Southeast Asian J Trop Med Public Health

REPEATED SCLEROTHERAPY SUCCESSFULLY TREATS A CHILD WITH IDIOPATHIC CHYLURIA: A CASE REPORT

Narumon Densupsoontorn1, Anirut Pattaragarn1 and Phichaya Sujijantararat2

1Department of Pediatrics, 2Department of , Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

Abstract. We describe a clinical course of idiopathic chyluria in a previously healthy 8-year-old Thai boy, with a 1-year history of cloudy white under- going antibiotic treatment. The patient was investigated for the causes but they all proved negative. Cystoscopy and retrograde pyelography demonstrated a renolymphatic fistula of the right kidney. The patient was refractory to a medium- chain triglyceride-rich diet. Ultimately, sclerotherapy with 1% povidone iodine was employed twice, which resulted in a resolution of the disorder. We emphasize that chyluria, even though a very rare condition of chylous disorders, but ultimately can be initially managed by providing a medium-chain triglyceride-rich diet and is curable by sclerotharapy. Importantly, medium-chain triglyceride-rich diet can be applied to treat other types of chylous disorders. Keywords: child, chyluria, medium-chain triglyceride-rich diet, sclerotherapy

INTRODUCTION reported cases (Stalens et al, 1992; Ganesh et al, 2007; McNeil et al, 2008). Chyluria is a rare condition of chy- lous leakage from lymphatic vessels The etiology of chyluria is categorized into urinary system through abnormal into two groups, which are (i) parasitic communicating tracts. Chyuria is found cause, viz, lymphatic , and (ii) non- in 10% and 34% of patients suffering parasitic cause, viz, congenital anomalies from filariasis in India and China, re- of lymphatic system, trauma, lymphatic spectively (Cui et al, 1990; Tandon et al, obstruction after surgery, tumor, tuberculo- 2004). Its incidence from radiofrequency sis, thoracic aneurysm, mesenteric adenitis, ablation for treatment of renal tumors and granulomatous disease (McNeil et al, is 41% (Kaur et al, 2011). To the best of 2008). Patients with chyluria might present our knowledge, no incidence of chyluria with milky urine, chylous clot, hematochy- in the general population and pediatric luria, dysuria, frequent urination, weight group has been published except for three loss, urinary retention, low back pain, renal colic, edema, or protein-energy malnutri- Correspondence: Narumon Densupsoontorn, tion (Nandy et al, 2004). Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang To date, in the Thai population only an Lang Road, Bangkok Noi, Bangkok 10700, elderly female with nephrotic syndrome Thailand. was reported to have chylous ascites and Tel: +66 (0) 2419 7000 ext 95947; Fax: +66 (0) chyluria, but evidences of lymphatic ob- 2411 3010 struction and lympho-renal fistula could E-mail: [email protected] not be substantiated (Lewsuwan et al,

360 Vol 48 No. 2 March 2017 Sclerotherapy in Idiopathic Chyluria

2006). Herein, clinical mani- festation, investigation to demonstrate lympho-renal connection, management protocol and finally cure of a previously healthy Thai boy with idiopathic chyluria are described.

