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Aldosterone Blockade Improves Endothelial Function in Obese Patients With the Metabolic Syndrome
NKF 2012 Spring Clinical Meetings Abstracts
149
151
THE LIKELIHOOD OF HYPERCALCEMIA ACROSS SERUM PTH LEVELS IN HEMODIALYSIS PATIENTS Jinnan Li, J. Zaritsky, M. Z. Molnar, J. J. Sim, E. Streja, C. P. Kovesdy, I. Salusky, and K. Kalantar-Zadeh. Harold Simmons Center, Harbor-UCLA, Torrance, CA, Salem VAMC, Salem, VA, David Geffen School of Medicine at UCLA, Los Angeles, CA; Kaiser Permanente, CA The correlates of serum PTH level in maintenance hemodialysis (MHD) are not well known. We hypothesized both lower and higher serum PTH level is associated with higher risk of hypercalcemia. Over an eight year period (7/2001-6/2009), we identified 106,760 MHD patients with PTH and calcium data in DaVita dialysis clinics. Logistic regression models were examined to assess the association between likelihood of hypercalcemia (Ca≥ 10.2 mg/dL) and serum PTH increments. Patients were 61±16 years old and included 45% women, 59% diabetics and 32% Blacks. Compared to the group with PTH 100-
5
30000
Unadjusted Case-mix Case-mix+MICS
25000
20000 2
15000
Frequency
Odds Ratio
3
10000
1
5000
0 0-<1
00
100-
<200
200-
<300
300-
<400
400-
<500
500-
<600
600-
<700
700-
<800
>=80
0
PTH (pg/mL)
<200 pg/ml (ref), patients with PTH <100, 500-<600, 600-<700, 700<800 and ≥800 pg/ml had more than two times, 33%, 64%, 63% and more than two times higher risk of hypercalcemia, respectively. Hence, the association of PTH level with high level of serum calcium is Ushaped, in that both very low levels and high levels of PTH are associated with hypercalcemia.
150 PROTEINURIA AND HYPERTENSION IN A PREGNANT PATIENT WITH DIABETES: WHEN TO BIOPSY? Kelly Liang, Devon Ramaeker, Nirav Shah, Sheldon Bastacky, Arun Jeyabalan; University of Pittsburgh, Pittsburgh, PA, USA BACKGROUND: Nephrotic range proteinuria, hypertension (HTN), and edema occurring at 20 weeks’ gestation in the setting of longstanding diabetes mellitus (DM) has a wide differential diagnosis. CASE PRESENTATION: A 40-year-old Caucasian female presented at 19 weeks’ gestation with worsening HTN (blood pressure (BP) 170/64), increase in proteinuria (3+ on urinalysis, 24-h urine protein 5.7 g/day), and mild leg edema, in the setting of a history of chronic HTN, type 1 DM since age 10 (no retinopathy), and smoking. She had a history of preeclampsia 16 years ago. She was on an angiotensin converting enzyme inhibitor (ACE-I) and a statin but discontinued them during pregnancy. She was hospitalized with concern for preeclampsia versus new onset renal disease versus diabetic nephropathy. BP was controlled with labetalol and diltiazem CD. Extensive serologic work-up was negative, and there was no other end organ involvement suggestive of preeclampsia. With better BP control, her proteinuria decreased to 3.2 g/day. Given the uncertain diagnosis and risks of empiric steroid therapy and/or delivery, she underwent renal biopsy. It revealed 2 out of 10 sclerotic glomeruli and mild mesangial expansion, but no findings to suggest diabetic nephropathy or preeclampsia. Electron microscopy revealed diffuse foot process fusion, consistent with minimal change disease (MCD), though unsampled focal segmental glomerulosclerosis could not be excluded. Based on these findings, she plans to continue the pregnancy with close monitoring. After delivery, she will restart her ACE-I and statin and consider initiation of steroids for treatment of MCD. DISCUSSION: Although proteinuria, HTN, and edema are hallmark findings of preeclampsia when presenting during the third trimester, the etiology is less clear at 20 weeks’ gestation. Therefore, the potential benefits of a renal biopsy were felt to outweigh the risks. CONCLUSION: The information from a renal biopsy performed during pregnancy may provide critical information to help guide treatment and assist in deciding whether to deliver prematurely, particularly when the etiology of nephrotic syndrome is unclear.
