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HIGHER VITAMIN B12 LEVELS ARE ASSOCIATED WITH MORTALITY IN HEMODIALYSIS PATIENTS
NKF 2015 Spring Clinical Meetings Abstracts
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ANTI-GBM DISEASE IN ALPORT SYNDROME 10 YEARS LATER: Swathi Pullela, Saurabh Gandhi, David Butcher, Keith Bellovich. St. John Hospital, Detroit, MI, USA. Alport syndrome is an inherited disorder characterized by mutations affecting Type IV collagen production, most commonly of the α5 chain. This syndrome progresses to ESRD in 90% of male patients where transplantation is the ideal treatment. In the first year, posttransplant anti-GBM disease can affect up to 5% of recipients but rarely beyond that time. We report a case of anti-GBM disease presenting 10 years beyond transplantation. A 35-year-old male was diagnosed with Alport Syndrome at age 3. He received a living related kidney transplant in February 2004. His maintenance immunosuppression was MMF, prednisone and tacrolimus. He experienced 2 episodes of biopsy proven antibodymediated rejection in 2008 and 2011 treated with IVIG and pulse steroids with resolution of the acute rejection. His creatinine stabilized at a baseline of 3.4 mg/dl until presenting to the hospital in August 2014 with complaints of dyspnea, edema and oliguria. He admitted to medication non-adherence while vacationing for 2 weeks prior to admission. Physical exam revealed trace bilateral lower extremity edema. Labs: cr 18.19 mg/dl, BUN 120 mg/dl, WBC 9.3, Hgb 10.5 gm/dl, platelets 137,000, Na 128, K 5.1, Cl 91, CO2 12. Tacrolimus level 3.7 ng/ml. Ultrasound of transplanted kidney was unremarkable. A renal biopsy was performed showing BANFF 2A rejection and diffuse fibro-cellular crescent formation. Immunofluorescence confirmed the diagnosis with diffuse linear staining of the basement membrane with antiGBM antibodies. GBM IgG antibody 5.7 AI. He received immediate IV steroids, plasmapharesis and IVIG. Unfortunately his kidney function did not improve and he remains dialysis dependent. In greater than 75% of cases, post transplant anti-GBM nephritis occurs within first year after transplantation. We present a unique case of anti-GBM disease ten years post transplantation due to medication non-adherence.
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MEMBRANOUS NEPHROPATHY DIAGNOSED DURING PREGNANCY Juan Quevedo, Muner Mohamed, Farhang Ebrahimi, Richmond University Medical Center, Staten Island, NY, USA A 28-year-old woman G7P2A132 with severe preeclampsia during last pregnancy that led to fetal demise at 25 weeks is admitted at 24 weeks of gestation due to severe bilateral leg edema. She had been normotensive off medication and with recent finding of dyslipidemia. On physical exam blood pressure was118/52 mmHg, pulse rate 75 beats per minute, respiratory rate 14, temperature 97.8 °F, pulse oxygen 99% with regular heart rhythm, clear lungs to auscultation, abdomen soft, gravid, non tender, and bilateral leg edema +2. Laboratory data showed: Hgb 10.8 g/dL; platelets, 263 x 103/uL; BUN, 9 mg/dL; creatinine, 0.3 mg/dL; serum albumin, 0.4 g/dL; 24 hr urine collection, 11.4 g with subsequent random urine protein creatinine ratio (PCR) as high as 28 gm in a day. Lower extremities venous duplex was negative for DVT. She was scheduled for renal biopsy which showed membranous nephropathy (MN) with phospholipase A2 receptor negative deposits. Immunofluorescence showed “full house” immunoglobulin staining with IgG predominance. Secondary MN was suggested in report, including differential diagnosis of Lupus nephritis class V. Clinically, patient did not present any lupus like symptom and antinuclear and double stranded DNA antibodies were normal as well as compliment levels (tested twice three months apart). Patient was started and discharged on prednisone, tacrolimus, and low molecular weight heparin which she has tolerated well so far and is continuing pregnancy uneventfully with improved edema, decreasing PCR at 9.5 gm, and stable renal function. This is an unusual case of MN diagnosed during pregnancy in which seronegative lupus nephritis class V is suspected. Nephrotic proteinuria early in pregnancy should raise a concern for possible intrinsic kidney disease and to consider renal biopsy particularly in the absence of hypertension.
