Chronic, Gross Caused by Idiopathic Robert L. Myette, MD, MSc, Amy Acker, MD, FRCPC

An otherwise healthy, 10-year-old boy presented with chronic, gross abstract hematuria. This persisted daily for 5 years despite extensive multidisciplinary workup with renal biopsy and resulted in severe iron deficiency anemia. The extensive workup and requirement for routine follow-up, investigations, and procedures led to significant psychosocial distress for the patient. Initially, it was thought the patient had a nutcracker phenomenon, but on closer inspection of his , an idiopathic, unilateral ureteric stricture was discovered and, after 8 weeks of stenting, resulted in complete resolution of the hematuria. Importantly, the patient’s psychosocial distress resolved after resolution of the hematuria and with the closure that came with a diagnosis.

Hematuria is defined as 5 or more red consideration; however, it is not true 3 blood cells (RBCs) in a sample hematuria. To further aid in diagnosis, Department of , Queen’s University at Kingston per high power field, observed on 3 urine microscopy to look at RBC Health Science Centre, Kingston, Ontario, Canada 4 separate occasions over the course of morphology is required. If they are Drs Acker and Myette conceptualized the case report 1 several weeks. Most often, there is eumorphic, considerations for and contributed to collecting data for the a glomerular or genitourinary tract underlying genitourinary manuscript, drafting the original manuscript, abnormality to accompany the must be entertained. Meatal reviewing the manuscript, and revising the fi hematuria, but in some instances, the can be seen after hypo- or epispadias manuscript; and both authors approved the nal manuscript as submitted and agree to be discolored urine may in fact be repair and can result in eumorphic accountable for all aspects of the work. hemoglobinuria, myoglobinuria, or food microscopic hematuria.3 When DOI: https://doi.org/10.1542/peds.2019-2549 or medication related.1 Hematuria is dysmorphic RBCs are seen, glomerular Accepted for publication Aug 30, 2019 most often recognized incidentally on disease must be considered and 1 screening urine studies. True proteinuria screened for. Address correspondence to Robert L. Myette, MD, MSc, Department of Pediatrics, Queen’s University at hematuria can be separated on the Idiopathic ureteric stricture is an Kingston Health Science Centre, Watkins 3, Kingston, basis of whether it is glomerular or apparently undescribed etiology of ON K7L2V7, Canada. E-mail: robert.myette@ nonglomerular in nature.1,2 queensu.ca chronic, gross hematuria in pediatric Nonglomerular causes can include patients. Ureteric stricture itself is PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, trauma, hypercalciuria, nephrolithiasis, 1098-4275). usually associated with an underlying cystitis, malignancy, and condition,5 with the most common Copyright © 2019 by the American Academy of diatheses. Glomerular causes can be Pediatrics etiology being urolithiasis, followed genetic in nature, including Alport FINANCIAL DISCLOSURE: second by ureteric manipulation and The authors have indicated syndrome and thin basement they have no financial relationships relevant to this previous radiation.5 Most episodes of membrane disease, which oftentimes article to disclose. gross hematuria associated with FUNDING: No external funding. manifest with gross hematuria. ureteric stricture are POTENTIAL CONFLICT OF INTEREST: Postinfectious glomerulonephritis postinstrumentation bleeding.5 The authors have (PIGN), vasculitides, and autoimmune indicated they have no potential conflicts of interest glomerulonephritides, including The patient was 10 years old at the to disclose. immunoglobulin A (IgA) nephropathy time of presentation with hematuria. and lupus nephritis, also present with He had a diagnosis of autism spectrum To cite: Myette RL and Acker A. Chronic, Gross glomerular hematuria.1 Benign disorder but was otherwise healthy Hematuria Caused by Idiopathic Ureteric Stricture. Pediatrics. 2019;144(6):e20192549 urethrorrhagia is an important with no significant past medical history

