Reduction in Serum Potassium in Stage 5 CKD Patients With Hyperkalemia Treated With ZS-9: A Pooled Analysis From 2 Phase 3 Trials

NKF 2016 Spring Clinical Meetings Abstracts

Case Report 337

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PREVALENCE, RISK FACTORS AND OUTCOME OF ACUTE GLOMERULAR EOSINOPHILIC INFILTRATION ASSOCIATED WITH INTERSTITIAL NEPHRITIS AND KIDNEY INJURY AT A HOSPITAL IN THE DEVELOPING DIABETES - A CASE SERIES WORLD 2 Louisette Soussan, Souganthi Soundararajan, Ellie Kelepouris, Hasan Ahmed Sokwala, Peter Waweru Munyu. Aga Khan University Arif,1Sandeep Aggarwal, Drexel University College of Medicine, Hospital, Nairobi 1, Laith Al-Rabadi, MBBS, * Rivka Ayalon, MD, Ramon G. Bonegio, MD, PhD,1 Philadelphia, PA, USA A lot of work has been done to describe the epidemiology of AKI in 2,y 3 4 Although interstitial infiltration is a known phenomenon, Jennifer E.does Ballard, Alancountries. M. Fujii, MD, Joeleosinophilic M. Henderson, MD, PhD, developed countries. The same not applyMD, for developing glomerular infiltration of eosinophils is1 rarely reported. We present a This study was designed to evaluate in a tertiaryMD, care1hospital in DavidAKI J. Salant, and Laurence H. Beck Jr, MD, PhD biopsy series of 6 cases from 2013-2015 with varying degree of Nairobi, Kenya. glomerular eosinophilic infiltration. We carried out a prospective cross sectional study to determine the Methods and Results – Pathological data was obtained by review of epidemiology of acute kidney injury in a tertiary care hospital in There is little information about pregnancy outcomes in patients with active nephropathy (MN), Clinical biopsy slides, electronmembranous and immunofluorescence microscopy. Kenya. (PLA major especially circulating to M-typedata phospholipase was obtained byAretrospective review. Results are as follows: 2 receptor chart 2R), the All patients over thethose age ofwith 12 years admittedautoantibodies to the hospital were forknown biopsy –case AKI of 4/6successful (67%), Proteinuria 3/6 (50%). autoantigen in and primary We present whatatwe be the first pregnancy in followed up prospectively those MN. diagnosed to have AKI anybelieve time to Indication – Mean age 60±8 the yearspatient (n=6); Males 4/6 (67%); Black MN.ofIn theDemographics year prior to pregnancy, developed a 39-year-old woman with PLA during their stay in hospital were assessed for2R-associated risk factors, mode 4/6 (67%), Caucasian 2/6 (33%). management and outcome. anasarca, hypoalbuminemia (albumin, 1.3-2.2 g/dL), and proteinuria (protein excretion, 29.2 g/d). Kidney biClinical characteristics – Diabetes mellitus 6/6 (100%); Hypertension A total of 102 patients were enrolled during the study period running seropositive for anti-PLA R autoantibodies. opsy revealed MN with staining for PLA2R, and the patient6/6was (100%); HIV 1/6 (17%); Baseline2serum creatinine 1.77±0.34 from 1st April 2007 to 31st December 2007.The period prevalence was She did not respond to conservative therapy and was treated with(n=6); intravenous rituximab >+3 (2 doses of 1 Peripheral g each). mg/dl Dipstick proteinuria 5/6 (83%); found to be 1050 per 100000. Higher values were found in the critical eosinophilia 0/6 (0%); Sterile pyuria followed 3/6 (50%).up without after presentation, found to be 6 weeks pregnant and was closely Seventyweeks one (69.9%) of the patientsshe werewas male, 81(80%) care areas.Several Outpatient medications – NSAID 2/68(33%); Proton range. pump inhibitor 3/6 further immunosuppressive treatment. Proteinuria remained with protein excretion in the to 12-g/d were African and the mean age of the cohort was 50.1 years. We found (50%); RAAS blocker use 4/6 (67%); Recent antibiotic use 2/6 (33%) levels declined were Circulating anti-PLA that 41(40%) of the patients were2R in the failure categorybut while riskstill anddetectable. At 38 weeks, a healthy baby girl was born, (1/6 quinolone, 1/6 cephalosporin). injury constituted and at 34birth (34%) commonest without 27(26%) proteinuria orrespectively.The at her subsequent 6-month postnatal visit. At the of delivery, mother Serology/virology datatime – ANA/dsDNA 1/6the (17%); HIV still 1/6 (17%); risk factorhad wasdetectable drug use especially angiotensin converting enzyme (IgG1), IgG3, and IgG4eosinophilic subclasses, although at >50% circulating anti-PLA2R of immunoglobulin G1 Biopsy finding – Glomerular infiltration (100%, inhibitors low (23.81%) on the background of volume depletion, non found in 1/6 cord Potential reasons for nodular the sclerosis titers. Only trace amounts of IgG4 anti-PLA2R wereglomeruli andblood. <50% glomeruli in 5/6); Diabetic steroidal anti-inflammatory drugs (14.29%), anti retroviral drugs lesions (50%); Eosinophilic interstitial nephritis 6/6 (100%); fetal3/6 circulation are discussed. discrepancy between anti-PLA2R levels in the maternal and (19.05% and diuretics (9.52%).The most common underlying MPGN 2/6 (33%); Interstitial fibrosis and tubular atrophy 5/6 (83% Am J Kidney Dis. 67(5):775-778. ª 2016 by the National Kidney Foundation, Inc. diagnoses were sepsis (50%), diabetes mellitus (34.31), malignancies moderate 4/6, severe 1/6). (25.49%), surgical (24.49%) and pulmonary diseases (22.5%). Only 32 In our case series, glomerular eosinophilic infiltration was seen in WORDS: (MN); nephrotic syndrome; M-typeinphospholipase A2 or without (31.37%) INDEX of all patients wereMembranous reviewed by a nephropathy nephrologist.Majority of association withpregnancy; interstitial nephritis diabetic patients with the patients, 88 (86.2%) managed conservatively. The rest were receptor (PLAwere R); autoantibody; placenta; rituximab; immunoglobulin G changes. (Ig G) subclass. 2 diabetic biopsy Further studies are required to determine the put on hemodialysis. Fifty (49%) patients had full recovery, 34 (33.3%) clinical-pathological significance of this phenomenon. had partial recovery while 1(0.98%) had persistent loss. Sixteen (15.68%) of the patients with acute kidney injury died during the index hospital admission. regnant patients with autoimmune disease may

