Open Access Indonesian Journal of Medical Reviews

Comparative Efficacy and Safety of Finerenone, Eplerenone, and Spironolactone on Cardiorenal Outcomes in Type 2 Diabetes with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis

Krismeikesari Krismeikesari — 2025-11-13

Mineralocorticoid receptor antagonists (MRAs) are critical for managing chronic kidney disease (CKD) in type 2 diabetes (T2D), yet a "residual risk" of cardiorenal progression persists. The comparative efficacy and safety of the novel non-steroidal MRA, finerenone, versus the traditional steroidal MRAs, spironolactone and eplerenone, have not been established in a comprehensive analysis. We conducted a network meta-analysis (NMA) to create an evidence-based hierarchy for these three agents. We performed a systematic review searching MEDLINE, Embase, and Cochrane CENTRAL through March 2025 for randomized controlled trials (RCTs) in patients with CKD and albuminuria (predominantly T2D) on baseline renin-angiotensin system (RAS) blockade. We compared finerenone, spironolactone, eplerenone, and placebo. The primary efficacy outcome was the percent change in urinary albumin-to-creatinine ratio (UACR). The primary safety outcome was the relative risk (RR) of hyperkalemia (serum potassium ³ 5.5 mmol/L). A Bayesian random-effects NMA was performed. Seven RCTs involving 15,749 patients were included. For UACR reduction, all MRAs were superior to placebo. Spironolactone (Surface Under the Cumulative Ranking [SUCRA]: 91.2%) and finerenone (SUCRA: 88.5%) were the most effective agents and were statistically indistinguishable. Both were significantly more potent than eplerenone (SUCRA: 58.1%). For hyperkalemia risk, spironolactone was definitively the least safe (SUCRA: 9.5%). Finerenone (RR vs. Spironolactone: 0.63; 95% Credible Interval [CrI]: 0.48–0.82) and eplerenone (RR vs. Spironolactone: 0.65; 95% CrI: 0.45–0.94) were significantly safer. The safety profiles of finerenone (SUCRA: 65.4%) and eplerenone (SUCRA: 62.1%) were comparable.In conclusion, finerenone and spironolactone demonstrate equivalent, superior anti-albuminuric efficacy. However, finerenone uniquely dissociates this high potency from the significant risk of hyperkalemia, offering a safety profile comparable to the less-potent eplerenone. Finerenone, therefore, represents an optimized therapeutic choice, balancing maximal renoprotective efficacy with a superior safety profile for patients with T2D and CKD.

Neurohormonal Synchronization in the Face of Exhaustion: Unveiling the Cortisol-Oxytocin Crosstalk in Type 2 Diabetes Patients with Severe Distress and HPA Axis Blunting

Adang Muhammad Gugun — 2025-11-25

Type 2 diabetes mellitus (T2DM) is increasingly conceptualized as a complex psychoneuroendocrine disorder. While acute physiological stress typically induces hypercortisolemia, chronic diabetes distress may lead to allostatic overload and Hypothalamic-Pituitary-Adrenal (HPA) axis blunting. The compensatory role of oxytocin, a stress-buffering neuropeptide, remains underexplored in this specific clinical phenotype. This study aimed to characterize the neuroendocrine phenotype of patients with uncontrolled T2DM and severe distress, specifically investigating the synchronization between serum cortisol and oxytocin as a marker of homeostatic regulation. In this analytic cross-sectional study, 86 patients with uncontrolled T2DM (HbA1c greater than or equal to 7.0%) and severe diabetes distress (Diabetes Distress Scale-17 mean score greater than or equal to 3.0) were recruited via purposive sampling. Strict exclusion criteria were applied for exogenous steroid use and renal failure to ensure biological validity. Fasting morning serum cortisol and oxytocin were analyzed using Enzyme-Linked Immunosorbent Assays (ELISA). Statistical analysis utilized Spearman’s rank correlation and multivariate linear regression, controlling for Body Mass Index and age. The cohort exhibited severe metabolic dysregulation (Mean HbA1c: 10.03 ± 2.10%) and psychological distress (Mean DDS: 4.65 ± 0.35). Paradoxically, mean morning cortisol was low-normal (170.32 ± 135.43 nmol/L), suggestive of HPA axis blunting rather than the expected hypercortisolemia. A robust positive correlation was observed between cortisol and oxytocin (r = 0.555, p < 0.001). Multivariate regression confirmed cortisol as a significant independent predictor of oxytocin levels (b = 0.521, p < 0.001), independent of metabolic confounders. In conclusion, patients with severe diabetes distress display a distinct phenotype of HPA axis exhaustion coupled with synchronized oxytocinergic activity. This suggests a preserved reactive mobilization mechanism where oxytocin is upregulated in tandem with adrenal output to buffer chronic allostatic load. These findings highlight the potential of the oxytocinergic system as a therapeutic target in diabetes burnout.

