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Allopurinol-Induced ANCA Glomerulonephritis
NKF 2016 Spring Clinical Meetings Abstracts
Case Report 325 PTH IMPROVEMENT AFTER IMPLEMENTATION OF MINERAL BONE DISEASE ROUNDS IN THE DIALYSIS UNIT, A QUALITY IMPROVEMENT INITIATIVE Jennifer Sheyman, Vinai Katragadda, Lindsey Repine, Cheryl Morris, Cassandra Wert, Tahnee Felker, Barbara Clark. Nephrology and Hypertension, Allegheny General Hospital, and Davita Northside Dialysis Unit, Pittsburgh, PA. Management of mineral bone disease (MBD) is challenging given the complex interaction of diet, phosphorus (P) binders, vitamin-D and calcimimetics and cannot be fully addressed by relying solely on vitamin D protocols. We report results after one year of multidisciplinary (MBD) monthly rounds. Step 1: Dietician reviews labs and meets with patient for review diet recall and binder use. Step 2: Dietician and MD meet and review step 1 as well as doxercalciferol (D) dose and cinacalcet (C) use / dose. If PTH is >400 and corrected Ca 8.4- 10, D dose is increased by 0.5-1 mcg increments. Once D dose > 5 mcg social worker begins process of authorization for C. If PTH >400 and corrected Ca >10, either change binder to non calcium binder, initiate or increase C before increase D. If PTH >400 and corrected Ca <8.4, increase D before begin or increase C. In all cases, if P > 5.5 diet suggestions made and/ or adjustment P binder dose/ type. Social worker obtains any authorization needed. Adjustment in D is not based on P level. Step 3: Nursing staff implements above changes and notes any deviation from computer generated D protocol. Deviation from protocol occurred 46-48% of the time. With this approach the percent of patients achieving target PTH (<600pg/ml) over past year has improved with PTH at target from 48% to 69%, (669+59 to 419+38 pg/ml, p<0.05) without adverse effect on Ca (8.8+0.08 to 8.9+0.08 mg/dl) or P (5.3+0.17 to 5.3+0.15 mg/dl). This was driven by gradual increase in doxercalciferol dose ( 3.6+0.3 to 4.3+0.3 mcg/each HD)and increase use of cinacalcet ( from 38 to 48 %).
326 ALLOPURINOL-INDUCED ANCA GLOMERULONEPHRITIS Mahesh Shrestha, Hemant Magoo, Vanesa Bijol, Ashish Verma. Saint Vincent Hospital, Worcester, MA. Prescription drugs are known to cause AKI and CKD usually due to tubulo-interstitial injury. Druginduced glomerular injury is lesser-known but important entity. It could be from direct cellular toxicity or sometimes, drug-induced immunemediated processes. Here, we review an unusual case of allopurinolinduced, ANCA-associated glomerulonephritis (GN). A 65-year-oldfemale with hypertension, diabetes and gout had chronic kidney disease (Cr 1.7-1.9 mg/dL) with nephrotic-range proteinuria presumed secondary to diabetic nephropathy. Over three months, her creatinine rose to 3.9 mg/dL. She was not taking any NSAIDs, had no recent exposure to intravenous contrast and her ARB were held given worsening Cr. She denied any rash or recent antibiotic exposure. ANA and p-ANCA were positive, with very high titers of anti-MPO. DsDNA and anti-histone antibodies were negative. Kidney biopsy showed ANCA-MPO positive crescentic glomerulonephritis with scattered trace IgG reactivity along with early diffuse and nodular diabetic glomerulosclerosis. Drug-induced GN was in the differential given the absence of an alternative explanation. The mesangial dense-deposits further substantiated drug-induced ANCA GN. Review of her medication list identified allopurinol as a potential offender that was was discontinued. She received prednisone and cyclophosphamide given severe kidney injury with cellular crescents. Creatinine plateaued and then improved slowly. Drug-induced autoimmunity with major organ involvement is seen in 0.05 percent patients exposed to the incriminated drug. Drug-induced, ANCA vasculitis should be considered in patients with a history of culprit drug exposure, high-titer anti-MPO antibodies with simultaneous elevation of ANA, anti-histone and anti-phospholipid antibody titers. Awareness of these associations is important in distinguishing drug-associated syndromes from their idiopathic counterparts, as this distinction is important in diagnosis, treatment and prognosis of these patients. Early recognition may lead to halting and even reversal of glomerular injury after discontinuation of the offending drug. Recognition is hampered by lack of published literature, diverse clinical manifestations and an absence of definitive biomarkers.
