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Pharmaceuticals
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New Development in Pharmacotherapy of Kidney Diseases
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New Development in Pharmacotherapy of Kidney Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (25 April 2026) | Viewed by 16676

Special Issue Editor

Dr. Chihchao Yang

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Guest Editor
Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Interests: chronic kidney disease (CKD); acute kidney injury (AKI); cardiovascular protection; kidney protection

Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit your research papers for a Special Issue of our journal, focusing on recent advances in pharmacotherapy for patients with kidney disease. This Special Issue aims to highlight the latest developments and innovations in the treatment of patients with both chronic and acute kidney disease, with an emphasis on cardiovascular and kidney protection, as well as the improvement of quality of life. Additionally, it will cover therapies that benefit bone health, endocrine function, electrolyte/mineral balance, gastrointestinal health, hematology, metabolism, neuromuscular function, and nutrition. We also welcome submissions on therapies that address specific symptoms and procedures related to kidney disease, such as uremic pruritus and the survival of dialysis access. We believe that your contributions will significantly enhance the understanding and management of kidney disease, ultimately improving patient outcomes and quality of life. We look forward to receiving your submissions and to the valuable insights your research will bring to this Special Issue.

Dr. Chihchao Yang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • chronic kidney disease (CKD)
  • acute kidney injury (AKI)
  • pharmacotherapy
  • cardiovascular protection
  • kidney protection
  • bone health
  • endocrine function
  • gut health
  • metabolism
  • neuromuscular function
  • nutrition
  • symptom management
  • sodium-glucose cotransporter-2 (SGLT-2) inhibitors
  • glucagon-like peptide-1 (GLP-1) receptor agonists
  • non-steroidal mineralocorticoid receptor antagonists (MRA)
  • endothelin receptor antagonists
  • anemia management
  • electrolyte abnormalities
  • dialysis
  • nephrotoxicity
  • drug interactions
  • uremic toxin
  • clinical trials
  • innovative therapies
  • protein-energy wasting
  • chronic kidney disease and bone mineral disease
  • inflammation
  • oxidation
  • diabetes
  • hypertension
  • obesity
  • hyperlipidemia
  • pruritus
  • osteoporosis
  • fracture
  • sarcopenia
  • protein-energy wasting

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Published Papers (6 papers)

