- Email: [email protected]
A Case of Mistaken Identity
NKF 2016 Spring Clinical Meetings Abstracts
Case Report 345
347
INVOLVEMENT OF FAMILIES AND PEERS IN THE CHOICE OF A CASE OF MISTAKEN IDENTITY: Dhivya Sundaramurthy, Saed DIALYSIS MODALITY IS LIMITED: THE EMPOWERING Nemr, Michael Germain, Baystate Medical center, Springfield,Ma,USA PATIENTS ON CHOICES FOR RENAL REPLACEMENT TTP (Thrombotic Thrombocytopenic Purpura) is a life threatening 2 THERAPY (EPOCH-RRT) STUDY Lalita Subramanian1, Junhui entity & misdiagnosis can prove fatal. Pathogenesis involves 1,2 Zhao1, Jarcy Zee1, Ron Pisoni, Bruce Robinson1, Francesca Tentori . 1, 2 1 1 1 microangiopathic anemia unlike syndrome which is Al-Rabadi, MBBS, * Rivka Ayalon, MD, Ramon hemolytic G. Bonegio, MD,Evans PhD, Arbor Research Laith Collaborative for Health, Ann Arbor, MI; Vanderbilt 2,y 3 4 Autoimmune hemolytic anemia (AIHA) & Immune Thrombocytopenic University Medical Center, Nashville, TN. Jennifer E. Ballard, MD, Alan M. Fujii, MD, Joel M. Henderson, MD, PhD, Given the sustained demands of dialysis on everyday lives, the 1 choice Purpura (ITP). Diagnosis of TTP is often 1 challenging due to long David J. Salant, MD, and Laurence H. Beck Jr, MD, PhD of a dialysis modality often affects loved ones. Peer mentoring turnaround time of ADAMST13 activity. Coombs test, positive in programs in which patients interact with peers with the same condition AIHA, is usually negative in TTP unless patient has Lupus. Here we are considered widely successful. However, the role of families and present a case of thrombocytopenia with positive Coombs test that led peers in dialysis modality selection is poorly understood. EPOCH-RRT There is little information about pregnancy outcomes in patients with active membranous nephropathy (MN), us off the track leading to a misdiagnosis of Evans syndrome. explored dialysis patients’ recollection of involvement of families, receptor the his major those withofcirculating to M-type A phospholipase A2male 2R), peers, and especially clinical staff in the choice their dialysis autoantibodies modality. 16 year old healthy was sent(PLA to the ER from PCP’s office in primary MN. We present what we believe to be firstpetechiae known case of successful(16,000/mm3). pregnancy in A patientautoantigen survey was developed in collaboration with a patient withthe diffuse & thrombocytopenia Lab work advisory panel and completedwoman by participants the 2US Dialysis R-associated MN. In therevealed year prior to of pregnancy, thehigh patient developed a 39-year-old with in PLA evidence hemolysis with LDH, low haptoglobin & few Outcomes anasarca, and Practice Patterns Study (DOPPS, N=1350) and hypoalbuminemia (albumin, 1.3-2.2 g/dL), and proteinuria (protein excretion, Kidney bispherocytes on peripheral smear (PS)29.2 withg/d). Coombs positivity Peritoneal DOPPS (PDOPPS, N=613) in 2015. For both HD and PD R,Over and the patientconsistent was seropositive for anti-PLA autoantibodies. opsyinvolvement revealed was MNmoderate with staining for(Figure PLA21). with Evans syndrome. He also 3.4gm proteinuria & 2R had patients, family (59-79%) She diddidnot to at conservative therapy with intravenous (2 complements doses of 1 g microscopic hematuria rituximab with negative & each). ANA. Prednisone 35% reported they notrespond know a peer the time of their decision;and was treated among those who did,weeks 30-40%after recalled no peer involvement. Clinical was initiated for Evans syndrome. Given persistent Several presentation, she was found to be 6 weeks pregnant and was closely followed upthrombocytopenia, without staff (especially nephrologists) were most commonly involved. hematuria & increasing schistocytosis on to PS 12-g/d on day 5,range. alternate further immunosuppressive