The association of idiopathic hypercalciuria and asymptomatic gross hematuria in children

doi:10.1016/S0022-3476(81)80390-3

The Journal of Pediatrics

Volume 99, Issue 5, November 1981, Pages 716-719

https://doi.org/10.1016/S0022-3476(81)80390-3 Get rights and content

Seven children with asymptomatic gross hematuria are described. Six had recurrent hematuria; one had a single episode. Occasional global glomerulosclerosis and/or mesangial electron dense deposits were present in the three patients in whom renal bipsy was performed; the changes were felt to be insufficient to account for the hematuria. None of the patients had urolithiasis or any significant urinary tract abnormality. One was an adopted child; a family history of urolithiasis was obtained in the other six. Idiopathic hypercalciuria was documented in six patients; the seventh subsequently passed a calcium oxalate calculus. One patient is 10 weeks of age at the time of this submission. Of the remainder, three patients received no specific therapy; renal calculi developed six months, six years, and eight years later. Three patients were treated with a thiazide diuretic soon after onset of hematuria and confirmation of idiopathic hypercalciuria; there was complete cessation of hematuria within five days with no recurrence as long as therapy was continued. We suggest that measurement of urinary calcium excretion as part of the initial evaluation of a child with gross hematuria may, in some cases, obviate invasive investigations and allow for effective therapy.

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Cited by (67)