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 144, number 6, December 2019:e20192549 CASE REPORT and no previous episodes of He underwent cystoscopy, which nutcracker phenomenon once again hematuria. He was given ruled out rhabdomyosarcoma and reported. Autotransplant on the a presumptive diagnosis of PIGN; arteriovenous malformation (AVM). A affected side was discussed, but however, C3 complement was normal. computed tomography scan was before this, full evaluation of the IgA levels were within normal limits. performed and revealed normal ureters was undertaken by direct The antinuclear antibody revealed corticomedullary differentiation, as visualization. This was .5 years after a positive speckled pattern but was was seen previously on the initial discovery of hematuria. low titer, and native DNA antibodies ultrasonography, with the added tested negative. Urine for adenovirus observation of normal parenchymal was performed, with resulted negative as did the urine enhancement without evidence of bilateral retrograde pyelography, and culture. Urinalysis revealed 31 blood, AVM. Almost 2 years after the initial revealed a left ureteric stricture but and microscopy showed erythrocytes presentation with hematuria, a renal normal ureterovesicular junctions packing the field of view. The biopsy was performed. An adequate (UVJs) bilaterally as well as a normal ∼ erythrocytes were not described as sample with 28 glomeruli was bladder. This stricture was noted 2 dysmorphic, and no casts were noted. obtained, and there was no evidence to 3 cm from the UVJ, and the His urine calcium was ,0.25 mmol/L, of sclerosis or segmental or ureteroscope was unable to pass. which, when used to calculate a urine interstitial fibrosis and no tubular There was frank blood noted coming calcium to creatinine ratio, was atrophy. A hematologist ruled out from the left before negligible. He was found to be a bleeding diathesis, and MRI ruled instrumentation. Given this, the normotensive with preserved renal out nutcracker phenomenon. He was stricture was stented. Around the function and had normal renal subsequently referred for a second time of this procedure, the patient ultrasonography. His clinical opinion. Concurrently, the patient was began to experience symptoms of fi examination revealed a well- having an increasingly hard time depression with super cial cutting. nourished, otherwise healthy boy managing his medical condition, and The patient suffered stent colic, which with no organomegaly or evidence of it was having significant negative complicated this matter further; genital trauma. psychosocial effects manifesting as however, the stent remained in situ depressive symptoms. for the planned 8-week duration. Over the next year, the child had After 3 years of gross hematuria with After stent removal, his urine cleared persistent, daily gross hematuria. His every void, he continued to have completely. He was quickly weaned hematuria was always throughout the normal renal function as well as from intravenous iron infusions with full stream, was not worse on normal routine blood panels aside spontaneous normalization of his initiation or termination, and there from anemia. He remained hemoglobin. Unfortunately, by this was no evidence of clots. If he was normotensive. His serial time, the patient was experiencing well hydrated, the color would examinations in clinic did not reveal significant depressive symptoms and occasionally be more red-pink; an etiology for his chronic hematuria. required referral to child and however, for the most part it The second team requested adolescent for ongoing resembled “tomato juice.” Because of an additional renal biopsy, which was supportive care. He was seen this, he developed iron deficiency undertaken and suspicious for IgA 8 months later and again continued to anemia, prompting further workup nephropathy but not confirmatory. have clear urine with no evidence of from a nephrologist. A tentative Concurrently, ruled out macro- or microscopic hematuria and diagnosis of PIGN was investigated, paroxysmal nocturnal had a normal hemoglobin level. He but other considerations included IgA hemoglobinuria. has ongoing follow-up with both his nephropathy, thin membrane disease, urologist and pediatrician. He was Alport syndrome, and foreign body. A computed tomography scan with discharged from the child and The patient did not have a course angiography of the kidneys and adolescent psychiatry team given typical of IgA nephropathy, there was bladder was performed by improvement in his depressive no history of sensorineural hearing interventional . This symptoms after diagnosis and fi loss, and ultrasonography con rmed revealed mild compression of the left resolution of his ureteric stricture. no foreign body. The patient’s renal renal vein as it passed over the function remained normal, but his anterior wall of the abdominal aorta, Hematuria is a relatively common, hemoglobin level continued to drop, suggestive of nutcracker incidental finding in pediatric and he required iron infusions phenomenon. The computed patients and is often associated with because of poor response and poor tomography scan was sent to an an underlying tolerance to high doses (8 mg/kg) of additional center for reinterpretation, or postinfectious cause. When gross daily oral iron supplements. with the finding of presumed in nature, it is commonly associated

