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Saudi Journal of Kidney Diseases and Transplantation
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REVIEW ARTICLE  
Year : 2019  |  Volume : 30  |  Issue : 2  |  Page : 309-314
Chyluria in pregnancy: Etiology, diagnosis, and management perspective


Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India

Click here for correspondence address and email

Date of Submission08-May-2018
Date of Acceptance16-Sep-2018
Date of Web Publication23-Apr-2019
 

   Abstract 


Chyluria is clinically described as passage of milky urine. Chyle is absorbed by intestinal lacteals and is composed of emulsified fats, few proteins, and fibrin in varying proportions. Parasitic chyluria is caused mainly by Wuchereria bancrofti infection. The incidence of chyluria in pregnancy is not uncommon in endemic regions. The literature pertaining tomedical management of chyluria in pregnancy is scant. The antifilarial drugs have potential teratogenic risk and are not recommended in pregnant patients. Hence, there is a management dilemma for managing patients with chyluria during pregnancy. In this review, we have tried to highlight the evidence-based diagnosis and management of chyluria in pregnancy.

How to cite this article:
Purkait B, Garg G, Singh M, Sharma A, Pandey S, Sankhwar SN. Chyluria in pregnancy: Etiology, diagnosis, and management perspective. Saudi J Kidney Dis Transpl 2019;30:309-14

How to cite this URL:
Purkait B, Garg G, Singh M, Sharma A, Pandey S, Sankhwar SN. Chyluria in pregnancy: Etiology, diagnosis, and management perspective. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 May 20];30:309-14. Available from: http://www.sjkdt.org/text.asp?2019/30/2/309/256837



   Introduction Top


Chyluria is clinically described as passage of milky urine. Chyle is absorbed by intestinal lacteals and is composed of emulsified fats, few proteins, and fibrin in varying proportions.[1] It is classified into two groups: parasitic and nonparasitic.[2] Parasitic chyluria is extremely rare in Europe, but endemic in Asia, Africa, and South America due to high prevalence of Wuchereria bancrofti infection.[3] The incidence of chyluria in pregnancy is not uncommon in endemic regions. Urinary evaluations constitute the basic step in the diagnosis and follow-up of patients with chyluria. The initial management of chyluria is conservative medical therapy that includes fat-restricted diet, antifilarial medication, and high fluid intake.[4] The antifilarial drugs have potential teratogenic risk and are not recommended in pregnant patients. The literature pertaining to the medical management of chyluria in pregnancy is scant. Hence, there is a management dilemma for managing patients with chyluria during pregnancy. In this review, we have tried to highlight the evidence-based diagnosis and management of chyluria in pregnancy.


   Search Results Top


We reviewed all the published articles on chyluria in pregnancy in the English language from 1920 to 2016. MEDLINE, Embase, Cochrane Library, and Google Scholar were searched for this purpose. References from the individual paper were also searched for relevant articles and information. These articles were reviewed and analyzed in detail to assess the following parameters: incidence and prevalence, etiology, pathogenesis, clinical presentation, diagnosis, conservative therapy, endoscopic sclerotherapy, and surgical therapy.

Chyluria and pregnancy, chyluria in pregnancy, chyluria, filariasis in pregnancy, antifilarial drugs in pregnancy, and instillation therapy in pregnancy were the keywords used in the search.


   Incidence and Prevalence Top


Chyluria is a chronic manifestation of lymphatic filariasis. Lymphatic filariasis is a parasitic disease transmitted by mosquito affecting around 120 million people in 80 tropical and subtropical countries.[5] Up to 2% of chronic filariasis patients developed chyluria.[2] About 30% of chyluria patients reside in India (23 million).[6] Chyluria is a disease affecting people of lower socioeconomic status and usually involves the rural population. However, chyluria is less frequent in female population. Ray and Rao described a 1:9 ratio of female:male population affected with chyluria.[7] Although the incidence and prevalence of chyluria in pregnancy is not defined in literature yet, it is quite prevalent in the endemic regions.


   Etiology and Pathogenesis Top


Chyluria is divided into two types depending on the etiology: parasitic and nonparasitic.[2] Parasitic chyluria is a late manifestation of lymphatic filariasis that usually occurs in young adults with or without microfilaremia. It is caused mainly by W. bancrofti (>90%), Brugia malayi, and rarely by other nematodes. Nonparasitic chyluria is uncommon, and the causes include congenital lymphourinary fistula, lymphangioma of urinary tract, megalymphatics with urethral/vesical fistula, thoracic duct stenoses, retroperitoneal lymphangiectasis, nephrotic syndrome, traumatic lymph urinary fistula, pregnancy, diabetes, and abscess.[8],[9] Pregnancy is a rare cause of nonparasitic chyluria. Chyluria may either arise de novo in pregnancy or pregnancy might precipitate preexisting chyluria.[10] Even in pregnancy, filarial etiology is the most common cause of chyluria. Chyluria leads to urinary loss of immunoglobulin through chylolymphatic fistula and may be associated with serious immunologic deficiency with loss of IgG and IgA.[1],[2],[3],[5],[10],[11] Thus, chyluria patients are prone for repeated infections. The effect of chyluria or its treatment on outcomes of pregnancy and any adverse effects to mother/fetus are not defined in the literature so far. However, having a benign nature, chyluria is expected not to cause any direct adverse effect on pregnancy outcomes.