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Research

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24 pages, 2016 KB  
Article
New-Onset Diabetes After Transplantation in Renal Recipients: A Pilot Comparative Study of Immediate vs. Extended-Release Tacrolimus Formulation
by Ioana Adela Ratiu, Florin Bănică, Corina Moisa, Bianca Pașca, Daniela Gîtea, Iulia Dana Grosu, Gabriel Cristian Bako, Oliviu Voștinaru, Wael Abu Dayyih and Lorena Filip
Pharmaceuticals 2025, 18(10), 1532; https://doi.org/10.3390/ph18101532 - 12 Oct 2025
Cited by 1 | Viewed by 1903
Abstract
Tacrolimus is frequently used in immunosuppressive therapy in renal transplant patients and is characterized by high toxicity, a low therapeutic index, and great individual variability. For these reasons, correct dosing is important to ensure patient safety by reducing the incidence of adverse effects [...] Read more.
Tacrolimus is frequently used in immunosuppressive therapy in renal transplant patients and is characterized by high toxicity, a low therapeutic index, and great individual variability. For these reasons, correct dosing is important to ensure patient safety by reducing the incidence of adverse effects while maintaining an optimal blood level that prevents graft loss. New-onset diabetes after transplantation (NODAT) affects 15–30% of patients treated with tacrolimus, with potential differences between immediate-release (IR) and extended-release (ER) formulations. Objective: This study seeks to compare the incidence of NODAT between IR tacrolimus and ER tacrolimus formulations in renal transplant patients and correlate it with in vitro release characteristics. Methods: This is a retrospective pilot study including 66 renal transplant patients (33 IR tacrolimus, 33 ER tacrolimus) followed for 5 years. NODAT was defined according to standard criteria. In vitro dissolution testing was performed at pH values of 1.2, 4.5, and 6.8, with sampling at 15, 30, 60, 90, 120, and 360 min. Results: The obtained results do not indicate differences regarding the incidence of diabetes mellitus in patients treated with the two forms of tacrolimus. The determined NODAT incidence was 42.4% (ER tacrolimus) vs. 39.4% (IR tacrolimus), p = 0.802, and ER tacrolimus showed slower release without significant pH-dependent variations. Conclusions: No significant differences in NODAT incidence were identified between formulations. The release–clinical outcome correlation requires validation in larger multicenter studies. These results contribute to the evidence base for tacrolimus formulation selection in renal transplant patients and other associated pathologies. Full article
(This article belongs to the Special Issue New Development in Pharmacotherapy of Kidney Diseases)
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13 pages, 566 KB  
Article
Evaluation of Statins Use in Hemodialysis Patients: A Retrospective Analysis of Clinical and Safety Outcomes
by Abdulmalik S. Alotaibi, Mohamed A. Albekery, Ahmed A. Alanazi, Ibrahim S. Alhomoud, Khalid A. Alamer, Mohammad Shawaqfeh, Reem H. Alshammari, Fayez Alhejaili, Muthana Al Sahlawi, Ibrahim Aldossary, Hajar Adel Aljuayl, Mohammad Alkathiri, Shmeylan Alharbi, Abdulkareem Albekairy and Abdulmalik Alkatheri
Pharmaceuticals 2025, 18(6), 911; https://doi.org/10.3390/ph18060911 - 18 Jun 2025
Cited by 1 | Viewed by 2982
Abstract
Background: Lipid metabolism disturbances are common in end-stage renal disease (ESRD) patients on hemodialysis (HD), leading to dyslipidemia, which is characterized by abnormal plasma lipids and lipoproteins. Although large randomized controlled trials have generally not demonstrated a survival benefit associated with statin therapy [...] Read more.
Background: Lipid metabolism disturbances are common in end-stage renal disease (ESRD) patients on hemodialysis (HD), leading to dyslipidemia, which is characterized by abnormal plasma lipids and lipoproteins. Although large randomized controlled trials have generally not demonstrated a survival benefit associated with statin therapy among patients receiving hemodialysis, limited observational studies have reported potential associations with improved clinical outcomes in this population. Methods: This retrospective cohort study investigated the clinical and safety outcomes of statin use in ESRD patients on HD with documented dyslipidemia over a two-year period from 1 January 2018 to 30 December 2019. The primary endpoints evaluated the clinical outcomes of statins by assessing changes in specific lipid parameters, including low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C). The secondary endpoints assessed safety by monitoring liver enzymes and creatine kinase (CK) levels. Results: Among 179 participants, diabetes mellitus was present in 134 patients (74.9%), while 168 patients (93.9%) had hypertension. Cardiovascular events occurred in 95 patients (53.1%). Statin therapy was administered to 146 patients (82.0%), with atorvastatin being the most frequently prescribed statin (69.3%). Modest reductions in LDL-C levels were observed in the rosuvastatin and atorvastatin groups, whereas slight increases were noted in the simvastatin and non-statin groups. None of these within-group changes were statistically significant. In the atorvastatin group, LDL-C decreased slightly from 2.058 to 2.003 mmol/L. The rosuvastatin group experienced a more pronounced LDL-C reduction from 2.607 to 2.113 mmol/L. Conversely, the simvastatin group showed an LDL-C increase from 1.550 to 1.901 mmol/L. Among the non-statin group, LDL-C increased from 2.678 to 2.820 mmol/L. Liver enzyme and CK levels fluctuated slightly but remained within normal ranges. Conclusions: This study evaluated statin therapy in hemodialysis patients with dyslipidemia. Although modest reductions in LDL-C levels were observed in the atorvastatin and rosuvastatin groups, statin therapy did not reduce the incidence of atherosclerotic events in hemodialysis patients with dyslipidemia. Additionally, statin use was not associated with any clinically or statistically significant effects. Full article
(This article belongs to the Special Issue New Development in Pharmacotherapy of Kidney Diseases)
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24 pages, 21945 KB  
Article
Drug Pair of Astragali Radix–Ligustri Lucidi Fructus Alleviates Acute Kidney Injury in Mice Induced by Ischemia–Reperfusion Through Inhibiting Ferroptosis
by Xuanhe Liu, Dan Zhang, Yuting Xie, Mengdan Wang, Xiaochun Chen, Weijie Yu, Yuming Ma, Jia Zeng, Qixuan Long, Guangrui Huang, Jie Geng and Anlong Xu
Pharmaceuticals 2025, 18(6), 789; https://doi.org/10.3390/ph18060789 - 25 May 2025
Cited by 2 | Viewed by 2172
Abstract
Background: Acute kidney injury (AKI), characterized by high morbidity and mortality, is primarily caused by renal ischemia–reperfusion injury (RIRI). Ferroptosis plays a key role in RIRI, yet its underlying mechanisms remain unclear. The drug pair of Astragali Radix–Ligustri Lucidi Fructus (DAL) shows promise [...] Read more.
Background: Acute kidney injury (AKI), characterized by high morbidity and mortality, is primarily caused by renal ischemia–reperfusion injury (RIRI). Ferroptosis plays a key role in RIRI, yet its underlying mechanisms remain unclear. The drug pair of Astragali Radix–Ligustri Lucidi Fructus (DAL) shows promise in renal diseases, but its protective effects against RIRI and associated molecular pathways via ferroptosis inhibition are unknown. This study aimed to investigate DAL’s therapeutic effects on RIRI and its mechanisms. Methods: A mouse model of bilateral renal ischemia–reperfusion was established. Renal function (serum creatinine, Scr; blood urea nitrogen, BUN), inflammatory cytokines (TNF-α, IFN-γ, IL-6), ferroptosis markers (GPX4, MDA, GSH, tissue iron), and pathological damage were evaluated. Transcriptomic sequencing and electron microscopy analyzed gene pathways and mitochondrial structure. In HK-2 cells, oxygen–glucose deprivation/reoxygenation (OGD/R) and RSL3-induced ferroptosis models were used to assess DAL-containing serum effects via cell viability, GPX4 expression, and mitochondrial morphology. LC-MS analyzed DAL’s chemical components, and network pharmacology predicted ferroptosis-related targets. Results: DAL significantly reduced Scr/BUN levels, alleviated tubular injury, fibrosis, and apoptosis, and downregulated inflammatory cytokines and damage markers. It inhibited ferroptosis by upregulating GPX4, decreasing MDA/tissue iron, and increasing GSH. Transcriptomics revealed enrichment in lipid metabolism pathways. DAL restored the mitochondrial cristae structure; DAL-containing serum improved cell viability, blocked RSL3-induced GPX4 downregulation, and mitigated mitochondrial dysfunction. Network pharmacology identified DAL’s potential active components and targets. Molecular docking validated binding affinity and interaction patterns of active components with targets. Conclusions: DAL protects against RIRI by upregulating GPX4, preserving the mitochondrial structure, and inhibiting ferroptosis, highlighting its therapeutic potential for AKI prevention and treatment. Full article
(This article belongs to the Special Issue New Development in Pharmacotherapy of Kidney Diseases)
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Review

