- Email: [email protected]
C3 Dominant MPGN and Anti-GBM Glomerulonephritis With Negative Anti-GBM Antibodies: A Rare Combination
NKF 2016 Spring Clinical Meetings Abstracts
Case Report 217
219
TRANSMEMBRANE PROTEIN 2 (TMEM2) AND POLYCYSTIN-1 MODIFIED-RELEASE CALCIFEDIOL TREATMENT OF SHPT INDICATES THAT HIGHER THAN EXPECTED SERUM 25D (PC1); A NOVEL INTERACTION, WHICH MAY FORM THE LEVELS MAY BE REQUIRED IN SUBJECTS WITH CKD. Joel BASIS OF A TEST FOR PKD. 2 Melnick1, Stephen Strugnell1, Sailaja Dharmanolla1, Carlos Garces1, Kerri McGreal, Madhulika Sharma, Darren Wallace, and Christopher J Martin Petkovich1, Charles Bishop1 and Stuart Sprague2. 1OPKO Ward, University of Kansas Medical Center, Kansas 1, City, KS, USA 1 1 Renal, Ramon Miami, FL and University Al-Rabadi, MBBS, * Rivka G.2Northshore Bonegio, MD, Health PhD,System, Background: Laith Autosomal Dominant Polycystic Kidney Disease Ayalon, MD, Evanston, IL 2,y disease. 3 4 (ADPKD) is a common hereditary cause of end stage renal Jennifer E. Ballard, MD, Alan M. Fujii, MD, Joel M. Henderson, MD, PhD, Vitamin D (ergocalciferol or cholecalciferol) repletion therapy is the Affected individuals have mutations in PKD1 or PKD2 genes, 1 1 current standard of care for correcting vitamin D insufficiency (VDI), David J. Salant, MD, and Laurence H. Beck Jr, MD, PhD generating defective polycystin -1 (PC1) or polycystin -2 (PC2) controlling secondary hyperparathyroidism (SHPT) and improving protein. TMEM2 is a novel protein with extensive homology to skeletal health in patients with chronic kidney disease (CKD) but is fibrocystin, the product of the polycystic kidney and hepatic disease unreliable and generally ineffective. We investigated the efficacy of It hasisbeen that urinary exosomes from outcomes in patients (PKHD1) gene. There littleshown information about pregnancy with active membranous (MN),doublemodified-release calcifediol (MRC) in nephropathy two identical 26-week individualsespecially with PKD1 those mutations have decreased levels of PC1 and placebo-controlled and a(PLA 26-week study in receptor the major with circulating autoantibodies to M-typeblind phospholipase A2 studies 2R),extension that levels of transmembrane protein 2 (TMEM2) are increased when patients with stage 3 orcase 4 CKD report the pregnancy integrated results. inwith primary MN. We present whatWe we believe to be the first known of and successful in compared autoantigen with individuals no mutations in the PKD genes. Data were pooled and analyzed from 429 patients with SHPT (plasma year prior to stage pregnancy, theandpatient developed a 39-year-old woman with PLA2R-associated sought to determine the expression status of TMEM2 in ADPKD andMN. In theiPTH>85 pg/mL), 3 or 4 CKD VDI (serum 25D of 10-29 whether TMEM2 interacts with PC1. anasarca, hypoalbuminemia (albumin, 1.3-2.2 g/dL), and proteinuria excretion, g/d). Kidney bi- once ng/mL) who (protein were randomized 2:1 to29.2 receive MRC or placebo Methods: Immunohistochemistry Sections from2ADPKD bedtime for 26 weeks. Most (83%) patients received MRC for R, and the patientdaily wasat seropositive for anti-PLA opsy revealed MN with(IHC): staining for PLA 2R autoantibodies. human kidney andrespond normal human kidney (NHK) tissues were 26with moreintravenous weeks. MRC dosing started 30 µg/dofand Shetissues did not to conservative therapy and was treated rituximab (2atdoses 1 gincreased each). in most (~75%) eligible patients to 60 µg/d after 12 weeks. Efficacy endpoints probed for presence of TMEM2 and PC1. Several weeks presentation, she was found pregnant and was closely followed upawithout included a mean increase in 25D to ≥30 ng/mL and mean 30% Immunoprecipitations (IP):after HEK293T cells were co-transfected withto be 6 weeks immunosuppressive remained with protein in the 8- to adverse 12-g/d events range. decrease in iPTH. excretion Safety endpoints included (AEs), full lengthfurther V5 tagged TMEM2 construct andtreatment. various Flag Proteinuria tagged N serum Ca urine Ca/Cr and tubular