Chyluria is endemic in South-east Asia, China, India, Japan, Taiwan and parts of Africa, Australia and South America. W. bancrofti infestation is responsible for >95% of parasitic chyluria in endemic regions.[123456] Over the last 18 years we have managed about 600 cases of chyluria, i.e., on an average 35 cases per year. Chyluria, haematochyluria and passage of chylous clots in urine and dysuria have been the common modes of presentation [Table 1]. Although this disease is not life threatening, 5-10% of our patients have presented with considerable weight loss and weakness secondary to chronic chyluria.
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Table 1: Presentation in last 100 patients
MATERIALS AND METHODS
In any patient presenting with history suggestive of chyluria we rule out others causes of milky white urine like phosphaturia (clears on adding 10% acetic acid), amorphous urates, severe pyuria, lipiduria secondary to fat embolism, pseudochylous urine and caseousuria due to renal tuberculosis; by urine routine microscopy, culture sensitivity and urine AFB. Presence of chyle in urine was confirmed simultaneously by doing simple tests like urine examination for lymphocyturia, ether test and Sudan black test. Chyluria was graded according to mode of presentation; grade I with milky white urine, grade II with whitish clots or episodes of clot retention, and grade III with haematochyluria. After a detailed clinical evaluation all patients were investigated for hemoglobin, total and differential leukocyte counts, serum proteins, creatinine and blood urea nitrogen. Intravenous urography (IVU) was done to exclude other urological diseases like tuberculosis and to confirm functional status of kidneys prior to starting sclerotherapy.
Management protocol was tailored according to severity of chyluria. In patients presenting with occasional history of chyluria, we prescribed dietary modifications like high protein low fat diet, promoting medium chain triglyceride intake along with diethylcarbamazine for 3 weeks [appendix 1]. All other patients who were treated by renal pelvic instillation of sclerosant (RPIS) were assessed by cystoscopy under local anaesthesia after a fatty meal (100 g butter with bread) the night before, to locate the side of the chylous efflux. A 5 F ureteric catheter was passed up to the renal pelvis of the affected side. Only one side was treated at one time in bilateral cases, which had a comparatively dark white efflux. Pelvic volume assessment is done at same time by instilling dye. We don't recommend routine retrograde pyelography to look for chylolymphatic connections as the amount of connections do not correlate with severity of chyluria or response to sclerotherapy.[1]
One percent silver nitrate solution is prepared by dissolving 2 g of silver nitrate powder in 200 ml of water in a bottle wrapped in black paper and was stored in a dark room, and autoclaved for sterilization. Silver nitrate induces an intense aseptic sclerosing obliterative inflammatory reaction in the lymphatic channels leading to immediate relief. The subsequent healing by fibrosis leads to permanent remission.
RESULTS
As far as type of sclerosant is considered, prior to 1999 we were routinely using 1% silver nitrate. Between January 1999 and June 2003, povidone iodine (0.2%) and dextrose (50%) were also used besides silver nitrate (1%). With these three sclerosants we conducted a randomized control trial in which the patients were randomized to one of the three sclerosants, i.e., 1% silver nitrate, 0.2% povidone iodine and 50% dextrose, using a random number table[1]. Keeping the ureteric catheter in situ, sclerosant solution was instilled at 8-h intervals to a total of nine doses. The patients were followed at 6 weeks and thereafter at 3-month intervals by clinical history and urinary chyle examination. Serum creatinine, ultrasonography and/or IVU were used after RPIS on the kidney. The immediate response to treatment was recorded on completing RPIS as the persistence or clearance of chyluria; the former was considered as failed therapy. Relapse of whitish urine after initial clearance of chyluria was recorded as recurrence and the interval between instituting therapy and recurrence was regarded as the disease-free duration. Success was defined as patients who had no relapse of chyluria up to the last follow up. Of 21 patients who received 50% dextrose, 12 (57%) had persistence and eight (38%) recurrence of chyluria at a mean follow up of 5.2 months; thus this arm was discontinued for ethical reasons. Of the remaining 85 patients, 44 were randomized to silver nitrate and 41 to povidone iodine. Patients in both groups were well matched in demographics disease characteristics (Table 2).
Table 2: The patients' characteristics
The mean follow up was 28.4 (3-53) months in the silver nitrate and 23.3 (3-48) months in the povidone group. Forty (91%) of the patients in the silver nitrate and 40 (98%) in the povidone group showed immediate clearance. The chyluria recurred in nine in each group (21 and 22%). Thus, after one course of RPIS 31 patients in each group were deemed a success. The cumulative success rate after two courses of RPIS was 82% (36/44) in the silver nitrate and 83% (34/41) in the povidone group. Five (11%) patients in the silver nitrate group had significant flank pain after each dose of RPIS and required injectable analgesics. Only one (2%) patient in the povidone group had flank pain after RPIS and required injectable analgesics. Follow-up ultrasonography or IVU showed no harmful effects of RPIS on the renal unit in either group.
Since June 2003 we have been using only 0.2% povidone iodine as sclerosant with good results and lesser side effects. Over last 2 years we have managed 60 such patents with recurrence in only three, which responded to second course of sclerotherapy. None of the patients required surgery during this period.