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20 pages, 356 KB  
Review
Belatacept in Solid Organ Transplantation: Current Kidney Applications, Future Perspectives in Other Organs, and Clinical Implications
by Salvatore Di Maria and Alessio Provenzani
Pharmaceuticals 2026, 19(2), 196; https://doi.org/10.3390/ph19020196 - 23 Jan 2026
Viewed by 1298
Abstract
Belatacept, a selective costimulation blocker targeting the CD28–CD80/86 pathway, represents a major innovation in solid organ transplantation immunosuppression. By providing upstream inhibition of T-cell activation without calcineurin inhibition, belatacept offers the potential for improved long-term graft and patient outcomes with reduced nephrotoxicity and [...] Read more.
Belatacept, a selective costimulation blocker targeting the CD28–CD80/86 pathway, represents a major innovation in solid organ transplantation immunosuppression. By providing upstream inhibition of T-cell activation without calcineurin inhibition, belatacept offers the potential for improved long-term graft and patient outcomes with reduced nephrotoxicity and metabolic adverse effects. This review summarizes the mechanistic rationale, pivotal evidence, and clinical experience supporting the use of belatacept as first-line or conversion therapy in solid organ transplantation, while addressing safety, pharmacoeconomic impact, and future research directions. A comprehensive analysis of pivotal phase II–III trials (BENEFIT, BENEFIT-EXT), recent prospective conversion studies, and ongoing trials in liver, heart, and lung transplantation was performed. Safety data and health–economic evaluations were critically appraised. In kidney transplantation, belatacept-based immunosuppression provides superior renal function and improved metabolic profiles compared with calcineurin inhibitors (CNIs), though with higher early acute rejection rates. In liver, heart, and lung transplantation, evidence remains limited, with de novo use contraindicated in liver grafts due to excess mortality and rejection. Conversion from CNI to belatacept in selected patients improves renal outcomes without compromising graft survival. Safety considerations include a higher risk of post-transplant lymphoproliferative disorder (PTLD) in Epstein–Barr virus-negative recipients. Belatacept represents a paradigm shift in transplant immunology by targeting upstream T-cell activation. While currently approved only for kidney transplantation, ongoing studies in thoracic and hepatic grafts may expand its therapeutic role. Personalized patient selection, combination regimens mitigating rejection risk, and real-world cost-effectiveness analyses will define its place in future precision immunosuppression strategies. Full article
(This article belongs to the Special Issue New Development in Pharmacotherapy of Kidney Diseases)
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41 pages, 3039 KB  
Review
Repurposing Diabetes Therapies in CKD: Mechanistic Insights, Clinical Outcomes and Safety of SGLT2i and GLP-1 RAs
by Syed Arman Rabbani, Mohamed El-Tanani, Rakesh Kumar, Manita Saini, Yahia El-Tanani, Shrestha Sharma, Alaa A. A. Aljabali, Eman Hajeer and Manfredi Rizzo
Pharmaceuticals 2025, 18(8), 1130; https://doi.org/10.3390/ph18081130 - 28 Jul 2025
Cited by 2 | Viewed by 6362
Abstract
Background: Chronic Kidney Disease (CKD) is a major global health issue, with diabetes being its primary cause and cardiovascular disease contributing significantly to patient mortality. Recently, two classes of medications—sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—have shown promise [...] Read more.
Background: Chronic Kidney Disease (CKD) is a major global health issue, with diabetes being its primary cause and cardiovascular disease contributing significantly to patient mortality. Recently, two classes of medications—sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—have shown promise in protecting both kidney and heart health beyond their effects on blood sugar control. Methods: We conducted a narrative review summarizing the findings of different clinical trials and mechanistic studies evaluating the effect of SGLT2i and GLP-1 RAs on kidney function, cardiovascular outcomes, and overall disease progression in patients with CKD and DKD. Results: SGLT2i significantly mitigate kidney injury by restoring tubuloglomerular feedback, reducing intraglomerular hypertension, and attenuating inflammation, fibrosis, and oxidative stress. GLP-1 RAs complement these effects by enhancing endothelial function, promoting weight and blood pressure control, and exerting direct anti-inflammatory and anti-fibrotic actions on renal tissues. Landmark trials—CREDENCE, DAPA-CKD, and EMPA-KIDNEY—demonstrate that SGLT2i reduce the risk of kidney failure and renal or cardiovascular death by 25–40% in both diabetic and non-diabetic CKD populations. Likewise, trials such as LEADER, SUSTAIN, and AWARD-7 confirm that GLP-1 RAs slow renal function decline and improve cardiovascular outcomes. Early evidence suggests that using both drugs together may offer even greater benefits through multiple mechanisms. Conclusions: SGLT2i and GLP-1 RAs have redefined the therapeutic landscape of CKD by offering organ-protective benefits that extend beyond glycemic control. Whether used individually or in combination, these agents represent a paradigm shift toward integrated cardiorenal-metabolic care. A deeper understanding of their mechanisms and clinical utility in both diabetic and non-diabetic populations can inform evidence-based strategies to slow disease progression, reduce cardiovascular risk, and improve long-term patient outcomes in CKD. Full article
(This article belongs to the Special Issue New Development in Pharmacotherapy of Kidney Diseases)
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Other

