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NKF 2007 Spring Clinical Meetings Abstracts
WHOLE BLOOD ACCUMULATION OF ASYMMETRIC DIMETHYLARGININE IN END-STAGE RENAL DISEASE Raylene Platel1, Scott Billecke2, Steven Whitesall2, Rachel L.Perlman2, Kenneth A.Jamerson2, Louis G. D’Alecy2, Crystal A. Gadegbeku2. 1. Wayne State University, Detroit, MI; 2.University of Michigan, Ann Arbor, MI Plasma asymmetric dimethylarginine (ADMA) is significantly elevated in patients with renal disease and associated with cardiovascular mortality. Our recent study with a rodent model indicates that whole blood (WB) possesses large concentrations of protein-incorporated ADMA and the proteolytic machinery necessary for its release. To explore the link between WB and plasma ADMA in humans, we compared plasma ADMA and ex vivo ADMA accumulation in blood from subjects with and without end stage renal disease (ESRD). Pre-dialysis blood samples were obtained from 13 ESRD patients receiving chronic outpatient hemodialysis and 13 subjects without kidney disease who were matched for age, gender, race and presence of diabetes and/or hypertension. ADMA plasma concentrations were measured at baseline and ADMA levels from WB supernatant (WBSUP, e.g. the soluble fraction of lysed blood) were quantified over a 5h ex vivo incubation. ADMA was measured by high-pressure liquid chromatography. Baseline values were compared using unpaired two sided t-tests. The slopes derived from ADMA accumulation in WBSUP incubations were analyzed with a marginal effects linear regression model. ESRD patients had higher plasma ADMA than matched controls (0.83±0.05 vs. 0.61±0.06 µM, p=0.05, respectively). Ex vivo incubation of WBSUP showed a significant accumulation of ADMA in both groups. However, the ESRD population had a 47% greater rate of accumulation than matched controls (p=0.04). These findings confirm our animal data and further support a role for whole blood as a potential source for pathophysiologic elevations of free plasma ADMA.
NGAL AND EXTRACELLULAR MATRIX PROTEINS IN TGFBETA INDUCED CHRONIC RENAL FIBROSIS Ponda M, Siconolfi-Baez L, Kopp JB, Angeletti RH, Hostetter TH, Bitzer M. Albert Einstein College of Medicine, Bronx, NY; NIDDK, Bethesda, MD Diagnosis and monitoring of chronic renal disease remains based on serum creatinine and albuminuria. Urinary markers for acute kidney injury are being developed but their validity in chronic renal disease is uncertain. Transforming growth factor-beta (TGFb) is a central mediator of chronic-progressive fibrosis. The Albumin-TGF-b1 transgenic mouse (TG) model is characterized by glomerulosclerosis and tubulo-interstitial fibrosis. We examined urine of these mice prior to (2 weeks of age) and after (4 weeks of age) the development of fibrotic changes. The results were cross-examined in another model of progressive renal fibrosis, the remnant rat model, 2, 4, and 6 weeks after surgery. Urinary protein was purified using cellulose membrane filters. Proteome composition was determined using 1D PAGE/Western blotting, and 2D gel electrophoresis/Mass spectrometry (MS). To compare urinary excretion with tissue expression, renal mRNA and protein levels of individual gene products were determined. We found collagen I and VI mRNA and protein expression and urinary excretion strongly increased in TG kidneys compared with WT at 4 weeks of age paralleling the progression of albuminuria. Major Urinary Protein-2 (MUP-2) excretion in the urine strongly decreased in TG mice with disease progression, which was associated with a reduction of production in live and kidney. Urinary Lipocalin-2/NGAL increased as expected, but Lipocalin-2 production also increased dramatically in liver and kidney tissue. These results indicate that urinary excretion of gene products can be used to monitor intrarenal expression for certain gene products. In addition, increased Lipocalin excretion may be at least partially secondary to increased production in the liver, and examination of the urinary proteome may provide new insights into mechanism and possible markers for progressive renal fibrosis.