treatment. Proteinuria remained with protein excretion in the 8There is an opportunity to increase family and peer involvement in diagnosis TTP/Atypical Uremic syndrome was levelsdecision-making. declined but This were still detectable. Atof38 weeks, a Hemolytic healthy baby girl was born, anti-PLA 2R shared the dialysisCirculating modality choice to promote entertained. Hence he was started on plasmapheresis empirically at birth or atwith hereach subsequent visit. At the time of delivery, the mother still while may result without in a betterproteinuria fit of the dialysis modality patient’s 6-month postnatal waiting for ADAMST13 His platelets normalized life, as wellhad as improved experience for theiranti-PLA families. 2R of immunoglobulin G1 (IgG1), IgG3, and activity. IgG4 subclasses, although after at 2 detectable circulating low ADAMST13 activity (<5) confirmed found in& acord blood. Potential reasons for TTP. the low titers. Only trace amounts of IgG4 anti-PLA2R wereexchanges Coombs positivity in TTP is extremely rare, with only 2 cases circulation are discussed. discrepancy between anti-PLA2R levels in the maternal and fetal reportedFoundation, so far. It’s veryInc. crucial to differentiate these 2 entities as the Am J Kidney Dis. 67(5):775-778. ª 2016 by the National Kidney management differs given different etio-pathogenesis. Non-specific polyclonal immune activation can lead to overlap of immunological INDEX WORDS: Membranous nephropathy (MN); nephrotic syndrome; pregnancy; M-type phospholipase A2 disorders like in our patient. Hence we should keep our differentials receptor (PLA2R); autoantibody; placenta; rituximab; immunoglobulin G (Ig G) subclass. broad, follow patient vigilantly & use lab markers like peripheral smear, urinanalysis etc diligently to clinch the right diagnosis which can be lifesaving. Hence we aim to drive home the message that coombs test can be positive in TTP. regnant patients with autoimmune disease may
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 346 circulating autoantibodies. Pregnant patients with ASSOCIATION BETWEEN VASCULAR ACCESS CREATION lupus or myasthenia can GLOMERULAR deliver babies with AND DECELERATION OFgravis ESTIMATED 1,2 FILTRATION RATE DECLINE LATE-STAGE CHRONIC corresponding disease inINthe neonate. Neonatal KIDNEY DISEASE PATIENTS TRANSITIONING TO END-STAGE 1 1 membranous nephropathy (MN) not associated RENAL DISEASE: Keiichi Sumida , Miklos Z Molnar , Praveen Kwith 1 Potukuchi1, Fridtjof Thomas , Junfirst L Lu1,described Jennie Jing2, Vanessa A and congenital infection was in 1990 Ravel2, Melissa Soohoo2, Connie M Rhee2, Elani Streja2, Kamyar 2the passive transfer 1,3 1 attributed to of maternal Kalantar-Zadeh , Csaba P Kovesdy , Division of Nephrology, anti3 University of Tennessee Healthantigens. Science Center, Memphis, bodies to putative renal More thanTN,a USA; decade 2 Division of Nephrology 4 and Hypertension, University of Californialater, Debiec et al identified the first antigen involved 3 Irvine, Orange, CA, USA; and Nephrology Section, Memphis VA TN, USAendopeptidase (NEP), a in Medical such Center, casesMemphis, as neutral Prior studies have suggested that creation of arterio-venous fistula metalloprotease present on the surface of the podocyte (AVF) or graft (AVG) may be associated with slowing of estimated andglomerular involved in the proteolytic regulation filtration rate (eGFR) decline. We hypothesizedof thatvasoacwith a mature vascular access are more likely to have with a tivepatients peptides. Debiec et al described a mother deceleration of eGFR decline. mutation NEPwho expression had formed Among preventing 52,172 U.S. veterans transitioned towho dialysis between 2007-2011,antibodies we identified 3,026 who had at least 3 