Presentation

The clinical presentation of chyluria in pregnancy is not different from nonpregnant individuals. Most common presentation is milky urine; other manifestations may be urinary retention, dysuria, fever, and hematuria.[11] Decreased fetal movement has also been reported in literature but whether chyluria caused the decreased fetal movement or decreased fetal movement helped in making an early diagnosis of chyluria is not clearly reported.[12] Patients usually present with milky urine with or without chylous clots passage depending on the clinical grading of chyluria. The severity of chyluria usually becomes higher as the trimester of pregnancy advances. The severity of chyluria can be graded according to the same prevalent clinical grading system as follows:[2],[4],[13],[14]

Grade I: single episode or ≤1 episode/year, not associated with whitish clots or clot retention,

Grade II: single episode or ≤1 episode/year, associated with the passage of whitish clots or clot retention, and

Grade III: ≥2 episodes/year or hematuria associated with the passage of blood clots or anemia.

Some patients may have a history of chyluria before their pregnancy, and they only become alert if the severity increases after pregnancy. Chyluria mostly presents in the second trimester (74.41%) followed by the third trimester (13.95%) and least in the first (11.62) trimester.[11]

Diagnosis

Chyluria is diagnosed in the usual manner in pregnancy by both clinical and biochemical examination.[15] Urine becomes milky white or may be associated with chylohematuria depending on the grade of chyluria. Biochemical confirmation is achieved with the chyle test and estimation of urinary lipids (triglycerides and cholesterol) and protein levels.[2],[3] Filarial etiology is confirmed using blood immunochromatography test (Binax-Alere, USA) and IgG/ IgM combo rapid test.[16]

Management

The management of chyluria in pregnancy is challenging as the options are limited. The initial medical therapy is not recommended in pregnancy.[17] The anti-filarial drugs, namely D Diethylcarbamazine (DEC), ivermectin, albendazole, and doxycycline have teratogenic potential.[18],[19] None of the drugs are tried in any of the clinical settings in pregnancy for chyluria. The US Federal Drug Administration (FDA) and the World Health Organization (WHO) do not allow the use of any of the drugs in pregnancy.[19] Thus, the first-line drug therapy is not allowed in pregnancy.

Spontaneous resolution

Spontaneous resolution can occur in chyluria. This occurs after pregnancy in the postpartum period. In a case report by Mount and Thong, spontaneous resolution of chyluria occurred after one to two weeks of pregnancy.[20] This patient had lower grade (Grade I) of chyluria; however, higher grades of chyluria may not resolve spontaneously.

Conservative management

The initial therapy of chyluria in pregnancy is conservative therapy which includes high fluid intake, avoidance of fatty and oily food, and intake of high-protein diet.[21] The recommended fat restriction may include 25–50 g/day. Dietary modification in chyluria in nonpregnant patients has been described by Ansari.[21] The impact of restriction of dietary intake in chyluria on fetomaternal outcome has not been studied. The management of chyluria in pregnancy is a challenging task. It is a debilitating disease causing malnutrition. Chyluria patients are usually from poor socioeconomic background and already have poor nutrition. This is a challenging situation since in pregnancy, the mother needs high caloric intake. Invariably, dietary compliance is not maintained properly which leads to high rate of nonresponders and failure of conservative therapy in pregnancy. Conservative therapy has low success and high noncompliance rate; 13% success rate was achieved in one study.[11] However, conservative therapy can be safely applied in all pregnant patients in all trimesters.

