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Obstructive uropathy in a HIV+ infant under indinavir treatment
Journal of Pediatric Urology (2007) 3, 512e513
CASE REPORT
Obstructive uropathy in a HIVD infant under indinavir treatment ´ a,*, S. Vivancos a, O. Berbel b, C. Domı´nguez a, A. Serrano-Durba F. Estornell a, F.J. Vera-Sempere c, C. Nome a, F. Garcı´a-Ibarra a a
Pediatric Urology Unit, Hospital Infantil La Fe, Avenida de Campanar 21, 46009 Valencia, Spain Pediatric Nephrology Unit, Hospital Infantil La Fe, Avenida de Campanar 21, 46009 Valencia, Spain c Pathology Department, Hospital Infantil La Fe, Avenida de Campanar 21, 46009 Valencia, Spain b
Received 28 February 2007; accepted 31 May 2007 Available online 13 August 2007
KEYWORDS Indinavir; Obstructive uropathy; Pediatrics
Abstract The case is presented of a 10-year-old HIVþ male with renoureteral pain, who developed an obstructive uropathy with renal function impairment and required endoscopic placement of a ureteral stent. Certain aspects of the epidemiology, clinical presentation, diagnosis, treatment and prevention are discussed. ª 2007 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Introduction
Case report
The use of new drugs (mainly indinavir) for the treatment of HIVþ patients has been associated with an increased incidence of urological complications. These can be summarized into 3 main syndromes: dysuria/urgency, symptomatic nephrolithiasis (4e15% [1,2]) and colic pain without calculi. The most frequent presentation is asymptomatic crystalluria, but all of them are rare in pediatric patients.
A 10-year-old HIVþ male, treated with indinavir, was admitted for severe left groin pain with hematuria and left groin tenderness on examination. Urine revealed sterile pyuria and microhematuria with pH 8. Blood creatinine levels rose transitorily up to 0.9 mg/dl during the acute episode, and the GFR fell to 100 ml/min/1.73 m2. X-ray and ultrasound showed dilatation of the left ureter and renal pelvis and material of high ecogenicity in the distal lumbar ureter, but not lithiasis. Intravenous pyelography showed a non-functioning left kidney. Isotopic studies (DMSA) evidenced a decrease in left renal function: 39.8% vs 60.2% in the right kidney. Conservative treatment was applied, but ultrasound confirmed an increase in the hydroureteronephrosis. A double-J ureteral stent was placed observing the emission
* Corresponding author. Unidad de Urologı´a Infatil, Hospital Infantil La Fe, Avenida de Campanar 21, 46009 Valencia, Spain. Tel.: þ34 96 3330776; fax: þ34 96 1973215. E-mail address: [email protected] (A. Serrano-Durba ´).
1477-5131/$30 ª 2007 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2007.05.008
Uropathy in a HIVþ infant of abundant small sand particles (Fig. 1). Under the microscope, these looked like conglomerates of crystalline structures, optically transparent, polyhedric or rhomboidal morphology that did not show refringence to polarized light. They were accompanied by many polymorphonuclear leukocytes with occasional eosinophils with fibrinous material nets. Following the placement of the stent, pain ceased and the GFR and creatinine values returned to normal. The stent was removed on the 14th day, and a new DMSA confirmed complete functional recovery.
Discussion The incidence of urinary tract obstruction associated with indinavir ranges from 4% to 15% [2,3]. The etiology is due to low solubility in water solutions that coexist with high urinary excretion. This facilitates the formation of birefringent crystals that can end up forming true calculi of indinavir monohydrate as well as stone formations of calcium oxalate [4]. Clinically, this condition can manifest in multiple ways, the most frequent one being asymptomatic crystalluria (20e33% [3]). Nephropathy caused by
513 the intratubular deposit of indinavir crystals has also been reported, although this has not yet been confirmed [3]. Renal function has been shown to be affected by an increase in creatinine levels in 62% [5] of patients with urological complications, but there was a return to initial values after establishment of specific treatment. Renal function impairment has also been described when indinavir is associated with non-steroidal anti-inflammatory drugs or trimethropim-sulphametoxazole [2]. A significantly higher pH has been reported in the urine of those patients that do not present crystalluria, although it usually oscillates between 5 and 6. Pyuria, proteinuria, hematuria and hypocitraturia have also been found [5]. Radiologically [6], plain X-ray is not useful, intravenous pyelography only confirms the diagnosis in 36.3% of cases, and ultrasound only shows obstructive changes that are secondary to lithiasis. CT scans are of no use. Diagnosis is based on the patient’s clinical presentation, and pharmacological etiology should be suspected in any case of child colic pain that is under indinavir treatment. Chromatography and spectrophotometry techniques can be used to detect the presence of crystals of monohydrate of indinavir in urine in order to confirm the diagnosis. The best treatment is the prevention of crystallization. To minimize this risk, water ingestion should be increased in order to achieve diuresis of 150 ml/h or higher during the first 3 h following administration. Sometimes, the use of ESWL or ureteral catheterization (3% of cases [2]) may be necessary. Concomitant administration of non-steroid analgesics or cotrimoxazole should be avoided.