alloimmuoutpatient anti-NEP duepatients to fetomaternal serum creatinine measurements both before and after AVF/AVG nization a previous miscarriage; antibodies creation.from We estimated eGFR slopes vs. time usingthese multilevel mixed effects fixed (demographics and comorbidities) and were tomodels crossadjusted the for placenta and cause subepithelial time-dependent confounders (BP and ACE inhibitor/ARB use) and deposits in the fetal kidney of a subsequent pregcompared eGFR slopes separately for the pre- and post-AVF/AVG period M-type overall and in patients stratified byA AVF/AVG maturation. 1,069 nancy. phospholipase (PLA 2 receptor 2R) patients without AVF/AVG who started dialysis with a catheter served wasas later identified as the major autoantigen for pricontrols, using a six-month time point prior to dialysis as cutoff to assessMN changein in slope. mary adults.5 Little literature exists about Mean age was 67 years, 98% were male and 75% diabetic. eGFR pregnancy outcomes in patients with nephrotic syndecline accelerated in the last 6 months prior to dialysis in patients drome to primary MN, deceleration with no ofdata withoutdue AVF/AVG, while a significant slopesavailable was seen after AVF/AVG creation (median, -5.1 vs. -15.5 and -5.6 vs. -4.1 ml We about pregnancy in PLA R-associated disease. 2 Findings were independent /min/1.73m2/year, P<0.001, respectively). present what maturation we believe first known case of of AVF/AVG status to and be werethe robust in adjusted models. The creation associated with an improvement of MN pregnancy inofaAVF/AVG patientis with PLA R-associated 2 eGFR slopes. Additional studies are needed to clarify the underlying who was seropositive for anti-PLA2R autoantibodies mechanisms. 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 348
before her current pregnancy. She had been treated for resistant SUCCESSFUL TREATMENT OF TUMOR-INDUCED LACTIC hypertension and TRIS-HYDROXYMETHYL lower-extremity edema AMINOMETHANE during the past year, ACIDOSIS WITH but her proteinuria had been overlooked. At presentation, (THAM): Dhivya Sundaramurthy, Miguel Rodriguez, Saed Nemr, serum Gregory Braden, Medical Center, Springfield, Ma, USA creatinine level Baystate was 1.52 mg/dL (corresponding to estimated Tumor induced type B lactic usually occurs glomerular filtration rate of acidosis 46 mL/min/1.73 m2inashematological calculated by malignancies. Resultant metabolic acidosis can lead to arrhythmias, thehypotension, isotope-dilution mass spectrometry–traceable 4-variable respiratory failure & coma rather than death from MDRD [Modification of aDiet Renal Disease] Study malignancy itself. We report patientinwith lymphoma-induced lactic equation); serum albumin level, compromise 1.5 g/dL; and urine protein acidosis with severe respiratory who 24-hour was successfully treated with29.2 THAM avoiding intubation. excretion, g. The kidney biopsy specimen revealed features 73 year man withMN dyspnea 2 weeks was strong found tostaining have typical of old primary withofadditional for the Kussmaul breathing & a palpable large right inguinal 10 x 9cm mass. PLA R antigen within immune deposits (Fig S1). 2 Biopsy a month ago had revealed unclassified necrotic tumor.Many Labs of the subepithelial were completely revealed aniondeposits gap metabolic acidosis with gap ofsurrounded 25, bicarbonateby of new 12mmol/L, membrane lactate of 10mmol/L, chloride of 7.38 of & the basement material (Figof 98mmol/L, S2), andpH35% PCO2 24mmHg. His respiratory status declined rapidly requiring ICU transfer for intubation. Lactate level rose to 14mmol/L & HCO3 dropped to 10mmol/L.THAM at a dose of 575ml via 0.3 mmol/L From thefor1Department of &Medicine, Section, and (calculated lean body weight base deficit)Renal was administered