Chief Complaint: Edema and Hydrops Abdominis.

History of presenting illness: The patient was hospitalized in October 2003 with chief complaints of albuminuria, hypoalbuminemia, edema, and hyperlipidemia, and he was diagnosed with minimal change disease following renal biopsy (Fig. 1A). He showed complete remission at 4 weeks after using 60 mg (1 mg/kg/day) of prednisolone (Solondo®; Yuhan Corporation, Seoul, Korea); he showed side effects during dose reduction such as blushing. Thus, the drug was switched to deflazacort (Calcort®; Handok Inc., Seoul, Korea), which was continuously taken. After 6 months of treatment, the patient showed complete remission of albuminuria, and thus he discontinued his intake of deflazacort. Two months later in June 2004, the first relapse occurred with at least 2 g/g for the spot urine protein/creatinine ratio, and thus the patient took 60 mg of deflazacort and then reached complete remission. Later, the patient's steroid intake was randomly discontinued and the patient showed a second relapse with a spot urine protein/creatinine ratio of 5.97 g/g in April 2005. The patient showed remission using 72 mg of deflazacort, after which 100 mg (50 mg, twice daily) of low-dose steroid and cyclosporine (Cipol-N®; Chong Kun Dang Pharmaceutical Corp., Seoul, Korea) were added for maintenance therapy. However, the patient did not take the drugs very well, so the cyclosporine was discontinued while he was maintained on a low-dose steroid and deflazacort at 12 mg/every other day. The spot urine protein/creatinine ratio in December 2006 and October 2007 was 12.42 g/g and 5.24 g/g, respectively, which were thus indicative of the third and fourth relapse episodes. Therefore, the combination therapy of deflazacort and cyclosporine was maintained. Most of the relapses were caused by the patient's arbitrary discontinuity of medication. After the fifth relapse in April 2010, with a spot urine protein/creatinine ratio of 11.51 g/g, another relapse occurred multiple times at 3–6-month intervals; thus, a renal biopsy was performed again in December 2012. The results showed no focal segmental glomerulosclerosis aside from minimal change disease (Fig. 1B, 1C, and 1D). Later, while observing the patient's progress on an outpatient basis, he was hospitalized due to hydrops abdominis and severe edema in November 2013.

Findings and laboratory opinions: At the time the patient was hospitalized, his height was 159 cm and his weight was 68 kg, which was 8 kg more than at the first medical examination. The patient presented with hydrops abdominis and edema, and his face was round, with a moon-like shape. The patient's blood pressure was 105/60 mmHg, and he had a pulse of 80 beats/minute, a body temperature of 36.5℃, and a respiration rate of 20 breaths/minute. The heart sound was clear and regular, and the chest findings were normal. He had no oppressive pain in either of his kidneys, and he exhibited pitting edema that was more severe than moderate in both pelvic limbs.

On peripheral blood examination, the patient's hemoglobin was 15.9 g/dL, hematocrit 45.2%, and leucocytes 8,780/mm³. During the serum electrolyte test, the patient's sodium was 136 mmol/L, potassium 4.6 mmol/L, chlorine 107 mmol/L, calcium 7.0 mg/dL, and phosphorous 5.2 mg/dL. During the serum biochemistry test, the patient's blood urea nitrogen was 17 mg/dL, creatinine 0.8 mg/dL, glomerular filtration rate 124.2 mL/min/1.73m², aspartate aminotransferase 30 U/L, alanine aminotransferase 22 U/L, alkaline phosphatase 250 U/L, and total bilirubin 0.5 mg/dL. The total cholesterol increased to 427 mg/dL and the albumin decreased to 1.6 g/dL. Antithrombin Ⅲ was 49.3% (normal range: 70%–130%), protein C was 158% (normal range: 70%–140%), and protein S was 102% (normal range: 60%–130%). With respect to the urinalysis, protein 3+, the erythrocyte count was 10–14 high-power fields (HPF), and the spot urine protein/creatinine ratio was 8.05 g/g. Chest radiograph showed normal results.

Treatment and clinical course: A diuretic was used to control the edema and hydrops abdominis, and 60 mg of prednisolone was used for at least 4 weeks to treat the relapse of minimal change disease; however, there was no change in the amount of albuminuria. Cyclophosphamide was about to be used, but the patient refused due to concerns of its side effects. On the abdominal ultrasound that was performed to check for hydrops abdominis, hepatic portal vein thrombosis was discovered, and thus the patient began to receive treatment using heparin and warfarin, which was adjusted within the prothrombin time range of 2–3 INR (International Normalized Range) (Fig. 2A). Due to thrombosis, prednisolone was reduced to 0.5 mg/kg/day, and the patient began to take 100 mg of cyclosporine twice a day. When using the steroid exclusively, the edema continued even after taking a high-dose furosemide intravenous injection, but it was somewhat controlled after adding cyclosporine; thus, the patient was discharged. Severe albuminuria continued and the albumin index fell to below 2.0 g/dL, even after using cyclosporine for 4 weeks; thus, 500 mg of MMF (Cellcept®; Roche Korea, Seoul, Korea) was added twice a day while gradually reducing the steroid. After using MMF for 4 weeks, the spot urine protein/creatinine ratio decreased to 2.25 g/g, so the steroid use was further reduced; 2 weeks later, the patient reached complete remission. Since then, he has been receiving combination therapy consisting of three drugs; he started taking 4.5 mg of deflazacort 1 time/day, 100 mg of cyclosporine 2 times/day, and 250 mg of MMF 2 times/day. He has been showing stable progress without relapse for at least a year thus far (Fig. 3A and 3B). The hepatic portal vein thrombus was completely gone as per the abdominal ultrasound taken in March 2015, and warfarin was discontinued a year and a half after beginning the thrombosis treatment (Fig. 2B).