Sulfadiazine-induced crystalline nephropathy: a case report of a reversible cause of acute kidney injury in advanced HIV

Abstract

Introduction

Crystal-induced acute kidney injury (AKI) is caused by the intratubular precipitation of crystals, which results in obstruction. Crystal-induced AKI mostly occurs as a result of acute uric acid nephropathy and following the administration of drugs or toxins that are poorly soluble.

Case description

A 23-year-old man presented with AIDS and 1 week history of right sided weakness. Brain MRI showed bilateral ring enhancing lesions. Patient was empirically started on pyrimethamine, sulfadiazine and leucovorin. Brain biopsy confirmed the diagnosis of toxoplasmosis. Hospital course was complicated by AKI and labs showed serum creatinine 2.0 mg/dL (baseline 0.8 mg/dL). Urinalysis showed no hematuria or pyuria with urine pH of 6. Examination of urine sediments under polarized light revealed multiple yellow brown asymmetric rosette shaped crystals (sulfonamide crystals). Sulfadiazine was discontinued and patient was switched to clindamycin. Patient was treated with IV fluids (sodium bicarbonate) for urinary alkalinization. The patient’s serum creatinine returned to baseline within 8 days.

Discussion

Sulfadiazine induced crystalluria is a serious complication in patients with AIDS who are treated for toxoplasmosis. Predisposing factors include high dose of sulfadiazine and volume depletion. It usually presents with AKI within 3 weeks of starting the medication. Treatment requires stopping the offending agent, aggressive IV hydration (urine output at least 1.5 L/day) and bicarbonate infusion for urinary alkalinization (goal pH > 7).

Conclusion

This case highlights sulfadiazine-induced crystal nephropathy as a reversible cause of AKI. Early drug withdrawal, aggressive hydration, and urinary alkalinization are crucial for recovery. Preventive measures, especially hydration and urine pH monitoring, can significantly reduce risk.

Background

Crystal-induced acute kidney injury (AKI) is a distinct form of renal impairment that results from the intratubular precipitation of crystalline substances, leading to mechanical obstruction of renal tubules, tubular epithelial injury, and subsequent inflammation [1]. These crystals may be endogenous, such as uric acid or oxalate, or exogenous, most commonly derived from medications that are poorly soluble in urine [2]. The obstruction caused by crystal deposition can result in acute tubular necrosis and interstitial nephritis if not recognized and treated promptly [3]. Common causes of crystal-induced nephropathy include acute uric acid nephropathy in tumor lysis syndrome, ethylene glycol intoxication (oxalate crystals), and certain medications such as acyclovir, indinavir, methotrexate, and sulfonamides [3, 4].

Among these, sulfadiazine-induced AKI is an important iatrogenic complication, particularly in immunocompromised individuals receiving treatment for Toxoplasma gondii encephalitis [5]. Sulfadiazine, a sulfonamide derivative, has limited solubility in acidic urine. When its concentration exceeds solubility limits, sulfadiazine and its acetylated metabolites precipitate as crystals within renal tubules, leading to nephrotoxicity [6]. The risk is heightened in conditions of volume depletion, high-dose therapy, and aciduria [6]. In patients with advanced HIV/AIDS, such as those with cerebral toxoplasmosis, these risk factors often coexist, increasing susceptibility to crystal nephropathy [5]. Early recognition and prompt management are essential to prevent permanent renal damage.

Case presentation

A 23-year-old man with a history of untreated human immunodeficiency virus (HIV) infection presented with a one-week history of progressive right-sided weakness, headache, and malaise. At presentation, the patient reported markedly reduced oral intake for several days due to malaise and anorexia. No gastrointestinal losses were reported. He also endorsed intermittent fever. On admission, vital signs were as follows: blood pressure 98/62 mmHg, heart rate 108 beats/min, temperature 101.1 °F, and oxygen saturation 99% on room air. Physical examination revealed dry mucous membranes and right-sided hemiparesis but was otherwise unremarkable. Laboratory tests showed a plasma HIV viral load of 274,000 copies/mL and a CD4 count of 2 cells/mm³, indicating advanced immunosuppression (AIDS). Baseline serum creatinine was 0.8 mg/dL.

Brain magnetic resonance imaging revealed multiple bilateral ring-enhancing lesions with surrounding edema, suggestive of cerebral toxoplasmosis. Empirical treatment was initiated with pyrimethamine 75 mg daily, sulfadiazine 1.5 g every 6 h, and leucovorin 25 mg daily, along with dexamethasone for cerebral edema. Additionally, the patient received prophylactic azithromycin and atovaquone. Stereotactic brain biopsy confirmed Toxoplasma gondii infection.

Eight days after starting anti-toxoplasmosis therapy, the patient’s urine output decreased to 0.4 ml/kg/hour with rising serum creatinine (2.0 mg/dL). Urinalysis showed no hematuria or pyuria, with a urine pH of 6. Microscopic examination of freshly collected urine under polarized light revealed numerous yellow-brown, asymmetric, rosette-shaped crystals with birefringence—findings characteristic of sulfonamide crystalluria (Fig. 1) [7]. The diagnosis of sulfadiazine-induced crystal nephropathy was established. Sulfadiazine was discontinued, and clindamycin 600 mg every six hours was substituted alongside pyrimethamine and leucovorin.