Downloaded from www.aappublications.org/news by guest on October 1, 2021 120 MYETTE and ACKER with trauma. Indeed, a recent study of progressive ureteric stricture an etiology is not readily apparent. the etiology of hematuria in 342 requiring surgical management. She Ureteric stricture can cause children revealed that over a 10-year presented with lumbar pain and significant injury with period, 14% were associated with microscopic hematuria, not gross associated morbidity and mortality. trauma, whereas 19% of patients had hematuria.10 She had previous Interestingly, our patient presented benign urethrorrhagia.3 Additionally, hysterectomy and hernia repair and with an uncommon finding in 14% had urinary tract infection. Of a past-treated multiple myeloma. An idiopathic ureteric stricture: isolated the 342 patients, 45 children had etiology for her strictures was never gross hematuria. Given the protracted underlying congenital abnormalities, determined.10 Bhatta Dhar et al7 course and significant psychosocial including vesicoureteral reflux (22 reviewed 2 patients with apparently impacts this diagnostic journey had children), posterior urethral valves idiopathic ureteric stricture, both of on the patient, it is important to (10 boys), and ureteropelvic junction whom were adult patients, 1 with consider ureteric stricture in the obstructions (8 children).3 Some of preexisting hypertension. One of the otherwise healthy patient with the boys enrolled in the study also patients had a single event of gross chronic, gross hematuria when all had proximal repairs hematuria.7 Lastly, Smith et al9 diagnostic modalities point to normal previously, which is a known risk described 4 cases of congenital findings. factor for gross hematuria.3 Five midureteric stricture and reviewed percent of children had urolithiasis. 13 additional cases from the None of the children had ureteric literature. Important to note, none of ABBREVIATIONS the patients were noted to have stricture. Lastly, for 34% of the AVM: arteriovenous malformation hematuria, and almost all cases were patient cohort, there was no known IgA: immunoglobulin A associated with an underlying etiology. The authors comment that PIGN: postinfectious urogenital malformation. because of their inability to perform glomerulonephritis cystoscopy or imaging on all patients, RBC: red blood cell it is possible the cause of gross In another study, a clear etiology for fi UVJ: ureterovesicular junction hematuria in those patients was self- ureteric stricture was identi ed in 24 of 25 patients.5 The most common limited nutcracker phenomenon or 3 cause of ureteral stricture was uretero-vascular malformation. In impacted calculi (60%). Additionally, REFERENCES fact, uretero-vascular malformation, 5 of the patients with impacted including uretero-iliac artery fistula 1. Massengill SF. Hematuria. Pediatr Rev. calculi had iatrogenic injuries during and AVM, represent life-threatening 2008;29(10):342–348 stone removal, which may have led to conditions characterized by 5 2. Diven SC, Travis LB. A practical primary 6 variations in stricture severity. Other significant gross hematuria. care approach to hematuria in etiologies for stricture included Although our patient had significant, children. Pediatr Nephrol. 2000;14(1): previous radiotherapy, , gross, and chronic hematuria, early 65–72 and non–calculus-related iatrogenic imaging studies did not reveal any 3. Greenfield SP, Williot P, Kaplan D. Gross injury.5 evidence of AVM. Additionally, there hematuria in children: a ten-year – were several ultrasonograms The patient described in this case review. Urology. 2007;69(1):166 169 performed that never revealed calculi, report did not have a history of 4. Kincaid-Smith P, Fairley K. The ureteropelvic junction, or UVJ urolithiasis, and each of his investigation of hematuria. Semin abnormalities. Urethrorrhagia was ultrasounds and scans revealed no Nephrol. 2005;25(3):127–135 not observed on cystoscopy. evidence of calculi, , 5. Tran H, Arsovska O, Paterson RF, Chew or hydroureter. He did not have any of BH. Evaluation of risk factors and Ureteric stricture can cause kidney the additional risk factors for ureteral treatment options in patients with fi damage, leading to signi cant stricture mentioned previously. ureteral stricture disease at a single morbidity or mortality. Its presence in Interestingly, once stented, and with institution. Can Urol Assoc J. 2015; – – the literature is limited, but a case no additional instrumentation, there 9(11 12):E921 E924 series of congenital midureteric was complete resolution of the 6. Leone L, Scarcella S, Dell’Atti L, et al. stricture exists as well as several case Uretero-iliac artery fistula: a challenge 5,7–9 hematuria, again suggestive that this reports of varying etiologies. isolated stricture was the cause of diagnosis for a life-threatening What is common among these studies this patient’s chronic, gross condition: monocentric experience and review of the literature. 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Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 144, number 6, December 2019 121 without evidence of malignancy. Urology. 9. Smith BG, Metwalli AR, Leach J, Cheng 10. de Diego Rodríguez E, Hernádez 2004;64(2):377–378 EY, Kropp BP. Congenital midureteral Castrillo A, Rado Velázquez MA, Gómez 8. Ayyat FM, Adams G. Congenital stricture in children diagnosed with Ortega JM. Idiopathic progressive midureteral strictures. Urology. 1985; antenatal hydronephrosis. Urology. bilateral ureteral stenosis [in Spanish]. 26(2):170–172 2004;64(5):1014–1019 Arch Esp Urol. 2007;60(2):201–205

Downloaded from www.aappublications.org/news by guest on October 1, 2021 122 MYETTE and ACKER Chronic, Gross Hematuria Caused by Idiopathic Ureteric Stricture Robert L. Myette and Amy Acker Pediatrics 2019;144; DOI: 10.1542/peds.2019-2549 originally published online November 15, 2019;

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Downloaded from www.aappublications.org/news by guest on October 1, 2021 Chronic, Gross Hematuria Caused by Idiopathic Ureteric Stricture Robert L. Myette and Amy Acker Pediatrics 2019;144; DOI: 10.1542/peds.2019-2549 originally published online November 15, 2019;

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