reabsorption P (TRP). terminus PC1constructs. Co-IPs were on membrane levels declined but were still detectable. Atand 38P,weeks, a healthy baby girl wasofborn, Circulating anti-PLA 2R performed Serum 25D response rates in the MRC group increased from 81 and preparations derivedproteinuria from the transfectants. without at birth or at her subsequent 6-month postnatal visit. At the time of delivery, the mother still 90% at 30 µg/d after 26 and 52 weeks, respectively, to >95% at 60 Results: Increased TMEM2 expression was detected on the apical (IgG1), IgG3, and IgG4group subclasses, at mean had detectable circulating anti-PLA2R of immunoglobulin G1 µg/d, versus 5% in the placebo (P<0.001).although At 52 weeks, aspect of cyst epithelial cells in ADPKD kidneys when compared to wasblood. 59 and 82 ng/mL at reasons the 30 and 60 found in25D cord Potential forµg/d thedose low kidneys. titers. Only trace amounts of an IgG4 anti-PLA2R weresteady-state Co-IP showed that there was interaction normal human levels. responseare ratesdiscussed. increased from 30 and 32% at 30 µg/d after levelstointhethe fetaliPTH circulation discrepancy between anti-PLA between PC-1 and TMEM2. The interaction was mapped N- maternal and 2R 26 and 52 weeks, respectively, to >50% at 60 µg/d, versus 9% in the terminal extra-cellular portion PC1 and TMEM2 ª appeared Am J Kidney Dis.of67(5):775-778. 2016 to byhave the National Kidney Foundation, Inc. placebo group (p<0.001). Serum and urine Ca and P were unchanged high affinity for the PKD domains within PC1. with dose and stable during treatment. AEs were comparable between Conclusion: Increased TMEM2 expression in ADPKD kidneys and dose and treatment groups. INDEX WORDS: Membranous nephropathy (MN); nephrotic syndrome; pregnancy; M-type phospholipase A2 urinary exosomes and the interaction of TMEM2 with PC1 suggests The efficacyGof(Ig MRC controlling SHPT in patients with stage 3 or receptor (PLA autoantibody; placenta; of rituximab; immunoglobulin G)insubclass. 2R);implicated that TMEM2 is a novel protein in the pathogenesis 4 CKD and VDI rose with dose as serum 25D increased beyond 30 ADPKD. The ratio of PC1/TMEM2 may have utility in the diagnosis of ng/mL without safety concerns. These data indicate that vitamin D pre-cystic disease and in monitoring the disease progression and sufficiency should be defined at a level above 30 ng/mL in patients response to treatment. with stage 3 or 4 CKD. Higher doses of MRC and associated 25D levels warrant further clinical evaluation. regnant patients with autoimmune disease may CASE REPORT
Pregnancy in a Patient With Primary Membranous Nephropathy and Circulating Anti-PLA R Antibodies: A Case Report
P
deliver newborns with a spectrum of clinical manifestations due to the transplacental passage of 218 circulating autoantibodies. Pregnant patients with INCIDENCE OF DIALYSIS REQUIRING ACUTE KIDNEY lupus or myasthenia gravis can deliver babies with INJURY IN ATRIAL FIBRILLATION: A NATIONAL 1 1,2 Ioannis Konstantinidis , Achint Patel1, PERSPECTIVE Swati Mehta1, in corresponding disease the neonate. Neonatal Shanti Patel1, Pranav Garimella2, Narendra Annapureddy3, Shiv Kumar 1. membranous nephropathy associated with G Coca1, Girish N(MN) Nadkarninot Agarwal4, Steven 1.Icahn school of medicinewas at Mount NYC, NY, USA.2.Tufts congenital infection firstSinai, described in 1990 and University,Boston,MA,USA.3.Vanderbilt,Nashville,TN,USA and attributed to the passive transfer of maternal anti4.UAMS,Little Rock,Arkansas,USA 3 for hospitalization. Atrial is a common reason bodies toFibrillation putative(AF) renal antigens. More than a decade However, there is limited 4 data on acute kidney injury requiring dialysis later, Debiec alaimed identified the first antigen involved (AKI-D) in AF.et We to assess temporal trends and outcomes in AF hospitalizations with a endopeptidase nationally representative database. a in AKI-D such incases as neutral (NEP), We reviewed the Healthcare Cost and Utilization Project’s metalloprotease present