A100
327
TREATMENT OF ESRD REQUIRING HD AND LDL-PHERESIS Ghodrat A Siami, Vanderbilt School of Medicine, Vanderbilt Medical Center, Nashville, TN, USA Patients with ESRD ON HD may have familial hypercholesterolemia , drug resistant requiring Al-Rabadi, MBBS,1,* Rivka LDL-pheresis. Homozygous patients Laith are unable to use cholesterol, so we evaluated the efficacy Jennifer E. Ballard, MD,2,y Alan and safety of eight different extracorporeal David J. Salant, MD,1 methods simultaneously to remove LDL. HD requires 4 hours, LDL-Pheresis 3-4 hours, together 7-8 hours, which is too long, & There isstaff. little information about pregnancy o inconvenient to the patient/ nursing We especially those with circulating autoantibod performed HD and Plasma Exchange, Membrane using Plasma Fractionation, Thermoautoantigen in primary MN. We present what filtration, Double-Filtrationa ,39-year-old Chemo-affinity woman with PLA2R-associate dextran sulfate, Liposorba LDL-Pheresis in our anasarca, hypoalbuminemia (albumin, 1.3-2. center and investigated result of LDL heparin opsy revealed MN with staining for PLA2R, a precipitation, HELP system, Other ImmunodidasnotAnti-Apo respond to conservative therapy a adsorption system were tried She such Several B or Anti-LP a, and LDL removal from weeks wholeafter presentation, she was fou further immunosuppressive treatment. Protei blood (DALI system). Pheresis, used in last 12 years for anti-PLA patients Circulating 2R levels declined but w with homozygous with good results. withoutEight proteinuria at birth or at her subseque different extracorporeal methods can be used in had detectable circulating anti-PLA2R of imm patient on HD at the same time to remove LDL . low titers. Only trace amounts of IgG4 ant Plasma Exchange is safe, effective but not discrepancy specific. Membrane Fractionation, Doublebetween anti-PLA2R levels in th Am Jare Kidney Dis. 67(5):775-778. ª 2016 by Filtration and Thermo-filtration safe, effective, and semi-specific for LDL Pheresis. Dextran sulfate affinity column, Liposorber, is INDEX WORDS: Membranous nephropathy ( safe, effective, and specific receptor for LDL-Pheresis. (PLA2R); autoantibody; placenta; ritu Immuno-adsorptions are safe, very specific to remove LDL, making it the best form of LDLPheresis. Simultaneous procedure is easy on HD patient/nursing staff.