A52
INFLUENCE OF KIDNEY FUNCTION ON RISK OF HEMORRHAGE AMONG PATIENTS TAKING WARFARIN Mohit Limdi, Michael Crowley, Nita Limdi, Michael Allon University of Alabama at Birmingham, Birmingham AL Chronic kidney disease (CKD) is common in paents with cardiovascular diseases. Doctors have noted that paents with CKD more adverse drug effects on cardiovascular medicaons (e.g. warfarin) as compared to those without CKD. The aim of this study is to determine if the risk of major hemorrhage is higher among paents with CKD and if the risk is higher in paents with Stage 3b CKD compared to Stage 3a CKD. Methods /Procedures: Glomerular filtraon rate (GFR) was calculated for 1248 paents on warfarin therapy. Incidence rates of hemorrhage were compared across kidney funcon. Time to hemorrhage was analyzed using survival analysis. The risk of hemorrhage was analyzed before and aer adjustment for clinical and genec factors. Results: As GFR decreases the incidence rate of major hemorrhage increases. Paents with stage 3b CKD have a 2.5 fold higher incidence of major hemorrhage than paents with stage 3a CKD. Compared to paents with GFR>60, those with stage 3b CKD are at a 2.1 fold higher risk of major hemorrhage (p=0.035) while those with stage 3a CKD are not at a higher risk (p= 0.98). Compared to paents with GFR>60, those with GFR<30 are at a 3.4 fold-higher risk (p<0.0001). Conclusion: This study shows that among paents taking warfarin kidney impairment is an important risk factor for developing major hemorrhage. Studies should be conducted to understand the risk-benefit of warfarin in paents with different levels of kidney funcon. The FDA should require clinical trials to recruit a study populaon that mimics the populaon seen in clinical pracce.
152 ALDOSTERONE BLOCKADE IMPROVES ENDOTHELIAL FUNCTION IN OBESE PATIENTS WITH THE METABOLIC SYNDROME Julio Cesar Moraes Lovisi, Danielle Guedes Andrade Ezequiel, Rogério Baumgratz de Paula, Thaís Chehuem Bicalho, Fernanda Castro Barros, Mônica Barros Costa NIEPEN-Federal University of Juiz de Fora, Minas Gerais - Brazil In recent years a role for aldosterone in the pathophysiology of the metabolic syndrome (MS) has been suggested. In this study we evaluated the effects of aldosterone blockade on blood pressure (BP), metabolic parameters as well as in brachial artery flow mediated vasodilatation (FMD) in non-diabetic obese individuals with the MS. Twenty seven subjects were enrolled in a protocol that included clinical evaluation, serum lipid profile and fasting plasma glucose analysis. Twenty-four hour ambulatory blood pressure monitoring and FMD analysis were performed both before and after 16 weeks of spironolactone (SPIRO) 50 mg once a day. Mean body mass index was 35.2±5.22kg/m2 and did not change significantly after SPIRO (35.6±3.64kg/m2). Systolic BP reduced from 137.5±9.69 to 124.1±1.78 mmHg and diastolic BP reduced from 88.9±7.98 to 81.1±5.64 mmHg before and after SPIRO treatment respectively (p<0.001). These findings were associated with HDL cholesterol levels increase (42.2±9.10 vs 47.8±7.08 mg/dL, p<0,001). Fasting plasma glucose (89.7±9.59 vs 91.6±10.64 mg/dL) and triglycerides (183.2±100.07 vs 182.5±118.84 mg/dL) levels did not change significantly after SPIRO. Flow mediated vasodilatation in brachial artery increased from 8.2±5.17% to 15.1±6.12% after SPIRO (p<0.001). In conclusion, aldosterone blockade in subjects with the MS improved endothelial function and decreased blood pressure with favorable effects on metabolic parameters.
