Fanconi syndrome (FS) is a rare proximal tubule disorder causing impaired reabsorption of bicarbonate, phosphate, glucose and amino acids, leading to metabolic acidosis, hypophosphataemia, glycosuria and aminoaciduria. In adults, acquired FS is more common; drug toxicity is a leading cause, with tenofovir disoproxil fumarate (TDF) a recognised culprit. Tenofovir disoproxil fumarate-associated FS may precipitate type 2 (proximal) renal tubular acidosis (RTA) with persistent non-anion gap acidaemia, plus osteomalacia and pathological fractures, including subtrochanteric fractures. Evidence guiding perioperative fluid and acid-base management is scarce. We report a patient with TDF-induced FS and type 2 RTA requiring orthopaedic surgery, outlining key principles for perioperative care.

A 29-year-old woman with human immunodeficiency virus, diagnosed in 2018 and treated with a TDF-based regimen (cluster of differentiation 4577 cells/mm³), presented with acute bilateral hip and back pain and progressive weight loss. She had a history of disseminated spinal tuberculosis, which had resulted in kyphoscoliosis and bilateral lower limb weakness, and had completed a 9-month course of targeted therapy in 2019. Over time, she developed osteoporosis and sustained bilateral subtrochanteric femur fractures.

On examination, she appeared chronically ill and was wheelchair bound. Neurological assessment revealed weakness and sensory loss in both lower limbs below L2, with absent sensation in the S1 distribution. The remainder of the systemic examination was unremarkable.

Differential diagnoses included TDF-related FS, renal osteodystrophy, primary hyperparathyroidism, vitamin D deficiency due to immobility and inherited osteomalacia. Investigations confirmed TDF-induced FS with type 2 RTA. Arterial and venous blood gases demonstrated persistent hyperchloraemic non-anion gap metabolic acidosis (NAGMA) with low pH, low bicarbonate and elevated chloride. Although the urine pH was 7.0, this did not exclude type 2 RTA. A urine anion gap (UAG) of 10.3 supported a renal tubular cause of the acidosis (Table 1).

She was optimised preoperatively by a multidisciplinary team including endocrinology, orthopaedics, anaesthesia and intensive care unit (ICU). Antiretroviral therapy was changed from TDF to abacavir and lamivudine and dolutegravir. Nephrotoxic agents were discontinued, electrolyte disturbances corrected and supplementation provided with vitamin D, calcium, potassium and iron. Analgesia was initiated, perioperative fluid and blood product plans were made, and ICU admission was arranged for postoperative management.

The patient underwent bilateral femur osteotomies and cephalomedullary nail fixation, correcting her deformity and stabilising both fractures.

On admission to the ICU, the patient was haemodynamically stable but had severe hyperchloraemic NAGMA (pH 7.22; base excess −11.3). This was characterised by low serum bicarbonate and elevated chloride. Based on the initial postoperative values (Sodium [Na] 139 mmol/L, Chloride [Cl] 118 mmol/L, bicarbonate [HCO₃] 15.3 mmol/L), the calculated anion gap was 5.7 mmol/L and the delta-delta ratio was −0.72, supporting a predominantly non-anion gap process despite mild postoperative lactate elevation. These findings were consistent with proximal (type 2) RTA in the setting of FS. Initial management included continuous haemodynamic and respiratory monitoring, strict input–output charting and urinary catheterisation for hourly urine output. Central venous access was secured to facilitate frequent blood sampling and guided fluid resuscitation.

Resuscitation was commenced with balanced crystalloid solutions to avoid worsening hyperchloraemic acidosis. Serial arterial blood gas samples were obtained every 4 h – 6 h to monitor acid-base status. Electrolytes were monitored closely, with targeted replacement of potassium, calcium and phosphate as required. From ICU admission at 20:00 on Day 1 until 11:00 on Day 2, the patient received approximately 800 mL of balanced crystalloid (Balsol), comprising 300 mL as an ongoing infusion and 500 mL as a bolus. She also received 300 mL packed red cells during the first postoperative night.

Although the initial pH was 7.22, bicarbonate therapy was not started immediately because the patient remained spontaneously breathing, haemodynamically stable and did not require vasopressors or ventilatory support. Initial management, therefore, prioritised chloride-sparing fluid therapy, transfusion and electrolyte correction, while serial blood gases were trended to determine whether the acidaemia would improve during the immediate postoperative period. However, as the acidosis persisted overnight and into Day 2, bicarbonate therapy was initiated at 12:00 on Day 2. An initial bolus of sodium bicarbonate was administered, followed by infusion of neat sodium bicarbonate at 20 mL/h, later reduced to 10 mL/h, with approximately 290 mL administered over the subsequent 19 h. Therapy was titrated to maintain a pH above 7.30 and serum bicarbonate between 20 mmol/L and 24 mmol/L. This resulted in steady improvement, with complete normalisation by Day 3 (pH 7.39; HCO₃ 26.4 mmol/L) (Figure 1). Lactate levels, mildly elevated postoperatively, also resolved with improved perfusion.

The patient remained spontaneously breathing and did not require vasopressors or mechanical ventilation. Pain was managed with multimodal analgesia and thromboprophylaxis was provided. Daily multidisciplinary rounds involving ICU, orthopaedics and endocrinology ensured coordinated management.

By the end of the third postoperative day, her acid-base balance was stable, electrolytes corrected, urine output adequate and renal function preserved. She was discharged from the ICU with normal acid-base status, transferred to the orthopaedic ward for rehabilitation and scheduled for outpatient follow-up to monitor renal function and bone health.