CASE REPORT

An 8-year-old boy pre- sented to a pediatric ne- phrologist for evaluation of passing cloudy white urine for 1 year. The patient had Fig 1–Gross appearance of cloudy white urine. difficulty in voiding urine particularly in the morning due to white ultra-heat temperature cow’s milk, fruits clots obstructing the urethra. Although and snacks. the patient had been treated for urinary Physical examination revealed afe- tract infection with oral antibiotics three brile, a blood pressure of 112/72 mm Hg, times during one year but with negative weight of 25 kg (at the 50th percentile), urine cultures, the symptoms still per- height of 124 cm (between the 25th and sisted. The results of urinalysis showed 50th percentiles), a visible BCG scar, no positive off and on and the hardening and thickening of the skin, patient still grew well with the normal no pitting edema or swelling of legs, no growth percentiles during the previous abdominal mass, normal urethral opening year. The physician was unaware of other and scrotum, no phimosis, and no super- uncommon conditions. ficial lymphadenopathy. The consulting pediatric nephrologist A complete blood count showed noticed that by drinking large amounts of hemoglobin level of 12.5 g/dl, a white water, the patient’s urine became clearer blood cell count of 7,300/mm3 with 49.2% and the patient could void urine without neutrophils, 38.9% lymphocytes, 8.3% difficulty. The patient had no history of monocytes, 3.3% eosinophils (absolute prolonged fever, burning sensation dur- eosinophils 240 cell/mm3), and a normal ing urination, brownish/reddish urine or platelet count. Blood chemistry revealed unexplained edema of extremities. No blood urea nitrogen level of 8 mg/dl, cre- history of blunt trauma at abdomen or atinine 0.4 mg/dl, cholesterol 158 mg/dl, back, elephantiasis, chronic cough, weight and albumin 3.5 g/dl. loss, joint pain, hair loss or skin lesions Urinalysis showed cloudy white color occurred. The patient had traveled to (Fig 1), specific gravity of 1.025, pH 6.0, Myanmar four years ago. There was no 4+ albumin level, no presence of sugar, family history of tuberculosis, chronic positive occult blood, no nitrite present, cough or kidney diseases. Dietary his- white blood cells of 3-5/high power field tory revealed regular intake of solid food, (HPF), red blood cells of 10-20/HPF with-

Vol 48 No. 2 March 2017 361 Southeast Asian J Trop Med Public Health

A A

B

B

C

Fig 2–Cystoscopy with retrograde pyelography. A) right side showing a lymphatic fistula tract at the right lower calyx (arrows); B) left side showing normal finding. out dysmorphic shape, and no presence of crystals. Urine triglyceride was 29 mg/dl whereas serum triglyceride was 137 mg/dl. A urine culture was negative. Fig 3–Examples of an MCT-rich diet menu. Based on the patient’s remarkable his- A) steamed rice, fried boiled egg white with tamarind sauce, and vegetable soup tory and urine triglyceride level, chyluria with chicken breast; B) fried rice with was diagnosed. The possible causes of egg white and chicken breast, vegetable chyluria were filariasis, abdominal tumor, soup with chicken breast, and papaya; C) or congenital anomaly. steamed rice, fried chicken breast, stirred Microfilaria in the blood was not fried mixed vegetables, and rose apple.

362 Vol 48 No. 2 March 2017 Sclerotherapy in Idiopathic Chyluria found and serologic test for antifilarial quently, urine triglyceride became measur- IgG was negative. Stool examination for able (4 mg/dl) 6 days later. Although the parasites and parasite eggs was negative. MCT-rich diet was re-introduced again, Ultrasonography of the urinary the patient’s urine kept being cloudy and system, intravenous pyelography and urine analysis showed protein at 4+ level computer tomography of abdomen and and triglyceride of 1,356 mg/dl. These re- pelvis disclosed no detectable abnormal sulted from the patient’s poor compliance findings. Radionuclide lymphoscintigra- with the MCT-rich diet. phy was conducted to determine site of With parents’ consent, sclerotherapy chylous leakage by intradermal injection under retrograde pyelography using 10 of Tc-99m dextran in the webs between the ml of 1% povidone iodine solution in- first and second toes of both feet, 1 mCi jected through a ureteric catheter into the per point. Immediate imaging for whole right renal pelvis under fluoroscopy guide body and dynamic imaging for abdomen was performed. The patient continued to were performed. There appeared faint consume the MCT-rich diet for 1 month af- accumulation of radioactivity in an area ter sclerotherapy and then was placed on located at the left lateral and superior to a normal diet. Chyluria was not resolved the , which might indicate completely based on the presence of urine leakage of lymph at the distal part of the protein at 4+ level and urine triglyceride left . of 43 mg/dl at day 51 after sclerotherapy. Cystoscopy demonstrated an efflux of On day 84 a second sclerotherapy with milky urine from the right but clear urine 20 ml of 1% povidone iodine solution from the left ureteric orifice. Retrograde was initiated. No adverse effects were pyelography demonstrated a lymphatic observed and the MCT-rich diet was dis- fistula tract at the right lower calyx (Fig continued a day after sclerotherapy. 2A) but normal left pyelography (Fig 2B). The patient’s progress was followed- Subsequent to a conservative treat- up several times post-sclerotherapy. The ment with a medium-chain triglyceride patient was asymptomatic and urine tests (MCT)-rich diet, urine became clearer showed the presence of neither protein and urine triglyceride and protein were nor triglyceride. Chyluria did not reap- undetectable. Neither clinical symptoms pear at a 4-year follow-up visit. nor signs of essential fatty acid deficiency and fat-soluble vitamin deficiencies were DISCUSSION observed. At 80 days of conservative MCT- rich diet treatment, the patient’s body We report a clinical progress of idio- weight and serum albumin level increased pathic chyluria in a previously healthy to 26.3 kg and 4.1 g/dl, respectively. At Thai boy. The patient was investigated this time the physician team thought that for possible causes but they all came up normal diet should be restored because all negative. The patient was refractory to an clinical symptoms and laboratory results MCT-rich diet. Finally, sclerotherapy with were normal without signs of essential 1% povidone iodine solution was em- fatty acid and fat-soluble vitamin defi- ployed twice and resolved the symptom. ciencies from the avoidance of long-chain Normally, urine does not contain tri- triglyceride in the treatment diet. Conse- glyceride and chyle is characterized by a