on the surface of the podocyte Nationwide Inpatient Sample (NIS) database for AF hospitalizations andusing involved in the proteolytic regulation ofa vasoacvalidated ICD-9CM codes and identified AKI-D using of AKI and dialysis procedure codes after excluding end tivecombination peptides. Debiec et al described a mother with a stage renal disease. We utilized Cochrane-Armitage test for temporal mutation preventing NEP expression who had formed trends in AKI-D and multivariable logistic regression to generate adjusted odds ratios (aOR) for AKI-D and its impact on anti-NEP antibodies due to predictors fetomaternal alloimmuoutcomes. There were 38, 04,555 hospitalizations with a primary nization from a previous miscarriage; these antibodies diagnosis of AF from 2002-2012. Of them, 3918(0.1%) were complicated with AKI-D. Incidence tripled 0.55/1000 were to cross the placenta andfrom cause subepithelial hospitalizations in 2002 to 1.50/1000 hospitalizations in 2012. The deposits in the fetal kidney of a subsequent pregincreased incidence of AKI-D was explained by demographic changes and increase in comorbidities. Significant A predictors of AKI-D included nancy. M-type phospholipase receptor (PLA 2 2R) race (aOR of 1.45; 95% CI 1.12-1.89); hypertension (aOR 1.57; wasblack later identified as the major autoantigen for pri95% CI 1.29-1.92); diabetes (aOR 1.58; 95% CI 1.32-1.89); chronic 5 kidney disease 2.36; 95%Little CI 1.89-2.94); sepsis (aOR 0.47; 95% mary MN in(aOR adults. literature exists about CI 6.79-13.23) and heart failure (aOR 2.73; 95% CI 2.27-3.29). AKI-D pregnancy outcomes in patients with nephrotic synwas associated with an in-hospital mortality (aOR 22.1; 95% CI 17.6drome to primary MN, (aOR with10.11; no 95% dataCI available 27.58) due and increased adverse discharge 3.2731.26). about pregnancy in PLA2R-associated disease. We Incidence of AKI-D in the setting of hospitalization for AF has present what believe to isbeassociated the first case of tripled over the we last decade. AKI-D withknown severe mortality and morbidity. should bewith focusedPLA on early identification of MN pregnancy inEfforts a patient R-associated 2 patients at risk and improved preventive efforts to improve outcomes in who seropositive thiswas vulnerable population. for anti-PLA2R autoantibodies throughout the course of her pregnancy. Am J Kidney Dis. 2016;67(5):A1-A118
A 39-year-old multiparous woman with morbid obesity presented for workup of severe nephrotic syndrome several months 220
before her current pregnancy. She had been treated for resistant C3 DOMINANT MPGN AND ANTI-GBM hypertension and lower-extremity edemaANTI-GBM during the past year, GLOMERULONEPHRITIS WITH NEGATIVE but her proteinuria hadCOMBINATION. been overlooked. AtMeouchy, presentation, serum ANTIBODIES: A RARE Joseph Gbemisola Adenuga, Division Nephrology and Hypertension, creatinine level was 1.52ofmg/dL (corresponding to Keck estimated School of Medicine, University Of Southern California,2Los Angeles, glomerular filtration rate of 46 mL/min/1.73 m as calculated by CA, USA the Anti-glomerular isotope-dilution mass spectrometry –traceable 4-variable basement membrane (anti-GBM) disease presents as MDRD of Diet in with Renal Disease] Study equaa rapidly[Modification progressive glomerulonephritis or without alveolar hemorrhage. is characterized circulating autoantibodies to tion); serum Italbumin level,by1.5 g/dL; and 24-hour specific urine protein α3-chain of29.2 the type IV collagen linear Immunoglobulin (Ig)G features excretion, g. The kidneyandbiopsy specimen revealed deposition along both the GBM and the alveolar basement membrane. typical of primary with additional strong staining The diagnosis requiresMN demonstration of anti-GBM Antibodies in the for the PLA within immune deposits Many serum kidney. The anti-GBM antibodies are of(Fig IgG1 S1). subclass and of the 2Rorantigen can in most cases be detected in the completely circulation using enzyme-linkedby new subepithelial deposits were surrounded immunosorbent