Hrev_master [page 30] [Emergency Care Journal 2025; 21:13710] Emergency Care Journal 2025 volume 21:13710 Abstract Hyperkalemia is a common electrolyte disturbance in hospital- ized patients, often caused by impaired renal potassium excretion due to hypoaldosteronism. Type 4 Renal Tubular Acidosis (RTA), commonly associated with diabetes mellitus and RAAS-inhibiting medications, is a significant consequence. We report a 56-year-old male with diabetes, hypertension, and coronary artery disease who developed type 4 RTA after starting telmisartan post-hip replace- ment. His course was complicated by pneumonia and worsening hyperkalemia, with arterial blood gas showing Normal Anion Gap Metabolic Acidosis (NAGMA) and a positive urinary anion gap. Discontinuing telmisartan and initiating hydrocortisone led to sig- nificant renal function improvement and potassium normalization. This case highlights the importance of caution when using RAAS inhibitors in high-risk patients and supports hydrocortisone as a viable alternative when fludrocortisone is unavailable. Case Report A 56-year-old male patient was referred to our department fol- lowing a complicated postoperative course. His medical history was significant for DM2, hypercholesterolemia, hypertension, and chronic stable coronary artery disease. His home medications included amlodipine and insulin; however, he reported poor adher- ence to his prescribed regimen. The patient had undergone right hip replacement surgery at the referring hospital, where the intra- operative course was uneventful. However, by postoperative day 7, his recovery was complicated by pneumonia associated with poor- ly controlled blood glucose levels and blood pressure, necessitat- ing his transfer to our hospital for further management. Upon admission, he presented with mild dyspnea but remained hemody- namically stable. Initial laboratory investigations revealed mild anemia, leuko- cytosis, and significantly elevated inflammatory markers, while other parameters were unremarkable. The patient had been receiv- ing subcutaneous Low Molecular Weight Heparin (LMWH) 60 mg/day since the first postoperative day for Deep Vein Thrombosis (DVT) prophylaxis and was initiated on antibiotics for his pneu- monia. Notably, he had no prior history of treatment with Angiotensin Receptor Blockers (ARBs), Angiotensin-Converting Enzyme inhibitors (ACE inhibitors), or Nonsteroidal Anti- Inflammatory Drugs (NSAIDs). Given his clinical status, telmisar- tan 40 mg once daily was introduced on postoperative day 8 to manage his hypertension (Supplementary Materials, Table 1). LMWH was discontinued on postoperative day 10 and replaced with aspirin. The patient remained clinically stable throughout his hospitalization. However, by postoperative day 10, his leukocyte count exhibited a gradual increase, peaking at 24.64 G/L on post- operative day 14 (Table 1). Concurrently, his platelet count increased from baseline, fluctuating between 511 and 636 G/L, likely reflecting reactive leukocytosis and thrombocytosis sec- ondary to anemia. On postoperative day 12, a rise in serum potas- sium levels to 5.1 mmol/L was noted and was managed with intra- venous furosemide (20 mg/day). However, by postoperative day 14, a marked increase in serum creatinine levels from a baseline of Correspondence: Thang Nguyen Ngoc, Intensive Care and Emergency Center, Phenikaa University Hospital, Kieu Mai Street, Ha Noi, Vietnam. Tel.: +84397913937 E-mail: anh3tue@gmail.com Key words: renal tubular acidosis; telmisartan; diabetes melitus; metabolic acidosis; case report. Ethics approval and consent to participate: no ethical committee approval was required for this case report by the Department, because this article does not contain any studies with human partic- ipants or animals. Informed consent was obtained from the patient included in this study. Written informed consent for publication of this case report and accompanying table was obtained from the patient. Availability of data and material: all data generated or analyzed dur- ing this study are available upon request. Conflict of interest: the authors have no conflicts of interest to declare Contributions: TNN, study concept, design, collection and assembly of data, manuscript original drafting; VNT, administrative support, provision of patients, contribution to manuscript writing and editing; SNB, contribution to manuscript writing and editing; MNN, contri- bution to manuscript writing and editing. All the authors read and approved the final version of the manuscript and agreed to be accountable for all aspects of the work. Acknowledgments: we sincerely thank the patient for granting per- mission to publish this case report. Received: 6 February 2025. Accepted: 29 May 2025. Early view: 24 June 2025. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2025 Licensee PAGEPress, Italy Emergency Care Journal 2025; 21:13710 doi:10.4081/ecj.2025.13710 Publisher's note: all claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Telmisartan-induced type 4 renal tubular acidosis: a case report Thang Nguyen Ngoc, Vy Nong Thao, Son Nguyen Ba, Nghia Nguyen Minh Phenikaa University Hospital, Ha Noi, Vietnam approximately 1 mg/dl was observed, alongside a peak serum potassium level of 5.6 mmol/L. Pseudohyperkalemia secondary to thrombocytosis was ruled out by repeated serum and plasma potas- sium measurements. Since the patient remained hemodynamically stable and euv- olemic throughout hospitalization, prerenal acute kidney injury due to hypovolemia was ruled out. To further evaluate the acute decline in renal function and persistent hyperkalemia—which appeared disproportionate to the degree of renal impairment—an Arterial Blood Gas (ABG) analysis was performed, revealing a NAGMA. A spot urine electrolyte analysis on postoperative day 15 demonstrated a positive Urinary Anion Gap (UAG) of 54.7. Urinalysis findings were unremarkable, with a pH of 6.5 and no evidence of infection, proteinuria, or ketonuria; however, serial urine pH measurements demonstrated an acidic trend. Given that other non-renal tubular acidosis causes of NAGMA were excluded, these findings were consistent with type 4 RTA. Due to the acute worsening of kidney function, refractory hyperkalemia, and suspected type 4 RTA, telmisartan was discon- tinued on postoperative day 15, and intravenous furosemide was continued to control hyperkalemia. Given the unavailability of flu- drocortisone in our department, hydrocortisone (200 mg/day) was initiated as an alternative to manage the patient’s tubular dysfunc- tion. Following the discontinuation of telmisartan and the introduc- tion of hydrocortisone, renal function improved significantly. By postoperative day 16, serum creatinine levels had returned to base- line (1.01 mg/dl), and serum potassium had decreased to 5.0 mmol/L. By postoperative day 17, potassium levels had further normalized to 4.1 mmol/L. The patient’s NAGMA also improved, with normalization of serum HCO4⁺ and a mild reduction in the urine anion gap. Given the patient’s clinical improvement, they were dis- charged on postoperative day 17 with a 10-day course of oral hydrocortisone. A follow-up evaluation three weeks later con- firmed a return to baseline creatinine levels (~1.01 mg/dl) and complete resolution of NAGMA and hyperkalemia. Discussion Hyperkalemia is one of the most frequently encountered elec- trolyte disturbances in hospitalized patients, with causes broadly classified into increased potassium intake, impaired renal excre- tion, transcellular shifts, or pseudohyperkalemia. When hyper- kalemia persists in the absence of an obvious cause, hypoaldos- teronism should be considered a primary etiology. Hypoaldosteronism may arise from either true aldosterone defi- ciency or aldosterone resistance, both of which impair renal potas- sium excretion. Type 4 RTA falls under this category and should be included in the initial diagnostic workup for unexplained hyper- kalemia. The pathophysiology of type 4 RTA is characterized by hyper- kalemia and NAGMA, primarily due to hypoaldosteronism, which is more commonly observed than aldosterone resistance.1 Hypoaldosteronism can be either acquired (secondary mineralo- corticoid deficiency) or, less frequently, inherited (primary miner- alocorticoid deficiency). The most prevalent cause of secondary mineralocorticoid deficiency is Hyporeninemic Hypoaldosteronism (HH), frequently associated with DM2 and certain medications that interfere with the RAAS.2 These include drugs that suppress renin synthesis, such as NSAIDs, nonselective beta-blockers, and calcineurin inhibitors, especially agents that directly inhibit aldosterone production, such as heparin, ACE inhibitors, ARBs, and renin inhibitors (e.g., aliskiren).3 Although most patients with HH are asymptomatic and present with mild to moderate hyperkalemia, the condition may become clinically sig- nificant when additional precipitating factors further disrupt potas- sium homeostasis.2 These factors include acute kidney injury, salt restriction, or medications such as ACE inhibitors, ARBs, potassi- um-sparing