage Kidney Disease: A Cross-Sectional Study

by Yuma Hirano, Tomoyuki Fujikura, Tomoya Yamaguchi, Akihiko Kato, Kenichi Kono, Naro Ohashi, Hideo Yasuda and Katsuya Yamauchi

J. Clin. Med. 2024, 13(21), 6332; https://doi.org/10.3390/jcm13216332 - 23 Oct 2024

Cited by 1 | Viewed by 2451

Abstract

Background/Objectives: The physical function of patients with chronic kidney disease gradually declines as kidney function deteriorates, and this decline becomes more pronounced after the initiation of dialysis. Encouraging the development of exercise habits from the initiation phase of dialysis is crucial. Increased exercise self-efficacy is essential for establishing these habits. However, the related factors at this stage are unclear. This study hypothesized that perceptions of exercise benefits and barriers are related to exercise self-efficacy and aimed to investigate this association. Methods: This single-center, cross-sectional study included 72 patients and assessed the stages of exercise behavior change, perceptions of exercise benefits and barriers, and exercise self-efficacy. Multiple regression analysis was used to examine the association between exercise self-efficacy and perceptions of the benefits and barriers of exercise. Results: Perceptions of exercise benefits were still significantly associated with self-efficacy for exercise after adjustment for age, gender, history of cardiovascular disease, diabetic kidney disease, living alone, employment, and physical function (β = 0.474, p < 0.001). Similarly, perceptions of exercise barriers were also significantly associated with self-efficacy for exercise (β = −0.410, p = 0.001). A subgroup analysis that only examined participants without exercise habits revealed a similar association. Conclusions: Perceptions of exercise benefits and barriers may be associated with exercise self-efficacy in patients with end-stage kidney disease during the initiation phase of dialysis. As patients are temporarily hospitalized during this phase, it provides an opportunity for intervention. Exercise education and supportive environments during hospitalization may enhance perceptions of exercise benefits, reduce perceptions of exercise barriers, and improve exercise self-efficacy. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Clinical Challenges and Management)

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21 pages, 2882 KB

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Hemoincompatibility in Hemodialysis-Related Therapies and Their Health Economic Perspectives

by Carsten Hornig, Sudhir K. Bowry, Fatih Kircelli, Dana Kendzia, Christian Apel and Bernard Canaud

J. Clin. Med. 2024, 13(20), 6165; https://doi.org/10.3390/jcm13206165 - 16 Oct 2024

Cited by 7 | Viewed by 3803

Abstract

Hemobiologic reactions associated with the hemoincompatibility of extracorporeal circuit material are an undesirable and inevitable consequence of all blood-contacting medical devices, typically considered only from a clinical perspective. In hemodialysis (HD), the blood of patients undergoes repetitive (at least thrice weekly for 4 h and lifelong) exposure to different polymeric materials that activate plasmatic pathways and blood cells. There is a general agreement that hemoincompatibility reactions, although unavoidable during extracorporeal therapies, are unphysiological contributors to non-hemodynamic dialysis-induced systemic stress and need to be curtailed. Strategies to lessen the periodic and direct effects of blood interacting with artificial surfaces to stimulate numerous biological pathways have focused mainly on the development of ‘more passive’ materials to decrease intradialytic morbidity. The indirect implications of this phenomenon, such as its impact on the overall delivery of care, have not been considered in detail. In this article, we explore, for the first time, the potential clinical and economic consequences of hemoincompatibility from a value-based healthcare (VBHC) perspective. As the fundamental tenet of VBHC is achieving the best clinical outcomes at the lowest cost, we examine the equation from the individual perspectives of the three key stakeholders of the dialysis care delivery processes: the patient, the provider, and the payer. For the patient, sub-optimal therapy caused by hemoincompatibility results in poor quality of life and various dialysis-associated conditions involving cost-impacting adjustments to lifestyles. For the provider, the decrease in income is attributed to factors such as an increase in workload and use of resources, dissatisfaction of the patient from the services provided, loss of reimbursement and direct revenue, or an increase in doctor–nurse turnover due to the complexity of managing care (nephrology encounters a chronic workforce shortage). The payer and healthcare system incur additional costs, e.g., increased hospitalization rates, including intensive care unit admissions, and increased medications and diagnostics to counteract adverse events and complications. Thus, hemoincompatibility reactions may be relevant from a socioeconomic perspective and may need to be addressed beyond just its clinical relevance to streamline the delivery of HD in terms of payability, future sustainability, and societal repercussions. Strategies to mitigate the economic impact and address the cost-effectiveness of the hemoincompatibility of extracorporeal kidney replacement therapy are proposed to conclude this comprehensive approach. Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Clinical Challenges and Management)

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