assay (ELISA). basement membrane material (Fig S2), and 35% of the We report a case of a 20 year old female patient who presents with a mixed nephritic/nephrotic syndrome (24-hours urinary protein of 10.2 g/d), normal creatinine at 0.7, C3 borderline low at 88 mg/dl and 1 mg/dl and negative serum anti-GBM. Renal biopsy normal From C4 theat 15 Department of Medicine, Renal Section, and Derevealed 2 different processes: a C3 dominant membranoproliferative 2 partments of Obstetrics and Gynecology, 3Pediatrics, and 4Paglomerulonephritis pattern and a superimposed anti-GBM nephritis thology and Laboratory Medicine, Boston University Medical with 50% active early crescents and linear IgG deposition on Center, Boston, MA.Work up for autoimmune diseases, infectious immunofluorescence. * diseases andaffiliation: C3 glomerulopathy including deficiency screen, Division Current Department of C5-9 Internal Medicine, CH50 screen, C3 Nephritic Factor ratio was negative. Patient was of Nephrology, University of Utah School of Medicine, Salt Lake induced with cyclophosphamide, pulse intravenous methylprednisolone City, UT. seven sessions of plasmapheresis with slow improvement and received y affiliation: Department of Obstetrics and Gynecology, ofCurrent her nephritic/nephrotic syndrome. Few cases of anti-GBM disease with negative anti-GBM Antibodies Medstar Washington Hospital Center, Washington, DC. have been reported in the literature, thoughtin to revised be either related to IgG4 27, Received June 29, 2015. Accepted form October subclass antibodies not detected on ELISA or it may be that the 2015. Originally published online December 29, 2015. antibodies were directed against the intact alpha3(IV)NC1 epitope. Address to of Laurence H.anti-GBM Beck Jr, MD, PhD, Our case iscorrespondence a unique combination MPGN and disease with negative which diagnosis and treatment very Renal Section,ELISA X-504, 650makes Albany St, Boston, MA 02118. E-mail: challenging. [email protected]
� 2016 by the National Kidney Foundation, Inc. 0272-6386 http://dx.doi.org/10.1053/j.ajkd.2015.10.031
775 A73
Case Report 217
219
TRANSMEMBRANE PROTEIN 2 (TMEM2) AND POLYCYSTIN-1 MODIFIED-RELEASE CALCIFEDIOL TREATMENT OF SHPT INDICATES THAT HIGHER THAN EXPECTED SERUM 25D (PC1); A NOVEL INTERACTION, WHICH MAY FORM THE LEVELS MAY BE REQUIRED IN SUBJECTS WITH CKD. Joel BASIS OF A TEST FOR PKD. 2 Melnick1, Stephen Strugnell1, Sailaja Dharmanolla1, Carlos Garces1, Kerri McGreal, Madhulika Sharma, Darren Wallace, and Christopher J Martin Petkovich1, Charles Bishop1 and Stuart Sprague2. 1OPKO Ward, University of Kansas Medical Center, Kansas 1, City, KS, USA 1 1 Renal, Ramon Miami, FL and University Al-Rabadi, MBBS, * Rivka G.2Northshore Bonegio, MD, Health PhD,System, Background: Laith Autosomal Dominant Polycystic Kidney Disease Ayalon, MD, Evanston, IL 2,y disease. 3 4 (ADPKD) is a common hereditary cause of end stage renal Jennifer E. Ballard, MD, Alan M. Fujii, MD, Joel M. Henderson, MD, PhD, Vitamin D (ergocalciferol or cholecalciferol) repletion therapy is the Affected individuals have mutations in PKD1 or PKD2 genes, 1 1 current standard of care for correcting vitamin D insufficiency (VDI), David J. Salant, MD, and Laurence H. Beck Jr, MD, PhD generating defective polycystin -1 (PC1) or polycystin -2 (PC2) controlling secondary hyperparathyroidism (SHPT) and improving protein. TMEM2 is a novel protein with extensive homology to skeletal health in patients with chronic kidney disease (CKD) but is fibrocystin, the product of the polycystic kidney and hepatic disease unreliable and generally ineffective. We investigated the efficacy of It hasisbeen that urinary exosomes from outcomes in patients (PKHD1) gene. There littleshown information about pregnancy with active membranous (MN),doublemodified-release calcifediol (MRC) in nephropathy two identical 26-week individualsespecially with PKD1 those mutations have decreased levels of PC1 and placebo-controlled and a(PLA 26-week study in receptor the major with