Am J Kidney Dis. 2012;59(4):A1-A92
149
151
THE LIKELIHOOD OF HYPERCALCEMIA ACROSS SERUM PTH LEVELS IN HEMODIALYSIS PATIENTS Jinnan Li, J. Zaritsky, M. Z. Molnar, J. J. Sim, E. Streja, C. P. Kovesdy, I. Salusky, and K. Kalantar-Zadeh. Harold Simmons Center, Harbor-UCLA, Torrance, CA, Salem VAMC, Salem, VA, David Geffen School of Medicine at UCLA, Los Angeles, CA; Kaiser Permanente, CA The correlates of serum PTH level in maintenance hemodialysis (MHD) are not well known. We hypothesized both lower and higher serum PTH level is associated with higher risk of hypercalcemia. Over an eight year period (7/2001-6/2009), we identified 106,760 MHD patients with PTH and calcium data in DaVita dialysis clinics. Logistic regression models were examined to assess the association between likelihood of hypercalcemia (Ca≥ 10.2 mg/dL) and serum PTH increments. Patients were 61±16 years old and included 45% women, 59% diabetics and 32% Blacks. Compared to the group with PTH 100-
5
30000
Unadjusted Case-mix Case-mix+MICS
25000
20000 2
15000
Frequency
Odds Ratio
3
10000
1
5000
0 0-<1
00
100-
<200
200-
<300
300-
<400
400-
<500
500-
<600
600-
<700
700-
<800
>=80
0
PTH (pg/mL)
<200 pg/ml (ref), patients with PTH <100, 500-<600, 600-<700, 700<800 and ≥800 pg/ml had more than two times, 33%, 64%, 63% and more than two times higher risk of hypercalcemia, respectively. Hence, the association of PTH level with high level of serum calcium is Ushaped, in that both very low levels and high levels of PTH are associated with hypercalcemia.
150 PROTEINURIA AND HYPERTENSION IN A PREGNANT PATIENT WITH DIABETES: WHEN TO BIOPSY? Kelly Liang, Devon Ramaeker, Nirav Shah, Sheldon Bastacky, Arun Jeyabalan; University of Pittsburgh, Pittsburgh, PA, USA BACKGROUND: Nephrotic range proteinuria, hypertension (HTN), and edema occurring at 20 weeks’ gestation in the setting of longstanding diabetes mellitus (DM) has a wide differential diagnosis. CASE PRESENTATION: A 40-year-old Caucasian female presented at 19 weeks’ gestation with worsening HTN (blood pressure (BP) 170/64), increase in proteinuria (3+ on urinalysis, 24-h urine protein 5.7 g/day), and mild leg edema, in the setting of a history of chronic HTN, type 1 DM since age 10 (no retinopathy), and smoking. She had a history of preeclampsia 16 years ago. She was on an angiotensin converting enzyme inhibitor (ACE-I) and a statin but discontinued them during pregnancy. She was hospitalized with concern for preeclampsia versus new onset renal disease versus diabetic nephropathy. BP was controlled with labetalol and diltiazem CD. Extensive serologic work-up was negative, and there was no other end organ involvement suggestive of preeclampsia. With better BP control, her proteinuria decreased to 3.2 g/day. Given the uncertain diagnosis and risks of empiric steroid therapy and/or delivery, she underwent renal biopsy. It revealed 2 out of 10 sclerotic glomeruli and mild mesangial expansion, but no findings to suggest diabetic nephropathy or preeclampsia. Electron microscopy revealed diffuse foot process fusion, consistent with minimal change disease (MCD), though unsampled focal segmental glomerulosclerosis could not be excluded. Based on these findings, she plans to continue the pregnancy with close monitoring. After delivery, she will restart her ACE-I and statin and consider initiation of steroids for treatment of MCD. DISCUSSION: Although proteinuria, HTN, and edema are hallmark findings of preeclampsia when presenting during the third trimester, the etiology is less clear at 20 weeks’ gestation. Therefore, the potential benefits of a renal biopsy were felt to outweigh the risks. CONCLUSION: The information from a renal biopsy performed during pregnancy may provide critical information to help guide treatment and assist in deciding whether to deliver prematurely, particularly when the etiology of nephrotic syndrome is unclear.
