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Iatrogenic Tertiary Hyperparathyroidism in a Case of Fabry Disease Treated With Agalsidase Beta
NKF 2012 Spring Clinical Meetings Abstracts
105
107
EXAMINING SURVIVAL GAIN OF THE ELDERLY KIDNEY TRANSPLANT RECIPIENTS COMPARED TO GENERAL POPULATION IN THE US Parta Hatamizadeh, Miklos Z Molnar, Elani Streja, Mahesh Krishnan, Csaba P Kovesdy, and Kamyar Kalantar-Zadeh. Harold Simmons Center, Harbor-UCLA, Torrance, CA, Salem VAMC, Salem, VA, DaVita, Denver, CO, CA. Individuals older than 65 years constitute the fastest growing population group in US. Similarly, the median age of kidney transplant recipients (KTR) has increased. The survival benefit of the elderly from kidney transplantation has not been clearly quantified. We compared the mortality rates and ratios across 3 age groups (15-<65, 65-<75 and ≥75 years old) between the KTRs (derived from the Scientific Registry of Transplant Recipients 2001-2006) and the general population (GP) using US population in 2005 (derived from the National Vital Statistics System). After calculating the crude mortality rates in KTRs and the GPs across 3 age groups, the relative risk (RR) of death was calculated for the 2 elderly groups compared to 15-<65 years (reference). Additionally, the ratio of mortality each RR for KTR to GP was estimated in each group. In our study the KTRs (n=155,005) were 45±16 years old and included 40% women and 19% diabetics. Even though kidney transplanted patients aged 65-<75 years and ≥75 years had a 75% and 96% higher mortality risk, respectively, than 15-<65 year-old group, the age-related rise in mortality was substantially lower across KTR than GP (see Table): ≥75 AGE GROUP 15-<65 65-<75 Kidney Transplant Recipients (KTR) (2001-06) (n=155,005) Crude death rates multiplied by 1000 RR Crude death rates multiplied by 1000 RR RR ratio KTR:GP
157 (155-159)
274 (267-281)
1.00 1.75 (1.72-1.77) General Population (GP) (2005)
307 (282-332) 1.96 (1.82-2.09)
3.1 (2.9-3.3)
21.4 (20.7-22.1)
76.6 (75.4-77.8)
1.00 1.00
6.9 (6.7-7.1) 0.25 (0.24-0.26)
24.7 (23.6-26.0) 0.08 (0.07-0.09)
Compared to GP, elderly KTR 65-<75 and ≥75 years exhibit 75% and 92% survival gain, respectively. The survival gains of kidney transplantation in the elderly warrant additional studies.
106 IATROGENIC TERTIARY HYPERPARATHYROIDISM IN A CASE OF FABRY DISEASE TREATED WITH AGALSIDASE BETA Hilana Hatoum1, Adepeju Jinadu1, Anita Patel1, Dhanwada Sudhaker Rao 2. 1: Nephrology Department. 2: Endocrinology Department. Henry Ford Hospital, Detroit, Michigan. Tertiary hyperthyroidism is a serious complication in ESRD and renal transplantation and the main treatment is still surgical. NKF KDOQI guidelines recommend recurrent measurement of iPTH as a first test for diagnosis and follow-up of hyperparathyroidism. But, the availability of different assays to measure iPTH affects the interpretation of the results and in some cases the management. A 50-Yr-O man with a history of ESRD secondary to Fabry disease status post living related kidney transplant was diagnosed with tertiary hyperparathyroidism due to persistently elevated iPTH (1200-1300 pg/mL) by using immunoreactivity based reaction assay. The patient was taking in addition to his immunosuppressive medications fabrazyme® (agalsidase beta) for his Fabry disease. The patient denied any complaints. Physical exam other than a palpable graft was unremarkable. Alkaline phosphatase, calcium, phosphorus and vitamin D levels were in normal ranges. Endocrine skeletal survey and bone densitometry were also normal. The patient was referred to a bone and mineral metabolism clinic for further evaluation. A repeated iPTH measure using a different assay showed a level of 123 mcg/mL. Because the patient was on fabrazyme that is a glycoprotein produced by non-human recombinant DNA technology (Chinese Hamster Ovary mammalian cell) and the generation of antibodies is not uncommon side effect of this drug. We presumed that the reason of this in vitro tertiary hyperparathyroidism as secondary to an interaction between our in house assay and possible antibodies induced by fabrazyme. The confirmation of falsely high iPTH level by using another assay was sane; it helped to avoid unnecessary invasive and costly procedures in an immunosuppressed patient. As a conclusion; the diagnosis of tertiary hyperparathyroidism remains a challenging entity in both nephrology and endocrinology fields. Pending evidence-based studies, it is reasonable to double check iPTH level with different assays in front of any atypical tertiary hyperparathyroidism before moving forward.
