Dextran-Sulfate Plasma Adsorption Lipoprotein Apheresis in Drug Resistant Primary Focal Segmental Glomerulosclerosis Patients: Results From a Prospective, Multicenter, Single-Arm Intervention Study
focal segmental glomerulosclerosis; lipoprotein apheresis; liposorber; nephrotic syndrome; proteinuria
Background: Focal segmental glomerulosclerosis (FSGS) causes end stage renal disease (ESRD) in significant proportion of patients worldwide. Primary FSGS carries poor prognosis and management of FSGS patients, refractory to standard treatments or resistant to steroids, remains a major challenge. Lipoprotein apheresis is a therapeutic approach for drug resistant primary FSGS and post-renal transplant primary FSGS recurrence. Objectives: To examine the safety and probable benefit at 1, 3, 6, 12, and 24-months following completion of apheresis treatment using Liposorber® LA-15 system in patients with nephrotic syndrome (NS), due to refractory primary FSGS or primary FSGS associated NS, in post renal transplant children. Material and Methods: Prospective, multicenter, single-arm intervention study using Liposorber® LA-15 system. Patients ≤21 years old with drug resistant or drug intolerant NS secondary to primary FSGS with glomerular filtration rate (GFR) ≥60 ml/min/1.73 m2 or post renal transplant patients ≤21 years old with primary FSGS associated NS were included in the study. Each patient had 12 dextran-sulfate plasma adsorption lipoprotein apheresis sessions over a period of 9 weeks. All patients were followed up at 1, 3, 6, 12, and 24-months following completion of treatment. Results: Of 17 patients enrolled, six were excluded from the outcome analysis (protocol deviations). Of the remaining 11 patients, all but one have completed apheresis treatments. Three patients were lost to follow-up immediately after completion of apheresis and excluded from outcome analysis. At one-month follow-up, 1 of 7 patients (14.3%) attained partial remission of NS while 2 of 4 subjects (50%) and 2 of 3 subjects (66.7%) had partial/complete remission at 3- and 6-months follow-up, respectively. One of two patients followed up for 12 months had complete remission and one patient had partial remission of NS after 24 months. Improved or stable eGFR was noted in all patients over the follow-up period. Conclusion: The results of our multicenter study showed improvement in the response rates to steroid or immunosuppressive therapy and induced complete or partial remission of proteinuria in some of the patients with drug resistant primary FSGS. The main limitation of our study is the small number of subjects and high dropout rate.
Raina Rupesh; Krishnappa Vinod; Sanchez-Kazi Cheryl; Quiroga Alejandro; Twombley Katherine E; Mathias Robert; Lo Megan; Chakraborty Ronith; Mahesh Shefali; Steinke Julia; Bunchman Timothy; Zaritsky Joshua
Frontiers in Pediatrics
2019
1905-07
Journal Article
<a href="http://doi.org/10.3389/fped.2019.00454" target="_blank" rel="noreferrer noopener">10.3389/fped.2019.00454</a>
PMID: 31850285 PMCID: PMC6902874
Waldenstrom's Macroglobulinemia And Nephrotic Syndrome With Membranous Nephropathy
antibody; glomerulonephritis; macroglobulinemia; membranous nephropathy; nephrotic syndrome; pathology; Urology & Nephrology; Waldenstrom's
Renal complications of Waldenstrom's macroglobulinemia (WM) are rarely observed. Nephrotic syndrome in association with WM has most often been secondary to amyloidosis. This article reports a case of WM with nephrotic syndrome as a result of membranous nephropathy with immunoglobulin M (IgM) deposition. A 44-year-old male diagnosed with WM 4 years previously, presented with heavy proteinuria (7.8 g/24 h). Kidney biopsy revealed expanded mesangium, thickened capillary loops and epimembranous spikes, with no significant interstitial inflammation or thickened tubular basement membranes. Immunofluorescence examination demonstrated strong granular staining of IgM and l light chains, with weaker C3 and C1q staining. Electron microscopy showed many subepithelial dense deposits, and fewer large subendothelial dense deposits. Treatment was directed at the patient's WM with maintenance rituximab and fludarabine. Subsequently, decreases were seen in both the patient's serum IgM and serum viscosity. With therapy for WM and the addition of an angiotensin receptor blocker, the patient's proteinuria also improved, from 7.8 g to 4.8 g/24 h. The patient continued to follow up with his hematologist and in 2009 creatinine was 1 mg/dl (76.26 mu mol/l), with a 24 h urine protein excretion of 0.159 g.
