Low-Density Lipoprotein Apheresis Therapy for Steroid- and Cyclosporine-Resistant Idiopathic Membranous Nephropathy

Abstract

We herein report three cases of Nephrotic Syndrome (NS) with idiopathic membranous nephropathy (IMN) in which the patients were resistant to steroid (PSL) and cyclosporine (CyA) therapy. All three patients had a high risk of renal failure because of persistently high levels of proteinuria. We performed low-density lipoprotein apheresis (LDL-A) and achieved complete remission in two cases. The third patients developed NS relapse and a deteriorating renal function; however, withdrawal from dialysis therapy was achieved. There are no proven therapies for treating patients with PSL-and CyA-resistant IMN with acute deteriorating renal function or difficulties in maintaining fluid balance. We evaluated the treatment course and physiological mechanisms and reviewed similar cases in the pertinent literature. A 75-year-old woman was admitted to our hospital with tibial edema and severe proteinuria that had persisted for one year. She presented with hypoalbuminemia and hypoproteinemia. Her laboratory data were as follows: total protein (TP) 5.1 g/day, albumin (Alb) 2.5 g/dL, low-density lipoprotein cholesterol (LDL-Chol) 298 mg/dL and urinary protein (U-pro) 4.1 g/dL. A renal biopsy performed on day 2 revealed membranous nephropathy (Fig. 1a, b). Two courses of intravenous methylprednisolone (mPSL; 0.5 g/ day) were administered over three consecutive days starting on days 19 and 53. Treatment with 50 mg (1 mg/kg) of prednisolone (PSL) was initiated after mPSL therapy on day 22. Seventy-five mg of cyclosporine (CyA) twice daily was added to the PSL therapy on day 37. The patient's CyA trough level was 96 mg/dL. Despite treatment with two courses of mPSL therapy, PSL therapy and CyA therapy, the heavy proteinuria and hypoproteinemia persisted. LDL-A therapy was commenced on day 67 and repeated twice a week for three weeks. Gradually, the proteinuria decreased and the serum protein levels increased (Fig. 2). After day 201, the estimated urinary protein level was <0.3 g/day. Complete remission (CR) was maintained for almost two years after discharge without the need for immunosuppressive therapy. Case 2A 35-year-old man was admitted to our hospital with tibial edema and severe proteinuria. He had been previously hospitalized for thrombotic thrombocytopenic purpura (TTP) almost four years earlier. He had recovered completely even without steroid therapy and suffered no relapses until the present day. The tibial edema was noticed almost five months prior to admission. On admission, laboratory data

A Prospective Observational Survey on the Long-Term Effect of LDL Apheresis on Drug-Resistant Nephrotic Syndrome

“…Several reports have evaluated the efficacy of LDL-A for non-FSGS diseases, such as MCNS [ 12 ], membranous nephropathy [ 13 , 14 ], lupus nephritis [ 15 , 16 , 17 ], and diabetic nephropathy [ 18 , 19 , 20 , 21 ], but most are case reports/series with a limited number of subjects. Although the number of subjects with each disease apart from FSGS is small, we examined a total of 16 subjects with non-FSGS registered in the POLARIS cohort and found that LDL-A treatment reduced the UP level in those patients at a comparable rate to that in FSGS cases immediately after treatment [ 10 ].…”

Intermittent high-volume hemofiltration promotes remission in steroid-resistant idiopathic nephrotic syndrome

“…Although studies have found a beneficial effect of plasma exchange and lipoprotein replacement on steroid resistance, 8,9 the underlying mechanism remains unknown. Shalhoub first hypothesized that certain circulating factors increase the protein permeability of the glomerular filtration barrier and researchers have further postulated that the major ''circulating factors'' responsible for steroid resistance are cytokines derived from dysfunctional T cells.…”

Long-term Low-density Lipoprotein Apheresis in a Patient with Refractory Idiopathic Membranous Glomerulonephritis

“…That study also showed that the favorable outcome rate was 50.0% in non-FSGS patients with diseases such as MCN, MGN, lupus nephritis, or DN, which was comparable to or better than the rate in FSGS patients. Sato also reported that LDL-A therapy showed similar efficacy for patients with idiopathic MGN or FSGS (10). …”