A Rare Case of Nephrogenic Diabetes Insipidus From Tenofovir

Abstract

Introduction: Diabetes insipidus (DI) is a clinical condition which manifests as excessive urine output, either because of impaired or inadequate antidiuretic hormone (ADH) secretion, or an inability of the kidneys to respond to ADH. Nephrogenic DI is more often drug induced. Recent clinical reports have shown that medications like tenofovir may result in nephrogenic DI as well. Tenofovir is a well-known nucleoside reverse transcriptase inhibitor analog of adenosine used in the management of both human immunodeficiency virus (HIV) and chronic hepatitis B. With its increased use, reports of adverse outcomes have been documented, mainly its effect on renal function including nephrogenic DI, renal failure and Fanconi syndrome. We present a case of nephrogenic DI whilst on Biktarvy (a combination of bictegravir, emtricitabine and tenofovir alafenamide). Case: A 59-year-old African American female with a history of HIV on Biktarvy, T2DM, HLD, HTN, MI, CAD, COPD presented to our hospital with weakness and falls for 1-2 months associated with polydipsia and polyuria. She had started Biktarvy for HIV about 2 months ago after which her symptoms got worse. Labs showed a serum Na of 151, potassium of 3.2 on admission with serum osmolality of 323 and urine osmolality of 134. During hospitalization, she was challenged with 100ug oral Desmopressin. Urine labs failed to correct after Desmopressin administration which was highly indicative of severe nephrogenic DI. The challenge was repeated with 200ug oral Desmopressin with similar results. Pituitary DI was considered given the patient’s falls; however urine osmolality did not improve following desmopressin challenge. Furthermore, her serum Co-peptin level was elevated at 36.1 that ruled out central DI. The patient’s hypokalemia was believed to be driving her nephrogenic DI which has been reported in various case reports with patients on Tenofovir, but has never been reported in patients taking Biktarvy (which includes Tenofovir Alafenamide). She was subsequently placed on fluid restriction during which time the patient’s serum Na and Cr increased while urine osmolality did not correct. HCTZ was ultimately started as a treatment for nephrogenic DI and patient was transitioned of biktarvy to lamivudine and dolutegravir. Her polyuria and polydipsia improved, however she developed hyponatremia likely because of HCTZ. Patient concentrating ability improved off biktarvy and HCTZ was discontinued on the day prior to discharge without issue. Her subsequent serum sodium and potassium levels were normal. Conclusions: Our case highlights a rare incidence of tenofovir induced hypokalemia leading to nephrogenic DI. This case illustrates the importance of monitoring patients on tenofovir for signs of renal [tubular] dysfunction. In a polyuric patient on tenofovir, there should be a high index of suspicion for nephrogenic diabetes insipidus.

Fanconi syndrome, diabetes insipidus, and acute kidney injury due to tenofovir disoproxil fumarate: A case report

“…Several studies have shown that TDF is associated with either AKI or chronic kidney disease through proximal tubal injury, either tubular necrosis or interstitial nephritis. 3,5,6,15 Indeed, our patient had pyuria with white blood cell casts suggestive of interstitial nephritis. Our case illustrates a component of tenofovir-induced Fanconi syndrome evidenced by the non-anion gap metabolic acidosis, normoglycemic glucosuria, proteinuria, hypokalaemia, hypophosphatemia, and a urine pH of 5.…”

“…15 Although rare, a few reports have suggested tenofovir can cause nephrogenic diabetes insipidus. [3][4][5][6][7] The cases reviewed make it clear that discontinuation of the drug is paramount and usually leads to overall improvement in all aspects of renal function. [3][4][5][6][7][10][11][12] Although our patient's baseline renal function wasn't recorded, it can be assumed that her renal impairment was attributed to the effects of tenofovir as it improved substantially after the treatment was discontinued.…”

“…[3][4][5][6][7] The cases reviewed make it clear that discontinuation of the drug is paramount and usually leads to overall improvement in all aspects of renal function. [3][4][5][6][7][10][11][12] Although our patient's baseline renal function wasn't recorded, it can be assumed that her renal impairment was attributed to the effects of tenofovir as it improved substantially after the treatment was discontinued. Several studies have shown that TDF is associated with either AKI or chronic kidney disease through proximal tubal injury, either tubular necrosis or interstitial nephritis.…”

“…This term usually refers to the potential complications of renal impairment and Fanconi syndrome, though there have also been reports of nephrogenic diabetes insipidus. [3][4][5][6][7] Risk factors for nephrotoxicity from tenofovir use include older age, low body weight, pre-existing renal impairment, advanced HIV, vascular disease, and concomitant use of protease inhibitors and nephrotoxic drugs. 8 Fanconi syndrome is a defect of the proximal tubule leading to malabsorption of various substances including glucose, electrolytes, amino acids and protein, and bicarbonate.…”

“…Nephrogenic diabetes insipidus can be associated with the use of certain drugs such as lithium, amphotericin B, cidofovir, tenofovir, and foscarnet. [3][4][5][6][7]13 In this paper, we describe a case of an HIV-positive woman on TLD with features suggestive of severe tenofovir-induced nephrotoxicity with an acute kidney injury (AKI), Fanconi syndrome, and nephrogenic diabetes insipidus in the absence of any other predisposing risk factors.…”