Severe Hyponatremia with Normokalemia in Pembrolizumab-Lenvatinib Combination Therapy for Metastatic Renal Cell Carcinoma: A Case of Suspected Secondary Adrenal Insufficiency and Clinical Differentials

Devina Ravelia Tiffany Subroto — 2025-11-27

The combination of Pembrolizumab and Lenvatinib has become the standard first-line treatment for advanced renal cell carcinoma (RCC). However, the overlapping toxicity profiles of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) create significant diagnostic challenges, particularly regarding electrolyte disturbances. Differentiating ICI-induced secondary adrenal insufficiency from TKI-induced toxicity or syndrome of inappropriate antidiuretic hormone (SIADH) is critical, especially in resource-limited settings where rapid hormonal assays are unavailable. A 67-year-old male with metastatic clear cell RCC presented with confusion, fatigue, and nausea 14 days after initiating palliative Pembrolizumab and Lenvatinib. He had a history of partial nephrectomy and was on Candesartan. Evaluation revealed severe hypotonic hyponatremia (113 mmol/L), acute kidney injury (Creatinine 2.2 mg/dL), and a hypertensive crisis (BP 229/138 mmHg). Notably, despite renal impairment and angiotensin receptor blocker therapy, potassium levels were normal (4.2 mmol/L). The hyponatremia was refractory to 3% hypertonic saline. Suspecting secondary adrenal insufficiency, empiric high-dose corticosteroids were administered, resulting in rapid normalization of serum sodium and resolution of symptoms. In conclusion, in patients receiving ICI-TKI therapy, the specific profile of severe hyponatremia with normokalemia—particularly in the context of renal insufficiency and RAAS blockade—serves as a high-value clinical indicator of preserved mineralocorticoid function. This points toward secondary adrenal insufficiency rather than primary adrenal injury or TKI-induced renal tubular acidosis. This case underscores the utility of deductive physiology in oncology practice.

Severe Erythema Nodosum Leprosum Complicated by Warm Autoimmune Hemolytic Anemia: Navigating the Immunosuppressive Paradox

Devina Ravelia Tiffany Subroto — 2025-12-23

Erythema nodosum leprosum (ENL) is a severe, systemic immune-complex mediated complication of multibacillary Hansen’s disease. While anemia of chronic disease is frequently observed in leprosy, the concurrent development of Warm Autoimmune Hemolytic Anemia (wAIHA) is an exceptionally rare and precarious clinical entity. This comorbidity creates a therapeutic paradox wherein the high-dose corticosteroids required to halt hemolysis may exacerbate the risk of sepsis in patients with necrotic skin lesions and compromised barrier function. We report the case of a 42-year-old male with multibacillary Hansen’s disease on multidrug therapy who presented with high-grade fever, progressive fatigue, and necrotic cutaneous lesions. Laboratory evaluation revealed life-threatening normocytic normochromic anemia (Hemoglobin 3.5 g/dL) and a leukemoid reaction (WBC 42,540/µL). Hemolysis was confirmed by elevated lactate dehydrogenase (564 U/L), indirect hyperbilirubinemia, and a strongly positive direct Coombs test (IgG). A diagnosis of wAIHA secondary to severe necrotic ENL was established. Standard high-dose pulse steroid therapy was deemed high-risk due to the patient’s extreme neutrophilia (NLR 80.25) and open necrotic ulcers. Consequently, a tailored regimen of intermediate-dose intravenous methylprednisolone (62.5 mg twice daily) combined with broad-spectrum antibiotics was initiated. This strategy successfully suppressed hemolysis and resolved the ENL reaction without precipitating secondary opportunistic infections. In conclusion, the coexistence of wAIHA and ENL suggests a shared mechanism of dysregulated T-cell immunity and molecular mimicry. This case demonstrates that in scenarios involving high infectious risk, an individualized, intermediate-dose corticosteroid protocol can achieve remission while mitigating the dangers of profound immunosuppression.