167 MENTAL SCORE IS BETTER THAN PHYSICAL SCORE IN A HEALTH SURVEY OF DIALYSIS PATIENTS Ishmael Qattash, Maliha Ahmed, Ahmed Mian, Jean Lee, Ziauddin Ahmed Drexel University College Of Medicine, Philadelphia The usefulness of the SF-36 health survey instrument in estimating disease burden is widely used. SF-36 measurement tool is now used in hemodialysis patient. The questionnaire reflects perceived present health condition, comparison of health status to 1 year ago, short term or last 4 weeks account of the lists of activities during a typical day, range of problems due to physical or emotional problems and their effects on social and family life, body pain and its effect in the normal activities, overall feelings and its effect on physical and emotional health, and lastly a statement about the perception of one’s health situation. All the above were placed in three categories. Physical Component summary (PCS) correlates with physical functioning, rolephysical, and body pain scales. Mental component summary (MCS) correlates with Mental health, role-emotional and social functioning scales. Mental health (MH) scale include nervousness, down in dumps, peaceful, sad and happy. The vitality, general health and social functioning scales correlates with both PCS and MCS. Thresholds below 52 in MH, 32 in PCS 34 and 42 in MCS correlates significantly with morbidity and mortality in general population. SF-36 survey questionnaire was given to patients in an urban dialysis unit. Average age 57 years, F:M 64:46, 40%diabetics, 10% amputee and total number surveyed was 92 patients. The social worker of the unit also compared her own personal observation with SF-36 results. SF-36 results revealed that 80.4%0( 74/92) of patients has higher Mental Health (MH) scale ( More than 52), 72.8% (67/92) has higher Mental component summary ( MCS) score ( More than 42) but only 43.3 %( 39/92) of the same group has higher Physical component summary (PCS) score. The SF-36 survey in dialysis patients reveals that mental component or MH and MCS have better score than physical or PCS score. A detail survey may be needed to explore the difference and the complex interaction between Mental and physical score in dialysis patients.
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SERUM FRUCTOSAMINE (SF), AN ALTERNATIVE MARKER OF GLYCEMIC CONTROL, PREDICTS HOSPITALIZATION AND INFECTION IN DIABETIC HEMODIALYSIS (DMHD) PATIENTS (PTS) BETTER THAN HEMOGLOBIN A1C (HBA1C) Muhammad A. Rafiq, Neal Mittman, Hina Chaudhry, Lalathaksha Kumbar, Brinda Desiraju, Morrell M. Avram. Avram Division of Nephrology, Long Island College Hospital, Brooklyn, NY, USA. Diabetes is the leading cause of end stage renal disease (ESRD) and is known mortality risk in HD pts. We have previously reported that SF may offer advantages over HbA1c as an alternative index of glycemic control in DMHD pts. The objective of this study was to examine the association of SF and HbA1c with morbidity and mortality in this population. We enrolled 100 DMHD outpatients treated at the Long Island College Hospital beginning in February 2005, and followed them for 15-21 months. Demographics, biochemical and clinical data including hospitalization and episodes of infection were recorded. HbA1c levels were measured by an immunoturbidimetric method. SF level was measured by a colorimetric method and was corrected for the concentration of serum albumin. The mean age was 63 years. Fiftyfour percent were women, and the majority were African-American (72%). Mean corrected SF and HbA1c were 977±231 (SD) µmol/g (range: 607-1994) and 7.3±1.7 (SD) % (range: 5-13.2), respectively. Pts who were hospitalized during the study period had higher levels of SF (1015 vs. 824 µmol/g, p<0.0001) but similar HbA1c (7.31 vs. 6.88%, p=0.24) compared to those who were not hospitalized. Pts (excluding those dialyzed via vascular catheters) with episodes of infection had higher corrected SF (1034 vs. 885, p=0.003), and HbA1c (7.65 vs. 6.75%, p=0.03). Corrected SF, but not HbA1c, was directly correlated with rate of hospitalization (r=0.52, p<0.0001), and number of hospital days (r=0.35, p=.009). SF (r=0.41, p=.003) and HbA1c (r=0.29, p=0.03) were directly correlated with number of episodes of infection in pts with AV access. Lower tertiles of SF had better survival, but the difference did not reach statistical significance. In summary, enrollment corrected SF, an alternative index of glycemia control, was more closely associated with hospitalization and infections in diabetic HD pts than HbA1c. The clinical significance of these findings needs to be confirmed in large prospective trials.
