Citation: Sarkissian S, Kahlon K, Walavalkar V, Siaghani P, Tran MH, et al. Renal Manifestations of Alternate Complement Pathway Dysregulation. J Urol Nephrol. 2015;2(1): 4. J Urol Nephrol August 2015 Vol.:2, Issue:1 © All rights are reserved by Harley et al. Renal Manifestations of Alternate Complement Pathway Dysregulation Abstra c t Irre g ula ritie s o f the a lte rna te c o mp le me nt p a thwa y c a n le a d to b o th re na l-limite d a nd syste mic p a tho lo g y. We p re se nt the c a se o f a tra nsp la nt re c ip ie nt with re na l d ise a se o f unkno wn e tio lo g y who d e ve lo p e d a c ute kid ne y injury in the we e ks fo llo wing tra nsp la nt a nd ma nife ste d d iffe re nt histo lo g ic a nd c linic a l p a tte rns o f a lte rna te c o mp le me nt p a thwa y me d ia te d immuno lo g ic injury a t d iffe re nt p o ints in he r p o st-tra nsp la nt c o urse . We se a rc he d Me d line fo r c a se s a nd stud ie s p e rta ining to a lte rna te c o mp le me nt p a thwa y re na l-a sso c ia te d d ise a se s, the ir p a tho lo g ic me c ha nisms, p o te ntia l tre a tme nt o p tio ns, and report our fndings. Introduction Alternate complement pathway (ACP) dysregulation and its varied clinical manifestations are an area of intense interest in contemporary nephrology research. Diagnoses such as atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis type 2, atypical post-infectious glomerulonephritis, and the relatively new entity known as C3 glomerulopathy, have been linked to aberrancies in the normal immunologic cascade following alternate complement pathway activation. Advances in ACP genetics have revealed heritable predispositions to such diagnoses and furthered the drive to develop targeted, accessible treatment options. Te growing number of patients on kidney transplant waiting lists with primary diagnoses among these entities has also spurned a need to carefully evaluate recipient candidacy given the signifcant possibility for disease recurrence and the limited treatment options currently available in such situations. We report a complicated case of ACP dysregulation in a kidney transplant recipient and provide a discussion of manifestations related to this pathology. Case A 47 year-old Hispanic female sufered from uncontrolled, chronic hypertension since her late 20s, had limited access to medical care, and presented to a nephrologist with advanced symptomatic CKD she was started on hemodialysis. As a result of her late presentation, her nephrologist determined a native biopsy would yield little data other than advanced glomerulosclerosis and thus one was deemed unwarranted and not performed. Afer a few years on hemodialysis, she underwent a living unrelated kidney transplant. She received the IL-2 inhibitor basiliximab for induction, was put on a rapid steroid taper, and started on maintenance tacrolimus and mycophenolic acid. She was discharged home with a nadir creatinine of 1.1 mg/dl. Two weeks later her creatinine had rebounded to 1.9 mg/dl. She had 3.5 grams proteinuria and an active urine sediment. Her peripheral smear was unremarkable and platelet count preserved. An allograf biopsy was done and showed proliferative glomerulonephritis without acute rejection. Immunofuorescence revealed granular, mesangial positive C3 staining and negative immunoglobulin and light chain staining. Electron microscopy demonstrated electron dense subepithelial and mesangial deposits. A preliminary pathologic diagnosis of post-infectious glomerulonephritis was made without any clinical evidence of antecedent infection. In the following weeks, labs revealed an IgG lambda monoclonal gammopathy in the serum and urine. A bone marrow biopsy was performed showing 2-3% plasma cells. Subsequently three doses of weekly cyclophosphamide and bortezomib with dexamethasone was administered and subsequent low dose steroid maintenance therapy was added and continued. Tereafer, her creatinine rose to 4.4 mg/dl. Other than a few rare schistocytes, evidence for a systemic microangiopathic process was decidedly unimpressive with stable hemoglobin levels and absence of hyperbilirubinemia throughout. Although the platelet count dropped on a single occasion to 139 K/mcL, all other counts were 150 K/mcL. A second renal allograf biopsy was performed. (see Table 1 for diagnostic test summary) Te second biopsy revealed evidence of glomerular thrombotic microangiopathy(TMA) with mesangiolysis, glomerular shrinking, and fbrin positive deposits by immunofuorescence. C3 mesangial staining persisted. Tubular lambda light chain staining was now positive. Electron microscopy showed subepithelial deposit is had decreased in size and now demonstrated occluded capillary lumens Sarmen Sarkissian 1 , Kanwarpal Kahlon 1 , Vighnesh Walavalkar 2 , Parwiz Siaghani 2 , Minh-Ha Tran 3 , and Kevin Harley 4 * 1 Department of Medicine, Divison of Hematology-Oncology, UC Irvine School of Medicine, 101 The City Dr S, Orange, CA 92868, USA 2 Department of Pathology, UC Irvine School of Medicine, 101 The City Dr S, Orange, CA 92868, USA 3 Departments of Pathology and Medicine, UC Irvine Health School of Medicine, 101 The City Dr S, Orange, CA 92868, USA 4 Department of Medicine, Division of Nephrology & Hypertension, UC Irvine Health School of Medicine, 101 The City Dr S, Orange, CA 92868, USA Address for Correspondence Kevin Harley, Department of Medicine, Division of Nephrology & Hypertension, UC Irvine Health School of Medicine, 101 The City Dr S, Orange, CA 92868, USA, Tel: 714-456-5142; E-mail: kharley@uci.edu Submission: 28 May 2015 Accepted: 04 August 2015 Published: 10 August 2015 Copyright: © 2015 Sarkissian S, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Reviewed & Approved by: Dr. Yasin Aydogmus, Specialist/ urologist, Etimesgut Military Hospital, Ankara, Turkey Case Report Open Access Journal of Urology & Nephrology