circulating autoantibodies to M-typeblind phospholipase A2 studies 2R),extension that levels of transmembrane protein 2 (TMEM2) are increased when patients with stage 3 orcase 4 CKD report the pregnancy integrated results. inwith primary MN. We present whatWe we believe to be the first known of and successful in compared autoantigen with individuals no mutations in the PKD genes. Data were pooled and analyzed from 429 patients with SHPT (plasma year prior to stage pregnancy, theandpatient developed a 39-year-old woman with PLA2R-associated sought to determine the expression status of TMEM2 in ADPKD andMN. In theiPTH>85 pg/mL), 3 or 4 CKD VDI (serum 25D of 10-29 whether TMEM2 interacts with PC1. anasarca, hypoalbuminemia (albumin, 1.3-2.2 g/dL), and proteinuria excretion, g/d). Kidney bi- once ng/mL) who (protein were randomized 2:1 to29.2 receive MRC or placebo Methods: Immunohistochemistry Sections from2ADPKD bedtime for 26 weeks. Most (83%) patients received MRC for R, and the patientdaily wasat seropositive for anti-PLA opsy revealed MN with(IHC): staining for PLA 2R autoantibodies. human kidney andrespond normal human kidney (NHK) tissues were 26with moreintravenous weeks. MRC dosing started 30 µg/dofand Shetissues did not to conservative therapy and was treated rituximab (2atdoses 1 gincreased each). in most (~75%) eligible patients to 60 µg/d after 12 weeks. Efficacy endpoints probed for presence of TMEM2 and PC1. Several weeks presentation, she was found pregnant and was closely followed upawithout included a mean increase in 25D to ≥30 ng/mL and mean 30% Immunoprecipitations (IP):after HEK293T cells were co-transfected withto be 6 weeks immunosuppressive remained with protein in the 8- to adverse 12-g/d events range. decrease in iPTH. excretion Safety endpoints included (AEs), full lengthfurther V5 tagged TMEM2 construct andtreatment. various Flag Proteinuria tagged N serum Ca urine Ca/Cr and tubular reabsorption P (TRP). terminus PC1constructs. Co-IPs were on membrane levels declined but were still detectable. Atand 38P,weeks, a healthy baby girl wasofborn, Circulating anti-PLA 2R performed Serum 25D response rates in the MRC group increased from 81 and preparations derivedproteinuria from the transfectants. without at birth or at her subsequent 6-month postnatal visit. At the time of delivery, the mother still 90% at 30 µg/d after 26 and 52 weeks, respectively, to >95% at 60 Results: Increased TMEM2 expression was detected on the apical (IgG1), IgG3, and IgG4group subclasses, at mean had detectable circulating anti-PLA2R of immunoglobulin G1 µg/d, versus 5% in the placebo (P<0.001).although At 52 weeks, aspect of cyst epithelial cells in ADPKD kidneys when compared to wasblood. 59 and 82 ng/mL at reasons the 30 and 60 found in25D cord Potential forµg/d thedose low kidneys. titers. Only trace amounts of an IgG4 anti-PLA2R weresteady-state Co-IP showed that there was interaction normal human levels. responseare ratesdiscussed. increased from 30 and 32% at 30 µg/d after levelstointhethe fetaliPTH circulation discrepancy between anti-PLA between PC-1 and TMEM2. The interaction was mapped N- maternal and 2R 26 and 52 weeks, respectively, to >50% at 60 µg/d, versus 9% in the terminal extra-cellular portion PC1 and TMEM2 ª appeared Am J Kidney Dis.of67(5):775-778. 2016 to byhave the National Kidney Foundation, Inc. placebo group (p<0.001). Serum and urine Ca and P were unchanged high affinity for the PKD domains within PC1. with dose and stable during treatment. AEs were comparable between Conclusion: Increased TMEM2 expression in ADPKD kidneys and dose and treatment groups. INDEX WORDS: Membranous nephropathy (MN); nephrotic syndrome; pregnancy; M-type phospholipase A2 urinary exosomes and the interaction of TMEM2 with PC1 suggests The efficacyGof(Ig MRC controlling SHPT in patients with stage 3 or receptor (PLA autoantibody; placenta; of rituximab; immunoglobulin G)insubclass. 2R);implicated that TMEM2 is a novel protein in the pathogenesis 4 CKD and VDI rose with dose as serum 25D increased beyond 30 ADPKD. The ratio of PC1/TMEM2 may have utility in the diagnosis of ng/mL without safety concerns. These data indicate that vitamin D pre-cystic disease and in monitoring the disease progression and sufficiency should be defined at a level above 30 ng/mL in patients response to treatment. with stage 3 or 4 CKD. Higher doses of MRC and associated 25D levels warrant further clinical evaluation. regnant patients with autoimmune disease may CASE REPORT