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16 pages, 969 KB  
Systematic Review
Effectiveness of Eicosapentaenoic and Docosahexaenoic Acid Supplementation for Reducing Uremic Pruritus: A Meta-Analysis of Randomized Controlled Trials
by Chia-An Chou, Lung-Chih Li, Wen-Chin Lee and Chiang-Chi Huang
Pharmaceuticals 2026, 19(1), 181; https://doi.org/10.3390/ph19010181 - 20 Jan 2026
Viewed by 908
Abstract
Background: Uremic pruritus is a distressing and common symptom in patients with end-stage renal disease. The development of uremic pruritus involves a multifactorial pathogenesis, including systemic inflammation, dysregulated immune responses, and altered opioid receptor activity. Omega-3 polyunsaturated fatty acids have been reported to [...] Read more.
Background: Uremic pruritus is a distressing and common symptom in patients with end-stage renal disease. The development of uremic pruritus involves a multifactorial pathogenesis, including systemic inflammation, dysregulated immune responses, and altered opioid receptor activity. Omega-3 polyunsaturated fatty acids have been reported to mitigate uremic pruritus symptoms. Among omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported as potential candidates for alleviating uremic pruritus due to their anti-inflammatory properties. Methods: A meta-analysis of seven randomized controlled trials was conducted to evaluate the efficacy of omega-3 supplementation in alleviating uremic pruritus among patients affected with end-stage renal disease. Effect sizes were calculated using Hedges’ g with a random-effects model. Heterogeneity, sensitivity, and meta-regression analyses were performed to explore influencing factors. Results: A total of 266 participants were included for analysis. Omega-3 supplementation significantly reduced pruritus severity compared with placebo. Sensitivity analyses were conducted to exclude a single large trial contributing to the results. Meta-regression indicated that higher EPA, DHA, and total omega-3 dosages, and longer treatment duration, were associated with reduced severity of the uremic pruritus than the placebo. No serious adverse events were reported. Conclusions: Omega-3 fatty acid supplementation significantly alleviates uremic pruritus in patients with ESRD. These findings support the use of omega-3 fatty acids as a safe and effective adjunct therapy. Further large-scale, long-term trials are warranted to verify these results and assess the long-term effects and safety of omega-3 fatty acids in attenuating uremic pruritus. Full article
(This article belongs to the Special Issue New Development in Pharmacotherapy of Kidney Diseases)
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