The Efficacy of Medical Prophylaxis in Children with Calcium Oxalate Urolithiasis After Percutaneous Nephrolithotomy

Abstract

Objective:

To evaluate whether medical prophylaxis decreases calcium oxalate stone recurrences in children after percutaneous nephrolithotomy (PNL) or not. To our knowledge this is the first study that evaluates this topic in children after PNL.

Patients and Methods:

We researched analysis of 42 children with calcium oxalate stone disease. They were divided into two groups. Twenty-two children who had a follow-up with medical prophylaxis after PNL were included in group I; 20 children who did not have medical prophylaxis were included in group II. They were all stone free and they were evaluated with 24-hour urine analysis and blood samples, abdominal X-ray, and ultrasonography. The average follow-up was 25.9 (12–42) months for group I and 24.6 (14–40) months for group II.

Results:

Age, gender, follow-up time, and 24-hour urine samples were similar between groups (p>0.05). New stone formation was detected in two (9.1%) and seven (35%) patients in group I and II, respectively. New stone formation seemed to be higher in group II, but because of the less number of patients, this difference was not statistically significant (p=0.062). The number of patients with recurrence was statistically higher in group II (p=0.032). Stone formation rate (SFR) was calculated as 0.034 and 0.2 per patient per year for group I and II, respectively. This difference of SFR between groups was statistically significant (p=0.028).

Conclusion:

Medical prophylaxis of children after PNL can reduce new stone formation and SFR. Although it was not statistically significant because of low patient numbers, higher recurrence rate was detected in patients who did not have medical prophylaxis.

Introduction

P ercutaneous nephrolithotomy (pnl) is an effective treatment procedure for especially large and complex renal calculi to make patients stone free. But, it is not sufficient for the continuation of this situation because underlying metabolic abnormalities remain. So, increased recurrence rate of urolithiasis is expected if there is any metabolic abnormality.

With this study, we aimed to determine whether medical therapy really decreases the relapse of urinary system calcium oxalate stone disease or not. To our knowledge, this is the first study that evaluates the impact of medical prophylaxis on calcium stone formation in children after PNL.

Patients and Methods

We performed a retrospective analysis of 42 children with calcium oxalate stone disease. They were performed PNL and underwent a metabolic evaluation between January 2008 and January 2012 at the Urology Department of Kecioren Training and Research Hospital.

Patients who had anatomic predisposing factors such as horseshoe kidney, ectopic kidney, ureteropelvic junction obstruction, rotation anomaly, and fusion anomaly were excluded. Patients with glomerular and tubular renal disease, chronic renal failure, and systemic immunological disease were also excluded. Stone disease was not associated with endocrinological or gastrointestinal disorders in all patients and we did not detect primary hyperparathyroidism.

Patients who underwent PNL and detected as stone free were included. They all had calcium oxalate stone formation. They were divided into two groups. Twenty-two children who had a follow-up with medical prophylaxis after PNL were included in group I; 20 children who did not have medical prophylaxis were included in group II. All of the patients were followed up with 3-month intervals for the first 6 months and 6-month intervals thereafter. They were assessed for stone recurrence and metabolic profile. They were asked about stone events like renal colic and spontaneous stone passage. New detection of stone or spontaneous passage of nonpreexisting stone was described as stone recurrence. In their follow-up, they were evaluated with abdominal X-ray and ultrasonography; intravenous urography or computed tomography was used if necessary. Stone formation rate (SFR) after PNL was calculated for each patient and each group.

Stones that were removed with surgery were analyzed by the X-ray diffraction technique using Philips PW 3710/1830 analyzer with Cu X-ray tube. In this study, all stone analysis results of patients were calcium oxalate.

The first spot urine sample in the morning was analyzed for detecting the infection, culture, density, and urine pH. Blood samples were analyzed for glucose, urea, creatinine, calcium, phosphorus, uric acid, magnesium, sodium, potassium, chlorine, and parathyroid hormone if necessary. Twenty-four hour urine samples were analyzed for calcium, uric acid, creatinine, oxalate, and citrate; volume was also measured. These analysis and imaging techniques were done before treatment and at each follow-up visit.

All patients in group I were treated with potassium citrate. This drug was given at a 1 mEq/kg daily dose as a Urocit-K wax matrix tablet with 5 mEq citrate per tablet. Patients in group II were not given any medical treatment. Patients in both groups were informed about the foods that included oxalates and they were advised to avoid these foods. They were asked to take fluids to achieve a minimum urine output of 25 mL/kg/day. Red meat protein was not restricted because the patients were children in the age of growth.