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NKF 2007 Spring Clinical Meetings Abstracts
WHOLE BLOOD ACCUMULATION OF ASYMMETRIC DIMETHYLARGININE IN END-STAGE RENAL DISEASE Raylene Platel1, Scott Billecke2, Steven Whitesall2, Rachel L.Perlman2, Kenneth A.Jamerson2, Louis G. D’Alecy2, Crystal A. Gadegbeku2. 1. Wayne State University, Detroit, MI; 2.University of Michigan, Ann Arbor, MI Plasma asymmetric dimethylarginine (ADMA) is significantly elevated in patients with renal disease and associated with cardiovascular mortality. Our recent study with a rodent model indicates that whole blood (WB) possesses large concentrations of protein-incorporated ADMA and the proteolytic machinery necessary for its release. To explore the link between WB and plasma ADMA in humans, we compared plasma ADMA and ex vivo ADMA accumulation in blood from subjects with and without end stage renal disease (ESRD). Pre-dialysis blood samples were obtained from 13 ESRD patients receiving chronic outpatient hemodialysis and 13 subjects without kidney disease who were matched for age, gender, race and presence of diabetes and/or hypertension. ADMA plasma concentrations were measured at baseline and ADMA levels from WB supernatant (WBSUP, e.g. the soluble fraction of lysed blood) were quantified over a 5h ex vivo incubation. ADMA was measured by high-pressure liquid chromatography. Baseline values were compared using unpaired two sided t-tests. The slopes derived from ADMA accumulation in WBSUP incubations were analyzed with a marginal effects linear regression model. ESRD patients had higher plasma ADMA than matched controls (0.83±0.05 vs. 0.61±0.06 µM, p=0.05, respectively). Ex vivo incubation of WBSUP showed a significant accumulation of ADMA in both groups. However, the ESRD population had a 47% greater rate of accumulation than matched controls (p=0.04). These findings confirm our animal data and further support a role for whole blood as a potential source for pathophysiologic elevations of free plasma ADMA.
NGAL AND EXTRACELLULAR MATRIX PROTEINS IN TGFBETA INDUCED CHRONIC RENAL FIBROSIS Ponda M, Siconolfi-Baez L, Kopp JB, Angeletti RH, Hostetter TH, Bitzer M. Albert Einstein College of Medicine, Bronx, NY; NIDDK, Bethesda, MD Diagnosis and monitoring of chronic renal disease remains based on serum creatinine and albuminuria. Urinary markers for acute kidney injury are being developed but their validity in chronic renal disease is uncertain. Transforming growth factor-beta (TGFb) is a central mediator of chronic-progressive fibrosis. The Albumin-TGF-b1 transgenic mouse (TG) model is characterized by glomerulosclerosis and tubulo-interstitial fibrosis. We examined urine of these mice prior to (2 weeks of age) and after (4 weeks of age) the development of fibrotic changes. The results were cross-examined in another model of progressive renal fibrosis, the remnant rat model, 2, 4, and 6 weeks after surgery. Urinary protein was purified using cellulose membrane filters. Proteome composition was determined using 1D PAGE/Western blotting, and 2D gel electrophoresis/Mass spectrometry (MS). To compare urinary excretion with tissue expression, renal mRNA and protein levels of individual gene products were determined. We found collagen I and VI mRNA and protein expression and urinary excretion strongly increased in TG kidneys compared with WT at 4 weeks of age paralleling the progression of albuminuria. Major Urinary Protein-2 (MUP-2) excretion in the urine strongly decreased in TG mice with disease progression, which was associated with a reduction of production in live and kidney. Urinary Lipocalin-2/NGAL increased as expected, but Lipocalin-2 production also increased dramatically in liver and kidney tissue. These results indicate that urinary excretion of gene products can be used to monitor intrarenal expression for certain gene products. In addition, increased Lipocalin excretion may be at least partially secondary to increased production in the liver, and examination of the urinary proteome may provide new insights into mechanism and possible markers for progressive renal fibrosis.