Am J Kidney Dis. 2012;59(4):A1-A92
TRENDS IN OBESITY AND KIDNEY DISEASE RISK FACTORS IN CHILDREN AND YOUNG ADULTS: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (NHANES III AND 1999-2008). G. M. Henriquez, H. Sarathy, J. Kumar, A. Skversky, M. Abramowitz, M. L. Melamed. Albert Einstein College of Medicine Bronx, NY; Weill Cornell Medical College New York, NY USA Obesity prevalence is increasing nationally across all ages. Obesity indirectly contributes to chronic kidney disease (CKD) through the development of diabetes and hypertension and may have direct effects as well. An association between the increase in prevalence of abdominal obesity and an increase in CKD risk factors has not been studied in a large population based study of children and young adults. We evaluated the changes in obesity prevalence over the past 20 years and its impact on CKD risk factors among children, adolescents and young adults ages 8-40 from NHANES 1988-2008 (n= 20,527) representative of 70,140,968 US residents. The prevalence of abdominal obesity (AO) (adult male >102cm, adult female > 88cm, pediatric population: 90th percentile for age and gender) increased from 23% in 1988-1996 to 36% in 2007-2008. This increase remained statistically significant after adjusting for demographic variables. There was a multivariable adjusted significant association between AO and higher risk of CKD risk factors, including systolic blood pressure (BP) [mean (SE)][+5.3 (0.2)], diastolic BP [+2.1 (0.3)], total cholesterol (+14.0 (1.0)), triglycerides [+50.9 (3.4)], LDL [+10.7(1.3)], HDL [-7.4 (0.3)], fasting plasma glucose [5.5 (0.7)], and fasting serum insulin [9.1 (0.5)]. AO was associated with a higher risk of microalbuminuria (OR 1.3 [1.1-1.6)] among adults ages 18-40 and with a higher risk of elevated C-reactive protein [OR 5.2 (4.5-6.0)] among children, adolescents and adults. Finally, AO was associated with a significantly higher estimated GFR by the Schwartz and CKDEPI equation [mean (SE)] [+4.5 (0.7)], respectively, in children and adults. Analyzing the data using body mass index instead of AO did not significantly alter these associations. In conclusion, AO has increased in prevalence in the US population aged 8-40 years of age. Even in this young cohort, AO predisposes to the development of CKD risk factors.
108 RENAL VEIN RENIN LEVELS IN ATHEROSCLEROTIC RENAL ARTERY STENOSIS (ARAS) DURING ACE INHIBITOR/ARB Rx Sandra M.S. Herrmann, Monika Gloviczki, Lilach Lerman, Stephen Textor, Mayo Clinic, Rochester, MN, USA. Renal vein renin (RVR) levels are limited as diagnostic tests, partly due to BP Rx, volume status, and putative reduction in their role during the evolution of renovascular hypertension. We sought to compare peripheral PRA and RVR in patients with unilateral ARAS (n=33, mean age 68±9.3) as compared to essential hypertensives (EH) (n=32, mean age 63±16.3) under fixed sodium intake and ACE/ARB Rx. Most (75%) were taking thiazide-class diuretics. Renal blood flow was measured by multi-detector CT (MDCT). PRA was measured on Day 1, while RVR was obtained 2 days later after an additional dose of i.v. furosemide. NET contribution PRA of each RVR was determined as (Renal vein-IVC)/IVC x 100 %( see table). The mean degree of stenosis in the ARAS was 73% by MDCT. Results: Parameters
EH(N=32)
ARAS(N=33)
p-value
PRAday 1
6.2±7.5
9.63±12.4
0.3301
%NET PRA
23±39
105±131
0.0037
Kidney RBFml/min
399.18±174
221.84±148
<0.0001
NET addition of RVR from the stenotic kidney correlated inversely with the proportional reduction in RBF (R=-.36, p=.03). Data also demonstrate enhanced stimulation of PRA levels from Day 1 to Day 3 in ARAS (p=.02) as compared to EH group (p=.0.18). Despite older age and longstanding hypertension, many patients with ARAS still demonstrate lateralization of NET PRA from the post-stenotic kidney. These data support the ongoing role of renin-angiotensin system activation in ARAS and may warrant the need for continued reninangiotensin system blockade during long-term therapy of ARAS.