220
All Cause Mortality Hazard Ratio
HIGHER VITAMIN B12 LEVELS ARE ASSOCIATED WITH MORTALITY IN HEMODIALYSIS PATIENTS. Hemn Qader1; Yoshitsugu Obi1; Hamid Moradi1; Csaba P Kovesdy2; Rajnish Mehrotra3; Kamyar Kalantar-Zadeh1; Elani Streja1. 1Harold Simmons Center, UC Irvine, Orange, CA; 2 Nephrology, Univ. Tennessee, Memphis, TN; 3Nephrology, Univ. Washington, Seattle, WA. Serum Vitamin B12 (B12) levels are significantly higher in patients with end-stage renal disease than in the general population but the association between B12 levels and risk of death in patients on hemodialysis (HD) is unknown. Here, we hypothesized that higher B12 levels are associated with a higher risk of all-cause mortality in HD patients. We examined the association of baseline B12 levels [<400 (reference), 400 to <550, 550 to <650, 650 to <750, and ≥750 pg/ml]with all-cause mortality in 12,968 incident HD patients who initiated dialysis between 2007 through 2011 using Cox models with multivariable adjustment for case-mix and the markers of malnutrition and inflammation complex (MICS). Patient were 63±15 years old, and included 50% women, 33% blacks and 50% 1.6 diabetics. In the fully 1.5 adjusted model, 1.4 compared to HD 1.3 patients with <400 1.2 pg/ml of B12, those with 550 to <650 pg/ml 1.1 of B12 had a 26% 1 higher risk of all-cause unadjusted 0.9 case mix mortality (HR 1.26, case mix & MICS 95%CI 1.10-1.44). 0.8 There was no <550 <400 <650 <750 750+ 00040 55 65 incremental increase Vitamin B12 (pg/mL) risk of death at higher levels of B12. In conclusion, higher serum B12 levels were associated with higher risk of mortality in HD patients. Further studies examining the utility of B12 as a predictive marker of mortality in HD patients are needed.
Am J Kidney Dis. 2015;65(4):A1-A93
SAFETY OF SODIUM ZIRCONIUM CYCLOSILICATE (ZS-9) IN HYPERKALEMIA: ANALYSIS OF GI EFFECTS IN THE PHASE 3 HARMONIZE STUDY. Wajeh Qunibi1, Mikhail Kosiborod1, Henrik S. Rasmussen2, Philip T. Lavin3, Alex Yang2, Edgar Lerma1; 1 HARMONIZE Study Group; 2ZS Pharma, Coppell, TX; 3Boston Biostatistics Research Foundation, Framingham, MA, USA Hyperkalemia (HK; serum K+ ≥5.1 mEq/L) is common in pts with CKD, HF and diabetes, and is associated with poor prognosis. Current standard of care for hyperkalemia is sodium polystyrene sulfonate (SPS), an organic polymer resin that has uncertain efficacy, is poorly tolerated, and may cause severe GI toxicity. ZS-9 is a nonabsorbed cation exchanger that selectively binds K + in the intestine. In the Phase 3 HARMONIZE trial, ZS-9 rapidly restored and maintained normal K+. Here we present details of GI-related tolerability and safety of ZS-9. HARMONIZE was an international, multicenter, randomized, double-blind Phase 3 trial evaluating long-term efficacy and safety of ZS-9 in patients with HK. Pts received 10g of ZS-9 TID for 48h in the acute open-label phase. Pts achieving normokalemia (K+ 3.5-5.0) were then randomized to once daily ZS-9 (5, 10, or 15g) or placebo (PBO) for 28 days in the maintenance phase. All AEs were recorded. GI AEs were less frequent in the ZS-9 group than PBO (5.9% ZS-9 [all doses] vs. 14.1% PBO). No drug-related serious GI AEs were reported. Table lists GI AEs in ≥2 pts during the maintenance phase. Diarrhea incidence was low in all groups, but constipation was >3x more frequent with PBO than ZS-9. PBO ZS-9 5g ZS-9 10g ZS-9 15g (n=85) (n=45) (n=51) (n=56) GI disorders, overall 12 (14.1%) 3 (6.7%) 1 (2.0%) 5 (8.9%) 1 (1.2%) 1 (2.2%) 0 0 Abdominal pain 6 (7.1%) 0 1 (2.0%) 1 (1.8%) Constipation 1 (1.2%) 0 0 2 (3.6%) Diarrhea 0 2 (4.4%) 0 0 Dyspepsia 1 (1.2%) 0 0 1 (1.8%) Nausea 1 (1.2%) 1 (2.2%) 0 0 Vomiting In the HARMONIZE study, ZS-9 was well tolerated, with a GI AE profile similar to placebo, suggesting that it is suitable for chronic use.