Perioperative fluid management in patients with RTA presents a unique challenge, particularly during major surgery. In this case, the postoperative acid-base disturbance was more accurately characterised as hyperchloraemic NAGMA, consistent with proximal (type 2) RTA. Pre-existing disturbances in acid-base homeostasis may be exacerbated in the perioperative period, particularly in the context of fluid shifts and chloride-rich resuscitation. The diagnosis of FS with proximal RTA was supported by evidence of generalised proximal tubular dysfunction, including glycosuria despite normoglycaemia, proteinuria, hypophosphataemia, hypokalaemia and bicarbonate wasting with metabolic acidosis in the setting of chronic TDF exposure. Urine pH and urine electrolyte findings were interpreted only as supportive biochemical data and not as diagnostic in isolation. The UAG is more useful in the assessment of distal acidification defects than in confirming proximal RTA.¹ Although the urine pH was 7.0, this does not exclude proximal RTA, as urine pH may be variable in this setting. In the context of TDF exposure, these findings were considered most consistent with TDF-induced FS and proximal (type 2) RTA. Fanconi syndrome, when acquired in adulthood, is most often drug-related, and TDF is a well-recognised cause.^1,2,3 In such patients, the combination of proximal tubular dysfunction and poor bone quality complicates both surgical and critical care management. Our patient, who developed TDF-induced FS with proximal (type 2) RTA, exemplifies these challenges in the perioperative setting.

In health, acid-base homeostasis is maintained by the lungs and kidneys. The lungs regulate arterial carbon dioxide (PaCO₂), while the kidneys excrete hydrogen ions and reabsorb bicarbonate. On average, metabolism generates approximately one mmol/kg of acid per day, primarily from sulphur-containing amino acids and dietary phosphates.¹ In proximal RTA, the kidneys fail to reclaim filtered bicarbonate, leading to bicarbonaturia, extracellular volume contraction and systemic acidosis.¹ These changes reduce buffering capacity and lower tolerance to anaesthesia and surgical stress, placing patients at increased risk of perioperative complications such as hypotension, arrhythmias and respiratory compromise.^1,4

Adult-acquired FS is characterised by global proximal tubular dysfunction with impaired reabsorption of glucose, phosphate, amino acids, uric acid and bicarbonate. This results in polyuria, glycosuria, electrolyte imbalance and persistent hyperchloraemic NAGMA.² Tenofovir disoproxil fumarate-induced FS may be clinically silent until complications such as bone pain, proximal myopathy or pathological fractures emerge, often necessitating orthopaedic surgery. In our case, the diagnosis was supported by the characteristic pattern of proximal tubular dysfunction together with chronic TDF exposure, and the patient’s osteoporosis contributed to bilateral subtrochanteric fractures requiring surgical fixation.^3,5

Fluid selection is a central component of perioperative management in FS with RTA. Normal saline (0.9% NaCl), although widely used, has a supraphysiological chloride concentration (154 mmol/L) and no bicarbonate precursors. Large volumes can precipitate iatrogenic hyperchloraemic acidosis, further worsening baseline metabolic derangements.^6,7 Consequently, it should be reserved for limited, targeted use. In contrast, balanced crystalloid solutions such as Lactated Ringer’s and Plasma-Lyte are more physiological. They contain bicarbonate precursors (lactate, acetate, gluconate) that are metabolised into bicarbonate, helping to buffer acidosis. The Saline Against Lactated Ringer’s or Plasma-Lyte in the Emergency Department (SALT-ED) and Isotonic Solutions and Major Adverse Renal Events Trial (SMART) demonstrated fewer renal complications and improved outcomes with balanced crystalloids compared to saline.^6,8 In our patient, approximately 800 mL of balanced crystalloid was administered between ICU admission and the initiation of bicarbonate therapy, including 500 mL as bolus therapy, which helped avoid further chloride loading while other contributors to the acidosis were addressed.

Sodium bicarbonate remains an essential therapy for moderate to severe metabolic acidosis in this context. In proximal RTA, ongoing bicarbonate losses require higher or continuous dosing, and treatment must be closely monitored to avoid complications such as fluid overload, hypokalaemia and paradoxical intracellular acidosis.^1,9 In this case, bicarbonate was introduced only after serial blood gases showed persistent acidaemia despite initial balanced crystalloid resuscitation, blood transfusion and electrolyte correction. Potassium citrate may also be considered, providing both alkali supplementation and urinary citrate, which reduces nephrolithiasis risk.¹⁰ Although not used in our case, it represents a valuable adjunct in selected patients, particularly those with fluid restriction or cardiovascular comorbidity. Dextrose-containing solutions such as 5% dextrose in water (D5W) may also have a role in mitigating glycosuria-induced free water loss. However, they lack electrolytes or buffering capacity and should not be used in isolation.^1,2

Critical care in the perioperative period must include frequent monitoring of arterial blood gases, serum electrolytes (particularly potassium, phosphate and bicarbonate) and fluid balance. Multidisciplinary coordination between anaesthesia, orthopaedics and intensive care teams is essential to anticipate and address dynamic changes.^4,6 In our patient, close collaboration enabled early initiation of balanced crystalloids, targeted electrolyte replacement and titrated bicarbonate therapy. Her acidosis resolved by the third postoperative day, and she was discharged from the ICU with normal acid-base status and stable renal function.

Managing perioperative fluids in patients with FS and proximal RTA presents unique challenges, especially during major orthopaedic surgery. Standard regimens may worsen underlying metabolic derangements, making an individualised, physiology-driven strategy essential. In this case, the combination of balanced crystalloids, carefully titrated bicarbonate and close interdisciplinary oversight enabled the restoration of acid-base balance and a safe surgical recovery.