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105
107
EXAMINING SURVIVAL GAIN OF THE ELDERLY KIDNEY TRANSPLANT RECIPIENTS COMPARED TO GENERAL POPULATION IN THE US Parta Hatamizadeh, Miklos Z Molnar, Elani Streja, Mahesh Krishnan, Csaba P Kovesdy, and Kamyar Kalantar-Zadeh. Harold Simmons Center, Harbor-UCLA, Torrance, CA, Salem VAMC, Salem, VA, DaVita, Denver, CO, CA. Individuals older than 65 years constitute the fastest growing population group in US. Similarly, the median age of kidney transplant recipients (KTR) has increased. The survival benefit of the elderly from kidney transplantation has not been clearly quantified. We compared the mortality rates and ratios across 3 age groups (15-<65, 65-<75 and ≥75 years old) between the KTRs (derived from the Scientific Registry of Transplant Recipients 2001-2006) and the general population (GP) using US population in 2005 (derived from the National Vital Statistics System). After calculating the crude mortality rates in KTRs and the GPs across 3 age groups, the relative risk (RR) of death was calculated for the 2 elderly groups compared to 15-<65 years (reference). Additionally, the ratio of mortality each RR for KTR to GP was estimated in each group. In our study the KTRs (n=155,005) were 45±16 years old and included 40% women and 19% diabetics. Even though kidney transplanted patients aged 65-<75 years and ≥75 years had a 75% and 96% higher mortality risk, respectively, than 15-<65 year-old group, the age-related rise in mortality was substantially lower across KTR than GP (see Table): ≥75 AGE GROUP 15-<65 65-<75 Kidney Transplant Recipients (KTR) (2001-06) (n=155,005) Crude death rates multiplied by 1000 RR Crude death rates multiplied by 1000 RR RR ratio KTR:GP
157 (155-159)
274 (267-281)
1.00 1.75 (1.72-1.77) General Population (GP) (2005)
307 (282-332) 1.96 (1.82-2.09)
3.1 (2.9-3.3)
21.4 (20.7-22.1)
76.6 (75.4-77.8)
1.00 1.00
6.9 (6.7-7.1) 0.25 (0.24-0.26)
24.7 (23.6-26.0) 0.08 (0.07-0.09)
Compared to GP, elderly KTR 65-<75 and ≥75 years exhibit 75% and 92% survival gain, respectively. The survival gains of kidney transplantation in the elderly warrant additional studies.
106 IATROGENIC TERTIARY HYPERPARATHYROIDISM IN A CASE OF FABRY DISEASE TREATED WITH AGALSIDASE BETA Hilana Hatoum1, Adepeju Jinadu1, Anita Patel1, Dhanwada Sudhaker Rao 2. 1: Nephrology Department. 2: Endocrinology Department. Henry Ford Hospital, Detroit, Michigan. Tertiary hyperthyroidism is a serious complication in ESRD and renal transplantation and the main treatment is still surgical. NKF KDOQI guidelines recommend recurrent measurement of iPTH as a first test for diagnosis and follow-up of hyperparathyroidism. But, the availability of different assays to measure iPTH affects the interpretation of the results and in some cases the management. A 50-Yr-O man with a history of ESRD secondary to Fabry disease status post living related kidney transplant was diagnosed with tertiary hyperparathyroidism due to persistently elevated iPTH (1200-1300 pg/mL) by using immunoreactivity based reaction assay. The patient was taking in addition to his immunosuppressive medications fabrazyme® (agalsidase beta) for his Fabry disease. The patient denied any complaints. Physical exam other than a palpable graft was unremarkable. Alkaline phosphatase, calcium, phosphorus and vitamin D levels were in normal ranges. Endocrine skeletal survey and bone densitometry were also normal. The patient was referred to a bone and mineral metabolism clinic for further evaluation. A repeated iPTH measure using a different assay showed a level of 123 mcg/mL. Because the patient was on fabrazyme that is a glycoprotein produced by non-human recombinant DNA technology (Chinese Hamster Ovary mammalian cell) and the generation of antibodies is not uncommon side effect of this drug. We presumed that the reason of this in vitro tertiary hyperparathyroidism as secondary to an interaction between our in house assay and possible antibodies induced by fabrazyme. The confirmation of falsely high iPTH level by using another assay was sane; it helped to avoid unnecessary invasive and costly procedures in an immunosuppressed patient. As a conclusion; the diagnosis of tertiary hyperparathyroidism remains a challenging entity in both nephrology and endocrinology fields. Pending evidence-based studies, it is reasonable to double check iPTH level with different assays in front of any atypical tertiary hyperparathyroidism before moving forward.