Conclusions Pharmacological etiology of renoureteral colic should be suspected in any child receiving indinavir treatment. Preventive measures against urinary tract obstruction should be prescribed in any child taking indinavir. Treatment should be established quickly and is based on conservative measures. In the event of incessant pain or ureteral obstruction a stent should be placed.
References
Figure 1 Microscopic image of polyhedric contour crystals that are optically empty, and immersed in a net of fibrinous material with frequent polymorphonuclear leukocytes (hematoxylin & eosin, 200).
[1] Gonzalo A. Nephropathy caused by crystal deposits induced by indinavir. Nefrologia 2001;21:337. [2] Hermieu JF, Prevot MH, Ravery V, Moulinier F, Delmas V, Bouvet E, et al. Nephritic colic due to indinavir. Presse Med 1998;27:465e7. [3] Kopp JB, Miller KD, Mican JA, Feuerstein IM, Vaughan E, Baker C, et al. Crystalluria and urinary tract abnormalities associated with indinavir. Ann Intern Med 1997;127:119e25. [4] Bruce RG, Munch LC, Hoven AD, Jerauld RS, Greenburg R, Porter WH, et al. Urolithiasis associated with the protease inhibitor indinavir. Urology 1997;50:513e8. [5] Boubaker K, Sudre P, Bally F, Vogel G, Meuwly JY, Glauser MP, et al. Changes in renal function associated with indinavir. AIDS 1998;12:F249e54. [6] Schwartz BF, Schenkman N, Armenakas NA, Stoller ML. Imaging characteristics of indinavir calculi. J Urol 1999;161:1085e7.
CASE REPORT
Obstructive uropathy in a HIVD infant under indinavir treatment ´ a,*, S. Vivancos a, O. Berbel b, C. Domı´nguez a, A. Serrano-Durba F. Estornell a, F.J. Vera-Sempere c, C. Nome a, F. Garcı´a-Ibarra a a
Pediatric Urology Unit, Hospital Infantil La Fe, Avenida de Campanar 21, 46009 Valencia, Spain Pediatric Nephrology Unit, Hospital Infantil La Fe, Avenida de Campanar 21, 46009 Valencia, Spain c Pathology Department, Hospital Infantil La Fe, Avenida de Campanar 21, 46009 Valencia, Spain b
Received 28 February 2007; accepted 31 May 2007 Available online 13 August 2007
KEYWORDS Indinavir; Obstructive uropathy; Pediatrics
Abstract The case is presented of a 10-year-old HIVþ male with renoureteral pain, who developed an obstructive uropathy with renal function impairment and required endoscopic placement of a ureteral stent. Certain aspects of the epidemiology, clinical presentation, diagnosis, treatment and prevention are discussed. ª 2007 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Introduction
Case report
The use of new drugs (mainly indinavir) for the treatment of HIVþ patients has been associated with an increased incidence of urological complications. These can be summarized into 3 main syndromes: dysuria/urgency, symptomatic nephrolithiasis (4e15% [1,2]) and colic pain without calculi. The most frequent presentation is asymptomatic crystalluria, but all of them are rare in pediatric patients.
A 10-year-old HIVþ male, treated with indinavir, was admitted for severe left groin pain with hematuria and left groin tenderness on examination. Urine revealed sterile pyuria and microhematuria with pH 8. Blood creatinine levels rose transitorily up to 0.9 mg/dl during the acute episode, and the GFR fell to 100 ml/min/1.73 m2. X-ray and ultrasound showed dilatation of the left ureter and renal pelvis and material of high ecogenicity in the distal lumbar ureter, but not lithiasis. Intravenous pyelography showed a non-functioning left kidney. Isotopic studies (DMSA) evidenced a decrease in left renal function: 39.8% vs 60.2% in the right kidney. Conservative treatment was applied, but ultrasound confirmed an increase in the hydroureteronephrosis. A double-J ureteral stent was placed observing the emission
* Corresponding author. Unidad de Urologı´a Infatil, Hospital Infantil La Fe, Avenida de Campanar 21, 46009 Valencia, Spain. Tel.: þ34 96 3330776; fax: þ34 96 1973215. E-mail address: [email protected] (A. Serrano-Durba ´).
