| Abstract|| |
Chyluria is usually associated with abnormal retrograde or collateral flow of lymph from intestinal lymphatics into lymphatics of the kidney, ureter or bladder. Chyluria has been described in patients with lymphoma, carcinoma, trauma, abscess, tuberculosis, filariasis, pregnancy and stenoses of the thoracic duct. In this case report we describe a patient who presented with chyluria associated with severe hyperlipidemia due to nephrotic syndrome induced by microscopic polyangiitis. Laboratory, histological and radiological examination did not show evidence of filarial infestation, tuberculous infection or malformation of the lymphatic system. Treatment with corticosteroids and cyclophosphamide resulted in improvement of hyperlipidemia and disappearance of chyluria.
Keywords: Chyluria, Hyperlipidemia, Nephrotic syndrome, Vasculitis.
|How to cite this article:|
El-Reshaid KA, Madda JP, Sherif MF. Chyluria Associated with Renal Vasculitis. Saudi J Kidney Dis Transpl 1998;9:152-6
| Introduction|| |
Chyluria is the passage of milky urine due to the leakage of lipid complexes, usually chylomicrons and very low density lipoproteins (VLDL), into the urinary tract  . Under normal conditions, chylomicrons are synthesized in the small intestine to transport dietary triglycerides and cholesterol. Hence, chyluria was invariably associated with abnormal retrograde or collateral flow of lymph from intestinal lymphatics into lymphatics of the kidney, ureter and bladder  . Chyluria has been described in patients with lymphoma carcinoma, trauma, abscess, tuberculosis, pregnancy and stenoses of the thoracic duct  . However filariasis and congenital malformation of the lymphatic systems remained the most common causes of the disorder especially in patients from south east Asia  . In this report we describe a patient who presented with nephrotic syndrome and chyluria secondary to renal vasculitis and did not have evidence of thoracic duct disease.
| Case History|| |
A 44-year old Indonesian woman was admitted to Al-Amiri hospital in Kuwait for evaluation of progressive lower limb edema. The condition started three months prior to admission and was associated with "periods" during which she passed "white and milky" urine. She did not have fever, weight loss, joint disease, skin rash, or abdominal pain. Her past medical history was significant for abdominal hysterectomy for uterine fibroids one year before. The patient had seven children, the youngest of whom was six years old. All her pregnancies ended by spontaneous vaginal delivery and were not associated with toxemia of pregnancy or laboratory evidence of renal disease.
On the present admission, she was afebrile with blood pressure 130/90 mm Hg. She had evident puffiness of both eyelids as well as sacral and lower limbs edema. Lymph nodes were not enlarged and systemic examination did not show any organomegaly.
Laboratory investigations showed normal peripheral leukocytic and eosinophil count (6 x 109 /L - 400/L respectively). Hemoglobin and platelet counts were normal. ESR was elevated at 70 mm/hour. The serum appeared milky and when kept overnight in a refrigerator at 4° C in the upright position, a white layer of cream was evident on the top and the layer beneath was clear. Serum cholesterol was 23 mmol/L and triglycerides 18 mmol/L. Serum creatinine was 121 umol/L and blood urea 8 mmol/L. Serum albumin was 9 g/L and total protein 42 g/L. Serum bilirubin, alanine aminotransferase and alkaline phosphatase were normal.
The urine was white in color and turbid. On microscopic examination it showed excess erythrocytes in the high power field (HPF), 5-8 leukocytes/HPF, and abundant fat globules. The latter were confirmed by Sudan III staining. Urine turbidity persisted after alkalinization of the urine, yet disappeared after addition of ether confirming the presence of chylomicrons. Creatinine clearance was 75 ml/min. and protein excretion was 11 g/day.
Chest X-ray did not show lung infiltrate or calcification. Ultrasound examination of the abdomen showed normal kidneys, liver, spleen and pancreas.
Serological investigations were negative for HbsAg, Anti-HCV antibodies, anti-HCV and anti-dsDNA. Serum complements were normal. Antineutrophil cytoplasmic antibodies (ANCA) were present at a titre of 1:1280 and on enzyme immunoassay showed antimyelo-peroxidase specificity. Nucleopore filtration did not show microfilaria in urine or blood  .
Percutaneous kidney biopsy showed an average of 35 glomeruli at each level, 13 of which were obsolete due to formation of fibrous crescents. The remaining glomeruli showed various stages of both cellular as well as fibrous crescents. The basement membrane was normal and the mesangium did not show cell proliferation or expansion [Figure - 1].