over De2 one hour following which lactate to 9 &3bicarbonate partments of Obstetrics and decreased Gynecology, Pediatrics, and 4Paimprovedand to 20Laboratory in 6hrs. He received 3 dosesBoston in 3 daysUniversity with correction thology Medicine, Medical of lactic acidosis. Repeat biopsy of the mass showed diffuse B cell Center, Boston, MA. lymphoma & methylprednisolone with chemotherapy was initiated. * Current affiliation: Internaltowards Medicine, Division Cancer cells can switchDepartment their metabolicofmachinery anerobic ofglycolysis Nephrology, University UtahO2 School of the Medicine, for ATP generationof despite presence, ‘WarburgSalt Lake effect’. City, UT.Other mechanisms are production of Insulin like Growth factor y Hypoxia inducible factor by tumor cells that accelerate glycolysis or Current affiliation: Department of Obstetrics and Gynecology, generating lactate. In the absence of liver metastasis as in our patient, Medstar Washington Hospital Center, Washington, DC. systemic acidosis can impair both hepatic lactate clearance & Received June(Cori 29, cycle) 2015.byAccepted revised form October 27, gluconeogenesis decreasinginhepatic perfusion. 2015. Originally published onlinewill December 2015. Bicarbonate infusion in this situation worsen the29, intracellular acidosis with paradoxical increase CO2 generation in non-intubated Address correspondence to in Laurence H. Beck Jr, MD, PhD, patients. THAMX-504, rapidly diffuses intracellularly, accepts protonsE-mail: & Renal Section, 650 Albany St, Boston, MAthe02118. forms ammonia that is excreted by the kidneys. It reverses both intra & [email protected] extracellular acidosis thus improving hepatic lactate clearance & � 2016 byof the Foundation, Inc. reactivation CoriNational cycle. OurKidney study showed that lymphoma-induced 0272-6386 lactic acidosis can be successfully treated with THAM.
http://dx.doi.org/10.1053/j.ajkd.2015.10.031 775 A105
Case Report 345
347
INVOLVEMENT OF FAMILIES AND PEERS IN THE CHOICE OF A CASE OF MISTAKEN IDENTITY: Dhivya Sundaramurthy, Saed DIALYSIS MODALITY IS LIMITED: THE EMPOWERING Nemr, Michael Germain, Baystate Medical center, Springfield,Ma,USA PATIENTS ON CHOICES FOR RENAL REPLACEMENT TTP (Thrombotic Thrombocytopenic Purpura) is a life threatening 2 THERAPY (EPOCH-RRT) STUDY Lalita Subramanian1, Junhui entity & misdiagnosis can prove fatal. Pathogenesis involves 1,2 Zhao1, Jarcy Zee1, Ron Pisoni, Bruce Robinson1, Francesca Tentori . 1, 2 1 1 1 microangiopathic anemia unlike syndrome which is Al-Rabadi, MBBS, * Rivka Ayalon, MD, Ramon hemolytic G. Bonegio, MD,Evans PhD, Arbor Research Laith Collaborative for Health, Ann Arbor, MI; Vanderbilt 2,y 3 4 Autoimmune hemolytic anemia (AIHA) & Immune Thrombocytopenic University Medical Center, Nashville, TN. Jennifer E. Ballard, MD, Alan M. Fujii, MD, Joel M. Henderson, MD, PhD, Given the sustained demands of dialysis on everyday lives, the 1 choice Purpura (ITP). Diagnosis of TTP is often 1 challenging due to long David J. Salant, MD, and Laurence H. Beck Jr, MD, PhD of a dialysis modality often affects loved ones. Peer mentoring turnaround time of ADAMST13 activity. Coombs test, positive in programs in which patients interact with peers with the same condition AIHA, is usually negative in TTP unless patient has Lupus. Here we are considered widely successful. However, the role of families and present a case of thrombocytopenia with positive Coombs test that led peers in dialysis modality selection is poorly understood. EPOCH-RRT There is little information about pregnancy outcomes in patients with active membranous nephropathy (MN), us off the track leading to a misdiagnosis of Evans syndrome. explored dialysis patients’ recollection of involvement of families, receptor the his major those withofcirculating to M-type A phospholipase A2male 2R), peers, and especially clinical staff in the choice their dialysis autoantibodies modality. 