Pregnancy in a Patient With Primary Membranous Nephropathy and Circulating Anti-PLA R Antibodies: A Case Report
P
deliver newborns with a spectrum of clinical manifestations due to the transplacental passage of 218 circulating autoantibodies. Pregnant patients with INCIDENCE OF DIALYSIS REQUIRING ACUTE KIDNEY lupus or myasthenia gravis can deliver babies with INJURY IN ATRIAL FIBRILLATION: A NATIONAL 1 1,2 Ioannis Konstantinidis , Achint Patel1, PERSPECTIVE Swati Mehta1, in corresponding disease the neonate. Neonatal Shanti Patel1, Pranav Garimella2, Narendra Annapureddy3, Shiv Kumar 1. membranous nephropathy associated with G Coca1, Girish N(MN) Nadkarninot Agarwal4, Steven 1.Icahn school of medicinewas at Mount NYC, NY, USA.2.Tufts congenital infection firstSinai, described in 1990 and University,Boston,MA,USA.3.Vanderbilt,Nashville,TN,USA and attributed to the passive transfer of maternal anti4.UAMS,Little Rock,Arkansas,USA 3 for hospitalization. Atrial is a common reason bodies toFibrillation putative(AF) renal antigens. More than a decade However, there is limited 4 data on acute kidney injury requiring dialysis later, Debiec alaimed identified the first antigen involved (AKI-D) in AF.et We to assess temporal trends and outcomes in AF hospitalizations with a endopeptidase nationally representative database. a in AKI-D such incases as neutral (NEP), We reviewed the Healthcare Cost and Utilization Project’s metalloprotease present on the surface of the podocyte Nationwide Inpatient Sample (NIS) database for AF hospitalizations andusing involved in the proteolytic regulation ofa vasoacvalidated ICD-9CM codes and identified AKI-D using of AKI and dialysis procedure codes after excluding end tivecombination peptides. Debiec et al described a mother with a stage renal disease. We utilized Cochrane-Armitage test for temporal mutation preventing NEP expression who had formed trends in AKI-D and multivariable logistic regression to generate adjusted odds ratios (aOR) for AKI-D and its impact on anti-NEP antibodies due to predictors fetomaternal alloimmuoutcomes. There were 38, 04,555 hospitalizations with a primary nization from a previous miscarriage; these antibodies diagnosis of AF from 2002-2012. Of them, 3918(0.1%) were complicated with AKI-D. Incidence tripled 0.55/1000 were to cross the placenta andfrom cause subepithelial hospitalizations in 2002 to 1.50/1000 hospitalizations in 2012. The deposits in the fetal kidney of a subsequent pregincreased incidence of AKI-D was explained by demographic changes and increase in comorbidities. Significant A predictors of AKI-D included nancy. M-type phospholipase receptor (PLA 2 2R) race (aOR of 1.45; 95% CI 1.12-1.89); hypertension (aOR 1.57; wasblack later identified as the major autoantigen for pri95% CI 1.29-1.92); diabetes (aOR 1.58; 95% CI 1.32-1.89); chronic 5 kidney disease 2.36; 95%Little CI 1.89-2.94); sepsis (aOR 0.47; 95% mary MN in(aOR adults. literature exists about CI 6.79-13.23) and heart failure (aOR 2.73; 95% CI 2.27-3.29). AKI-D pregnancy outcomes in patients with nephrotic synwas associated with an in-hospital mortality (aOR 22.1; 95% CI 17.6drome to primary MN, (aOR with10.11; no 95% dataCI available 27.58) due and increased adverse discharge 3.2731.26). about pregnancy in PLA2R-associated disease. We Incidence of AKI-D in the setting of hospitalization for AF has present what believe to isbeassociated the first case of tripled over the we last decade. AKI-D withknown severe mortality and morbidity. should bewith focusedPLA on early identification of MN pregnancy inEfforts a patient R-associated 2 patients at risk and improved preventive efforts to improve outcomes in who seropositive thiswas vulnerable population. for anti-PLA2R autoantibodies throughout the course of her pregnancy. Am J Kidney Dis. 2016;67(5):A1-A118