Antifilarial drugs

The cornerstone of chyluria management in nonpregnant individuals is antifilarial drug therapy. The most commonly prescribed drugs are DEC and albendazole. Recently, ivermectin and doxycycline are also being used in chyluria as single or combination therapy. The safety and efficacy of these drugs have not been studied yet in pregnant patients. There are some animal studies that show that teratogenicity is not increased with these drugs. Also reported are some community-based studies, which have inadvertently used antifilarial drugs in pregnant mothers either in the first or second trimester. In a community filariasis program, Gyapong et al studied effects on pregnancy outcomes. They used albendazole and ivermectin inadvertently to child-bearing women (50 patients). They found overall that the relative risk for congenital malformations following exposure was 0.82 and concluded that there was no evidence of a higher risk of congenital malformation or abortions in those who are inadvertently exposed to antihelminthic drugs.[22] In a three-year community-based study of ivermectin in onchocerciasis, 203 children born to women inadvertently treated during pregnancy were identified, and there was no significant difference in birth defects between treated and untreated population. The authors concluded that further surveillance is necessary before recommending this medication.[23] The WHO has promoted the use of antihelminthic drugs including albendazole (antifilarial) for reduction of hookworm and improvement of anemia after the first trimester in high endemic areas only (prevalence >20%–30%), but at the same time, they recommended safety trial for longterm efficacy regarding teratogenicity. In a study from Nepal, they administered single dose (400 mg) of albendazole in the third trimester to prevent hookworm infestation.[24] They reported no increase in birth defects. In 2006, the WHO recommended the use of albendazole for soil-transmitted helminthiasis in pregnancy during the second or third trimester.[25] In studies conducted by Torlesse and Elliott et al in which a single dose of albendazole (400 mg) was given in the second trimester to decrease hookworm infection, the authors found no increase in perinatal morbidity or mortality.[26],[27] In a Cochrane review by Salam et al on the effect of administration of antihelminthics for soil-transmitted helminths during pregnancy, the authors concluded that there was insufficient evidence to recommend the use of antihelminthics for pregnant women after the first trimester of pregnancy and also insufficient data to support any adverse effect on the fetus.[28] In a review of 49 cases of inadvertent treatment with albendazole in the first trimester, no abnormal birth outcomes were recorded.[29] In another report on the safety of albendazole use in pregnancy, there were no cases of malformation after inadvertent exposure of 15 patients with albendazole, but the sample size was small in all these studies.[30] Antihelminthics are not widely used during pregnancy because of the lack of adequate information regarding their safety in pregnancy. Other drugs (DEC/ivermectin/doxycycline) have not been tried in any trial like albendazole. None of these studies demonstrated increased rates of congenital anomalies or birth defects. Still, the US-FDA and WHO have not recommended the use of antifilarial drugs in pregnancy.


   Sclerosing Instillation Therapy Top


Some patients in pregnancy may not respond to conservative therapy or sclerosing instillation therapy. In these cases, a second Renal pelvic instillation sclerotherapy or surgical correction is the last option. However, surgery in pregnant patients has its own limitations with high risk to mother and fetus. Considering the debilitating nature of refractory chyluria, patients may choose termination of pregnancy during the first trimester. In a series by Mahmood et al, they had two patients who decided to terminate the pregnancy for refractory chyluria.[11] Both the cases were in the first trimester. Chyluria is a benign disease, and termination seems to be not justified. Instillation therapy has variable success rates ranging between 65% and 80% in the normal population.[4],[13],[31] The only minimally invasive hope of intractable chyluria in pregnancy is endoscopic sclerotherapy. Few studies are there about sclerotherapy in pregnancy.[11] The sclerosing agents used are either povidone-iodine (0.1%–0.2%) or silver nitrate (1%). The schedule and dose are not defined in the literature but seems to be the same as for nonpregnant patients. There is real concern of infectious complications in pregnant patients. The success rate in pregnancy is not different from normal patients. In a study by Mahmood et al, the authors demonstrated that 13/43 cases showed improvement after the first session and 19/43 cases after two sessions of sclerotherapy; three patients did not respond to sclerotherapy and responded after cesarean section (CS).[11] They (Mahmood et al) used 5 mL of 25% dextrose with normal saline with povidone-iodine, nine doses at eight hourly intervals. The other commonly used agents in nonpregnant cases, povidone-iodine and silver nitrate, may also be used since there is no or minimal systemic absorption and hence no risk of teratogenicity. Most of the present literature recommends povidone-iodine rather than silver nitrate with similar efficacy. Silver nitrate has higher complication rate. In an older series by Yamauchi of 56 patients with chyluria, 37 cases were seen in pregnancy. All patients were treated with silver nitrate instillation therapy. Pregnant patients had higher incidence of pyelonephritis.[32] Cystoscopy and instillation should be done under good sterile technique to avoid introduction of infection. Complication from infection may be disastrous in pregnancy. Proper counseling of possible complications should be explained to the mother before undertaking any invasive therapy. The optimum doses and choice of sclerosing agents have not been studied in pregnancy. Efficacy of singledose instillation in chyluria has been studied. However, the minimal doses that clear urine grossly may help decide the optimum doses in pregnant patients with less complications.

Surgery

The role of open/laparoscopic surgery in pregnancy has not been studied till now. Some case reports are published of chylolymphatic disconnection in pregnancy. Surgery in pregnancy has some limitations and possible complications with added complication to the fetus.

Role of drug trial in pregnancy

For ethical reason, trial of drugs in pregnancy is not possible. Unless safe and effective antifilarial drugs come into practice, chyluria in pregnancy may be challenging. Some patients may have treatment deferred till delivery, particularly if they are in advanced pregnancy.


   Conclusions Top


Chyluria in pregnancy is challenging. Conservative medical therapy is the main therapy. Antifilarial drugs are not recommended till date. Refractory chyluria can be treated with instillation therapy or rarely surgery after thorough discussion with patients.


   Recommendation Top


Chyluria in pregnancy is challenging from management perspective. Conservative medical therapy has limited success rate. None of the antifilarial drugs are safe for use in pregnancy. Endoscopic sclerotherapy is recommended for persistent chyluria with its own risk. Data in the management of chyluria have not been studied adequately. Further research in drug trail in pregnancy is needed for better understanding.

Conflict of interests: None declared.



 
   References Top

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Correspondence Address:
Gaurav Garg
Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh
India
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DOI: 10.4103/1319-2442.256837

PMID: 31031366

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