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247 De Novo Al Amyloidosis Presenting in a Renal Allograft: A Report of Two Cases
NKF 2011 Spring Clinical Meetings Abstracts
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247 TRANSPLANT CENTER DIFFERENCES: A NEW METHOD TO MEASURE THE GAP IN OUTCOMES Stefanos Zenios1,2, Glenn Atias1, Charles McCulloch3, Constantia PetrouError! Bookmark not defined.,4 1-Culmini Inc., 2-Stanford University, 3-UC San Francisco Standardized patient and graft survival rates across transplant centers aim to predict future performance. We compared the predictive accuracy of standardized rates with the observed-to-expected (O/E) method to an alternative method that is based on generalized mixed effects (ME) method. Data were from the United States Renal Data System. We compared root mean square errors for the difference between the estimates obtained by both methods using past data to estimates obtained from a future time period. The ME method has a lower root mean square error for graft failure and patient mortality. The difference in root mean square error ranged from 1.0% to 3.7%. For the ME method the highest error was for predicting future 3-year graft survival with the O/E method (6.6%) and the lowest was for predicting future 3-year patient survival with the ME method (2.1%). Standardized estimates with the ME method had a much smaller range between the 5th and 95th percentile compared to the O/E method: 7.5% for 3-year graft failure compared to 21.6% for the O/E method; 4.7% for 3-year patient survival compared to 15.4%. This ME range is clinically significant: 20% of all deaths and 25% of all graft failures in the 3 years after transplant could be eliminated if all centers matched the outcomes of the best center. However, this range did not change since the introduction of public reporting indicating that centers do not yet have strong incentives to change their behavior.
246 C1Q NEPHROPATHY VS. MESANGIOPATHIC GLOMERULOPATHY IN A PATIENT WITH CHRONIC HEPATITIS C INFECTION Ufoma Philemon, Khalid Bashir, Dept. of Medicine, Morehouse School of Medicine, Atlanta, GA, USA. A 49 year old female with past medical history of hypertension, chronic hepatitis C infection, cirrhosis of the liver and left ureteral stone presented to our ED with complaints of new-onset bilateral lower extremity edema of five days duration, associated with shortness of breath and sub-sternal chest pain. Physical examination revealed an obese female, with normal blood pressure and 3+ bilateral lower extremity edema from the level of ankles up to the knees. Laboratory abnormalities included serum albumin of 2.3 gm/dl, proteinuria of 4.5 gm/day, C3 of 82mg/dl, C4 of 9 mg/dl and microscopic hematuria. ANA, anti-DNA, ANCA and HIV antibody was negative. HCV RNA-PCR was 207.77 x 1000 IU/ml. Renal USG, persantine cardiac scan and leg Doppler studies were normal. CT-guided percutaneous kidney biopsy was done. LM revealed segmental mesangial hypercellularity and matrix increase with very mild interstitial fibrosis and tubular atrophy but no endocapillary proliferation or cellular crescents. Immunofluorescence microscopy revealed 2+ mesangial C1q and C3 staining and 2+ paramesangial IgM staining. EM revealed abundant mesangial immune deposits and patchy foot process effacement without subendothelial, intramembranous or subepithelial dense deposits. Immunoperoxidase staining for hepatitis C antigen was negative. This case illustrates changes consistent with mesangiopathic glomerulopathy of uncertain classification. None of the classic glomerulonephritities (GNs) associated with hepatitis C infection i.e., membranoproliferative GN (MPGN), cryoglobulinemic GN or membranous GN were seen in our patient. Mesangioproliferative GNs have infrequently been described with hepatitis C infection and may sometimes serve as precursor lesions for MPGN. Alternatively, patient may have C1q Nephropathy (C1qN) typically characterized as a variant of focal sclerosis showing mesangial hypercellularity and mesangial C1q deposition. The association between C1qN and hepatitis C infection is unknown.