Pregnancy in a Patient Wit and Circulating Anti-P
P
regnant patients with autoimmune disease deliver newborns with a spectrum of cl manifestations due to the transplacental passa 328 circulating autoantibodies. Pregnant patients CHARACTERIZING THE BURDEN OF ANEMIA IN END-STAGE 1 1 lupus myasthenia gravis can deliver babies Adam G. Walker, RENAL DISEASE PATIENTS: Scottor Sibbel, 2 Trudy B. Pendergraft,2 Seancorresponding Zhao,2 Louise Sargent-Heuer, Shaum disease in the neonate.1,2 Neo Kabadi,2 Steven M. Brunelli,1 1 2 membranous nephropathy DaVita Clinical Research, Minneapolis, MN, USA; AstraZeneca, (MN) not associated Wilmington, DE, USA congenital infection was first described in 199 Despite being recognized as common, the precise prevalence of attributed to patients the passive anemia among end-stage renal disease (ESRD) in the US istransfer of maternal unknown, in part because there is no consensus definition. Treatment bodies to putative renal antigens.3 More than a d with an erythropoiesis-stimulating agent (ESA) is one4indication that a later, Debiec et al identified the first antigen inv patient is considered anemic, as is a hemoglobin (Hb) level consistent in such cases aslabeling). neutral endopeptidase (NE with candidacy for ESA initiation (<10 g/dL per FDA In this investigation, we examined the prevalence of anemia in a largeon the surface of the pod metalloprotease present representative cohort of contemporary dialysis patients in the US using and involved proteolytic regulation of va the compound definition: treatment with ESA or in Hb the <10 g/dL. The cross-sectional analysis was tive based peptides. on data for theDebiec calendar month et al described a mother w January 2015. Results are reported for the overall population and mutation preventing NEP expression who had fo separately for hemodialysis (HD) and peritoneal dialysis (PD) patients. Dialysis Patients Hb <10 g/dL antibodies ESAESA+to fetomaternal alloi anti-NEP due Y 34,038 nization from797 a previous miscarriage; these antib Overall (N=159,377) N 23,577 100,965 were to cross the placenta and cause subepit Y 570 30,317 HD (N=142,406) deposits in the fetal kidney of a subsequent N 18,371 93,148 nancy. M-type A2 receptor (PL Y 238 phospholipase 3,710 PD (N=16,971) 5,206 wasN later identified as 7,817 the major autoantigen fo The prevalence of anemia was 85.2% among all dialysis patients, and 5 adults. Little literature exists was 87.1% and 69.3% withinmary the HD MN and PD in subgroups, respectively. Overall, 97.7% patients withpregnancy Hb <10 g/dL were treated within ESA. outcomes patients with nephrotic Among all ESA-treated patients, 25.2% had Hb <10 g/dL; this drome due to primary MN, with no data ava proportion was 24.6% and 32.2% in the HD and PD subgroups, about pregnancy in PLA2R-associated disease respectively. In this large cohort of contemporary dialysiswe patients in the US, present what believe to the be the first known ca prevalence of anemia was 85.2%. The majority of anemic patients were pregnancy in a patient with PLA2R-associated treated with ESAs. Study sponsored by AstraZeneca. who was seropositive for anti-PLA2R autoantib throughout the course of her pregnancy. Am J Kidney Dis. 2016;67(5):A1-A118
Case Report 325 PTH IMPROVEMENT AFTER IMPLEMENTATION OF MINERAL BONE DISEASE ROUNDS IN THE DIALYSIS UNIT, A QUALITY IMPROVEMENT INITIATIVE Jennifer Sheyman, Vinai Katragadda, Lindsey Repine, Cheryl Morris, Cassandra Wert, Tahnee Felker, Barbara Clark. Nephrology and Hypertension, Allegheny General Hospital, and Davita Northside Dialysis Unit, Pittsburgh, PA. Management of mineral bone disease (MBD) is challenging given the complex interaction of diet, phosphorus (P) binders, vitamin-D and calcimimetics and cannot be fully addressed by relying solely on vitamin D protocols. We report results after one year of multidisciplinary (MBD) monthly rounds. Step 1: Dietician reviews labs and meets with patient for review diet recall and binder use. Step 2: Dietician and MD meet and review step 1 as well as doxercalciferol (D) dose and cinacalcet (C) use / dose. If PTH is >400 and corrected Ca 8.4- 10, D dose is increased by 0.5-1 mcg increments. Once D dose > 5 mcg social worker begins process of authorization for C. If PTH >400 and corrected Ca >10, either change binder to non calcium binder, initiate or increase C before increase D. If PTH >400 and corrected Ca <8.4, increase D before begin or increase C. In all cases, if P > 5.5 diet suggestions made and/ or adjustment P binder dose/ type. Social worker obtains any authorization needed. Adjustment in D is not based on P level. Step 3: Nursing staff implements above changes and notes any deviation from computer generated D protocol. Deviation from protocol occurred 46-48% of the time. With this approach the percent of patients achieving target PTH (<600pg/ml) over past year has improved with PTH at target from 48% to 69%, (669+59 to 419+38 pg/ml, p<0.05) without adverse effect on Ca (8.8+0.08 to 8.9+0.08 mg/dl) or P (5.3+0.17 to 5.3+0.15 mg/dl). This was driven by gradual increase in doxercalciferol dose ( 3.6+0.3 to 4.3+0.3 mcg/each HD)and increase use of cinacalcet ( from 38 to 48 %).