diuretics, or heparin.4 In this case report, we describe a male patient with DM2 who developed type 4 RTA following the initiation of Telmisartan, an ARB commonly used in clinical prac- tice. Although type 4 RTA is a recognized side effect of RAAS inhibitors, detailed case reports specifically linking telmisartan to type 4 RTA are limited in the literature. The pathophysiological basis of type 4 RTA involves impaired aldosterone activity, which leads to reduced sodium (Na⁺) reab- sorption in the distal nephron. This, in turn, diminishes the electro- chemical gradient required for potassium (K⁺) and hydrogen (H⁺) excretion, resulting in hyperkalemia and metabolic acidosis. Additionally, hyperkalemia inhibits renal ammonium (NH4⁺) pro- duction in the proximal tubule, further impairing acid excretion and exacerbating acidosis.5 Key laboratory findings in this patient were consistent with a diagnosis of type 4 RTA. These included persistent hyperkalemia that was disproportionate to the degree of renal dysfunction and potassium intake, mildly reduced serum bicarbonate, NAGMA, and a positive UAG—all hallmark features of type 4 RTA. In type 4 RTA, urine pH is often still acidic (<5.5) because H⁺ secretion via ATP-dependent proton pumps in the distal nephron is partially preserved. However, the overall acid excretion is impaired due to reduced NH4⁺ production, which limits the kid- ney’s ability to buffer and eliminate acid effectively. That said, some patients may initially present with a urine pH >5.5, especial- ly early in the disease course. This can occur when H⁺ secretion is transiently impaired, even though the mechanisms for acidification are intact. In our patient, the initial urine pH was 6.5, but with pro- gression and treatment, subsequent measurements showed a clear acidification trend, with the urine pH ultimately decreasing to 5.5, which signifies the patient’s ability to acidify urine. Patients with diabetes mellitus are particularly vulnerable to type 4 RTA due to dysregulation of the RAAS, increasing their risk of hyperkalemia.6 The introduction of RAAS inhibitors, such as ARBs, can further aggravate this imbalance, potentially triggering type 4 RTA, as observed in this case. Notably, the patient achieved normokalemia and a return to baseline creatinine levels shortly after discontinuing Telmisartan and initiating hydrocortisone (200 mg/day). This outcome is par- ticularly significant, as type 4 RTA is conventionally managed with fludrocortisone to correct aldosterone deficiency.7 The successful use of hydrocortisone in this case suggests its potential role as a therapeutic alternative when fludrocortisone is unavailable. The primary limitation of this case report is the inability to per- form a more comprehensive diagnostic workup, such as measuring aldosterone levels or calculating the urine osmolal gap, due to tem- porary limitations in local laboratory resources. References 1. Phelps KR, Lieberman RL, Oh MS, et al. Pathophysiology of the syndrome of hyporeninemic hypoaldosteronism. Metabolism 1980;29:186–99. 2. Sousa AGP, Cabral JV de S, El-Feghaly WB, et al. Case Report [Emergency Care Journal 2025; 21:13710] [page 31] Hyporeninemic hypoaldosteronism and diabetes mellitus: pathophysiology assumptions, clinical aspects and implica- tions for management. World J Diabetes 2016;7:101–11. 3. Farkas J. Non-anion-gap metabolic acidosis (NAGMA). EMCrit Project. Available from: https://emcrit.org/ibcc/nagma/ 4. Galbiati F. Type IV RTA in chronic adrenal insufficiency and concomitant lisinopril treatment. Case Rep Endocrinol 2020;2020:8897112. 5. Harris AN, Grimm PR, Lee HW, et al. Mechanism of hyper- kalemia-induced metabolic acidosis. J Am Soc Nephrol 2018;29:1411. 6. Bello CHPRT, Duarte JS, Vasconcelos C, et al. Diabetes melli- tus and hyperkalemic renal tubular acidosis: case reports and literature review. J Bras Nefrol 2017;39:481-5. 7. Palmer BF, Kelepouris E, Clegg DJ. Renal tubular acidosis and management strategies: a narrative review. Adv Ther 2021;38:949–68. Case Report [page 32] [Emergency Care Journal 2025; 21:13710] Online supplementary materials Table 1. Changes in the laboratory values of the patient over 10 postoperative days (from day 7 to day 17). "N/A" denotes that the laboratory values were not available for a given day. Additionally, a selection of the patient’s in-hospital medications is documented. The green bars indicate the duration during which the patient received the medications, while the white bars denote periods when the medications were either withheld or discontinued.