Pregnancy in a Patient With Primary Membranous Nephropathy and Circulating Anti-PLA R Antibodies: A Case Report

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deliver newborns with a spectrum of clinical manifestations due to the transplacental passage of 338 circulating autoantibodies. Pregnant patients with A PATIENT WITH TUBEROUS SCLEROSIS COMPLEX lupus or myasthenia gravis can deliver babies with PRESENTING WITH AKI AND MULTIPLE 1,2MYELOMA corresponding disease in the neonate. Neonatal George Soryal, Syed S Haqqie, Rahim Dhanani, Rafia Chaudhry, membranous nephropathy (MN) not associated with Arif Asif, Albany Medical College Albany, NY congenital infection was first described in 1990 and Tuberous Sclerosis Complex (TSC) is an autosomal dominant attributed to the passive transfer of maternal antidisorder with an incidence of 1:10,000. TSC is an inherited 3 neurocutaneous disorder is characterized involvement bodies to putative renalthat antigens. Moreby than a decadeof 4 many organ systems, including hamartomas of the brain, eyes, later, Debiec et al identified the first antigen involved liver,as kidney, and skin. We present a rare case of a in heart, suchlung, cases neutral endopeptidase (NEP), TSC and renal impairment duethe to multiple A 66-yearmetalloprotease present on surfacemyeloma. of the podocyte male who in hadthe a history of tuberous sclerosis, seizure andoldinvolved proteolytic regulation of vasoacand mental retardation, with angiomyolipoma of kidney tivedisorder, peptides. Debiec et al described a mother with a with stage III chronic kidney disease, presented with AKI with mutation preventing NEP expression who had formed creatinine of 9.4 and BUN of 77. During the workup of AKI anti-NEP antibodies due to fetomaternal alloimmudiagnosis of MM was made with elevated lambda light chains nization from a previous miscarriage; thesemyelomas antibodies and bone marrow biopsy demonstrated multiple with were to cross the placenta and cause subepithelial plasma cell 30%. Flow cytometer showed aberrant clonal plasma deposits in the positive fetal kidney subsequent pregcells population for CD38of andaCD 56 and CD 136, and nancy. M-type phospholipase A receptor (PLA cytoplasmic kappa. The family refused2 the kidney biopsy and 2R) wastreatment later identified askidney the major for MM. The functionautoantigen deteriorated for pri5 necessitating initiation of dialysis. Patient continues do mary MN intheadults. Little literature exists to about well on dialysis at a follow-up of 18 months. While TSC patients pregnancy outcomes in patients with nephrotic synare at due an increased risk for MN, malignant tumors in the drome to primary with no primarily data available kidneys brain, and soft the developmentdisease. of multipleWe about pregnancy in tissues, PLA2R-associated myeloma has not been previously reported. To the best of our present what we believe to be the first known case of knowledge this is the first report of MM in a patient with TSC. pregnancy in a patient with PLA2R-associated MN who was seropositive for anti-PLA2R autoantibodies throughout the course of her pregnancy. Am J Kidney Dis. 2016;67(5):A1-A118