A 39-year-old multiparous woman with morbid obesity presented for workup of severe nephrotic syndrome several months 220
before her current pregnancy. She had been treated for resistant C3 DOMINANT MPGN AND ANTI-GBM hypertension and lower-extremity edemaANTI-GBM during the past year, GLOMERULONEPHRITIS WITH NEGATIVE but her proteinuria hadCOMBINATION. been overlooked. AtMeouchy, presentation, serum ANTIBODIES: A RARE Joseph Gbemisola Adenuga, Division Nephrology and Hypertension, creatinine level was 1.52ofmg/dL (corresponding to Keck estimated School of Medicine, University Of Southern California,2Los Angeles, glomerular filtration rate of 46 mL/min/1.73 m as calculated by CA, USA the Anti-glomerular isotope-dilution mass spectrometry –traceable 4-variable basement membrane (anti-GBM) disease presents as MDRD of Diet in with Renal Disease] Study equaa rapidly[Modification progressive glomerulonephritis or without alveolar hemorrhage. is characterized circulating autoantibodies to tion); serum Italbumin level,by1.5 g/dL; and 24-hour specific urine protein α3-chain of29.2 the type IV collagen linear Immunoglobulin (Ig)G features excretion, g. The kidneyandbiopsy specimen revealed deposition along both the GBM and the alveolar basement membrane. typical of primary with additional strong staining The diagnosis requiresMN demonstration of anti-GBM Antibodies in the for the PLA within immune deposits Many serum kidney. The anti-GBM antibodies are of(Fig IgG1 S1). subclass and of the 2Rorantigen can in most cases be detected in the completely circulation using enzyme-linkedby new subepithelial deposits were surrounded immunosorbent assay (ELISA). basement membrane material (Fig S2), and 35% of the We report a case of a 20 year old female patient who presents with a mixed nephritic/nephrotic syndrome (24-hours urinary protein of 10.2 g/d), normal creatinine at 0.7, C3 borderline low at 88 mg/dl and 1 mg/dl and negative serum anti-GBM. Renal biopsy normal From C4 theat 15 Department of Medicine, Renal Section, and Derevealed 2 different processes: a C3 dominant membranoproliferative 2 partments of Obstetrics and Gynecology, 3Pediatrics, and 4Paglomerulonephritis pattern and a superimposed anti-GBM nephritis thology and Laboratory Medicine, Boston University Medical with 50% active early crescents and linear IgG deposition on Center, Boston, MA.Work up for autoimmune diseases, infectious immunofluorescence. * diseases andaffiliation: C3 glomerulopathy including deficiency screen, Division Current Department of C5-9 Internal Medicine, CH50 screen, C3 Nephritic Factor ratio was negative. Patient was of Nephrology, University of Utah School of Medicine, Salt Lake induced with cyclophosphamide, pulse intravenous methylprednisolone City, UT. seven sessions of plasmapheresis with slow improvement and received y affiliation: Department of Obstetrics and Gynecology, ofCurrent her nephritic/nephrotic syndrome. Few cases of anti-GBM disease with negative anti-GBM Antibodies Medstar Washington Hospital Center, Washington, DC. have been reported in the literature, thoughtin to revised be either related to IgG4 27, Received June 29, 2015. Accepted form October subclass antibodies not detected on ELISA or it may be that the 2015. Originally published online December 29, 2015. antibodies were directed against the intact alpha3(IV)NC1 epitope. Address to of Laurence H.anti-GBM Beck Jr, MD, PhD, Our case iscorrespondence a unique combination MPGN and disease with negative which diagnosis and treatment very Renal Section,ELISA X-504, 650makes Albany St, Boston, MA 02118. E-mail: challenging. [email protected]
� 2016 by the National Kidney Foundation, Inc. 0272-6386 http://dx.doi.org/10.1053/j.ajkd.2015.10.031
775 A73