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Abstract

Clinical Nephrology, Vol. 105 – No. 5/2026 (341-351)

Systemic effects of metabolic acidosis 

Raymond Chen, Caitlin Kumala, Lynh Vu, and Biff F. Palmer

Departments of Education and Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
Metabolic acidosis is a primary reduction in serum bicarbonate concentration and a consequent decrease in blood pH, which has profound implications for systemic physiology. This literature review synthesizes the current evidence of metabolic acidosis’s effect on cardiovascular, vascular, pulmonary, gastrointestinal, endocrine, musculoskeletal, renal, and metabolic systems. Cardiovascular effects include impaired cardiac contractility, altered ion exchange currents, and decreased β-adrenergic response. Vascular response is dependent on vessel size, promoting vasodilation in large arteries and vasoconstriction in small vessels via NO and Ca²⁺-dependent pathways. Pulmonary adaptations include hyperventilation, altered hemoglobin–oxygen affinity via the Bohr effect, and increased pulmonary vascular resistance. Gastrointestinal effects include activation of acid-sensitive neuronal pathways causing increased mucus gel thickness, HCO<sub>3</sub>⁻ secretion, and mucosal blood flow. Endocrine effects include growth hormone resistance, decreased thyroid hormone secretion, and negative shifts in Ca²⁺-PO4- balance. Renal effects include predisposition to calcium-oxalate stones and acceleration of chronic kidney disease through inflammatory mechanisms. Overall, this review aims to explore the physiological effects of metabolic acidosis, highlighting mechanism contributing to organ dysfunction.Correspondence to:
Prof. Biff F. Palmer, MD
Departments of Education and Internal Medicine
Texas Tech University Health Sciences Center
5001 El Paso, Texas 79905, USA
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 106 – No. 4/2026 (299-314)

Beyond erythropoiesis-stimulating agents: The evolving role of hypoxia-inducible factor stabilizers in anemia of chronic kidney disease 

Joel Shah¹, William Wells-Gatnik¹, Kunal Sharma¹, Sidhartha Senapati¹, Lakshmi Kattamuri¹, Aimee Hechanova², Fernanda Payan-Schober², and Biff F. Palmer³

¹Department of Internal Medicine, ²Department of Nephrology, and ³Departments of Education and Internal Medicine, Texas Tech University Health Sciences Center El Paso, TX, USA
Anemia is one of the most common complications affecting individuals with chronic kidney disease (CKD). It is driven primarily by relative erythropoietin (EPO) deficiency, chronic inflammation, and altered iron metabolism. Emerging therapies, known as hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), offer a novel oral treatment approach by stabilizing intracellular HIF levels to mimic tissue hypoxia and stimulate endogenous EPO production. This comprehensive narrative review synthesizes literature indexed in PubMed, MEDLINE, Scopus, and Web of Science to evaluate the efficacy of HIF stabilizers in the anemia of CKD compared to current guideline-directed therapies worldwide. Phase 3 clinical trials consistently demonstrate that HIF-PHIs are non-inferior to conventional erythropoiesis-stimulating agents (ESAs) and superior to placebo in increasing and maintaining hemoglobin levels in both dialysis-dependent and non-dialysis-dependent CKD patients. Additionally, HIF-PHIs improve iron mobilization and utilization by decreasing hepcidin levels. However, trials have raised safety concerns regarding cardiovascular outcomes, including major adverse cardiovascular events, and an increased incidence of thromboembolic events, particularly in non-dialysis-dependent populations. These safety signals have led to divergent global regulatory pathways, with the United States Food and Drug Administration largely restricting approvals to dialysis-dependent patients, while agencies in Europe and Japan have granted broader authorizations. As a growing body of literature accumulates, HIF-PHIs offer a promising oral alternative to ESAs that addresses both relative EPO deficiency and iron sequestration. While they have the potential to become a new standard of care, therapy initiation requires individualized risk-benefit assessments, and continued post-marketing surveillance is necessary to fully elucidate long-term cardiovascular and thromboembolic risks.Correspondence to:
Prof. Biff F. Palmer, MD
Departments of Education and Internal Medicine
Texas Tech University Health Sciences Center
5001 El Paso, TX 79905, USA
Email: [email protected]

Abstract

Nehaa Sohail¹, Sabrina Zheng¹, Zuhair Zaidi², Ayaan Sohail³, Wesam Abdel-Jaber¹, Inaaya Lodhi⁴, Sino Mehrmal⁵, Misha V. Koshelev⁶, and Biff F. Palmer¹

¹Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, ²UT Southwestern Medical School, Dallas, ³John P. and Kathrine G. McGovern Medical School, University of Texas Health Science Center at Houston, Houston, ⁴University of North Texas, Denton, TX, ⁵Epiphany Dermatology, St. Louis, MO, and ⁶Department of Dermatology, University of Texas Health Science Center at Houston, Houston, TX, USA
Patients undergoing Mohs micrographic surgery (MMS) on perioperative diuretics represent a medically complex population, yet the impact of diuretic use on postoperative outcomes remains underexplored. Despite use in patients with cardiometabolic comorbidities, limited research has evaluated how perioperative diuretic exposure influences postoperative outcomes following MMS. This study investigates the association between perioperative diuretic use and postoperative outcomes following MMS. Utilizing the TriNetX database, MMS patients were matched on a 1 : 1 basis according to perioperative diuretic use. Outcome variables were evaluated over a 30- and 90-day follow-up period. Among 37,781 matched patients, diuretic use was associated with higher odds of surgical site infection at both 30 days (OR 1.29, 95% CI 1.03 – 1.62, p = 0.03) and 90 days (OR 1.36, 95% CI 1.12 – 1.65, p < 0.001), as well as substantially increased odds of rash or cellulitis at 30 days (OR 1.95, 95% CI 1.68 – 2.26, p < 0.001) and 90 days (OR 1.92, 95% CI 1.74 – 2.13, p < 0.001). Perioperative diuretic use was linked to increased odds of infection, rash or cellulitis, postoperative pain, opioid use, emergency department visits, sepsis, and short-term mortality, with time-to-event analysis identifying loop and osmotic diuretics as the primary drivers of risk. Correspondence to:
Nehaa Sohail, MBA, 5001 El Paso Drive, El Paso, TX 79905, USA
Email: [email protected]

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