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All Journal Jambi Medical Journal : Jurnal Kedokteran dan Kesehatan Majalah Kedokteran Sriwijaya Biomedical Journal of Indonesia Molecular and Cellular Biomedical Sciences (MCBS) Bioscientia Medicina : Journal of Biomedicine and Translational Research Indonesian Journal of Kidney and Hypertension Jurnal Menara Medika Open Access Indonesian Journal of Medical Reviews Bioscientia Medicina : Journal of Biomedicine and Translational Research PHARMACOLOGY, MEDICAL REPORTS, ORTHOPEDIC, AND ILLNESS DETAILS (COMORBID) Journal Of World Science Jurnal Penyakit Dalam Indonesia
Zulkhair Ali
Department Of Internal Medicine, Dr. Mohammad Hoesin Hospital, Palembang, Indonesia / Department Of Internal Medicine, Faculty Of Medicine, Universitas Sriwijaya, Palembang, Indonesia
Biochemistry, Genetics & Molecular Biology Computer Science & IT Dentistry Economics, Econometrics & Finance Engineering Health Professions Immunology & microbiology Law, Crime, Criminology & Criminal Justice Medicine & Pharmacology Neuroscience Nursing Public Health Social Sciences

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Effectiveness of Renal Denervation Therapy in Persistent Hypertension: A Meta-Analysis Mulia, Deddy Primadona; Syahpri Putra Wangsa; Kgs. M. Yusuf Arief Akbar; Edy Nur Rachman; Chairil Makky; Eva Julita; Zulkhair Ali; Novadian Suhaimi; Suprapti Slamet; Ian Effendi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 8 No. 8 (2024): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v8i8.1049

Abstract

Background: Persistent hypertension is a global health problem that requires effective therapy. Renal denervation (RDN) therapy is emerging as a promising new option. This meta-analysis aims to evaluate the effectiveness of RDN in patients with persistent hypertension. Methods: We performed a systematic search in PubMed, Scopus, and the Cochrane Library for studies evaluating the effectiveness of RDN in patients with persistent hypertension. Data were extracted and analyzed using a random effects model. Results: A total of 12 studies with a total of 1,024 patients were included in this meta-analysis. RDN demonstrated significant reductions in systolic and diastolic blood pressure compared with controls (MD -12.3 mmHg [95% CI -15.8 to -8.8] for systolic blood pressure and MD -6.1 mmHg [95% CI -8.2 to -4.0] for blood pressure diastolic). The effectiveness of RDN is higher in patients with more severe hypertension and in patients who are unresponsive to antihypertensive drugs. Conclusion: RDN is an effective therapy for persistent hypertension, especially in patients with more severe hypertension and in patients who are unresponsive to antihypertensive drugs.
Effectiveness of Renal Denervation Therapy in Persistent Hypertension: A Meta-Analysis Mulia, Deddy Primadona; Syahpri Putra Wangsa; Kgs. M. Yusuf Arief Akbar; Edy Nur Rachman; Chairil Makky; Eva Julita; Zulkhair Ali; Novadian Suhaimi; Suprapti Slamet; Ian Effendi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 8 No. 8 (2024): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v8i8.1049

Abstract

Background: Persistent hypertension is a global health problem that requires effective therapy. Renal denervation (RDN) therapy is emerging as a promising new option. This meta-analysis aims to evaluate the effectiveness of RDN in patients with persistent hypertension. Methods: We performed a systematic search in PubMed, Scopus, and the Cochrane Library for studies evaluating the effectiveness of RDN in patients with persistent hypertension. Data were extracted and analyzed using a random effects model. Results: A total of 12 studies with a total of 1,024 patients were included in this meta-analysis. RDN demonstrated significant reductions in systolic and diastolic blood pressure compared with controls (MD -12.3 mmHg [95% CI -15.8 to -8.8] for systolic blood pressure and MD -6.1 mmHg [95% CI -8.2 to -4.0] for blood pressure diastolic). The effectiveness of RDN is higher in patients with more severe hypertension and in patients who are unresponsive to antihypertensive drugs. Conclusion: RDN is an effective therapy for persistent hypertension, especially in patients with more severe hypertension and in patients who are unresponsive to antihypertensive drugs.
Is It a Tumor or Not? A Case of Focal Segmental Glomerulosclerosis Secondary to Type 2 Diabetes with a Concomitant Renal Pseudotumor Rery TF Yuniarti; Ian Effendi; Zulkhair Ali; Novadian; Suprapti; Elfiani; Novandra AP; Dila Siti Hamidah; Fadil Pramudhya Husein; Ika Kartika Edi P
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 8 No. 12 (2024): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v8i12.1154