326 ALLOPURINOL-INDUCED ANCA GLOMERULONEPHRITIS Mahesh Shrestha, Hemant Magoo, Vanesa Bijol, Ashish Verma. Saint Vincent Hospital, Worcester, MA. Prescription drugs are known to cause AKI and CKD usually due to tubulo-interstitial injury. Druginduced glomerular injury is lesser-known but important entity. It could be from direct cellular toxicity or sometimes, drug-induced immunemediated processes. Here, we review an unusual case of allopurinolinduced, ANCA-associated glomerulonephritis (GN). A 65-year-oldfemale with hypertension, diabetes and gout had chronic kidney disease (Cr 1.7-1.9 mg/dL) with nephrotic-range proteinuria presumed secondary to diabetic nephropathy. Over three months, her creatinine rose to 3.9 mg/dL. She was not taking any NSAIDs, had no recent exposure to intravenous contrast and her ARB were held given worsening Cr. She denied any rash or recent antibiotic exposure. ANA and p-ANCA were positive, with very high titers of anti-MPO. DsDNA and anti-histone antibodies were negative. Kidney biopsy showed ANCA-MPO positive crescentic glomerulonephritis with scattered trace IgG reactivity along with early diffuse and nodular diabetic glomerulosclerosis. Drug-induced GN was in the differential given the absence of an alternative explanation. The mesangial dense-deposits further substantiated drug-induced ANCA GN. Review of her medication list identified allopurinol as a potential offender that was was discontinued. She received prednisone and cyclophosphamide given severe kidney injury with cellular crescents. Creatinine plateaued and then improved slowly. Drug-induced autoimmunity with major organ involvement is seen in 0.05 percent patients exposed to the incriminated drug. Drug-induced, ANCA vasculitis should be considered in patients with a history of culprit drug exposure, high-titer anti-MPO antibodies with simultaneous elevation of ANA, anti-histone and anti-phospholipid antibody titers. Awareness of these associations is important in distinguishing drug-associated syndromes from their idiopathic counterparts, as this distinction is important in diagnosis, treatment and prognosis of these patients. Early recognition may lead to halting and even reversal of glomerular injury after discontinuation of the offending drug. Recognition is hampered by lack of published literature, diverse clinical manifestations and an absence of definitive biomarkers.
A100
327
TREATMENT OF ESRD REQUIRING HD AND LDL-PHERESIS Ghodrat A Siami, Vanderbilt School of Medicine, Vanderbilt Medical Center, Nashville, TN, USA Patients with ESRD ON HD may have familial hypercholesterolemia , drug resistant requiring Al-Rabadi, MBBS,1,* Rivka LDL-pheresis. Homozygous patients Laith are unable to use cholesterol, so we evaluated the efficacy Jennifer E. Ballard, MD,2,y Alan and safety of eight different extracorporeal David J. Salant, MD,1 methods simultaneously to remove LDL. HD requires 4 hours, LDL-Pheresis 3-4 hours, together 7-8 hours, which is too long, & There isstaff. little information about pregnancy o inconvenient to the patient/ nursing We especially those with circulating autoantibod performed HD and Plasma Exchange, Membrane using Plasma Fractionation, Thermoautoantigen in primary MN. We present what filtration, Double-Filtrationa ,39-year-old Chemo-affinity woman with PLA2R-associate dextran sulfate, Liposorba LDL-Pheresis in our anasarca, hypoalbuminemia (albumin, 1.3-2. center and investigated result of LDL heparin opsy revealed MN with staining for PLA2R, a precipitation, HELP system, Other ImmunodidasnotAnti-Apo respond to conservative therapy a adsorption system were tried She such Several B or Anti-LP a, and LDL removal from weeks wholeafter presentation, she was fou further immunosuppressive treatment. Protei blood (DALI system). Pheresis, used in last 12 years for anti-PLA patients Circulating 2R levels declined but w with homozygous with good results. withoutEight proteinuria at birth or at her subseque different extracorporeal methods can be used in had detectable circulating anti-PLA2R of imm patient on HD at the same time to remove LDL . low titers. Only trace amounts of IgG4 ant Plasma Exchange is safe, effective but not discrepancy specific. Membrane Fractionation, Doublebetween anti-PLA2R levels in th Am Jare Kidney Dis. 67(5):775-778. ª 2016 by Filtration and Thermo-filtration safe, effective, and semi-specific for LDL Pheresis. Dextran sulfate affinity column, Liposorber, is INDEX WORDS: Membranous nephropathy ( safe, effective, and specific receptor for LDL-Pheresis. (PLA2R); autoantibody; placenta; ritu Immuno-adsorptions are safe, very specific to remove LDL, making it the best form of LDLPheresis. Simultaneous procedure is easy on HD patient/nursing staff.