Nephrolithiasis and Nephrocalcinosis From Topiramate Therapy in Children With Epilepsy
2018, Kidney International Reports
Citation Excerpt :
There is an inverse relationship between a child’s age and the UCa/Cr ratio: a child younger than 1 year has a mean UCa/Cr level of <0.8 mg/mg, whereas a child older than 5 years can be expected to have an “adult” value of <0.21 mg/mg.23,24 However, children with a UCa/Cr ratio >0.21 are at risk for developing gross hematuria, dysuria, urinary urgency, urinary tract infections, and nephrolithiasis.25–29 Hypercalciuria is an important predisposing factor in the development of renal calcium deposition; thus, younger children may be at higher risk for the adverse renal side effects of topiramate.
Adults treated with topiramate may develop nephrolithiasis, but its frequency in children on topiramate is unknown. Topiramate inhibits renal carbonic anhydrase, which can lead to renal tubular acidosis and hypercalciuria. We studied 40 consecutive children who initiated topiramate therapy for seizures between January 1997 and February 2003, followed for a mean of 36 months.
Serum electrolytes, urinary calcium/creatinine ratios, and renal ultrasonography were performed before topiramate and every 6 months thereafter.
Four children developed nephrolithiasis and/or nephrocalcinosis, which resolved on discontinuation of topiramate. In 40 patients, the mean urinary calcium/creatinine ratio increased over time (P < 0.001). The mean serum bicarbonate in 40 patients decreased over time (P < 0.01). Twenty-three children had urinary calcium/creatinine ratios before topiramate. Nine children with baseline hypercalciuria (defined as urinary calcium/creatinine >0.21) were compared with the 14 children with baseline normal urinary calcium excretion. A greater increase in urinary calcium/creatinine ratios occurred in hypercalciuric children (P < 0.001) and a greater decrease in serum bicarbonate levels occurred in the hypercalciuric children (P < 0.05) compared with children with baseline normal calcium excretion. Greater urinary calcium excretion was associated with increasing doses of topiramate (P = 0.039).
Our study shows that long-term therapy with topiramate in children is associated with persistent hypercalciuria and metabolic acidosis, which can lead to nephrocalcinosis and/or nephrolithiasis. All children initiating topiramate therapy should have baseline and follow-up urinary calcium/creatinine studies, serum electrolytes, and periodic renal ultrasonography, if the urinary calcium/creatinine ratio increases to a level above normal for age.
Why we need a higher suspicion index of urolithiasis in children
2017, Journal of Pediatric Urology
Citation Excerpt :
When the calculus is identified by imaging or found in the urine, the diagnosis is certain and the management is generally well established [8]. In recent decades, however, evidence from various parts of world has increased that children with symptoms of urolithiasis and urinary solute excretion abnormalities leading to stone formation did not show identifiable stones [9–21]. This covers a large group of children presenting with symptoms rather common in the general population such as abdominal pain, hematuria, and dysuria, which are often faced by general practitioners and pediatricians.
Most children with symptoms of urolithiasis and urinary solute excretion abnormalities leading to stone formation have no calculi revealed by ultrasound or X-ray plain film (“occult urolithiasis”). This covers a large group of children presenting with common symptoms such as abdominal pain, hematuria, and dysuria, often faced by general practitioners and pediatricians. However, half or more of children with urolithiasis could present with abdominal/flank pain without specific urinary symptoms.
We review the current evidence about prevalence, clinical presentation, and radiological detection of overt and “occult” urolithiasis in children, aiming to give readers the instruments to suspect and diagnose urolithiasis while avoiding cost-ineffective and undue diagnostic procedures.
It is important to investigate for urolithiasis first by ultrasound and, in specific cases, by urinary metabolic and different imaging studies in the following groups: 1) in children with non-glomerular hematuria or/and dysuria not presenting inflammation of external genitalia; 2) in children with acute/sub-acute or infrequent recurrent abdominal pain and family history of urolithiasis in first or second degree relatives or being at higher risk of developing stones although hematuria and dysuria are lacking; 3) in children under 8 years old, even though pain is central or diffuse to the whole abdomen; and 4) in children presenting risk factors or conditions predisposing to urolithiasis. Finally, it seems reasonable to repeat ultrasound 1–2 years later also in children with “occult” urolithiasis and high risk of developing stones to detect any (re-)appearance of calculi.
Intermittent massive haematuria as the clinical manifestation of renal hypercalciuria - A case report
2009, Pediatria Polska
Okresowo występujący makroskopowy krwiomocz jest objawem o małej swoistości i często przysparza dużych trudności diagnostycznych.
W pracy przedstawiamy przebieg diagnostyki i leczenia 7-letniego chłopca przyjętego do Kliniki Pediatrii z powodu okresowo występującego masywnego krwiomoczu.
W okresie 2 miesięcy poprzedzających hospitalizację u chłopca kilkakrotnie obserwowano incydenty krwiomoczu, a w badaniach moczu stwierdzano krwinkomocz bez białkomoczu. Na podstawie przeprowadzonej diagnostyki, po wykluczeniu wielu innych przyczyn, u chłopca rozpoznano hiperkalciurię nerkową. Włączono leczenie hydrochlorotiazydem i tlenkiem magnezu, uzyskując normalizację hiperkalciurii oraz ustąpienie incydentów krwinkomoczu i normalizację w zakresie badania osadu moczu.
Hiperkalciuria powinna być uwzględniania w diagnostyce różnicowej okresowego krwiomoczu. Ze względu na nieswoisty charakter analizowanego objawu i jego możliwe powiązania z chorobami o poważnym rokowaniu, pomimo ustalenia rozpoznania konieczna jest staranna dalsza obserwacja naszego pacjenta.
Intermittent massive haematuria is a non-specific symptom and it may be difficult to establish its reason.
We describe the medical history of 7 y. old boy, who was admitted to Pediatric Clinic due to intermittent massive haematuria.
Several incidents of massive haematuria were observed in the patient within two months before admission. Microscopic haematuria with no proteinuria was also confirmed in urinalysis. After excluding many other reasons of haematuria the renal hypercalciuria was finally diagnosed. Treatment with hydrochlorothiazide and magnesium oxide was introduced, and normalization of hypercalciuria was reached. During therapy no incidents of haematuria were observed and most of urinalysis were in normal limits.