Evaluation of Morphine-Sparing Efficacy with Low-Dose Ketamine in Pediatric Postoperative Pain: A Pilot Randomized Controlled Trial

Naim Ismail Imunu — 2025-12-23

Postoperative pain management in the pediatric population requires a delicate balance between effective analgesia and the minimization of opioid-related adverse events, particularly respiratory depression. While multimodal analgesia is the standard of care, the optimal dose-reduction potential of opioids when combined with N-methyl-D-aspartate (NMDA) antagonists remains undefined. We conducted a prospective, single-center, pilot randomized controlled trial using a double-blind observer protocol. Twenty pediatric patients aged 2 months to 7 years undergoing elective surgery were randomized into four groups. The control group (Group M) received standard continuous morphine at 0.33 µg/kg/min. Three intervention groups received fixed low-dose ketamine at 0.33 µg/kg/min combined with tapered morphine doses: Group KM-1 at 0.23 µg/kg/min, Group KM-2 at 0.16 µg/kg/min, and Group KM-3 at 0.06 µg/kg/min. The primary outcome was analgesic efficacy assessed by FLACC scores at 24 hours. Secondary outcomes included hemodynamic stability and rescue analgesia requirements. Baseline characteristics were comparable across groups. At 24 hours, the median FLACC scores were comparable between the high-dose control (Median 2.0; Interquartile Range 1.5–2.0) and the lowest morphine group (Group KM-3: Median 2.0; Interquartile Range 1.5–2.0; p = 0.438). Group KM-3 achieved an 81% reduction in morphine consumption with a 0% rescue analgesia rate, identical to the control group. In conclusion, preliminary data from this pilot study suggest that low-dose ketamine may permit a substantial reduction in morphine dosage of up to 81% without compromising analgesic efficacy. These findings warrant confirmation in larger, fully powered multicenter trials.

Penile Preservation in a Young Adult with Aggressive Spindle Cell Carcinoma: A Case of Wide Local Excision and Glanular Reconstruction in a Resource-Limited Setting

Dony Marthen Bani — 2025-12-26

Penile sarcomatoid squamous cell carcinoma, also known as spindle cell carcinoma, is a rare and aggressive malignancy characterized by biphasic histology. Its management in young adults under 40 years of age is challenging, particularly in resource-limited settings where advanced diagnostic adjuncts like immunohistochemistry are often unavailable, necessitating reliance on morphological diagnosis and clinical acumen. We report the case of a 36-year-old uncircumcised male presenting with a rapidly growing, 2.5 cm exophytic glanular mass (cT2N0M0). Diagnostic workup relied on clinical assessment and morphological evaluation to rule out differentials, as immunohistochemical markers were unavailable. The patient underwent penile-sparing wide local excision (WLE) with intraoperative frozen section control (5 mm margins) and primary glanular reconstruction. Due to the high-grade histology and resource constraints preventing dynamic sentinel node biopsy, the patient was managed with a strict active surveillance protocol for the inguinal basin. Histopathology using Hematoxylin and Eosin (H&E) staining confirmed a high-grade malignancy with a predominant population of atypical spindle cells arranged in fascicles, consistent with Spindle Cell Carcinoma. Deep and lateral margins were negative. At 12-month follow-up, the patient remains disease-free with no evidence of local recurrence or inguinal lymphadenopathy. The International Index of Erectile Function (IIEF-5) score remained stable (23/25), indicating excellent functional preservation. In conclusion, penile preservation via WLE is a viable option for selected cases of Spindle Cell Carcinoma. In resource-limited settings where immunohistochemistry is inaccessible, accurate diagnosis relies on identifying characteristic morphological features on H&E staining combined with clinical history. Strict surveillance is mandatory to monitor for nodal progression in the absence of invasive staging.

