Hydrochlorothiazide-induced tubulointerstitial nephritis in a patient with Dent disease.

Abstract

Sir, Dent disease is an X-linked renal tubular disorder characterized by low-molecular-weight proteinuria and combinations of hypercalciuria, nephrolithiasis, nephrocalcinosis and aminoaciduria. Some have progressive renal failure. It is caused by mutations in CLCN5 gene encoding chloride/proton exchanger CLC-5 [1]. Nephrolithiasis and nephrocalcinosis increase risk of loss of renal function [2]. Hypercalciuria is a risk factor for stone formation. Thiazide diuretics reduce hypercalciuria and are recommended for treatment of Dent disease [3]. We describe acute renal failure (ARF) in a patient with Dent disease treated with hydrochlorothiazide. Dent disease was diagnosed in a 12-year-old boy with rickets, short stature, renal insufficiency, hypophosphataemia, hypercalciuria, aminoaciduria, proteinuria and increased β2-microglobulin excretion. CLCN5 gene sequence analysis showed a G→C nucleotide substitution in exon 9 of the CLCN5 gene. He was treated with angiotensin-converting enzyme inhibitor to reduce proteinuria and preserve renal function. This was complicated by increase in serum creatinine (sCr) and discontinued. For hypercalciuria, he was treated with hydrochlorothiazide (0.5 mg/kg/day) and citrate. At that time he was 13 years old, with sCr 1.4 mg/dl and estimated glomerular filtration rate 72 ml/min/1.73 m2 (Figure ​(Figure1).1). Eleven weeks later he was asymptomatic without fever, rash, arthralgia or oliguria. Physical examination, hydration and blood pressure were normal. sCr was 11.1 mg/dl, phosphorus 9.4 mg/dl, uric acid 9.7 mg/dl, potassium 4.0 mmol/l, bicarbonate 26 mmol/l and haemoglobin 9.8 g/dl. White blood cell (WBC) count was 9600/cm2 with 4.1% eosinophils (count 394). Urinalysis showed one plus protein, 10–25 WBCs and negative stain for eosinophils. Renal ultrasound showed 0.3 cm stone in the upper pole of the left kidney, without renal oedema or enlargement. There was no history of drug allergies or use of nephrotoxic medications. Presumptive diagnosis was tubular interstitial nephritis (TIN) induced by hydrochlorothiazide, which was then discontinued. sCr decreased only to 10.1 mg/dl in the next 2 days, and therefore he was treated with methylprednisolone (10 mg/kg/dose) for 3 days followed by oral prednisone, 60 mg/day, for 5 days. sCr was 4.9 mg/dl at the start of corticosteroid taper. This resulted in near-complete restoration of renal function (sCr 2.3 mg/dl) (Figure ​(Figure1).1). Therefore, a renal biopsy was not done. Fig. 1 Serum creatinine and treatment used in patient with Dent disease. Renal complications of thiazide diuretics are acute TIN and ARF, typically developing 4–10 weeks after starting therapy. Withdrawal of the medication, with or without corticosteroids, restored renal function in reported cases [4]. Thiazides are classified as sulfonamides, which can cause hypersensitivity reactions, such as acute TIN. Renal biopsies of patients with ARF associated with thiazides show acute TIN without immune complex or anti-tubular basement membrane antibody deposits [4]. The report on use of hydrochlorothiazide in children with Dent disease described muscle cramps, hypovolaemia, hypokalaemia and hyponatraemia [5]. Our patient developed ARF as a complication of treatment of hypercalciuria with a thiazide diuretic. This should be kept in mind when prescribing thiazide diuretic to these patients. Conflict of interest statement. None declared.