Hypercalciuria should be considered as one of possible reasons for intermittent massive haematuria. Our patient, although diagnosed, needs long-lasting thorough follow-up because of non-specific character of analysed symptom and its possible relations to many disorders with very serious outcome.
Study of renal morphology and function in children with nocturnal enuresis. Relationship with sensitivity or resistance to desmopressin
2005, Anales de Pediatria
En los últimos años, se ha descrito que, con frecuencia, los niños con enuresis nocturna presentan hipercalciuria. Así mismo, se acaba de comunicar que los niños con enuresis nocturna resistente a desmopresina tienen una capacidad de concentración renal superior a la de aquellos pacientes con enuresis sensible a ese fármaco.
Estudiar la función renal y la eliminación urinaria de calcio y registrar los antecedentes familiares de enuresis y de litiasis en un grupo de niños enuréticos respondedores y resistentes a desmopresina controlados en nuestro hospital.
Cohorte de 60 pacientes, 42 varones y 18 mujeres, que fueron remitidos al hospital por padecer enuresis nocturna.
Se detectó hipercalciuria en 26 niños (43,3 %) e hipocitraturia en ocho (13,3 %). La frecuencia de hipercalciuria fue superior en los pacientes resistentes con respecto a los sensibles a desmopresina, sin diferencias estadísticamente significativas. En 11 niños se detectaron anomalies morfológicas ecográficas renales. No se comprobaron diferencias en el manejo renal del agua al distribuir a los pacientes según el grado de sensibilidad a la desmopresina.
En nuestra serie se demuestra la elevada frecuencia de hipercalciuria en niños con enuresis nocturna. No observamos diferencias en la osmolalidad urinaria maxima entre los niños sensibles y los resistentes a la desmopresina.
In the last few years, there have been reports that children with nocturnal enuresis frequently have hypercalciuria.Likewise, children with desmopressin-resistant enuresis have recently been reported to have a higher renal concentration capacity than patients with desmopressinsensitive enuresis.
To study renal function and urinary calcium excretion and to register familial history of enuresis and urolithiasis in a group of children with enuresis, whether responders or nonresponders to desmopressin, followed-up in our hospital.
A cohort of 60 patients (42 boys and 18 girls) who were referred to the hospital because of nocturnal enuresis.
Hypercalciuria was detected in 26 children (43.3 %) and hypocitraturia in eight (13.3 %). The frequency of hyper-calciuria was higher in desmopressin-resistant patients than in desmopressin-sensitive patients, but this difference was not statistically significant. Sonographic renal morphological anomalies were detected in 11 children (18.3 %). No differences in renal handling of water were detected when the patients were distributed according to the grade of sensitivity to desmopressin.
In our cohort we found a high frequency of hypercalciuria in children with nocturnal enuresis. No differences were observed in maximal urinary osmolality among desmopressin-resistant and desmopressin-sensitive children.
Evaluation of hematuria in children
2004, Urologic Clinics of North America
Association of thin basement membrane nephropathy with hypercalciuria, hyperuricosuria and nephrolithiasis
1998, Kidney International
Association of thin basement membrane nephropathy with hypercalciuria, hyperuricosuria and nephrolithiasis.
Familial persistent microhematuria with normal renal function is the most common presentation of thin basement membrane nephropathy (TBMN). Gross hematuria episodes and loin pain attacks are other manifestations of the disease. On the other hand, it has been shown that hypercalciuria (HC) and hyperuricosuria (HU) can produce both gross or microscopic non-glomerular hematuria, in addition to their role in renal stone formation.
We studied the prevalence of HC, HU and nephrolithiasis in a group of 27 biopsy-proven TBMN as well as in 19 non-biopsied first-degree relatives with persistent microhematuria and 25 first-degree relatives without microhematuria. A group of 27 patients with IgA nephropathy (IgAN) and persistent microhematuria, and another group of 20 healthy subjects without known renal diseases were selected as control groups.
Ten (37%) patients with TBMN and 8 (42%) relatives with microhematuria showed HC and/or HU at presentation; relatives without microhematuria, IgAN patients and normal controls showed a significantly lower prevalence of HC and HU. The prevalence of previous nephrolithiasis among TBMN patients (25%) was significantly higher than in IgAN patients (3%; P < 0.05). Family history of nephrolithiasis was recorded in 14 (51%) of the 27 TBMN families, in contrast with 2 of 27 (7%) with IgAN and 1 of 20 (5%) in normal controls (P < 0.05). The prevalence of nephrolithiasis, gross hematuria bouts and loin pain episodes among TBMN patients and microhematuric relatives showing HC and/or HU at presentation (44%, 44% and 27%, respectively) were significantly higher than those of TBMN patients and microhematuric relatives with normal calcium and uric acid urinary excretions (10%, 7% and 3%, respectively; P < 0.05). At the end of follow-up (8.8 ± 4.1 years in TBMN patients and 9.1 ± 4.2 years in relatives with microhematuria), all the cases maintained normal renal function.
We found a high prevalence of HC, HU, and nephrolithiasis among TBMN patients and relatives with microhematuria. Our study also shows a significant relationship between the presence of HC and/or HU and the prevalence of nephrolithiasis, gross hematuria bouts and loin pain episodes.

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^†

Supported in part by the Pediatric NephrologyFoundation, Incorporated, Houston, Texas.

Presented in part at APS-SPR, San Francisco, California, April 28, 1981.

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Original articleThe association of idiopathic hypercalciuria and asymptomatic gross hematuria in children†

J Pediatr

J Pediatr

Metabolism

Metabolism

Benign recurrent hematuria

Am J Dis Child

Recurrent hematuria in 17 children

Br Med J

Symptomless hematuria in childhood

Br Med J

Urinary excretion of calcium and magnesium in children

Arch Dis Child

Original article
The association of idiopathic hypercalciuria and asymptomatic gross hematuria in children†