Am J Kidney Dis. 2012;59(4):A1-A92
TRENDS IN OBESITY AND KIDNEY DISEASE RISK FACTORS IN CHILDREN AND YOUNG ADULTS: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (NHANES III AND 1999-2008). G. M. Henriquez, H. Sarathy, J. Kumar, A. Skversky, M. Abramowitz, M. L. Melamed. Albert Einstein College of Medicine Bronx, NY; Weill Cornell Medical College New York, NY USA Obesity prevalence is increasing nationally across all ages. Obesity indirectly contributes to chronic kidney disease (CKD) through the development of diabetes and hypertension and may have direct effects as well. An association between the increase in prevalence of abdominal obesity and an increase in CKD risk factors has not been studied in a large population based study of children and young adults. We evaluated the changes in obesity prevalence over the past 20 years and its impact on CKD risk factors among children, adolescents and young adults ages 8-40 from NHANES 1988-2008 (n= 20,527) representative of 70,140,968 US residents. The prevalence of abdominal obesity (AO) (adult male >102cm, adult female > 88cm, pediatric population: 90th percentile for age and gender) increased from 23% in 1988-1996 to 36% in 2007-2008. This increase remained statistically significant after adjusting for demographic variables. There was a multivariable adjusted significant association between AO and higher risk of CKD risk factors, including systolic blood pressure (BP) [mean (SE)][+5.3 (0.2)], diastolic BP [+2.1 (0.3)], total cholesterol (+14.0 (1.0)), triglycerides [+50.9 (3.4)], LDL [+10.7(1.3)], HDL [-7.4 (0.3)], fasting plasma glucose [5.5 (0.7)], and fasting serum insulin [9.1 (0.5)]. AO was associated with a higher risk of microalbuminuria (OR 1.3 [1.1-1.6)] among adults ages 18-40 and with a higher risk of elevated C-reactive protein [OR 5.2 (4.5-6.0)] among children, adolescents and adults. Finally, AO was associated with a significantly higher estimated GFR by the Schwartz and CKDEPI equation [mean (SE)] [+4.5 (0.7)], respectively, in children and adults. Analyzing the data using body mass index instead of AO did not significantly alter these associations. In conclusion, AO has increased in prevalence in the US population aged 8-40 years of age. Even in this young cohort, AO predisposes to the development of CKD risk factors.
108 RENAL VEIN RENIN LEVELS IN ATHEROSCLEROTIC RENAL ARTERY STENOSIS (ARAS) DURING ACE INHIBITOR/ARB Rx Sandra M.S. Herrmann, Monika Gloviczki, Lilach Lerman, Stephen Textor, Mayo Clinic, Rochester, MN, USA. Renal vein renin (RVR) levels are limited as diagnostic tests, partly due to BP Rx, volume status, and putative reduction in their role during the evolution of renovascular hypertension. We sought to compare peripheral PRA and RVR in patients with unilateral ARAS (n=33, mean age 68±9.3) as compared to essential hypertensives (EH) (n=32, mean age 63±16.3) under fixed sodium intake and ACE/ARB Rx. Most (75%) were taking thiazide-class diuretics. Renal blood flow was measured by multi-detector CT (MDCT). PRA was measured on Day 1, while RVR was obtained 2 days later after an additional dose of i.v. furosemide. NET contribution PRA of each RVR was determined as (Renal vein-IVC)/IVC x 100 %( see table). The mean degree of stenosis in the ARAS was 73% by MDCT. Results: Parameters
EH(N=32)
ARAS(N=33)
p-value
PRAday 1
6.2±7.5
9.63±12.4
0.3301
%NET PRA
23±39
105±131
0.0037
Kidney RBFml/min
399.18±174
221.84±148
<0.0001
NET addition of RVR from the stenotic kidney correlated inversely with the proportional reduction in RBF (R=-.36, p=.03). Data also demonstrate enhanced stimulation of PRA levels from Day 1 to Day 3 in ARAS (p=.02) as compared to EH group (p=.0.18). Despite older age and longstanding hypertension, many patients with ARAS still demonstrate lateralization of NET PRA from the post-stenotic kidney. These data support the ongoing role of renin-angiotensin system activation in ARAS and may warrant the need for continued reninangiotensin system blockade during long-term therapy of ARAS.
A41