Lee B; Smith R S; Tanphaichitr N; Novak R; Robertson S; Haller N A
Scandinavian Journal of Urology and Nephrology
2011
2011-12
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.3109/00365599.2011.568954" target="_blank" rel="noreferrer noopener">10.3109/00365599.2011.568954</a>
Membranous glomerulonephritis: treatment response and outcome in children
childhood; chlorambucil; clinical course; cyclophosphamide; cyclophosphamide; glomerular-filtration-rate; glomerulonephropathy; glomerulosclerosis; Membranous; Membranous glomerulonephritis; methylprednisolone; nephropathy; nephrotic; Nephrotic syndrome; Pediatrics; syndrome; systemic lupus erythematosus; Urology & Nephrology
The aim of this study was to characterize clinical features, treatment response, and outcome of idiopathic membranous glomerulonephritis (MGN) in a single-center cohort of children. A retrospective review of biopsy-proven idiopathic MGN in 12 children (mean age 11.9 years) was undertaken. Presentation was nephrotic syndrome (NS) (75%), hematuria/proteinuria (17%), and asymptomatic proteinuria (8%). Ten patients (83%) with NS and nephrotic range proteinuria (NRP) were treated with prednisone, and two patients with non-NRP were not treated with immunosuppressive medications. Steroid response in the treated patients was complete (10%), partial (40%), and absent (50%), respectively. Oral cyclophosphamide was used in seven patients of whom five were steroid resistant, one was steroid dependent, and one was partially responsive. At the mean follow up of 27 months, outcome parameters included an estimated glomerular filtration rate of 128 cc/min per 1.73 m(2), albumin of 4.2 gm/dL, and a urine protein/creatinine ratio of 0.87 [median 0.16 (range 0.02-6.52)]. Remission was complete in 75% of the patients and partial in 17%. One patient (8%) with chronic kidney disease (stage 2) was unresponsive to therapy. Complete remission was significantly associated with the absence of chronic histological changes (p=0.03). In conclusion, children with NS and/or NRP associated with MGN appear to have a good prognosis when treated with a combination of corticosteroids and cyclophosphamide.
Valentini R P; Mattoo T K; Kapur G; Imam A
Pediatric Nephrology
2009
2009-02
Journal Article
<a href="http://doi.org/10.1007/s00467-008-1005-9" target="_blank" rel="noreferrer noopener">10.1007/s00467-008-1005-9</a>
An update on LDL apheresis for nephrotic syndrome.
Focal segmental glomerulosclerosis; Hyperlipidemia; Liposorber(R) LA-15 System; Low-density lipoprotein apheresis; Nephrotic syndrome; Podocyte injury
Low-density lipoprotein (LDL) apheresis has been used increasingly in clinical practice for the treatment of renal diseases with nephrotic syndrome (NS), specifically focal segmental glomerulosclerosis (FSGS). Persistent hyperlipidemia for prolonged periods is nephrotoxic and leads to chronic progressive glomerular and tubulointerstitial injury. Effective management of hyperlipidemia with
Raina Rupesh; Krishnappa Vinod
Pediatric nephrology (Berlin, Germany)
2018
2018-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00467-018-4061-9" target="_blank" rel="noreferrer noopener">10.1007/s00467-018-4061-9</a>