Fig. 1.

Yellow-brown asymmetric rosette-shaped crystals consistent with sulfonamide crystalluria were observed under polarized light microscopy. Images were captured at 40× objective magnification (400× total magnification) with a digital microscope camera. Illumination was provided using a brightfield halogen/LED light source

Aggressive intravenous hydration was initiated with isotonic saline (2.5 L over the first 12 h), followed by a sodium bicarbonate infusion (150 mEq in D5W at 125 mL/hr) to achieve urinary alkalinization. The goal was to maintain urine pH > 7.0 and urine output > 2 L/day.The patient’s urine output began improving within 24 h of fluid initiation, and our target urine output and urine pH were achieved within 48 h. The patient’s renal function improved, returning to baseline after eight days. Follow-up urinalysis confirmed resolution of crystalluria. He was discharged with stable renal function on the modified regimen. Following the switch to clindamycin, the patient completed the full recommended treatment course without clinical or radiographic evidence of treatment failure. His neurologic symptoms continued to improve, and follow-up imaging showed progressive resolution of the cerebral lesions. Regarding his renal function and HIV course, serum creatinine remained normal at 0.9 mg/dL at 1 month and 0.8 mg/dL at 4 months. Antiretroviral therapy was initiated after stabilization, and by the 4-month follow-up, the HIV viral load had become undetectable, with a CD4 count of 54 cells/mm³.

Discussion

Sulfadiazine-induced crystal nephropathy is a recognized but uncommon cause of AKI, particularly in patients with AIDS treated for T. gondii infection [5]. The mechanism involves precipitation of sulfadiazine and its acetylated metabolites within renal tubules, especially in concentrated and acidic urine [6]. These crystals can obstruct renal tubules, cause tubular injury, and provoke inflammation leading to acute tubular necrosis [3].

Sulfadiazine has a pKa of approximately 6.5; at urinary pH < 6.5, a substantial fraction of the drug remains non-ionized and poorly soluble, promoting crystallization [6]. Risk factors include high doses, volume depletion, preexisting renal impairment, acidic urine, and concomitant nephrotoxic drugs. In HIV-infected patients, volume depletion from fever or poor intake further increases the risk.

Clinically, sulfadiazine crystal nephropathy usually presents within 1–3 weeks of treatment as an acute rise in serum creatinine, often without hematuria or pyuria [7]. Some patients experience flank pain or dysuria. Diagnosis relies on identifying the pathognomonic yellow-brown, rosette-shaped sulfonamide crystals in urine sediment [7]. Imaging may show radiolucent calculi or obstruction. Kidney biopsy is the gold standard for establishing diagnosis. In our patient, the combination of marked crystalluria, timing of sulfadiazine initiation, and the complete resolution of kidney injury following drug discontinuation reduced the clinical utility and the additive value of pursuing a kidney biopsy, acknowledging the risk/benefit evaluation at that given point [5]. Crystalluria has been reported in up to 29% of patients receiving sulfadiazine. Existing literature also indicates that acute kidney injury is more prominent in patients with HIV/AIDS than in HIV-negative individuals, with reported risks of approximately 7.5% and 4%, respectively [8]. The cornerstone of management is immediate discontinuation of sulfadiazine, aggressive hydration, and urinary alkalinization [5, 6] Intravenous sodium bicarbonate is commonly used to maintain urine pH > 7.0. Alternative agents such as clindamycin, azithromycin, or atovaquone can substitute for sulfadiazine [5]. Early intervention typically results in full recovery of renal function, while delays can lead to chronic kidney disease.

Preventive strategies include adequate hydration, urinary alkalinization, and close monitoring of renal function and urinalysis during therapy [3, 6].

Conclusion

This case highlights sulfadiazine-induced crystal nephropathy as a reversible cause of AKI in patients with T. gondii encephalitis. Clinicians should maintain a high index of suspicion for this complication in patients with advanced HIV receiving sulfadiazine. Early drug withdrawal, aggressive hydration, and urinary alkalinization are crucial for recovery. Preventive measures —especially hydration and urine pH monitoring— can significantly reduce risk.

Abbreviations

AKI

Acute kidney injury

T.gondii

Toxoplasma gondii

HIV

Human immunodeficiency virus

AIDS

Acquired immunodeficiency syndrome

Author contributions

ZA wrote the first draft. MH, and EC reviewed and edited the manuscript. All authors read and approved the final manuscript.

Funding

None.

Data availability

Not applicable.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal.

Disclosures

Mohamad Hanouneh reports serving on a speaker’s bureau for Bayer, Novo Nordisk, Lilly and Boehringer Ingelheim. The remaining authors have nothing to disclose.

Competing interests

The authors declare no competing interests.