A78
DE NOVO AL AMYLOIDOSIS PRESENTING IN A RENAL ALLOGRAFT: A REPORT OF TWO CASES. Jyothishree Pinnaka, Pankaj Manocha, Stephen Pastan. Department of Medicine, Emory University School of Medicine. Case One: A 79-year-old Caucasian woman with polycystic kidney disease underwent deceased donor renal transplantation in 1998. In January 2010 she presented with leg swelling and fatigue. 24 hour urine revealed 3.3 grams of protein; serum creatinine (SCr) was 1.4 mg/dL. Serum immunofixation revealed a lambda light chain paraprotein not observed on serum protein electrophoresis (SPEP). Urine electrophoresis showed 74 mg of free lambda light chain per 24 hours. Renal transplant biopsy showed amyloidosis with positive Congo red staining; 10 nM non-branching fibrils were present on electron microscopy (EM); immunofluorescence (IF) was not obtained. Bone marrow (BM) biopsy revealed a mild plasmacytosis. The patient was treated with melphalan and prednisone but expired due to progressive renal and heart failure. Case Two: A 65-year-old African American woman developed end stage renal disease presumably due to hypertension. Monoclonal gammopathy of unknown significance vs. asymptomatic multiple myeloma was identified prior to renal transplant. SPEP was negative but serum immunofixation revealed an IgA lambda paraprotein. BM biopsy showed 10% plasma cells. She underwent living related renal transplantation in 2004. In 2010 the 24 hour urine protein was 3.5 gm; SCr was 0.94 mg/dL. Serum and urine electrophoreses revealed an IgA lambda paraprotein and abnormal lambda light chains. Renal allograft biopsy revealed amyloidosis with positive Congo red staining; 10 nM non-branching fibrils were present on EM. IF showed preponderant staining for lambda light chains. Multiple myeloma was diagnosed and the patient recently started treatment with Velcade, melphalan and dexamethasone. AL amyloidosis is a rare cause of proteinuria in renal transplant patients and should be considered particularly in patients with evidence of monoclonal gammopathy. To our knowledge, there are only two other prior reported cases of de novo AL amyloidosis presenting in a renal allograft.
248 PREVALENCE OF DIAGNOSED RISK FACTORS IN UNDERSERVED PATIENTS WITHOUT CREATININE MEASUREMENTS IS HIGH Laura Plantinga, Delphine Tuot, Vanessa Grubbs, and Neil Powe Center for Vulnerable Populations, San Francisco General Hospital, and University of California, San Francisco, CA, USA Diabetes and hypertension account for the vast majority of CKD in the United States. Persons with these risk factors should be tested regularly for declines in kidney function. A cohort of 1617 adult (>20 years) patients with at least 12 months of follow-up and two or more primary care visits, but without recorded creatinine measurements, was randomly selected within the San Francisco Department of Public Health Community Health Network (a consortium of >30 clinics delivering care to underserved patients) , starting in January 2005. ICD-9 diagnostic coding in outpatient, inpatient, and emergency department records defined diagnosed diabetes (250.x, 249.x) and hypertension (401.x-404.x, 997.91). The majority of this untested cohort had neither diabetes nor hypertension (93.9%); however, while only 1.1% had diabetes, 5.5% had hypertension (6.1% with either condition). With adjustment for age, race/ethnicity, gender, poverty, insurance, and language, both middle (45-64 years) vs. younger (20-44 years) age [OR=2.22, 95% CI (1.25-3.94)] and black vs. white race/ethnicity [3.18 (1.54-6.55)] were statistically significantly associated with higher odds of having either diagnosed risk factor in this cohort. Medicare vs. Medicaid insurance was also marginally associated with higher odds of having these conditions [2.72 (0.90-8.22)]. Similarly, middle age and black race were associated with higher risk of having hypertension alone; for diabetes, the associations were similar but not statistically significant. Other insurance vs. Medicaid was associated with decreased odds of having diabetes alone [0.17 (0.04-0.84)]. Up to 6% of underserved patients who have not had creatinine measured may have powerful, diagnosed risk factors for CKD (hypertension and diabetes) that are not recognized by providers. Provider education regarding appropriate creatinine testing in the setting of known CKD risk factors may be warranted to optimize preventive care.
Am J Kidney Dis. 2011;57(4):A1-A108
245
247 TRANSPLANT CENTER DIFFERENCES: A NEW METHOD TO MEASURE THE GAP IN OUTCOMES Stefanos Zenios1,2, Glenn Atias1, Charles McCulloch3, Constantia PetrouError! Bookmark not defined.,4 1-Culmini Inc., 2-Stanford University, 3-UC San Francisco Standardized patient and graft survival rates across transplant centers aim to predict future performance. We compared the predictive accuracy of standardized rates with the observed-to-expected (O/E) method to an alternative method that is based on generalized mixed effects (ME) method. Data were from the United States Renal Data System. We compared root mean square errors for the difference between the estimates obtained by both methods using past data to estimates obtained from a future time period. The ME method has a lower root mean square error for graft failure and patient mortality. The difference in root mean square error ranged from 1.0% to 3.7%. For the ME method the highest error was for predicting future 3-year graft survival with the O/E method (6.6%) and the lowest was for predicting future 3-year patient survival with the ME method (2.1%). Standardized estimates with the ME method had a much smaller range between the 5th and 95th percentile compared to the O/E method: 7.5% for 3-year graft failure compared to 21.6% for the O/E method; 4.7% for 3-year patient survival compared to 15.4%. This ME range is clinically significant: 20% of all deaths and 25% of all graft failures in the 3 years after transplant could be eliminated if all centers matched the outcomes of the best center. However, this range did not change since the introduction of public reporting indicating that centers do not yet have strong incentives to change their behavior.