Abstract

Background: Focal segmental glomerulosclerosis (FSGS) is a histologic pattern of glomerular injury that can be primary or secondary to various conditions, including obesity, diabetes, and hypertension. Renal masses, often detected incidentally, can be benign or malignant, with renal cell carcinoma (RCC) being the most common. This case report presents a patient with FSGS secondary to type 2 diabetes and a concomitant renal pseudotumor, initially suspected to be RCC. Case presentation: A 60-year-old woman presented with weakness, fever, and weight loss. Imaging revealed a renal mass, initially suspected to be RCC. A kidney biopsy revealed FSGS, and further evaluation confirmed type 2 diabetes. After controlling her diabetes and hypertension, the renal mass regressed, suggesting a pseudotumor. Conclusion: This case highlights the importance of considering pseudotumors in the differential diagnosis of renal masses, especially in patients with comorbidities such as diabetes. A kidney biopsy can help avoid unnecessary invasive procedures like nephrectomy.
Bridging the Therapeutic Gap: A Systematic Review and Meta-Analysis on the Efficacy, Safety, and Pathophysiological Impact of Sodium Zirconium Cyclosilicate in Enabling Guideline-Directed Medical Therapy Edy Nur Rachman; Ian Effendi; Zulkhair Ali; Novadian; Suprapti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 1 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i1.1489

Abstract

Background: Hyperkalemia is a life-threatening complication of chronic kidney disease (CKD) and heart failure (HF), primarily impeding the use of life-saving renin-angiotensin-aldosterone system inhibitors (RAASi). This systematic review and meta-analysis evaluate the evidence for sodium zirconium cyclosilicate (SZC) in managing hyperkalemia and enabling RAASi therapy. Methods: This systematic review searched Medline, Embase, and Cochrane CENTRAL to September 2025. Dual reviewers independently screened, extracted data, and assessed bias (Cochrane RoB 2, Newcastle-Ottawa Scale). We included RCTs and observational studies of SZC in adults with hyperkalemia. A random-effects meta-analysis was performed on RCTs reporting maintenance-phase efficacy and safety. Results: The search yielded 1,254 citations, with 6 pivotal studies included. The meta-analysis of 3 RCTs found that SZC (5-10g daily) was significantly more effective than placebo at maintaining normokalemia over 12-28 days. The pooled mean difference in serum K+ was -0.58 mEq/L (95% CI: -0.65 to -0.51; I2 = 0%). SZC did increase the risk of edema (pooled Risk Ratio: 2.95; 95% CI: 1.51 to 5.76; I2 = 0%). The narrative synthesis of observational data confirmed that SZC use was associated with a >2.5-fold increase in the likelihood of continuing RAASi therapy. Conclusion: Sodium zirconium cyclosilicate is a highly effective and rapidly acting agent for both acute correction and chronic management of hyperkalemia. Our meta-analysis provides a precise estimate of its high maintenance-phase efficacy. Its primary clinical benefit lies in providing a renal-independent pathway for potassium excretion, thereby "uncoupling" potassium levels from RAASi use and bridging a critical treatment gap.
Modulation of TGF-β/Smad and Nrf2 Signaling Pathways by Thymoquinone in the Attenuation of Renal Fibrosis: A Systematic Review and Meta-Analysis of Pre-clinical Models Chairil Makky; Ian Effendi; Zulkhair Ali; Novadian; Suprapti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 1 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i1.1491

Abstract

Background: Renal fibrosis is the irreversible, final common pathway for all progressive forms of chronic kidney disease (CKD), leading to end-stage renal disease. Its pathogenesis is characterized by the over-activation of pro-fibrotic signaling, chiefly the Transforming Growth Factor-beta (TGF-β)/Smad pathway, and the failure of endogenous cytoprotective mechanisms like the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response. Thymoquinone (TQ), the primary bioactive constituent of Nigella sativa, is a pleiotropic compound with known anti-inflammatory and antioxidant properties. This study was designed to systematically quantify its mechanistic efficacy in modulating the core Nrf2 and TGF-β pathways in established pre-clinical models of renal fibrosis and injury. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. We performed a comprehensive search of major databases (including PubMed and Scopus) for pre-clinical in vivo studies published between 2014 and 2025 that investigated TQ monotherapy or TQ-dominant combination therapy in rodent models of renal injury. The eight studies that met the inclusion criteria utilized diverse models: Unilateral Ureteral Obstruction (UUO), cisplatin-induced nephrotoxicity, gentamicin-induced nephrotoxicity, 5-fluorouracil (5-FU)-induced acute kidney injury (AKI), lipopolysaccharide (LPS)-induced inflammation, carfilzomib (CFZ)-induced renal impairment, and ischemia-reperfusion (IRI). Primary outcomes were the expression of renal Nrf2 and TGF-β1. Secondary outcomes included markers of fibrosis (collagen deposition, histology scores), renal function (BUN, creatinine), oxidative stress (MDA, SOD, GSH, CAT), and inflammation (TNF-α, NF-κB, IL-6, IL-1β). Data were pooled using a random-effects model, and primary analyses were stratified by injury model subgroup. Results: Thymoquinone treatment resulted in a profound and significant upregulation of the protective Nrf2 pathway (SMD: 2.38; 95% CI [1.05, 3.71]; p < 0.001; 3 studies) and its downstream target Heme Oxygenase-1 (HO-1). Concurrently, TQ treatment markedly suppressed the primary pro-fibrotic driver, TGF-β1 (SMD: -2.09; 95% CI [-2.99, -1.19]; p < 0.001; 2 studies). This pivotal dual modulation translated into significant functional and structural improvements. TQ robustly attenuated renal fibrosis scores (SMD: -1.89; 95% CI [-2.55, -1.23]; p < 0.001; 2 studies). Stratified subgroup analysis showed TQ significantly improved renal function in both chemotoxic AKI models (BUN SMD: -2.31; 95% CI [-3.22, -1.40]) and chronic obstructive/fibrosis models (BUN SMD: -1.17; 95% CI [-1.75, -0.59]). This functional protection was underpinned by potent, broad-spectrum reversal of oxidative stress and inflammation across all subgroups. Conclusion: Thymoquinone consistently ameliorates renal injury and fibrosis across a wide spectrum of pre-clinical models. Its mechanism of action is multifaceted, critically involving the dual modulation of opposing pro-fibrotic and protective pathways: it suppresses the TGF-β1 cascade while simultaneously activating and restoring the Nrf2 antioxidant response. This body of evidence strongly supports Thymoquinone as a high-potential candidate for translational research and development as a novel, network-targeting therapy for human renal fibrosis.
Beyond Phosphate Binding: A Systematic Review and Meta-Analysis on the Efficacy and Safety of the Novel Paracellular Phosphate Inhibitor, Tenapanor, for Hyperphosphatemia in Dialysis Patients Eva Julita; Ian Effendi; Zulkhair Ali; Novadian; Suprapti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 1 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i1.1492