16 year old healthy was sent(PLA to the ER from PCP’s office in primary MN. We present what we believe to be firstpetechiae known case of successful(16,000/mm3). pregnancy in A patientautoantigen survey was developed in collaboration with a patient withthe diffuse & thrombocytopenia Lab work advisory panel and completedwoman by participants the 2US Dialysis R-associated MN. In therevealed year prior to of pregnancy, thehigh patient developed a 39-year-old with in PLA evidence hemolysis with LDH, low haptoglobin & few Outcomes anasarca, and Practice Patterns Study (DOPPS, N=1350) and hypoalbuminemia (albumin, 1.3-2.2 g/dL), and proteinuria (protein excretion, Kidney bispherocytes on peripheral smear (PS)29.2 withg/d). Coombs positivity Peritoneal DOPPS (PDOPPS, N=613) in 2015. For both HD and PD R,Over and the patientconsistent was seropositive for anti-PLA autoantibodies. opsyinvolvement revealed was MNmoderate with staining for(Figure PLA21). with Evans syndrome. He also 3.4gm proteinuria & 2R had patients, family (59-79%) She diddidnot to at conservative therapy with intravenous (2 complements doses of 1 g microscopic hematuria rituximab with negative & each). ANA. Prednisone 35% reported they notrespond know a peer the time of their decision;and was treated among those who did,weeks 30-40%after recalled no peer involvement. Clinical was initiated for Evans syndrome. Given persistent Several presentation, she was found to be 6 weeks pregnant and was closely followed upthrombocytopenia, without staff (especially nephrologists) were most commonly involved. hematuria & increasing schistocytosis on to PS 12-g/d on day 5,range. alternate further immunosuppressive treatment. Proteinuria remained with protein excretion in the 8There is an opportunity to increase family and peer involvement in diagnosis TTP/Atypical Uremic syndrome was levelsdecision-making. declined but This were still detectable. Atof38 weeks, a Hemolytic healthy baby girl was born, anti-PLA 2R shared the dialysisCirculating modality choice to promote entertained. Hence he was started on plasmapheresis empirically at birth or atwith hereach subsequent visit. At the time of delivery, the mother still while may result without in a betterproteinuria fit of the dialysis modality patient’s 6-month postnatal waiting for ADAMST13 His platelets normalized life, as wellhad as improved experience for theiranti-PLA families. 2R of immunoglobulin G1 (IgG1), IgG3, and activity. IgG4 subclasses, although after at 2 detectable circulating low ADAMST13 activity (<5) confirmed found in& acord blood. Potential reasons for TTP. the low titers. Only trace amounts of IgG4 anti-PLA2R wereexchanges Coombs positivity in TTP is extremely rare, with only 2 cases circulation are discussed. discrepancy between anti-PLA2R levels in the maternal and fetal reportedFoundation, so far. It’s veryInc. crucial to differentiate these 2 entities as the Am J Kidney Dis. 67(5):775-778. ª 2016 by the National Kidney management differs given different etio-pathogenesis. Non-specific polyclonal immune activation can lead to overlap of immunological INDEX WORDS: Membranous nephropathy (MN); nephrotic syndrome; pregnancy; M-type phospholipase A2 disorders like in our patient. Hence we should keep our differentials receptor (PLA2R); autoantibody; placenta; rituximab; immunoglobulin G (Ig G) subclass. broad, follow patient vigilantly & use lab markers like peripheral smear, urinanalysis etc diligently to clinch the right diagnosis which can be lifesaving. Hence we aim to drive home the message that coombs test can be positive in TTP. regnant patients with autoimmune disease may