For the analysis of data, Statistical Program for Social Sciences 15.0 packet program was used. As a result of the normality test of data, Mann–Whitney U test was applied for binary groups when researching the difference between groups. Chi-square analysis was used as a dependency test. When researching the difference between groups, the significance degree was 0.05 and it's indicated that if p<0.05 there is a significant difference between groups, and if p>0.05 there is no significant difference.

Results

Boy/girl ratio was 17/5 and 12/8 in group I and II, respectively. There was no statistically significant difference for gender between the groups (p=0.381) (Table 1). Mean patient age was 7.9 (3–16) years and 7.5 (4–16) years for group I and II, respectively (Table 2). There was no statistically significant difference between group I and II (p=0.583). A total of four (18.2%) children in group I and five (25%) children in group II had a history of recurrent urolithiasis. (Table 1) While 41 patients had unilateral kidney calculus, only one patient had bilateral calculus. That patient underwent bilateral PNL simultaneously.

Table 1.

Distrubution of Gender, History of Recurrence, and Recurrence in Follow-up

	Group I		Group II		Total		Chi-square analysis
	n	%	n	%	N	%	Chi-square	p
Gender
Boy	17	77.3	12	60.0	29	69.0
Girl	5	22.7	8	40.0	13	31.0
Total	22	100.0	20	100.0	42	100.0	0.765	0.381
History of recurrence
Primary	18	81.8	15	75.0	33	78.6
Secondary	4	18.2	5	25.0	9	21.4
Total	22	100.0	20	100.0	42	100.0	Fisher's exact	0.714
Recurrence in follow-up
Absence of recurrence	20	90.9	13	65.0	33	78.6
Existence of recurrence	2	9.1	7	35.0	9	21.4
Total	22	100.0	20	100.0	42	100.0	Fisher's exact	0.062

Table 2.

Distrubution of Age, Follow-up Time, Number of Recurrence, and Stone Recurrence Rate

								Mann–Whitney U
	Groups	n	Mean	Median	Minimum	Maximum	SD	Mean rank	U	p
Age (year)	Group I	22	7.9	7.0	3.0	16.0	3.9	22.5	198.5	0.583
	Group II	20	7.5	6.0	4.0	16.0	4.0	20.4
Follow-up time (month)	Group I	22	25.9	27.0	12.0	42.0	9.8	22.4	200	0.614
	Group II	20	24.6	22.5	14.0	40.0	6.8	20.5
Number of recurrence	Group I	22	0.1	0.0	0.0	1.0	0.3	18.8	161	0.037
	Group II	20	0.5	0.0	0.0	2.0	0.3	24.5
SFR (per patient per year)	Group I	22	0.034	0.0	0.0	0.5	0.1	18.7	157.5	0.028
	Group II	20	0.2	0.0	0.0	1.0	0.3	24.6

SFR, stone formation rate

When the urine parameters in 24 hours were analyzed in their first visit after PNL, hypocitraturia was the most frequent anomaly in both groups. In group I, hypocitraturia was detected in 54.5%. Hypercalciuria followed it at 50%. The rate was defined as hyperuricuria 22.7%, hyperoxaluria 13.6%, and low urine volume 31.8%. In group II, hypocitraturia was detected in 55%. The rate was defined as hypercalciuria 35%, hyperuricuria 20%, hyperoxaluria 5%, and low urine volume 20%. The difference of these parameters between two groups was not statistically significant (p>0.05) (Table 3). Four (18.2%) of 22 patients in group I and 6 (30%) of 20 patients in group II did not have any disturbance in their metabolic evaluation. Of 20 patients in group II, 5 patients had recurrence history before they were offered medical prophylaxis but they didn't want to use it because of gastric complaints or its taste.

Table 3.