Adiposity-Induced Voiding Dysfunction: Unraveling the Association Between Overweight Status and Symptom Severity in Non-Retentive Benign Prostatic Hyperplasia

Iman Hakim Wicaksana — 2026-01-07

Benign prostatic hyperplasia (BPH) has historically been viewed through a prostato-centric lens, attributing lower urinary tract symptoms (LUTS) primarily to prostatic volume and mechanical obstruction. However, this model fails to account for the substantial symptom burden observed in patients without significant retention or massive enlargement. Emerging evidence suggests that systemic metabolic dysregulation, particularly adiposity, plays a crucial role in the pathophysiology of LUTS. This study aims to evaluate the association between Overweight status and the subjective severity of LUTS in a specific cohort of non-retentive BPH patients, thereby isolating metabolic contributors from acute mechanical failure. We conducted an observational analytic cross-sectional study at the Urology Polyclinic of RSUD Dr. Moewardi, Surakarta, Indonesia, from June 2024 to January 2025. The study enrolled 110 men diagnosed with BPH who met strict criteria for non-retentive status (post-void residual <150 mL, no indwelling catheter). Participants were stratified into normal BMI (<25 kg/m²) and Overweight (≥25 kg/m²) groups. Symptom severity was quantified using the International Prostate Symptom Score (IPSS). Data were analyzed using the Mann-Whitney U test and Chi-square analysis. The cohort comprised 72 (65.5%) normal-weight and 38 (34.5%) overweight patients. A statistically significant disparity in symptom severity was observed. The overweight group exhibited a significantly higher mean IPSS (17.87 ± 5.18) compared to the normal group (11.54 ± 4.71) (p<0.001). Notably, 44.7% of overweight patients presented with severe LUTS, compared to only 5.6% of normal-weight patients. Conversely, 90.9% of patients with mild symptoms belonged to the normal-weight group. In conclusion, overweight status is significantly associated with increased LUTS severity in non-retentive BPH patients. The findings suggest that adiposity exacerbates voiding dysfunction through systemic inflammatory, hormonal, and autonomic pathways independent of urinary retention. These results advocate for the integration of weight management as a core therapeutic strategy in BPH care.

Hemodynamic Stability via Ultrasound-Guided Axillary Brachial Plexus Block with Levobupivacaine-Dexamethasone in a Patient with Impending Thyroid Storm and Hand Fracture

Anak Agung Ngurah Aryawangsa — 2026-02-02

The perioperative management of patients with uncontrolled hyperthyroidism requiring emergency surgery presents an acute clinical challenge, as surgical trauma and anesthesia can precipitate a life-threatening thyroid storm. This case report examines the strategic role of regional anesthesia in mitigating such risks through complete afferent blockade and sympathetic stabilization. A 28-year-old male presented with multiple right-hand fractures following a motorcycle accident. The patient had a history of untreated hyperthyroidism for one year and exhibited classic clinical thyrotoxicosis, including tachycardia of 104 bpm, hypertension of 164/90 mmHg, bilateral exophthalmos, and hyperkinesis. Laboratory investigations confirmed primary hyperthyroidism with a markedly elevated free T4 of 86.6 pmol/L and suppressed TSH. His Burch-Wartofsky Point Scale (BWPS) score was calculated at 30, indicating an impending thyroid storm. Following rapid medical optimization with propylthiouracil, propranolol, hydrocortisone, and amlodipine, surgical intervention was successfully performed under ultrasound-guided axillary brachial plexus block. The anesthetic mixture comprised 20 mL of 0.5 percent levobupivacaine and 8 mg of perineural dexamethasone. The patient demonstrated remarkable hemodynamic stability throughout the two-hour procedure, maintaining a systolic blood pressure between 115 and 135 mmHg and a heart rate between 82 and 94 bpm, without progressing to a thyroid crisis. In conclusion, ultrasound-guided regional anesthesia, specifically the axillary approach, offers a superior safety profile for thyrotoxic patients by avoiding airway instrumentation and preventing the sympathetic surges associated with general anesthesia. The synergistic use of levobupivacaine and dexamethasone provides a dual benefit of enhanced cardiac safety and peripheral endocrine stabilization.