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 346 circulating autoantibodies. Pregnant patients with ASSOCIATION BETWEEN VASCULAR ACCESS CREATION lupus or myasthenia can GLOMERULAR deliver babies with AND DECELERATION OFgravis ESTIMATED 1,2 FILTRATION RATE DECLINE LATE-STAGE CHRONIC corresponding disease inINthe neonate. Neonatal KIDNEY DISEASE PATIENTS TRANSITIONING TO END-STAGE 1 1 membranous nephropathy (MN) not associated RENAL DISEASE: Keiichi Sumida , Miklos Z Molnar , Praveen Kwith 1 Potukuchi1, Fridtjof Thomas , Junfirst L Lu1,described Jennie Jing2, Vanessa A and congenital infection was in 1990 Ravel2, Melissa Soohoo2, Connie M Rhee2, Elani Streja2, Kamyar 2the passive transfer 1,3 1 attributed to of maternal Kalantar-Zadeh , Csaba P Kovesdy , Division of Nephrology, anti3 University of Tennessee Healthantigens. Science Center, Memphis, bodies to putative renal More thanTN,a USA; decade 2 Division of Nephrology 4 and Hypertension, University of Californialater, Debiec et al identified the first antigen involved 3 Irvine, Orange, CA, USA; and Nephrology Section, Memphis VA TN, USAendopeptidase (NEP), a in Medical such Center, casesMemphis, as neutral Prior studies have suggested that creation of arterio-venous fistula metalloprotease present on the surface of the podocyte (AVF) or graft (AVG) may be associated with slowing of estimated andglomerular involved in the proteolytic regulation filtration rate (eGFR) decline. We hypothesizedof thatvasoacwith a mature vascular access are more likely to have with a tivepatients peptides. Debiec et al described a mother deceleration of eGFR decline. mutation NEPwho expression had formed Among preventing 52,172 U.S. veterans transitioned towho dialysis between 2007-2011,antibodies we identified 3,026 who had at least 3 alloimmuoutpatient anti-NEP duepatients to fetomaternal serum creatinine measurements both before and after AVF/AVG nization a previous miscarriage; antibodies creation.from We estimated eGFR slopes vs. time usingthese multilevel mixed effects fixed (demographics and comorbidities) and were tomodels crossadjusted the for placenta and cause subepithelial time-dependent confounders (BP and ACE inhibitor/ARB use) and deposits in the fetal kidney of a subsequent pregcompared eGFR slopes separately for the pre- and post-AVF/AVG period M-type overall and in patients stratified byA AVF/AVG maturation. 1,069 nancy. phospholipase (PLA 2 receptor 2R) patients without AVF/AVG who started dialysis with a catheter served wasas later identified as the major autoantigen for pricontrols, using a six-month time point prior to dialysis as cutoff to assessMN changein in slope. mary adults.5 Little literature exists about Mean age was 67 years, 98% were male and 75% diabetic. eGFR pregnancy outcomes in patients with nephrotic syndecline accelerated in the last 6 months prior to dialysis in patients drome to primary MN, deceleration with no ofdata withoutdue AVF/AVG, while a significant slopesavailable was seen after AVF/AVG creation (median, -5.1 vs. -15.5 and -5.6 vs. -4.1 ml We about pregnancy in PLA R-associated disease. 2 Findings were independent /min/1.73m2/year, P<0.001, respectively). present what maturation we believe first known case of of AVF/AVG status to and be werethe robust in adjusted models. The creation associated with an improvement of MN pregnancy inofaAVF/AVG patientis with PLA R-associated 2 eGFR slopes. Additional studies are needed to clarify the underlying who was seropositive for anti-PLA2R autoantibodies mechanisms. 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 348
before her current pregnancy. She had been treated for resistant SUCCESSFUL TREATMENT OF TUMOR-INDUCED LACTIC hypertension and TRIS-HYDROXYMETHYL lower-extremity edema AMINOMETHANE during the past year, ACIDOSIS WITH but her proteinuria had been overlooked. At presentation, (THAM): Dhivya Sundaramurthy, Miguel Rodriguez, Saed Nemr, serum Gregory Braden, Medical Center, Springfield, Ma, USA creatinine level Baystate was 1.52 mg/dL (corresponding to estimated Tumor induced type B lactic usually occurs glomerular filtration rate of acidosis 46 mL/min/1.73 m2inashematological calculated by malignancies. Resultant metabolic acidosis can lead to arrhythmias, thehypotension, isotope-dilution mass spectrometry–traceable 4-variable respiratory failure & coma rather than death from MDRD [Modification of aDiet Renal Disease] Study malignancy itself. We report patientinwith lymphoma-induced lactic equation); serum albumin level, compromise 1.5 g/dL; and urine protein acidosis with severe respiratory who 24-hour was successfully treated with29.2 THAM avoiding intubation. excretion, g. The kidney biopsy specimen revealed features 73 year man withMN dyspnea 2 weeks was strong found tostaining have typical of old primary withofadditional for the Kussmaul breathing & a palpable large right inguinal 10 x 9cm mass. PLA R antigen within immune deposits (Fig S1). 2 Biopsy a month ago had revealed unclassified necrotic tumor.Many Labs of the subepithelial were completely revealed aniondeposits gap metabolic acidosis with gap ofsurrounded 25, bicarbonateby of new 12mmol/L, membrane lactate of 10mmol/L, chloride of 7.38 of & the basement material (Figof 98mmol/L, S2), andpH35% PCO2 24mmHg. His respiratory status declined rapidly requiring ICU transfer for intubation. Lactate level rose to 14mmol/L & HCO3 dropped to 10mmol/L.THAM at a dose of 575ml via 0.3 mmol/L From thefor1Department of &Medicine, Section, and (calculated lean body weight base deficit)Renal was administered over De2 one hour following which lactate to 9 &3bicarbonate partments of Obstetrics and decreased Gynecology, Pediatrics, and 4Paimprovedand to 20Laboratory in 6hrs. He received 3 dosesBoston in 3 daysUniversity with correction thology Medicine, Medical of lactic acidosis. Repeat biopsy of the mass showed diffuse B cell Center, Boston, MA. lymphoma & methylprednisolone with chemotherapy was initiated. * Current affiliation: Internaltowards Medicine, Division Cancer cells can switchDepartment their metabolicofmachinery anerobic ofglycolysis Nephrology, University UtahO2 School of the Medicine, for ATP generationof despite presence, ‘WarburgSalt Lake effect’. City, UT.Other mechanisms are production of Insulin like Growth factor y Hypoxia inducible factor by tumor cells that accelerate glycolysis or Current affiliation: Department of Obstetrics and Gynecology, generating lactate. In the absence of liver metastasis as in our patient, Medstar Washington Hospital Center, Washington, DC. systemic acidosis can impair both hepatic lactate clearance & Received June(Cori 29, cycle) 2015.byAccepted revised form October 27, gluconeogenesis decreasinginhepatic perfusion. 2015. Originally published onlinewill December 2015. Bicarbonate infusion in this situation worsen the29, intracellular acidosis with paradoxical increase CO2 generation in non-intubated Address correspondence to in Laurence H. Beck Jr, MD, PhD, patients. THAMX-504, rapidly diffuses intracellularly, accepts protonsE-mail: & Renal Section, 650 Albany St, Boston, MAthe02118. forms ammonia that is excreted by the kidneys. It reverses both intra & [email protected] extracellular acidosis thus improving hepatic lactate clearance & � 2016 byof the Foundation, Inc. reactivation CoriNational cycle. OurKidney study showed that lymphoma-induced 0272-6386 lactic acidosis can be successfully treated with THAM.
http://dx.doi.org/10.1053/j.ajkd.2015.10.031 775 A105