Clinical Kidney Journal, 2018, 1–3 doi: 10.1093/ckj/sfy009 Exceptional Case EXCEPTIONAL CASE Treatment of fibrillary glomerulonephritis with use of repository corticotropin injections 1,2,3 1 4 Natallia Maroz , Sharon Reuben and Tibor Nadasdy 1 2 3 Kettering Medical Center, OH, USA, Renal Physicians Inc., Wright State University, OH, USA and Department of Pathology, The Ohio State University Wexner Medical Center, OH, USA Correspondence and offprint requests to: Natallia Maroz; E-mail: email@example.com ABSTRACT Fibrillary glomerulonephritis (FGN) is a rare idiopathic condition linked to malignancy, autoimmune disorders, monoclonal gammopathies and hepatitis C virus. It usually has a poor prognosis, resulting in progression to end-stage renal disease within a few years, given the lack of standardized treatment. Repository corticotrophin (RC) injections are approved for use in a variety of nephrotic syndromes, but are not routinely considered for treatment of FGN. We present a case in which a patient with FGN began treatment with RC 3 months after diagnosis. The patient has attained partial remission with complete resolution of nephrotic syndrome and stabilization of renal function. Keywords: ﬁbrillary glomerulonephritis, immunotherapy, nephrotic-range proteinuria, partial remission, repository corticotropin kidney disease, which had progressed to Stage 4 over several INTRODUCTION years. Fibrillary glomerulonephritis (FGN) remains an uncommon His medical history included uncontrolled hypertension, pathology found in only 1% of renal biopsies. FGN is identified hyperlipidemia, hyperthyroidism treated with radioactive by the aggregation of randomly arranged fibrils or microtubular iodine 10 years prior and obesity. Prescribed medications structures, 10–20 nm in diameter. Diagnosis is made by electron included amlodipine, lisinopril, levothyroxine and aspirin. microscopy. FGN fibrils stain dominantly or codominantly for Physical examination revealed an obese man with body immunoglobulins G4 and IgG1 with C3 staining and are distin- mass index 35.6 kg/m , blood pressure of 162/90 mmHg and guished from amyloid fibrillary deposition disease by staining 2þ pitting edema of the lower extremities. The remainder of his negative for Congo red . examination was unremarkable. The etiology of FGN appears idiopathic but is associated with The creatinine level declined from 2.2 to 2.7 mg/dL within a autoimmune disorders, monoclonal gammopathies, malignancy month. He had nephrotic-range proteinuria of 5.1 g/day as well and hepatitis C virus in up to 33% of cases. Poor prognosis is typi- as hematuria. Results for other analyses, including hepatitis B cal and invariably results in end-stage renal disease (ESRD) within and C viral serologies, human immunodeficiency virus status, 2–6 years [2, 3]. antineutrophilic cytoplasmic antibody, serum and urine protein electrophoreses, complement levels and renal ultrasound were unremarkable. His renal biopsy in December 2013 showed CASE REPORT advanced-stage FGN. A 66-year-old African American man was referred for outpa- Light microscopy of paraffin sections stained with hematox- tient nephrology evaluation in October 2013 for chronic ylin and eosin, periodic acid–Schiff (PAS) and PAS-trichrome Received: 5.11.2017. Editorial decision: 19.1.2018 V C The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact firstname.lastname@example.org Downloaded from https://academic.oup.com/ckj/advance-article-abstract/doi/10.1093/ckj/sfy009/4944887 by Ed 'DeepDyve' Gillespie user on 12 July 2018 2| N. Maroz et al. showed prominent mesangial expansion and widespread, seg- (RC), which is approved for use in a nephrotic-range proteinuria. mental irregular capillary loop thickening. Two-thirds of the This medication was chosen in order to avoid the severe sys- renal cortices showed interstitial fibrosis and tubular atrophy. temic immunosuppressive effects of alternative cytotoxic A Congo red stain was negative. agents such as rituximab, particularly, at his level of progressed Direct immunofluorescence (DIF) of the renal cortex fibrosis and interstitial scarring. showed strong smudgy-to-granular glomerular staining for He was started on RC 40 U/mL twice weekly for 2 weeks, after IgG and the kappa light chains. Slightly weaker, moderate and which the dose was increased to 80 U/mL twice weekly. We ini- weak glomerular staining was noted for C3 and the lambda tially observed a rise in proteinuria, with a peak of 8.9 g/day light chains, respectively. Immunofluorescence with the IgG 1 month into treatment, followed by a decline over the following subclass antibodies revealed strong glomerular staining for several months with edema resolution and stabilization of the IgG1, weak staining for IgG4 