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Gut Microbiota in Chronic Kidney Disease: A Narrative Literature Review Abdillah, Novandra; Zulklhair Ali; Novadian; Ian Effendi; Suprapti; Elfiani; Rery TF Yuniarti
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 8 No. 4 (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.v8i4.976

Chronic kidney disease (CKD) is a growing public health problem related to loss of kidney function and cardiovascular disease as the main causes of morbidity and mortality in CKD. It is known that CKD is associated with intestinal dysbiosis. There is an influence of the gut microbiota on the gut-kidney axis and it works reciprocally: on the one hand, CKD significantly changes the composition and function of the gut microbiota. On the other hand, gut microbiota is able to manipulate the processes that cause the emergence and progression of CKD through inflammatory, endocrine and neurological pathways. Understanding the complex interactions between gut and kidney microbiota may provide novel nephroprotective interventions to prevent the progression of CKD by therapeutically targeting balance of gut microbiota composition.

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

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

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 (2026): 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

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 (2026): 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

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 (2026): 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

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.

Therapeutic Efficacy of Thymoquinone in Attenuating Obstructive Renal Fibrosis: A Dose-Response Analysis of Tumor Necrosis Factor-Alpha Suppression and Histopathological Remodeling Edy Nur Rachman; Suprapti; Muhammad Irsan Saleh; Ian Effendi; Zulkhair Ali; Novadian
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i5.1583

Background: Chronic kidney disease is characterized by progressive renal fibrosis, a maladaptive process driven by chronic inflammation and extracellular matrix accumulation. Tumor necrosis factor-alpha (TNF-α) plays a central role in this fibrogenic cascade. Thymoquinone (TQ), the primary bioactive compound of Nigella sativa, exhibits potent anti-inflammatory properties. Methods: In this therapeutic intervention model, 107 male Wistar rats were subjected to Unilateral Ureteral Obstruction (UUO). To test TQ's ability to halt established fibrogenesis, treatment was delayed until day 7 post-obstruction. Rats were randomized to receive TQ intraperitoneally at 5, 10, or 20 mg/kg body weight for 14 days. Outcomes included renal function (urea/creatinine), tubulointerstitial injury (PAS staining), fibrosis area (Sirius Red staining), and localized TNF-α mRNA expression (reverse transcriptase PCR normalized to GAPDH). Data were analyzed using ANOVA followed by Tukey’s Honestly Significant Difference (HSD) test. Results: UUO induced significant structural injury and upregulated TNF-α expression compared to sham controls (p < 0.001). TQ intervention significantly reduced the tubulointerstitial injury score, with the greatest reduction at 20 mg/kg (p < 0.01). The positively stained fibrotic area exhibited a U-shaped response, maximally decreased at the 10 mg/kg dose (p < 0.01). Similarly, TNF-α mRNA relative expression was significantly suppressed by TQ, exhibiting a pharmacological ceiling effect at 10 mg/kg (p < 0.01). Conclusion: Thymoquinone administered therapeutically mitigates established structural renal fibrosis and tubulointerstitial injury by downregulating TNF-α-mediated inflammation. A 10 mg/kg dose represents the optimal therapeutic threshold for anti-fibrotic efficacy in obstructive nephropathy.

Therapeutic Efficacy of Thymoquinone in Attenuating Obstructive Renal Fibrosis: A Dose-Response Analysis of Tumor Necrosis Factor-Alpha Suppression and Histopathological Remodeling Edy Nur Rachman; Suprapti; Muhammad Irsan Saleh; Ian Effendi; Zulkhair Ali; Novadian
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i5.1583

Background: Chronic kidney disease is characterized by progressive renal fibrosis, a maladaptive process driven by chronic inflammation and extracellular matrix accumulation. Tumor necrosis factor-alpha (TNF-α) plays a central role in this fibrogenic cascade. Thymoquinone (TQ), the primary bioactive compound of Nigella sativa, exhibits potent anti-inflammatory properties. Methods: In this therapeutic intervention model, 107 male Wistar rats were subjected to Unilateral Ureteral Obstruction (UUO). To test TQ's ability to halt established fibrogenesis, treatment was delayed until day 7 post-obstruction. Rats were randomized to receive TQ intraperitoneally at 5, 10, or 20 mg/kg body weight for 14 days. Outcomes included renal function (urea/creatinine), tubulointerstitial injury (PAS staining), fibrosis area (Sirius Red staining), and localized TNF-α mRNA expression (reverse transcriptase PCR normalized to GAPDH). Data were analyzed using ANOVA followed by Tukey’s Honestly Significant Difference (HSD) test. Results: UUO induced significant structural injury and upregulated TNF-α expression compared to sham controls (p < 0.001). TQ intervention significantly reduced the tubulointerstitial injury score, with the greatest reduction at 20 mg/kg (p < 0.01). The positively stained fibrotic area exhibited a U-shaped response, maximally decreased at the 10 mg/kg dose (p < 0.01). Similarly, TNF-α mRNA relative expression was significantly suppressed by TQ, exhibiting a pharmacological ceiling effect at 10 mg/kg (p < 0.01). Conclusion: Thymoquinone administered therapeutically mitigates established structural renal fibrosis and tubulointerstitial injury by downregulating TNF-α-mediated inflammation. A 10 mg/kg dose represents the optimal therapeutic threshold for anti-fibrotic efficacy in obstructive nephropathy.

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