Membranous glomerulopathy and treatment with Acthar®: a case study
At an initial visit in September 2006, a 46-year-old white male presented with edema, blood pressure indicative of hypertension (144/94 mmHg), heart rate of 76 beats per minute, and creatinine of 1.4 mg/dL (123.76 μmol/L). He had experienced sudden onset of edema in his feet and legs 5 weeks prior to this initial visit, which caused him serious concern. At a height of 5 feet 8 inches (172.72 cm) and weighing 235 lbs (105.75 kg; up about 35 lbs [15.75 kg] from his usual weight), his body mass index was 35.7. He had not been on any medication regimen. Laboratory values included 24-hour urinary protein at >7,500 mg/dL (750.0 g/L) and cholesterol at 307 mg/dL (7.9513 mmol/L; low-density lipoprotein, 224 mg/dL [5.8016 mmol/L]). He was negative for cancer screening, hepatitis B and C panel, antinuclear antibody, rheumatoid factor, and rapid plasmid reagin. He was started on olmesartan medoxomil-hydrochlorothiazide 40/25 mg for hypertension and proteinuria and simvastatin 40 mg for elevated cholesterol.\nThe patient was scheduled for a kidney biopsy for nephrotic range proteinuria in October 2006, which resulted in a diagnosis of idiopathic membranous glomerulopathy. Lisinopril 40 mg twice daily was added to his medication regimen. At this time, his creatinine was at 1.3 mg/dL (114.92 μmol/L).\nThe patient’s membranous glomerulopathy progressed from October 2006 to July 2009, as revealed by laboratory results. During this period, he remained on an angiotensin receptor blocker (olmesartan medoxomil-hydrochlorothiazide) and angiotensin-converting enzyme inhibitor (lisinopril) treatment regimen. Since no improvement was observed, he then received cyclosporine A for 6 months, to which he was relatively adherent. No improvement was observed 3 months after initiation of cyclosporine A, so prednisone was added. Three months later, he developed shingles and was admitted to the hospital due to what was felt to be complications of cyclosporine A plus prednisone. Both cyclosporine A and prednisone were tapered off after the patient requested all immunosuppressive medications be stopped. Three months later, he agreed to be treated with mycophenolate, which he received for approximately 12 months but only during the last 3 months did he take it as prescribed.\nThe patient was agreeable to trying Acthar (80 USP U/mL) and received treatment from September 2009 to October 2010; his laboratory values during this period are summarized in . Acthar was self-administered subcutaneously at an initial dose of 40 U every 72 hours. After 3 months, the dose was increased to 80 U every 72 hours. In April 2010, his urinary protein levels rose to 9,520 mg/dL (952.0 g/L), and he required additional antihypertensive therapy. By July 2010, his urinary protein had dropped to 2,948 mg/dL (294.8 g/L). Thus, it took approximately 10 months of Acthar treatment to improve his urinary protein levels. By October 2010, his urinary protein levels had decreased further to 1,628 mg/dL (162.8 g/L). As shown in , in addition to the decline in urinary protein levels, the patient experienced decreases in creatinine and albumin levels, an increase in creatinine clearance, and modest weight gain while receiving treatment with Acthar.\nActhar treatment was stopped in October 2010 for several reasons. First, one year of ACTH treatment has been shown in European studies to be sufficient for resolving proteinuria.– In addition, the patient’s laboratory results indicated clinically significant improvement in his signs of membranous nephropathy. Finally, the patient reported that his quality of life had improved, and he was not experiencing any symptoms of membranous nephropathy. He felt well and was able to return to his previous lifestyle.\nThe laboratory results since halting Acthar are also shown in . Urinary protein levels continued to decline overall, from 407 mg/dL (40.7 g/L) in December 2010, with slight elevation to 451 mg/dL (45.1 g/L; still within normal range) in March 2011, to 189 mg/dL (18.9 g/L) in September 2011. His protein to creatinine ratio was 0.58 in January 2012, and at that time his medications were limited to an angiotensin-converting enzyme inhibitor (lisinopril) and angiotensin receptor blocker (olmesartan medoxomil-hydrochlorothiazide). As of May 1, 2012, his blood pressure was 124/78 mmHg, he weighed 199 lbs (89.55 kg), his heart rate was 81 beats per minute, and there was no evidence of edema. Current medications include olmesartan medoxomil-hydrochlorothiazide 40/12.5 mg once daily, lisinopril 40 mg once daily, and simvastatin 40 mg once daily.