A52
INFLUENCE OF KIDNEY FUNCTION ON RISK OF HEMORRHAGE AMONG PATIENTS TAKING WARFARIN Mohit Limdi, Michael Crowley, Nita Limdi, Michael Allon University of Alabama at Birmingham, Birmingham AL Chronic kidney disease (CKD) is common in paents with cardiovascular diseases. Doctors have noted that paents with CKD more adverse drug effects on cardiovascular medicaons (e.g. warfarin) as compared to those without CKD. The aim of this study is to determine if the risk of major hemorrhage is higher among paents with CKD and if the risk is higher in paents with Stage 3b CKD compared to Stage 3a CKD. Methods /Procedures: Glomerular filtraon rate (GFR) was calculated for 1248 paents on warfarin therapy. Incidence rates of hemorrhage were compared across kidney funcon. Time to hemorrhage was analyzed using survival analysis. The risk of hemorrhage was analyzed before and aer adjustment for clinical and genec factors. Results: As GFR decreases the incidence rate of major hemorrhage increases. Paents with stage 3b CKD have a 2.5 fold higher incidence of major hemorrhage than paents with stage 3a CKD. Compared to paents with GFR>60, those with stage 3b CKD are at a 2.1 fold higher risk of major hemorrhage (p=0.035) while those with stage 3a CKD are not at a higher risk (p= 0.98). Compared to paents with GFR>60, those with GFR<30 are at a 3.4 fold-higher risk (p<0.0001). Conclusion: This study shows that among paents taking warfarin kidney impairment is an important risk factor for developing major hemorrhage. Studies should be conducted to understand the risk-benefit of warfarin in paents with different levels of kidney funcon. The FDA should require clinical trials to recruit a study populaon that mimics the populaon seen in clinical pracce.
152 ALDOSTERONE BLOCKADE IMPROVES ENDOTHELIAL FUNCTION IN OBESE PATIENTS WITH THE METABOLIC SYNDROME Julio Cesar Moraes Lovisi, Danielle Guedes Andrade Ezequiel, Rogério Baumgratz de Paula, Thaís Chehuem Bicalho, Fernanda Castro Barros, Mônica Barros Costa NIEPEN-Federal University of Juiz de Fora, Minas Gerais - Brazil In recent years a role for aldosterone in the pathophysiology of the metabolic syndrome (MS) has been suggested. In this study we evaluated the effects of aldosterone blockade on blood pressure (BP), metabolic parameters as well as in brachial artery flow mediated vasodilatation (FMD) in non-diabetic obese individuals with the MS. Twenty seven subjects were enrolled in a protocol that included clinical evaluation, serum lipid profile and fasting plasma glucose analysis. Twenty-four hour ambulatory blood pressure monitoring and FMD analysis were performed both before and after 16 weeks of spironolactone (SPIRO) 50 mg once a day. Mean body mass index was 35.2±5.22kg/m2 and did not change significantly after SPIRO (35.6±3.64kg/m2). Systolic BP reduced from 137.5±9.69 to 124.1±1.78 mmHg and diastolic BP reduced from 88.9±7.98 to 81.1±5.64 mmHg before and after SPIRO treatment respectively (p<0.001). These findings were associated with HDL cholesterol levels increase (42.2±9.10 vs 47.8±7.08 mg/dL, p<0,001). Fasting plasma glucose (89.7±9.59 vs 91.6±10.64 mg/dL) and triglycerides (183.2±100.07 vs 182.5±118.84 mg/dL) levels did not change significantly after SPIRO. Flow mediated vasodilatation in brachial artery increased from 8.2±5.17% to 15.1±6.12% after SPIRO (p<0.001). In conclusion, aldosterone blockade in subjects with the MS improved endothelial function and decreased blood pressure with favorable effects on metabolic parameters.
Am J Kidney Dis. 2012;59(4):A1-A92