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ANTI-GBM DISEASE IN ALPORT SYNDROME 10 YEARS LATER: Swathi Pullela, Saurabh Gandhi, David Butcher, Keith Bellovich. St. John Hospital, Detroit, MI, USA. Alport syndrome is an inherited disorder characterized by mutations affecting Type IV collagen production, most commonly of the α5 chain. This syndrome progresses to ESRD in 90% of male patients where transplantation is the ideal treatment. In the first year, posttransplant anti-GBM disease can affect up to 5% of recipients but rarely beyond that time. We report a case of anti-GBM disease presenting 10 years beyond transplantation. A 35-year-old male was diagnosed with Alport Syndrome at age 3. He received a living related kidney transplant in February 2004. His maintenance immunosuppression was MMF, prednisone and tacrolimus. He experienced 2 episodes of biopsy proven antibodymediated rejection in 2008 and 2011 treated with IVIG and pulse steroids with resolution of the acute rejection. His creatinine stabilized at a baseline of 3.4 mg/dl until presenting to the hospital in August 2014 with complaints of dyspnea, edema and oliguria. He admitted to medication non-adherence while vacationing for 2 weeks prior to admission. Physical exam revealed trace bilateral lower extremity edema. Labs: cr 18.19 mg/dl, BUN 120 mg/dl, WBC 9.3, Hgb 10.5 gm/dl, platelets 137,000, Na 128, K 5.1, Cl 91, CO2 12. Tacrolimus level 3.7 ng/ml. Ultrasound of transplanted kidney was unremarkable. A renal biopsy was performed showing BANFF 2A rejection and diffuse fibro-cellular crescent formation. Immunofluorescence confirmed the diagnosis with diffuse linear staining of the basement membrane with antiGBM antibodies. GBM IgG antibody 5.7 AI. He received immediate IV steroids, plasmapharesis and IVIG. Unfortunately his kidney function did not improve and he remains dialysis dependent. In greater than 75% of cases, post transplant anti-GBM nephritis occurs within first year after transplantation. We present a unique case of anti-GBM disease ten years post transplantation due to medication non-adherence.
218
MEMBRANOUS NEPHROPATHY DIAGNOSED DURING PREGNANCY Juan Quevedo, Muner Mohamed, Farhang Ebrahimi, Richmond University Medical Center, Staten Island, NY, USA A 28-year-old woman G7P2A132 with severe preeclampsia during last pregnancy that led to fetal demise at 25 weeks is admitted at 24 weeks of gestation due to severe bilateral leg edema. She had been normotensive off medication and with recent finding of dyslipidemia. On physical exam blood pressure was118/52 mmHg, pulse rate 75 beats per minute, respiratory rate 14, temperature 97.8 °F, pulse oxygen 99% with regular heart rhythm, clear lungs to auscultation, abdomen soft, gravid, non tender, and bilateral leg edema +2. Laboratory data showed: Hgb 10.8 g/dL; platelets, 263 x 103/uL; BUN, 9 mg/dL; creatinine, 0.3 mg/dL; serum albumin, 0.4 g/dL; 24 hr urine collection, 11.4 g with subsequent random urine protein creatinine ratio (PCR) as high as 28 gm in a day. Lower extremities venous duplex was negative for DVT. She was scheduled for renal biopsy which showed membranous nephropathy (MN) with phospholipase A2 receptor negative deposits. Immunofluorescence showed “full house” immunoglobulin staining with IgG predominance. Secondary MN was suggested in report, including differential diagnosis of Lupus nephritis class V. Clinically, patient did not present any lupus like symptom and antinuclear and double stranded DNA antibodies were normal as well as compliment levels (tested twice three months apart). Patient was started and discharged on prednisone, tacrolimus, and low molecular weight heparin which she has tolerated well so far and is continuing pregnancy uneventfully with improved edema, decreasing PCR at 9.5 gm, and stable renal function. This is an unusual case of MN diagnosed during pregnancy in which seronegative lupus nephritis class V is suspected. Nephrotic proteinuria early in pregnancy should raise a concern for possible intrinsic kidney disease and to consider renal biopsy particularly in the absence of hypertension.