and no staining for IgG2 and IgG3 creatinine. After 6 months of treatment, the dose of RC was (Figure 1). reduced to 40 U/mL twice weekly in order to minimize the Electron microscopy revealed abundant deposition of ran- potential adverse effects. Within 8 months of initiating RC treat- domly arranged rigid fibrillary material in the mesangium and ment, proteinuria resolved to <1 g/day. The patient tolerated along the glomerular capillary loops within the thickened glo- the therapy quite well and had no worsening of hypertension merular basement membrane. Fibril diameter was 19.0 6 control, hypokalemia or hyperglycemia. He experienced mood 1.8 nm. swings and mild darkening of the skin, but surprisingly reported Three months after his biopsy-proven diagnosis, the patient improved level of energy and memory. After 4 years of follow- agreed to a trial of treatment with repository corticotrophin up, he has attained partial remission, with complete resolution of nephrotic syndrome and stabilization of renal function com- pleting 45 months of therapy. DISCUSSION Various immunosuppressive agents such as rituximab, cyclo- phosphamide and steroids have been used for FGN to demon- strate partial remission and/or stabilization of renal function for a period ranging from months to a few years only, before pro- gression to ESRD [3–5]. RC has demonstrated a plausible therapeutic effect on an array of glomerulopathies with nephrotic syndrome. The whole spectrum of RC mechanisms is currently under investigation. Direct immunomodulation of melanocortin receptors to medi- ate podocyte apoptosis and effacement is of particular interest. It has been suggested that the action of RC has an inherent anti- inflammatory property, reducing B- and T-cell activity via ster- oidogenesis upon binding to the adrenal cortex melanocortin receptor . While our initial intention was to treat our patient with RC therapy for 6 months, per the manufacturer’s recommenda- tions, in order to improve proteinuria and stabilize renal func- tion, we continued the patient on therapy for a longer duration to sustain the achieved partial remission and to postpone pro- gression to ESRD. We observed an excellent response over the course of the first 45 months of treatment. Few observational reports have demonstrated variable out- comes with use of RC in patients with FGN. Our case supports the consideration of trying this agent as a first-line therapy in patients with advanced disease in the hope of avoiding side effects of other immunosuppressive or cytotoxic agents. Further analyses are necessary to establish a sustainable and reproduci- ble response to therapy. CONFLICT OF INTEREST STATEMENT FIGURE 1: (A) Enlarged glomerulus with mesangial expansion and segmental glo- The results presented in this paper have not been published merular capillary thickening, hematoxylin and eosin, 400. (B) Methenamine silver previously in whole or part, except in abstract format. stain is weak to negative in the expanded mesangium. Jones methenamine silver, 400. (C) DIF with antibody to immunoglobulin G1 (IgG1) shows smudgy mesangial and segmental glomerular capillary staining, 400. (D) DIF with antibody to IgG2 is REFERENCES negative, 400. (E) DIF with an antibody to IgG3 is also negative, 400. (F) DIF with 1. Fogo A, Qureshi N, Horn RG. Morphologic and clinical features antibody to IgG4 shows similar staining to IgG1, 400. (G) Electron microscopy of of ﬁbrillary glomerulonephritis versus immunotactoid glo- the mesangium reveals prominent deposition of ﬁbrillary material. Uranyl ace- tate-lead citrate, original magniﬁcation 30 000. merulopathy. Am J Kidney Dis 1993; 22: 367–377 Downloaded from https://academic.oup.com/ckj/advance-article-abstract/doi/10.1093/ckj/sfy009/4944887 by Ed 'DeepDyve' Gillespie user on 12 July 2018 Treatment of fibrillary glomerulonephritis with use of RC | 3 4. Nasr SH, Valeri AM, Cornell LD et al. Fibrillary glomeruloneph- 2. Hogan J, Restivo M, Canetta PA et al. Rituximab treatment for ﬁbrillary glomerulonephritis. Nephrol Dial Transplant 2014; 29: ritis: a report of 66 cases from a single institution. Clin J Am Soc 1925–1931 Nephrol 2011; 6: 775–784 3. Javaugue V, Karras A, Glowacki Fet al. Long-term kidney dis- 5. Bomback AS, Radhakrishnan J. Treatment of nephrotic syn- ease outcomes in ﬁbrillary glomerulonephritis: a case series drome with adrenocorticotropic hormone (ACTH). Discov Med of 27 patients. Am J Kidney Dis 2013; 62: 679–690 2011; 12: 91–96 Downloaded from https://academic.oup.com/ckj/advance-article-abstract/doi/10.1093/ckj/sfy009/4944887 by Ed 'DeepDyve' Gillespie user on 12 July 2018
Clinical Kidney Journal – Oxford University Press
Published: Mar 20, 2018
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera