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DYSPNEA IN A PATIENT WITH ENLARGED KIDNEYS
NKF 2014 Spring Clinical Meetings Abstracts
385 PREVALENCE OF GLOMERULONEPHRITIS IN THE US: INSIGHTS FROM A LARGE ADMINISTRATIVE DATASET James B. Wetmore,1,2 Haifeng Guo,2 and David T. Gilbertson2 1 Hennepin County Medical Center and 2Chronic Disease Research Group, Minneapolis, MN, USA Glomerulonephritis (GN) is a serious disorder that can lead to endstage renal disease and other serious morbid conditions. However, because no large-scale examination of GN prevalence has been undertaken using a large administrative database, the prevalence of GN is unknown. Using data from the Optum Clinformatics employer group health plan (EGHP) from 2007-11, we used an ICD-9 claims-based approach to establish the annual presence of a primary GN (≥ 2 ICD-9 codes for a GN > 30 days apart, plus ≥ 1 code for resultant renal disease occurring on or after the first GN code) or a systemic immunologic disorder resulting in a GN (≥ 3 ICD-9 codes at least 3 days apart for an immunologic disorder, plus ≥ 2 subsequent ICD-9 codes for a GN or resultant renal disease ≥ 30 days apart). The dataset consisted of 8,117,165 individuals (50.9% female) in 2007 and 8,187,563 individuals (50.4% female) in 2011. In 2007, 3682 individuals (0.05%, 95% CIs 0.05% – 0.05%) had a GN, increasing in absolute terms in 2011 to 4339 individuals (0.05%, 95% CIs 0.05% – 0.05%). Mean age was significantly higher for those with a GN compared with those without in both 2007 (50.4 vs. 35.6 years, P < 0.0001) and 2011 (50.9 vs. 35.7, P < 0.0001). Systemic immunologic diseases accounted for approximately 38% of GNs in 2007 and 42% in 2011. This is the first estimate of GN prevalence reflecting a large community-dwelling population. While the percentage of individuals with evidence of a GN in the period studied is modest, the absolute numbers are likely to be large in the US as a whole. Further work examining changes in GN incidence and prevalence, including the influence of gender and race, medications used for treatment of GN, and clinical outcomes of GNs, should be undertaken.
386 HYPONATREMIA AS A RESULT OF POSTTRAUMATIC PRIMARY POLYDIPSIA WITHOUT PSYCHIATRIC DISORDER Jennifer E. Williamson, Sean Maddock, Anna MorenoGalvan, Vania Castillo, Roger Carbajal, Department of Medicine, New York Medical College, Metropolitan Hospital Center, New York, NY Primary polydipsia is etiologically associated with psychiatric disorders. We present a case of posttraumatic primary polydipsia without major psychiatric features. This is a 58 year-male with history of multiple admissions due to alcohol intoxication and alcohol withdrawal. Since August 2013, where a bilateral frontal hemorrhage was documented on CT scan, the patient has been presenting with compulsive water ingestion and acute episodes of hyponatremia. There were no previous episodes of hyponatremia before intracraneal bleeding. Continous thorough psychiatry evaluation did not reveal psychotic or major psychiatric features. Work up revealed euvolemic hypotonic hyponatremia with appropriate low urine osmolality (<100 mOsm/kg).This suggests that the main mechanism that played a role in the development of acute episodes of hyponatremia was primary polydipsia. In addition, time-relationships between compulsive water intake, development of acute episodes of hyponatremia, and intracranial hemorrhage, suggest a traumatic etiology of primary polydipsia. Head trauma can result in chronic isolated primary polydipsia without an associated major psychiatric disorder.
Am J Kidney Dis. 2014;63(5):A1-A121
387 IN VITRO ION EXCHANGE CAPACITY AND SELECTIVITY OF ZS-9, A NOVEL, SELECTIVE CATION TRAP FOR THE TREATMENT OF HYPERKALEMIA: Alex Yang1, Alejandro Leon2, Mark Nuttall2, John J. Low3, Henrik S. Rasmussen2; 1Xelay Acumen, Inc., Belmont, CA; 2ZS Pharma Inc., Coppell, TX; and 3Consultant, Schaumburg, IL, USA. Hyperkalemia is associated with significant mortality and limits use of life-saving RAAS inhibitors, yet prevalent treatments are poorly tolerated and not always effective. Differentiated from traditional organic polymers (ie, Kayexalate®), ZS-9 is an insoluble, nonsystemic inorganic cation exchanger that preferentially entraps K+ over divalent (Ca2+, Mg2+) and other monovalent (eg, Na +) cations in the gastrointestinal tract. ZS-9’s lattice structure provides high K+ selectivity, analogous to the physiologic selectivity filters in in vivo K+ channels. To assess K+ exchange capacity (KEC) in vitro, ZS-9 and Kayexalate were added to a solution of K+, Ca2+ and Mg2+ at concentration ratios (1:0.5:0.5, 1:1:1, 1:2:2) representing a 4-fold range. After equilibration, the ion binding of each was quantified. Selectivity ratios were calculated as [K+] / [Ca2+] + [Mg2+]. In vitro equilibrium kinetics at various gastrointestinal pHs were also measured. At the 3 concentration ratios, ZS-9 did not show any exchange capacity for Ca2+ and Mg2+; for calculation purposes, 0.05 mEq/g was assumed for each. KEC (mEq/g) for Kayexalate and ZS-9, respectively, were: 1:0.5:0.5 ratio, 0.5 and 2.8; 1:1:1 ratio, 0.3 and 2.7; 1:2:2 ratio, 0.3 and 2.6. At all 3 concentration ratios, ZS-9 was over 25-times more selective for K+ than Ca2+ or Mg2+, whereas Kayexalate’s selectivity for K+ was 0.2-0.3 times its selectivity for Ca2+ or Mg2+. Thermodynamically, ZS-9 with K+ is more stable than ZS-9 with Na+ by 20 kcal/mol. At various gastrointestinal pHs, maximal K+ entrapment occurred between 30 seconds and 10 minutes. ZS-9’s KEC is approximately 6-9-fold higher than Kayexalate’s in the presence of Ca2+ and Mg2+. ZS-9’s selectivity for K+ is approximately 80-125-times higher than Kayexalate’s. ZS-9 equilibrated rapidly in the pH environments of the gastrointestinal tract. If approved, ZS-9 may represent a novel, first-in-class therapy for hyperkalemia with improved capacity, selectivity and speed.
388 DYSPNEA IN A PATIENT WITH ENLARGED KIDNEYS Mahdi Yazdany, Arthur Cohen, Russell Brynes, Raimund Hirschberg, & Sharon G Adler. Harbor UCLA & USC, Torrance & LA, CA, USA Case presentation: 44 M with hypertension and asthma for 4 years presented with cough, fever, and SOB. Initial evaluation revealed tachycardia, hypoxia and crackles in both lungs, spider angioma on the chest and scar of right parotidectomy, which was done a few years prior for enlarged gland. A V/Q scan was negative and CXR and chest CT showed diffuse reticulonodular opacities. Initial labs showed elevated BUN and Cr, eosinophilia, and elevated ANA, serum IgE, IgG, and IgG4 with hypocomplementemia. Urinalysis showed non-nephrotic proteinuria. Renal ultrasound revealed massive nephromegaly. Due to chest CT findings and persistent hypoxia, BAL was performed, which showed 2 species of Aspergillus. A renal biopsy was performed that showed characteristic findings of dense infiltrates of lymphoplasmacytic cells of IgG4 predominance with storiform fibrosis consistent with IgG4- related disease. To confirm the systemic nature of the disease, we obtained lymph node and parotid biopsy tissues from 2010 and retrospectively stained for IgG and IgG4. The diagnosis of IgG4-related disease was confirmed and explained virtually all of the patient’s signs and symptoms. The patient was started on Voriconazole and prednisone with improvement in renal function and IgG and IgG4 levels. There is a specific IgG4 response to Aspergillus exposure. IgG and IgE anti-Aspergillus precipitins are pending to determine whether allergic bronchopulmonary aspergillosis contributed to the development of IgG4 related disease in this patient. Conclusion: IgG4-RD is a fibroinflammatory condition of unknown etiology. The association between bronchopulmonary aspergillosis and IgG4-RD has not been described in the past, suggesting a stimulus for IgG4 synthesis in this patient with an apparent Th2 immune predisposition.
A115
385 PREVALENCE OF GLOMERULONEPHRITIS IN THE US: INSIGHTS FROM A LARGE ADMINISTRATIVE DATASET James B. Wetmore,1,2 Haifeng Guo,2 and David T. Gilbertson2 1 Hennepin County Medical Center and 2Chronic Disease Research Group, Minneapolis, MN, USA Glomerulonephritis (GN) is a serious disorder that can lead to endstage renal disease and other serious morbid conditions. However, because no large-scale examination of GN prevalence has been undertaken using a large administrative database, the prevalence of GN is unknown. Using data from the Optum Clinformatics employer group health plan (EGHP) from 2007-11, we used an ICD-9 claims-based approach to establish the annual presence of a primary GN (≥ 2 ICD-9 codes for a GN > 30 days apart, plus ≥ 1 code for resultant renal disease occurring on or after the first GN code) or a systemic immunologic disorder resulting in a GN (≥ 3 ICD-9 codes at least 3 days apart for an immunologic disorder, plus ≥ 2 subsequent ICD-9 codes for a GN or resultant renal disease ≥ 30 days apart). The dataset consisted of 8,117,165 individuals (50.9% female) in 2007 and 8,187,563 individuals (50.4% female) in 2011. In 2007, 3682 individuals (0.05%, 95% CIs 0.05% – 0.05%) had a GN, increasing in absolute terms in 2011 to 4339 individuals (0.05%, 95% CIs 0.05% – 0.05%). Mean age was significantly higher for those with a GN compared with those without in both 2007 (50.4 vs. 35.6 years, P < 0.0001) and 2011 (50.9 vs. 35.7, P < 0.0001). Systemic immunologic diseases accounted for approximately 38% of GNs in 2007 and 42% in 2011. This is the first estimate of GN prevalence reflecting a large community-dwelling population. While the percentage of individuals with evidence of a GN in the period studied is modest, the absolute numbers are likely to be large in the US as a whole. Further work examining changes in GN incidence and prevalence, including the influence of gender and race, medications used for treatment of GN, and clinical outcomes of GNs, should be undertaken.
386 HYPONATREMIA AS A RESULT OF POSTTRAUMATIC PRIMARY POLYDIPSIA WITHOUT PSYCHIATRIC DISORDER Jennifer E. Williamson, Sean Maddock, Anna MorenoGalvan, Vania Castillo, Roger Carbajal, Department of Medicine, New York Medical College, Metropolitan Hospital Center, New York, NY Primary polydipsia is etiologically associated with psychiatric disorders. We present a case of posttraumatic primary polydipsia without major psychiatric features. This is a 58 year-male with history of multiple admissions due to alcohol intoxication and alcohol withdrawal. Since August 2013, where a bilateral frontal hemorrhage was documented on CT scan, the patient has been presenting with compulsive water ingestion and acute episodes of hyponatremia. There were no previous episodes of hyponatremia before intracraneal bleeding. Continous thorough psychiatry evaluation did not reveal psychotic or major psychiatric features. Work up revealed euvolemic hypotonic hyponatremia with appropriate low urine osmolality (<100 mOsm/kg).This suggests that the main mechanism that played a role in the development of acute episodes of hyponatremia was primary polydipsia. In addition, time-relationships between compulsive water intake, development of acute episodes of hyponatremia, and intracranial hemorrhage, suggest a traumatic etiology of primary polydipsia. Head trauma can result in chronic isolated primary polydipsia without an associated major psychiatric disorder.
Am J Kidney Dis. 2014;63(5):A1-A121
387 IN VITRO ION EXCHANGE CAPACITY AND SELECTIVITY OF ZS-9, A NOVEL, SELECTIVE CATION TRAP FOR THE TREATMENT OF HYPERKALEMIA: Alex Yang1, Alejandro Leon2, Mark Nuttall2, John J. Low3, Henrik S. Rasmussen2; 1Xelay Acumen, Inc., Belmont, CA; 2ZS Pharma Inc., Coppell, TX; and 3Consultant, Schaumburg, IL, USA. Hyperkalemia is associated with significant mortality and limits use of life-saving RAAS inhibitors, yet prevalent treatments are poorly tolerated and not always effective. Differentiated from traditional organic polymers (ie, Kayexalate®), ZS-9 is an insoluble, nonsystemic inorganic cation exchanger that preferentially entraps K+ over divalent (Ca2+, Mg2+) and other monovalent (eg, Na +) cations in the gastrointestinal tract. ZS-9’s lattice structure provides high K+ selectivity, analogous to the physiologic selectivity filters in in vivo K+ channels. To assess K+ exchange capacity (KEC) in vitro, ZS-9 and Kayexalate were added to a solution of K+, Ca2+ and Mg2+ at concentration ratios (1:0.5:0.5, 1:1:1, 1:2:2) representing a 4-fold range. After equilibration, the ion binding of each was quantified. Selectivity ratios were calculated as [K+] / [Ca2+] + [Mg2+]. In vitro equilibrium kinetics at various gastrointestinal pHs were also measured. At the 3 concentration ratios, ZS-9 did not show any exchange capacity for Ca2+ and Mg2+; for calculation purposes, 0.05 mEq/g was assumed for each. KEC (mEq/g) for Kayexalate and ZS-9, respectively, were: 1:0.5:0.5 ratio, 0.5 and 2.8; 1:1:1 ratio, 0.3 and 2.7; 1:2:2 ratio, 0.3 and 2.6. At all 3 concentration ratios, ZS-9 was over 25-times more selective for K+ than Ca2+ or Mg2+, whereas Kayexalate’s selectivity for K+ was 0.2-0.3 times its selectivity for Ca2+ or Mg2+. Thermodynamically, ZS-9 with K+ is more stable than ZS-9 with Na+ by 20 kcal/mol. At various gastrointestinal pHs, maximal K+ entrapment occurred between 30 seconds and 10 minutes. ZS-9’s KEC is approximately 6-9-fold higher than Kayexalate’s in the presence of Ca2+ and Mg2+. ZS-9’s selectivity for K+ is approximately 80-125-times higher than Kayexalate’s. ZS-9 equilibrated rapidly in the pH environments of the gastrointestinal tract. If approved, ZS-9 may represent a novel, first-in-class therapy for hyperkalemia with improved capacity, selectivity and speed.
388 DYSPNEA IN A PATIENT WITH ENLARGED KIDNEYS Mahdi Yazdany, Arthur Cohen, Russell Brynes, Raimund Hirschberg, & Sharon G Adler. Harbor UCLA & USC, Torrance & LA, CA, USA Case presentation: 44 M with hypertension and asthma for 4 years presented with cough, fever, and SOB. Initial evaluation revealed tachycardia, hypoxia and crackles in both lungs, spider angioma on the chest and scar of right parotidectomy, which was done a few years prior for enlarged gland. A V/Q scan was negative and CXR and chest CT showed diffuse reticulonodular opacities. Initial labs showed elevated BUN and Cr, eosinophilia, and elevated ANA, serum IgE, IgG, and IgG4 with hypocomplementemia. Urinalysis showed non-nephrotic proteinuria. Renal ultrasound revealed massive nephromegaly. Due to chest CT findings and persistent hypoxia, BAL was performed, which showed 2 species of Aspergillus. A renal biopsy was performed that showed characteristic findings of dense infiltrates of lymphoplasmacytic cells of IgG4 predominance with storiform fibrosis consistent with IgG4- related disease. To confirm the systemic nature of the disease, we obtained lymph node and parotid biopsy tissues from 2010 and retrospectively stained for IgG and IgG4. The diagnosis of IgG4-related disease was confirmed and explained virtually all of the patient’s signs and symptoms. The patient was started on Voriconazole and prednisone with improvement in renal function and IgG and IgG4 levels. There is a specific IgG4 response to Aspergillus exposure. IgG and IgE anti-Aspergillus precipitins are pending to determine whether allergic bronchopulmonary aspergillosis contributed to the development of IgG4 related disease in this patient. Conclusion: IgG4-RD is a fibroinflammatory condition of unknown etiology. The association between bronchopulmonary aspergillosis and IgG4-RD has not been described in the past, suggesting a stimulus for IgG4 synthesis in this patient with an apparent Th2 immune predisposition.
A115