DISCUSSION
Chyluria is due to the passage of chyle into the urine giving it a typical milky appearance. Filariasis is the commonest cause, which is endemic problem in various Indian states. Over the last 18 years we have managed about 600 cases of chyluria. These patients presented with various complaints like passage of white colour urine, haematuria (haematochyluria), passage of chylous clots in urine and dysuria. Treatment was customized according to severity of chyluria. In patients presenting with occasional history of chyluria, we prescribed dietary modifications like high protein low fat diet, promoting medium chain triglyceride intake along with diethylcarbamazine for 3 weeks (appendix 1). Those not responding to above treatment were subjected to RPIS. Before 1999 we routinely used 1% silver nitrate. Between January 1999 and June 2003, povidone iodine (0.2%) and dextrose (50%) were also used besides silver nitrate (1%).
So far the silver nitrate is the most extensively used sclerosant. We observed that procuring and precisely weighing good quality silver nitrate, its water insolubility, susceptibility to light and the need for autoclaving the solution were the main disadvantages in choosing it as a preferred agent, especially for small hospitals and clinics. It was also difficult to maintain an exact concentration of solution as some of the water evaporates in the autoclave. Moreover, the need for freshly prepared solution in each patient sometimes results in an 8-24 h delay in starting therapy. Flank pain, nausea and vomiting were common and hematuria occasionally seen after silver nitrate RPIS. An anaphylactic reaction is a theoretical possibility after its entry into the blood through pyelovenous flow. Spillage at the PUJ or ureter may cause stricture formation as it can cause chemical inflammation. In some cases reports, silver nitrate has been incriminated in renal papillary necrosis, arterial hemorrhage or acute renal failure after pelvicalyceal system cast formation.[3456] One death has also been reported after bilateral instillation of 3% silver nitrate, with the development of acute renal failure and bilateral multiple ureteric strictures.[6] At the same time we would like to emphasize that there has been no such complication in our experience of nearly 500 patients over 16 years of use. It could be due to strict adherence to guidelines and taking utmost precautions, which are as follows:
- Never instill AGNO3 bilaterally at one time;
- Never over distend the renal pelvis;
- Never use more than 1% silver nitrate;
- Never wash renal pelvis with normal saline as it may precipitate silver nitrate, which will form pelvic casts and obstruction;
- All aseptic precautions should be strictly observed.
However, 0.2% povidone iodine is easy to reconstitute, easily available and its quality can easily be ensured. Presently the experience with povidone iodine is little less as compared with silvernitrate but its equivalent results in the present study should pave the way for others to use it as a much safer alternative to silver nitrate. So, we recommend 0.2% povidone iodine as first line sclerotherapy for chyluria.
As far as frequency of sclerosant instillation is considered in an unpublished study we found that 8-h instillation for 3 days to be more economical and less cumbersome regimen as compared to weekly instillation for 6 weeks. Moreover, recurrence rate was higher in patients on weekly regimen as compared to those on 8-h instillation for 3 days [Figure 1]. So we have been following 8-h instillation for 3 days regimen at our institute.
Figure 1: Study comparing weekly with 8 h sclerosant instillation
At our centre we reserve surgery for patients who don't respond to two courses of sclerotherapy. Amongst the various surgical options for chyluria we have done open chylolymphatic disconnection in only four cases, and laparoscopic disconnection in two cases. All cases of open chylolymphatic disconnection were done in silver nitrate sclerotherapy failures and were doing well till last follow up. None of our cases has required lymphovenous anastomosis, auto transplant or nephrectomy till date.
CONCLUSION
Based on our experience, in the management of chyluria we feel that most of the patients respond to dietary management, antifilarial drugs and one or at the most two courses of sclerotherapy. Small number of patients who fail this treatment, chylolymphatic disconnection (open or laparoscopic) is a good surgical option with dependable long-term results.
EDITORIAL COMMENTS
Use of sclerosants has been a popular treatment for controlling symptomatic chyluria. There are no experimental/properly done studies available in the literature about the safety of instillation of silver nitrate. Silver nitrate is not approved for internal use. Clinical experience suggests that dilute concentrations varying from 0.5 - 1% of silver nitrate are probably the safest. Increasing the concentration of silver nitrate, blocking the PUJ or injecting under high pressure/large volume could lead to disastrous consequences. For a disease like chyluria which essentially runs a benign course, loss of even one renal unit or death of a patient could be difficult to justify. Fortunately the use of povidone iodine appears to be safe and should replace silver nitrate injection. We still need to perform multicenter long term studies to document safety and efficacy of this treatment.
REFERENCES
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3. Dash SC, Bhargav Y, Saxena S, Agarwal SK, Tiwari SC, Dinda A. Acute renal failure and renal papillary necrosis following instillation of silver nitrate for treatment of chyluria Nephrol Dial Transplant. 1996;11:1841–2
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6. Mandhani A, Kapoor R, Gupta RK, Rao HS. Can silver nitrate instillation for the treatment of chyluria be fatal? Br J Urol. 1998;82:926–7