Pregnancy in a Patient Wit and Circulating Anti-P
P
regnant patients with autoimmune disease deliver newborns with a spectrum of cl manifestations due to the transplacental passa 328 circulating autoantibodies. Pregnant patients CHARACTERIZING THE BURDEN OF ANEMIA IN END-STAGE 1 1 lupus myasthenia gravis can deliver babies Adam G. Walker, RENAL DISEASE PATIENTS: Scottor Sibbel, 2 Trudy B. Pendergraft,2 Seancorresponding Zhao,2 Louise Sargent-Heuer, Shaum disease in the neonate.1,2 Neo Kabadi,2 Steven M. Brunelli,1 1 2 membranous nephropathy DaVita Clinical Research, Minneapolis, MN, USA; AstraZeneca, (MN) not associated Wilmington, DE, USA congenital infection was first described in 199 Despite being recognized as common, the precise prevalence of attributed to patients the passive anemia among end-stage renal disease (ESRD) in the US istransfer of maternal unknown, in part because there is no consensus definition. Treatment bodies to putative renal antigens.3 More than a d with an erythropoiesis-stimulating agent (ESA) is one4indication that a later, Debiec et al identified the first antigen inv patient is considered anemic, as is a hemoglobin (Hb) level consistent in such cases aslabeling). neutral endopeptidase (NE with candidacy for ESA initiation (<10 g/dL per FDA In this investigation, we examined the prevalence of anemia in a largeon the surface of the pod metalloprotease present representative cohort of contemporary dialysis patients in the US using and involved proteolytic regulation of va the compound definition: treatment with ESA or in Hb the <10 g/dL. The cross-sectional analysis was tive based peptides. on data for theDebiec calendar month et al described a mother w January 2015. Results are reported for the overall population and mutation preventing NEP expression who had fo separately for hemodialysis (HD) and peritoneal dialysis (PD) patients. Dialysis Patients Hb <10 g/dL antibodies ESAESA+to fetomaternal alloi anti-NEP due Y 34,038 nization from797 a previous miscarriage; these antib Overall (N=159,377) N 23,577 100,965 were to cross the placenta and cause subepit Y 570 30,317 HD (N=142,406) deposits in the fetal kidney of a subsequent N 18,371 93,148 nancy. M-type A2 receptor (PL Y 238 phospholipase 3,710 PD (N=16,971) 5,206 wasN later identified as 7,817 the major autoantigen fo The prevalence of anemia was 85.2% among all dialysis patients, and 5 adults. Little literature exists was 87.1% and 69.3% withinmary the HD MN and PD in subgroups, respectively. Overall, 97.7% patients withpregnancy Hb <10 g/dL were treated within ESA. outcomes patients with nephrotic Among all ESA-treated patients, 25.2% had Hb <10 g/dL; this drome due to primary MN, with no data ava proportion was 24.6% and 32.2% in the HD and PD subgroups, about pregnancy in PLA2R-associated disease respectively. In this large cohort of contemporary dialysiswe patients in the US, present what believe to the be the first known ca prevalence of anemia was 85.2%. The majority of anemic patients were pregnancy in a patient with PLA2R-associated treated with ESAs. Study sponsored by AstraZeneca. who was seropositive for anti-PLA2R autoantib throughout the course of her pregnancy. Am J Kidney Dis. 2016;67(5):A1-A118