Vol 48 No. 2 March 2017 363 Southeast Asian J Trop Med Public Health high content of triglyceride (in a form of diotracers used in lymphoscintigraphy chylomicrons), albumin, globulin, lym- are colloidal (eg, Tc-99m sulfur, or Tc-99m phocytes and certain electrolytes. Point- albumin) and non-colloidal tracers (eg, of-care test to confirm chylous effusion is Tc-99m dextran). Injection techniques conducted by adding a solvent for fat, eg, consist of intradermal and subcutaneous chloroform or ether, into the turbid white injections. The lymphoscintigraphic result urine, which dissolves lipid substances of our patient did not correlate with find- to produce a clear urine solution (Stalens ings from cystoscopy and retrograde py- et al, 1992; Cheng et al, 2006). Two studies elography, which could not be explained reported that patients with chyluria pre- in spite of a dual uptake mechanism of sented with nephrotic-range proteinuria Tc-99m dextran, thus indicating the need in milky white urine (Cheng et al, 2006; of more specific tests to identify the loca- Pakki Venkata et al, 2009). tion of the lymphatic leakage responsible Once chyuria is diagnosed, its cause for chyluria (Yuan et al, 2006). Metabolic has to be investigated. Causes of chyluria status, eg, weight loss, protein and lipid include filariasis, pyuria, tuberculosis, status in patients with chyluria should lipiduria, , and phospha- also be assessed. turia. The tropics and sub-tropics of Treatment modalities consist of con- Asia, Africa, Western Pacific, and parts servative and invasive methods (Stalens of the Caribbean and South America are et al, 1992; Tandon et al, 2004; Sharma et al, the geographic distribution of lymphatic 2008). Conservative treatment consists of filariasis, caused by , an MCT-rich diet, in which a long-chain Brugia malayi and Brugia timori infection triglyceride (LCT)-restriction diet is sub- (CDC, 2013). All investigations of our stituted with MCT oil, purely extracted patient did not demonstrate any evidence from coconut oil. Fatty acids in most of filariasis and hyperoxaluria. In addition dietary triglycerides are long-chain fatty the patient had no history of tuberculosis acids that are incorporated into chylo- contact and symptoms or of previous microns and transported through the abdominal operation and no presence of lymphatic vessels. However, medium- tumors from imaging studies. chain fatty acids are absorbed passively A previous healthy history and and are directly transported through the normal findings from roentgenographic portal vein. Thus, LCT restriction results studies suggested idiopathic or congenital in a decreased production of chyle and, lympho-renal fistula. Lymphatic imaging finally obliteration of lymphatic vessels. to locate the site of communicating fistula In brief, ingredients of an MCT-rich includes contrast lymphangiography and diet consist of rice, rice noodle, egg white, lymphoscintigraphy (WHO, 1992). Lym- chicken breast without skin, MCT oil, phangiography is an accurate invasive green leafy vegetables without seeds, car- test, requiring an experienced physician, rot, non-fat milk, and fruits without seeds and possibly complicating injury to lym- depending on the age of the patients. phatic vessels. On the other hand, lym- Vegetable seed oils, nuts or bean, other phoscintigraphy is a simple, physiologic, protein sources, and their derivatives are less-invasive, and less complicated test, not allowed. Examples of an MCT-rich diet using radionuclide technique to detect menu are steamed rice, fried rice with egg lymphatic obstruction and leakage. Ra- white and chicken breast, fried boiled egg