CASE REPORT

A 39-year-old multiparous woman with morbid obesity presented for workup of severe nephrotic syndrome several months 340

before her current pregnancy. She had been treated for resistant REDUCTION IN SERUM POTASSIUM IN STAGE 5 CKD hypertension and HYPERKALEMIA lower-extremityTREATED edema during the past year, PATIENTS WITH WITH ZS-9: A POOLED ANALYSIShad FROM 2 PHASE 3 TRIALS. Bruce Spinowitz,serum but her proteinuria been overlooked. At presentation, New York Presbyterian Queens, NY, NY; Mohamed El-Shahawy, creatinine level was 1.52 mg/dLLos(corresponding toPhilip estimated Academic Medical Research Institute, Angeles, CA,2 USA; glomerular filtration rate ofResearch 46 mL/min/1.73 m as calculated T. Lavin, Boston Biostatistics Foundation, Framingham, MA; by Menoyo, Henrik Rasmussen, Bhupinder Singh, ZS Pharma, 4-variable San theJoseisotope-dilution mass spectrometry –traceable Mateo, CA; Pablo Pergola, Renal Associates, San Antonio, TX MDRD [Modification of Diet Renal Disease] The incidence of hyperkalemia (HK;inserum K+≥5.1 mEq/L) Study increasesequaas chronic kidney diseaselevel, (CKD)1.5 progresses highly prevalent tion); serum albumin g/dL; and andis24-hour urine inprotein the stage 529.2 CKD/end stagekidney renal disease (ESRD) population. HK is features a excretion, g. The biopsy specimen revealed frequent cause of hospitalization in the ESRD population, and is typical of with primary MN with additional staining associated a substantial increase in all-causestrong mortality during for the hospitalization. RAAS inhibitors (RAASi) known to of the PLA within immune deposits (Figare S1). Many 2R antigen Although have both renoprotective and cardioprotective effects, patients (pts) on subepithelial deposits were completely surrounded by new RAASi are at increased risk for hyperkalemia, which limits the basement membrane material S2), and 35% of the utilization of these life-saving therapies.(Fig Sodium zirconium cyclosilicate (ZS-9) is thought to be a novel, nonabsorbed selective cation trap that selectively binds K+ throughout the GI tract. In 2 large double-blind, placebo-controlled, randomized Phase 3 trials 1 and HARMONIZE [JAMA]), HK pts received ZS-9 (ZS-003 [NEJM] From the Department of Medicine, Renal Section, and DeTID for initial 248h, followed by QD treatment for 12 3 days (ZS-003) or 4 partments of ObstetricsThis and Gynecology, Pediatrics, 28 days (HARMONIZE). subgroup analysis included pts withand Pathology and who Laboratory Medicine, Boston Medical stage 5 CKD received ZS-9 10g TID pooled fromUniversity these two Phase 3 studies. Center, Boston, MA. * A total of 42 of 1011 pts from both studies had stage 5 CKD and Current affiliation: Department Medicine, Division received ZS-9 10g TID. Median age was of 65 Internal yrs; 60% were on RAASi; baseline K+University was 5.7 mEq/L. ZS-9 significantly reduced serum K+ Lake ofmean Nephrology, of Utah School of Medicine, Salt as early as 1h after administration (Figure); at 48h, 94% of pts City, UT. + normalized and mean K reduction was 1.2 mEq/L. In the QD y Current affiliation: Department of Obstetrics Gynecology, maintenance phase, GI rates of adverse events were 3.5%and for ZS-9 and 6.6% forWashington placebo; constipation and Center, diarrhea were most common. Medstar Hospital Washington, DC.

Received June 29, 2015. Accepted in revised form October 27, 2015. Originally published online December 29, 2015. Address correspondence to Laurence H. Beck Jr, MD, PhD, Renal Section, X-504, 650 Albany St, Boston, MA 02118. E-mail: ZS-9 rapidly normalized K+ within hours in stage 5 CKD pts and was [email protected] generally suggesting a role in managing acute � 2016well by tolerated, the National Kidney Foundation, Inc. HK in this population. 0272-6386 http://dx.doi.org/10.1053/j.ajkd.2015.10.031 775 A103