167 MENTAL SCORE IS BETTER THAN PHYSICAL SCORE IN A HEALTH SURVEY OF DIALYSIS PATIENTS Ishmael Qattash, Maliha Ahmed, Ahmed Mian, Jean Lee, Ziauddin Ahmed Drexel University College Of Medicine, Philadelphia The usefulness of the SF-36 health survey instrument in estimating disease burden is widely used. SF-36 measurement tool is now used in hemodialysis patient. The questionnaire reflects perceived present health condition, comparison of health status to 1 year ago, short term or last 4 weeks account of the lists of activities during a typical day, range of problems due to physical or emotional problems and their effects on social and family life, body pain and its effect in the normal activities, overall feelings and its effect on physical and emotional health, and lastly a statement about the perception of one’s health situation. All the above were placed in three categories. Physical Component summary (PCS) correlates with physical functioning, rolephysical, and body pain scales. Mental component summary (MCS) correlates with Mental health, role-emotional and social functioning scales. Mental health (MH) scale include nervousness, down in dumps, peaceful, sad and happy. The vitality, general health and social functioning scales correlates with both PCS and MCS. Thresholds below 52 in MH, 32 in PCS 34 and 42 in MCS correlates significantly with morbidity and mortality in general population. SF-36 survey questionnaire was given to patients in an urban dialysis unit. Average age 57 years, F:M 64:46, 40%diabetics, 10% amputee and total number surveyed was 92 patients. The social worker of the unit also compared her own personal observation with SF-36 results. SF-36 results revealed that 80.4%0( 74/92) of patients has higher Mental Health (MH) scale ( More than 52), 72.8% (67/92) has higher Mental component summary ( MCS) score ( More than 42) but only 43.3 %( 39/92) of the same group has higher Physical component summary (PCS) score. The SF-36 survey in dialysis patients reveals that mental component or MH and MCS have better score than physical or PCS score. A detail survey may be needed to explore the difference and the complex interaction between Mental and physical score in dialysis patients.
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SERUM FRUCTOSAMINE (SF), AN ALTERNATIVE MARKER OF GLYCEMIC CONTROL, PREDICTS HOSPITALIZATION AND INFECTION IN DIABETIC HEMODIALYSIS (DMHD) PATIENTS (PTS) BETTER THAN HEMOGLOBIN A1C (HBA1C) Muhammad A. Rafiq, Neal Mittman, Hina Chaudhry, Lalathaksha Kumbar, Brinda Desiraju, Morrell M. Avram. Avram Division of Nephrology, Long Island College Hospital, Brooklyn, NY, USA. Diabetes is the leading cause of end stage renal disease (ESRD) and is known mortality risk in HD pts. We have previously reported that SF may offer advantages over HbA1c as an alternative index of glycemic control in DMHD pts. The objective of this study was to examine the association of SF and HbA1c with morbidity and mortality in this population. We enrolled 100 DMHD outpatients treated at the Long Island College Hospital beginning in February 2005, and followed them for 15-21 months. Demographics, biochemical and clinical data including hospitalization and episodes of infection were recorded. HbA1c levels were measured by an immunoturbidimetric method. SF level was measured by a colorimetric method and was corrected for the concentration of serum albumin. The mean age was 63 years. Fiftyfour percent were women, and the majority were African-American (72%). Mean corrected SF and HbA1c were 977±231 (SD) µmol/g (range: 607-1994) and 7.3±1.7 (SD) % (range: 5-13.2), respectively. Pts who were hospitalized during the study period had higher levels of SF (1015 vs. 824 µmol/g, p<0.0001) but similar HbA1c (7.31 vs. 6.88%, p=0.24) compared to those who were not hospitalized. Pts (excluding those dialyzed via vascular catheters) with episodes of infection had higher corrected SF (1034 vs. 885, p=0.003), and HbA1c (7.65 vs. 6.75%, p=0.03). Corrected SF, but not HbA1c, was directly correlated with rate of hospitalization (r=0.52, p<0.0001), and number of hospital days (r=0.35, p=.009). SF (r=0.41, p=.003) and HbA1c (r=0.29, p=0.03) were directly correlated with number of episodes of infection in pts with AV access. Lower tertiles of SF had better survival, but the difference did not reach statistical significance. In summary, enrollment corrected SF, an alternative index of glycemia control, was more closely associated with hospitalization and infections in diabetic HD pts than HbA1c. The clinical significance of these findings needs to be confirmed in large prospective trials.