364 Vol 48 No. 2 March 2017 Sclerotherapy in Idiopathic Chyluria white with tamarind sauce, fried chicken nephrosis, and sepsis (Nandy et al, 2004; breast, stirred fried mixed vegetables, veg- Tandon et al, 2004). In order to avoid such etable soup with chicken breast, and fruits serious adverse effects, povidone iodine (Fig 3). An MCT-rich diet is in principle a was chosen as the sclerosant agent in the specific dietary treatment for chylous leak- present case. There has been no intensive age conditions, such as chylothorax and intervention in asymptomatic cases of chylopericardium (Densupsoontorn et al, congenital fistula between the lymphatic 2005, 2014), chylous ascites (Densupsoon- system and bladder (Stalens et al, 1992). torn et al, 2009), and chyluria. Compliance Results of the treatment modality are with the diet and clinical symptoms and variable depending on severity. Nandy signs of both essential fatty acids (EFA) and et al (2004) reported that 4/50 (8%) patients fat-soluble vitamin deficiencies should be with chyluria responded to conservative monitored during treatment with an MCT- treatment, 40 (80%) to a combination of rich diet. Blood test for triene-to-tetraene 5% povidone iodine solution and 50% ratio should be performed if EFA deficiency dextrose, and 2 (4%) to nephropexy and is indicated. Intravenous lipid emulsion chylolymphatic disconnection. McNeil and fat-soluble vitamins may be supple- et al (2008) described a favorable outcome mented parenterally. If water-miscible of primary tumor resection in a boy with forms of oral vitamin A, D, E, and K are metanephric adenoma-associated chylu- available, they should be recommended. ria. Ganesh et al (2007) reported a success On the other hand, LCT fat-restricted diet in laparoscopic lymphorenal disconnec- is much less palatable than normal diet, tion in a 5-year old boy with symptomatic which may cause a patient’s low compli- chyluria who failed to respond to conser- ance with such special diet in the long term. vative management. Sharma et al (2008) Invasive treatment includes surgery reported that 35/50 patients with chyluria and sclerotherapy. Surgery is indicated if respond well to a single pelvic renal instil- refractory or unresponsive to conservative lation therapy using 5% povidone iodine treatment (Stalens et al, 1992; Ganesh et al, solution with contrast agent, whereas 2007), as severe symptoms endangering 5 patients needed a second instillation. life (severe, acute and continuous chyluria In the present case, 1% povidone iodine resulting in cachexia) or significant weight solution was retrogradely instilled twice loss can occur (Tandon et al, 2004). Lapa- at a 12-week interval with good outcome. roscopic or open operation is aimed to In summary, we report a previously disconnect lymphorenal communication. healthy Thai boy with idiopathic chyluria, Sclerotherapy, a less invasive method than which was likely caused by congenital lym- surgery, involves injecting a drug directly phorenal fistula based on the absence of an into the lymphatic vessels causing irrita- underlying disease. The patient presented tion, scaring, and finally shrinkage (Nandy with cloudy white urine and difficulty in et al, 2004; Tandon et al, 2004; Ganesh et al, urination due to a white proteinaceous 2007). Sclerosing agents include silver ni- clot obstructing the urethra. The diagnosis trate, povidone iodine, sodium iodide/bro- was delayed due to unawareness of this mide, or 50% dextrose. Severe side effects uncommon condition. The patient was of silver nitrate were reported including refractory to an MCT-rich diet without sclerosis of the collecting system, ureteral any complications. Finally, sclerotherapy stricture, anuria, interstitial nephritis, pyo- with 1% povidone iodine was employed

Vol 48 No. 2 March 2017 365 Southeast Asian J Trop Med Public Health twice resulting in a favorable outcome. The radiofrequency ablation of renal tumors. J interesting features of this case to general Vasc Interv Radiol 2011; 22: 924-7. practitioners, especially pediatricians and Lewsuwan S, Kanjanabuch T, Avihingsanon Y, urologists, are high suspicion of this condi- Praditpornsilpa K, Eiam-Ong S. A rare case tion, proper diagnosis and approach, and of chylous ascites and chyluria in an adult appropriate treatment modality. nephrotic syndrome with focal segmental glomerulosclerosis. J Med Assoc Thai 2006; REFERENCES 89 (suppl 2): S253-6. McNeil JC, Corbett ST, Kuruvilla S, Jones EA. Centers for Disease Control and Prevention Metanephric adenoma in a five-year-old (CDC). Lymphatic filariasis. Atlanta: CDC, boy presenting with chyluria: case report 2013. [Cited 2015 Apr 7]. Available from: and review of literature. Urology 2008; 72: http://www.cdc.gov/parasites/lymphat- 545-7. icfilariasis/ Nandy PR, Dwivedi US, Vyas N, Prasad M, Cheng JT, Mohan S, Nasr SH, D’Agati VD. Dutta B, Singh PB. Povidone iodine and Chyluria presenting as milky urine and dextrose solution combination sclerother- nephrotic-range proteinuria. Kidney Int apy in chyluria. Urology 2004; 64: 1107-9. 2006; 70: 1518-22. Pakki Venkata UR, Callum M, Neuman M, Cui ZH, Liu B, Lin XJ, et al. [Epidemiological Smith RN, Trebbin W. Quiz page May survey on patients with advanced filariasis 2009: Lymphaticourinary fistula causing in Shandong Province with bancroftian chyluria and nephrotic-range proteinuria. filariasis basically eliminated]. Zhongguo Am J Kidney Dis 2009; 53: A33-4. Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Sharma G, Chitale V, Karva R, Sharma A, Du- Za Zhi 1990; 8: 245-8. rug AB. Fluoroscopy guided instillation Densupsoontorn N, Jirapinyo P, Aanpreung therapy in chyluria using combination of P, Laohapensang M, Parichatikanond P. povidone iodine with contrast agent. Is a Congenital chylous ascites: the roles of single instillation sufficient?Int Braz J Urol fibrin glue and CD31. Acta Paediatr 2009; 2008; 34: 270-5. 98: 1847-9. Stalens JP, Falk M, Howmann-Giles R, Roy LP. Densupsoontorn N, Jirapinyo P, Tirapongporn “Milky” urine--a child with chyluria. Eur H, et al. Fat-soluble vitamins and plasma J Pediatr 1992; 151: 61-2. and erythrocyte membrane fatty acids in Tandon V, Singh H, Dwivedi US, Mahmood M, chylothorax pediatric patients receiving a Singh PB. Filarial chyluria: long-term ex- medium-chain triglyceride-rich diet. J Clin perience of a university hospital in India. Biochem Nutr 2014; 55: 174-7. Int J Urol 2004; 11: 193-8. Densupsoontorn NS, Jirapinyo P, Wongarn World Health Organization (WHO). Lymphatic R, et al. Management of chylothorax and filariasis: the disease and its control: fifth chylopericardium in pediatric patients: report of the WHO Expert Committee on experiences at Siriraj Hospital, Bangkok. Filariasis. Geneva: WHO, 1992; 821: 14-5. Asia Pac J Clin Nutr 2005; 14: 182-7. [Cited 2015 Apr 7]. Available from: http:// Ganesh KS, Rao S, D’Cruz AJ. Successful apps.who.int/iris/handle/10665/39309 laparoscopic management of unilateral Yuan Z, Chen L, Luo Q, Zhu J, Lu H, Zhu R. The chyluria in a 5 year old. J Pediatr Urol 2007; role of radionuclide lymphoscintigraphy 3: 63-5. in extremity lymphedema. Ann Nucl Med Kaur H, Matin SF, Javadi S, et al. Chyluria after 2006; 20: 341-4.

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