Abstract

Background: Hyperphosphatemia is a critical driver of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) undergoing dialysis. Current management, reliant on phosphate binders, is hampered by high pill burden and poor adherence. Tenapanor, a first-in-class, minimally-absorbed sodium/hydrogen exchanger 3 (NHE3) inhibitor, reduces paracellular phosphate absorption. We performed a systematic review and meta-analysis of all available Phase 3 trials to quantify its efficacy and safety. Methods: We searched PubMed, Embase, and Cochrane CENTRAL through October 2025 for Phase 3 clinical trials evaluating tenapanor for hyperphosphatemia in dialysis patients. Data were extracted from 6 eligible studies (N=1573). We conducted separate random-effects meta-analyses for different study designs: 1) parallel-group monotherapy vs. placebo, 2) withdrawal-design monotherapy vs. placebo, 3) parallel-group add-on therapy vs. placebo, and 4) safety (diarrhea incidence) vs. placebo. Efficacy was measured by Mean Difference (MD) in serum phosphate change; safety by Risk Ratio (RR). Results: Tenapanor demonstrated significant efficacy across all study designs. In parallel-group monotherapy (1 study, N=167), tenapanor was superior to placebo (MD: -1.89 mg/dL; 95% CI: -2.36 to -1.42). In withdrawal-design studies (2 RCTs, N=373), tenapanor maintained serum phosphate levels significantly better than placebo (Pooled MD: -0.75 mg/dL; 95% CI: -1.05 to -0.45; I2=0%). As an add-on therapy (1 RCT, N=235), tenapanor provided additional phosphate reduction versus binders alone (MD: -0.65 mg/dL; 95% CI: -0.96 to -0.35). Tenapanor significantly increased the risk of diarrhea versus placebo (3 RCTs, N=521; Pooled RR: 4.10; 95% CI: 2.50 to 6.72; I2=30%), which was the primary adverse event leading to discontinuation. Conclusion: Tenapanor represents a new mechanistic paradigm for hyperphosphatemia management. It is a highly effective phosphate-lowering agent, both as monotherapy and add-on therapy, but is associated with a significant, mechanism-based risk of gastrointestinal side effects.
Co-Authors Abdul Hakim R Ade Yonata Ade Yonata, Ade Agustina H Akbar, Kgs. M. Yusuf Arief Akbar, M Yusuf Arief Ali Ghanie Alif Fathur Rachman, Muhammad Alwi Shahab Alwi Shahab Anggelia Puspasari Arief Akbar, Kgs M Yusuf Arif, Cut Wulan Chairil Makky Christin, Theresia Citra Maharani Deddy Primadona Mulia Devi, SNA Ratnasari Dila Siti Hamidah Eddy Mart Salim Edy Nur Rachman Effendi, Ian Elfiani Elfiani Elfiani Emilia Emilia Erial Bahar Erial Bahar Erial Bahar, Erial Erwin Sukandi Eva Julita Fadil Pramudhya Hoesain Fadil Pramudhya Husein Fadil Pramudya Fauzan Azhari, Fauzan Ferawaty, Ferawaty Ferry Usnizar Ferry Yusrizal Fitri Rahmariani Fitria Koeshardani Harun Hudari Huntari Harahap Ian Effendi Ian Effendi Ian Effendi Ika Kartika Ika Kartika Edi P Indrajaya, Taufik Irawan, Rico Irfannuddin Irfannuddin Istiqomah, Amelia Junaidi A Kartika, Herleni Kendenan, Margaretha Kgs M Yusuf Arief Akbar Kgs. M. Yusuf Arief Akbar kurniati, nova Kusrini, Ida Legiran Legiran Lidiawati Handayani Lilik Pranata M Yusuf Arief Akbar Mediarty Mediarty Syahrir Muhammad Irsan Saleh Muhammad Yusri Mulia, Deddy Primadona Nova Kurniati Novadian Novadian Novadian Novadian, Novadian Novadian Suhaimi Novadian Suhaimi Novadian Suhaimi Novandra AP Nurul Ramadhani Umareta Nyimas Natasha Ayu Shafira R.M. Suryadi Tjekyan Radiyati Umi Partan Ramadhan, Philosophia Ratna Maila Dewi Anggraini Reinanda Marizki R Rery TF Yuniarti RM Suryadi Tjekyan Rostika Dewi Shahab, Alwi Slamet, Suprapti SNA Ratnasari Devi Suhaimi, Novadian Suprapti Suprapti Slamet Suprapti Suprapti Suprapti Suprapti Syahpri Putra Wangsa Taufik Indrajaya Taufik Indrajaya Trinovita Andraini Wangsa, Syahpri Putra Yudhie Tanta Yulianto kusnadi