220
All Cause Mortality Hazard Ratio
HIGHER VITAMIN B12 LEVELS ARE ASSOCIATED WITH MORTALITY IN HEMODIALYSIS PATIENTS. Hemn Qader1; Yoshitsugu Obi1; Hamid Moradi1; Csaba P Kovesdy2; Rajnish Mehrotra3; Kamyar Kalantar-Zadeh1; Elani Streja1. 1Harold Simmons Center, UC Irvine, Orange, CA; 2 Nephrology, Univ. Tennessee, Memphis, TN; 3Nephrology, Univ. Washington, Seattle, WA. Serum Vitamin B12 (B12) levels are significantly higher in patients with end-stage renal disease than in the general population but the association between B12 levels and risk of death in patients on hemodialysis (HD) is unknown. Here, we hypothesized that higher B12 levels are associated with a higher risk of all-cause mortality in HD patients. We examined the association of baseline B12 levels [<400 (reference), 400 to <550, 550 to <650, 650 to <750, and ≥750 pg/ml]with all-cause mortality in 12,968 incident HD patients who initiated dialysis between 2007 through 2011 using Cox models with multivariable adjustment for case-mix and the markers of malnutrition and inflammation complex (MICS). Patient were 63±15 years old, and included 50% women, 33% blacks and 50% 1.6 diabetics. In the fully 1.5 adjusted model, 1.4 compared to HD 1.3 patients with <400 1.2 pg/ml of B12, those with 550 to <650 pg/ml 1.1 of B12 had a 26% 1 higher risk of all-cause unadjusted 0.9 case mix mortality (HR 1.26, case mix & MICS 95%CI 1.10-1.44). 0.8 There was no <550 <400 <650 <750 750+ 00040 55 65 incremental increase Vitamin B12 (pg/mL) risk of death at higher levels of B12. In conclusion, higher serum B12 levels were associated with higher risk of mortality in HD patients. Further studies examining the utility of B12 as a predictive marker of mortality in HD patients are needed.
Am J Kidney Dis. 2015;65(4):A1-A93
SAFETY OF SODIUM ZIRCONIUM CYCLOSILICATE (ZS-9) IN HYPERKALEMIA: ANALYSIS OF GI EFFECTS IN THE PHASE 3 HARMONIZE STUDY. Wajeh Qunibi1, Mikhail Kosiborod1, Henrik S. Rasmussen2, Philip T. Lavin3, Alex Yang2, Edgar Lerma1; 1 HARMONIZE Study Group; 2ZS Pharma, Coppell, TX; 3Boston Biostatistics Research Foundation, Framingham, MA, USA Hyperkalemia (HK; serum K+ ≥5.1 mEq/L) is common in pts with CKD, HF and diabetes, and is associated with poor prognosis. Current standard of care for hyperkalemia is sodium polystyrene sulfonate (SPS), an organic polymer resin that has uncertain efficacy, is poorly tolerated, and may cause severe GI toxicity. ZS-9 is a nonabsorbed cation exchanger that selectively binds K + in the intestine. In the Phase 3 HARMONIZE trial, ZS-9 rapidly restored and maintained normal K+. Here we present details of GI-related tolerability and safety of ZS-9. HARMONIZE was an international, multicenter, randomized, double-blind Phase 3 trial evaluating long-term efficacy and safety of ZS-9 in patients with HK. Pts received 10g of ZS-9 TID for 48h in the acute open-label phase. Pts achieving normokalemia (K+ 3.5-5.0) were then randomized to once daily ZS-9 (5, 10, or 15g) or placebo (PBO) for 28 days in the maintenance phase. All AEs were recorded. GI AEs were less frequent in the ZS-9 group than PBO (5.9% ZS-9 [all doses] vs. 14.1% PBO). No drug-related serious GI AEs were reported. Table lists GI AEs in ≥2 pts during the maintenance phase. Diarrhea incidence was low in all groups, but constipation was >3x more frequent with PBO than ZS-9. PBO ZS-9 5g ZS-9 10g ZS-9 15g (n=85) (n=45) (n=51) (n=56) GI disorders, overall 12 (14.1%) 3 (6.7%) 1 (2.0%) 5 (8.9%) 1 (1.2%) 1 (2.2%) 0 0 Abdominal pain 6 (7.1%) 0 1 (2.0%) 1 (1.8%) Constipation 1 (1.2%) 0 0 2 (3.6%) Diarrhea 0 2 (4.4%) 0 0 Dyspepsia 1 (1.2%) 0 0 1 (1.8%) Nausea 1 (1.2%) 1 (2.2%) 0 0 Vomiting In the HARMONIZE study, ZS-9 was well tolerated, with a GI AE profile similar to placebo, suggesting that it is suitable for chronic use.
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