1477-5131/$30 ª 2007 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2007.05.008
Uropathy in a HIVþ infant of abundant small sand particles (Fig. 1). Under the microscope, these looked like conglomerates of crystalline structures, optically transparent, polyhedric or rhomboidal morphology that did not show refringence to polarized light. They were accompanied by many polymorphonuclear leukocytes with occasional eosinophils with fibrinous material nets. Following the placement of the stent, pain ceased and the GFR and creatinine values returned to normal. The stent was removed on the 14th day, and a new DMSA confirmed complete functional recovery.
Discussion The incidence of urinary tract obstruction associated with indinavir ranges from 4% to 15% [2,3]. The etiology is due to low solubility in water solutions that coexist with high urinary excretion. This facilitates the formation of birefringent crystals that can end up forming true calculi of indinavir monohydrate as well as stone formations of calcium oxalate [4]. Clinically, this condition can manifest in multiple ways, the most frequent one being asymptomatic crystalluria (20e33% [3]). Nephropathy caused by
513 the intratubular deposit of indinavir crystals has also been reported, although this has not yet been confirmed [3]. Renal function has been shown to be affected by an increase in creatinine levels in 62% [5] of patients with urological complications, but there was a return to initial values after establishment of specific treatment. Renal function impairment has also been described when indinavir is associated with non-steroidal anti-inflammatory drugs or trimethropim-sulphametoxazole [2]. A significantly higher pH has been reported in the urine of those patients that do not present crystalluria, although it usually oscillates between 5 and 6. Pyuria, proteinuria, hematuria and hypocitraturia have also been found [5]. Radiologically [6], plain X-ray is not useful, intravenous pyelography only confirms the diagnosis in 36.3% of cases, and ultrasound only shows obstructive changes that are secondary to lithiasis. CT scans are of no use. Diagnosis is based on the patient’s clinical presentation, and pharmacological etiology should be suspected in any case of child colic pain that is under indinavir treatment. Chromatography and spectrophotometry techniques can be used to detect the presence of crystals of monohydrate of indinavir in urine in order to confirm the diagnosis. The best treatment is the prevention of crystallization. To minimize this risk, water ingestion should be increased in order to achieve diuresis of 150 ml/h or higher during the first 3 h following administration. Sometimes, the use of ESWL or ureteral catheterization (3% of cases [2]) may be necessary. Concomitant administration of non-steroid analgesics or cotrimoxazole should be avoided.
Conclusions Pharmacological etiology of renoureteral colic should be suspected in any child receiving indinavir treatment. Preventive measures against urinary tract obstruction should be prescribed in any child taking indinavir. Treatment should be established quickly and is based on conservative measures. In the event of incessant pain or ureteral obstruction a stent should be placed.
References
Figure 1 Microscopic image of polyhedric contour crystals that are optically empty, and immersed in a net of fibrinous material with frequent polymorphonuclear leukocytes (hematoxylin & eosin, 200).
[1] Gonzalo A. Nephropathy caused by crystal deposits induced by indinavir. Nefrologia 2001;21:337. [2] Hermieu JF, Prevot MH, Ravery V, Moulinier F, Delmas V, Bouvet E, et al. Nephritic colic due to indinavir. Presse Med 1998;27:465e7. [3] Kopp JB, Miller KD, Mican JA, Feuerstein IM, Vaughan E, Baker C, et al. Crystalluria and urinary tract abnormalities associated with indinavir. Ann Intern Med 1997;127:119e25. [4] Bruce RG, Munch LC, Hoven AD, Jerauld RS, Greenburg R, Porter WH, et al. Urolithiasis associated with the protease inhibitor indinavir. Urology 1997;50:513e8. [5] Boubaker K, Sudre P, Bally F, Vogel G, Meuwly JY, Glauser MP, et al. Changes in renal function associated with indinavir. AIDS 1998;12:F249e54. [6] Schwartz BF, Schenkman N, Armenakas NA, Stoller ML. Imaging characteristics of indinavir calculi. J Urol 1999;161:1085e7.