Blood vessels showed marked atherosclerotic changes without fragmentation of elastic lamina. Immunoflourescent stains were negative for immunoglobulin or complement deposition. On examination by electron microscopy, the glomerular and Bowman's basement membrane appeared of normal thickness and did not show unusual deposits [Figure - 2].
CAT scan examination of the chest and abdomen did not show lymphadenopathy or abnormal fluid collections. Selective arterio-graphy of the coeliac and renal arteries disclosed multiple microaneurysms [Figure - 3]. Lymphangiogram did not show any communication between the lymphatic vessels and the urinary tract.
The patient received methylprednisone pulse therapy (Ig IV daily for 3 days) followed by prednisone 1 mg/kg daily for 4 weeks, which were tapered and then maintained for 2-year-period. In addition, she received cyclophosphamide pulse therapy (1 g IV monthly, for 6 successive months, and then every three months for a total period of two years).
Few weeks after initiation of immunosuppressive therapy, edema improved and the urine turbidity disappeared. Three months later, creatinine clearance became normal at 86 ml/min. and protein excretion decreased to 1.1 g/day. At that time, serum cholesterol and triglycerides fell to 11 mmol/L and to 3.5 mmol/L respectively, and urine microscopy did not show evidence of urinary fat globules. Over the last three years, no relapse was encountered.
| Discussion|| |
The patient described in this case report came from an area endemic with filariasis. However, she did not have evidence of active filarial infestation on testing with nucleopore filtration, besides the absence of immune deposits, both on immunofluorescence and electron microscopic examination of the kidney tissue. These results were a cogent argument against a possible role for filarialinduced glomerular disease  .
Moreover, lymphangiographic studies confirmed the absence of lymphatic malformations in the region of the urinary tract, which might have contributed to the development or exacerbation of chyluria  .
Based on the results of the biochemical, histological and radiological investigations, our patient had microscopic polyangiitis according to the Chapel Hill Consensus conference classification of vasculitis  . Though nephrotic syndrome is not a common presentation of this disease, it was described as the initial presentation of different forms of vasculitis  . Furthermore, the existence of different subclasses of crescentic as well as necrotizing glomerulonephritis with chronic mode of onset and less florid disease-course have been reported in three retrospective studies ,, and a recent prospective one  .
To our knowledge, severe hyperlipidemia secondary to nephrotic syndrome and vasculitis, similar to that seen in our patient was never reported. In our patient, the favorable response of chyluria to immunosuppressive treatment indicates a cause and effect phenomenon. On the other hand, the "episodic" passage of milky urine for three months prior to her recent admission might have been a reflection of the episodic nature of poly-arteritis disease, which indicates leakage of lipids during the stage of active vascular damage and remission during fibrosis 
The mechanism of chyluria, in our patient is intriguing. Under normal conditions, chylomicrons are synthesized by the small intestine to transport dietary triglycerides and cholesterol from sites of absorption in the intestinal epithelium to various cells in the body. Subsequently, they are hydrolyzed by plasma lipoprotein lipase and their remnants are cleared rapidly by the liver. In patients with severe nephrotic syndrome, these two metabolic mechanisms are impaired and/or overwhelmed leading to hyperlipidemia and accumulation of chylomicrons  . Furthermore, the triglyceride: cholesterol ratio was not 5-10:1, which characterize chyluria due to dietary and/or lymphatic disease and the genetic form of hyperlipidemia type-I, which is characterized by the presence of isolated defect in lipoprotein lipase.
Our patient must have had impaired lipid metabolism at different level(s). Such phenomenon has been described in association with different autoimmune diseases e.g. systemic lupus erythematosis producing type-I hyperchylomicronemia due to the binding of IgG or IgM antibodies to heparin and decreasing the activity of lipoprotein lipase. Furthermore, some monoclonal gammopathy syndromes viz. multiple myeloma, macroglobulinemia and lymphoma may produce type-Ill and type-IV hyperlipidemia states due to formation of immune complexes between immunoglobulins and chylomicron remnants and/or VLDL, thereby decreasing their metabolism  . In our patient, glomerular lipiduria is the most likely mechanism for chyluria, yet a direct vascular protein leakage through the diseased small vessels, similar to that seen in patients with fat embolism  , can not be excluded.
| Acknowledgment|| |
The authors are indebted to Dr. Hafeez Mugal (Biochemistry Department, Al-Amiri Hospital) for his technical support in confirming the diagnosis of chyluria in our patient.
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Kamel Abdulmohsen El-Reshaid
Department of Medicine, Faculty of Medicine, P.O. Box 24923, 13110 Safat
[Figure - 1], [Figure - 2], [Figure - 3]