Distrubution of 24-Hour Urine Analysis Results

		Group I		Group II		Total		Chi-square analysis
24-Hour urine analysis (normal range)		n	%	n	%	n	%	Chi-square	p
Citrate (>320 mg/day)	Normal	10	45.5	9	45	19	45.2
	Low	12	54.5	11	55	23	54.8
	Total	22	100.0	20	100.0	42	100.0	0	1
Calcium (<4 mg/kg/day)	Normal	11	50.0	13	65.0	24	57.1
	High	11	50.0	7	35.0	18	42.9
	Total	22	100.0	20	100.0	42	100.0	0.447	0.504
Oxalate (<38/mg/day)	Normal	19	86.4	19	95.0	38	90.5
	High	3	13.6	1	5.0	4	9.5
	Total	22	100.0	20	100.0	42	100.0	Fisher's exact	0.608
Uric Acid (<10 mg/kg/day)	Normal	17	77.3	16	80.0	33	78.6
	High	5	22.7	4	20.0	9	21.4
	Total	22	100.0	20	100.0	42	100.0	Fisher's exact	1
Volume (>25 mL/kg/day)	Normal	15	68.2	16	80.0	31	73.8
	Low	7	31.8	4	20.0	11	26.2
	Total	22	100.0	20	100.0	42	100.0	0.269	0.491

The average follow-up was 25.9 (12–42) months for group I, 24.6 (14–40) months for group II. During the follow-up, recurrence of urolithiasis was detected in two (9.1%) patients in group I. They had only one recurrence history in their follow-up and the SFR was calculated as 0.034 per patient per year for this group. In group II, recurrence of urolithiasis was detected in seven (35%) patients. Two of them had recurrence twice while others had once. The SFR was 0.2 per patient per year for group II. The difference of SFR between groups was statistically significant (p=0.028) (Table 2).

Discussion

PNL is an effective procedure even for children.^1

–5 But this procedure is not sufficient for the continuation of the stone-free situation, because the underlying metabolic disorders remain. When the expectation of long life span is taken into consideration for children, it is of utmost importance to discover the underlying metabolic disorders and to give medical prophylaxis to prevent relapse.

In a study published by Soygür et al, adult patients with calcium oxalate stone were assessed after shockwave lithotripsy (SWL) with 12 months follow-up. They revealed that patients who were stone free and had medical treatment were not detected with stone recurrence, while the recurrence rate was 28.5% in untreated patients.⁶ Sarica et al⁷ published a similar study on children. They evaluated 96 children who had SWL treatment. Fifty-two of them were given oral potassium citrate 1 mEq/kg daily and others were not. Follow-up range was 24.4 (12–36.6) months. Stone-free children receiving potassium citrate had significant less stone formation compared with the group undergoing no specific therapy (7.6% and 34.6%, respectively).⁷ Another article also investigated the efficacy of medical treatment after SWL in adults and they found similar results.⁸

Kang et al⁹ evaluated adult patients with urinary system stone disease after PNL. They presented the follow-up results of 70 adult patients after PNL. Their follow-up length was at least 1 year. Forty-nine patients of all had medical treatment after PNL, while others did not. They demonstrated that medical therapy after PNL reduces stone formation and recurrence rate in adult patients with or without residual stone fragments.⁹ In another study, regular medical therapy for 24–42 months was given to 64 of 313 patients with urolithiasis. The stone recurrence rate in the group that was given regular medical therapy was 7.8%. On the other hand, stone recurrence rate in the group that was not given any medical therapy was 46.2%. They demonstrated that medical prophylaxis was useful for the prevention of stone recurrence.¹⁰

There are more articles that described the efficacy of medical treatment in child and adult patients with urolithiasis.^11,12

In this article, we evaluated whether medical prophylaxis decreases the calcium oxalate stone recurrences or not. To our knowledge this is the first study that evaluated this topic in children after PNL. Average follow-up in our series was 25.9 (12–42) months for group I, which had medical treatment and 24.6 (14–40) months for group II, which did not have any medication. Follow-up length was at least 1 year because the risk for stone recurrence is higher within first year after the initial attack.¹³ During the follow-up period, new stone formation was detected in two (9.1%) and seven (35%) patients in group I and II, respectively. New stone formation seemed to be high in group II, but because of the less number of patients, this difference was not statistically significant (p=0.062). In group I, recurrence was detected in two patients and the number of recurrence was one for both patients. In group II, recurrence was detected in seven patients and the number of recurrence was one for five patients and two for two patients. The number of recurrence was statistically higher in group II (p=0.032). SFR was calculated as 0.034 and 0.2 per patient per year for group I and II, respectively. This difference for SFR between groups was statistically significant (p=0.028).

Conclusion

The stone analysis and metabolic evaluation is an important entity for pediatric patients with urolithiasis. So we can decide how to manage the treatment of this illness. In our series, we demonstrated that medical prophylaxis of children after PNL can reduce the number of new stone formation and SFR. Although it was not statistically significant because of low patient numbers, higher recurrence rate was detected in patients who did not have medical prophylaxis.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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