246 C1Q NEPHROPATHY VS. MESANGIOPATHIC GLOMERULOPATHY IN A PATIENT WITH CHRONIC HEPATITIS C INFECTION Ufoma Philemon, Khalid Bashir, Dept. of Medicine, Morehouse School of Medicine, Atlanta, GA, USA. A 49 year old female with past medical history of hypertension, chronic hepatitis C infection, cirrhosis of the liver and left ureteral stone presented to our ED with complaints of new-onset bilateral lower extremity edema of five days duration, associated with shortness of breath and sub-sternal chest pain. Physical examination revealed an obese female, with normal blood pressure and 3+ bilateral lower extremity edema from the level of ankles up to the knees. Laboratory abnormalities included serum albumin of 2.3 gm/dl, proteinuria of 4.5 gm/day, C3 of 82mg/dl, C4 of 9 mg/dl and microscopic hematuria. ANA, anti-DNA, ANCA and HIV antibody was negative. HCV RNA-PCR was 207.77 x 1000 IU/ml. Renal USG, persantine cardiac scan and leg Doppler studies were normal. CT-guided percutaneous kidney biopsy was done. LM revealed segmental mesangial hypercellularity and matrix increase with very mild interstitial fibrosis and tubular atrophy but no endocapillary proliferation or cellular crescents. Immunofluorescence microscopy revealed 2+ mesangial C1q and C3 staining and 2+ paramesangial IgM staining. EM revealed abundant mesangial immune deposits and patchy foot process effacement without subendothelial, intramembranous or subepithelial dense deposits. Immunoperoxidase staining for hepatitis C antigen was negative. This case illustrates changes consistent with mesangiopathic glomerulopathy of uncertain classification. None of the classic glomerulonephritities (GNs) associated with hepatitis C infection i.e., membranoproliferative GN (MPGN), cryoglobulinemic GN or membranous GN were seen in our patient. Mesangioproliferative GNs have infrequently been described with hepatitis C infection and may sometimes serve as precursor lesions for MPGN. Alternatively, patient may have C1q Nephropathy (C1qN) typically characterized as a variant of focal sclerosis showing mesangial hypercellularity and mesangial C1q deposition. The association between C1qN and hepatitis C infection is unknown.
A78
DE NOVO AL AMYLOIDOSIS PRESENTING IN A RENAL ALLOGRAFT: A REPORT OF TWO CASES. Jyothishree Pinnaka, Pankaj Manocha, Stephen Pastan. Department of Medicine, Emory University School of Medicine. Case One: A 79-year-old Caucasian woman with polycystic kidney disease underwent deceased donor renal transplantation in 1998. In January 2010 she presented with leg swelling and fatigue. 24 hour urine revealed 3.3 grams of protein; serum creatinine (SCr) was 1.4 mg/dL. Serum immunofixation revealed a lambda light chain paraprotein not observed on serum protein electrophoresis (SPEP). Urine electrophoresis showed 74 mg of free lambda light chain per 24 hours. Renal transplant biopsy showed amyloidosis with positive Congo red staining; 10 nM non-branching fibrils were present on electron microscopy (EM); immunofluorescence (IF) was not obtained. Bone marrow (BM) biopsy revealed a mild plasmacytosis. The patient was treated with melphalan and prednisone but expired due to progressive renal and heart failure. Case Two: A 65-year-old African American woman developed end stage renal disease presumably due to hypertension. Monoclonal gammopathy of unknown significance vs. asymptomatic multiple myeloma was identified prior to renal transplant. SPEP was negative but serum immunofixation revealed an IgA lambda paraprotein. BM biopsy showed 10% plasma cells. She underwent living related renal transplantation in 2004. In 2010 the 24 hour urine protein was 3.5 gm; SCr was 0.94 mg/dL. Serum and urine electrophoreses revealed an IgA lambda paraprotein and abnormal lambda light chains. Renal allograft biopsy revealed amyloidosis with positive Congo red staining; 10 nM non-branching fibrils were present on EM. IF showed preponderant staining for lambda light chains. Multiple myeloma was diagnosed and the patient recently started treatment with Velcade, melphalan and dexamethasone. AL amyloidosis is a rare cause of proteinuria in renal transplant patients and should be considered particularly in patients with evidence of monoclonal gammopathy. To our knowledge, there are only two other prior reported cases of de novo AL amyloidosis presenting in a renal allograft.
248 PREVALENCE OF DIAGNOSED RISK FACTORS IN UNDERSERVED PATIENTS WITHOUT CREATININE MEASUREMENTS IS HIGH Laura Plantinga, Delphine Tuot, Vanessa Grubbs, and Neil Powe Center for Vulnerable Populations, San Francisco General Hospital, and University of California, San Francisco, CA, USA Diabetes and hypertension account for the vast majority of CKD in the United States. Persons with these risk factors should be tested regularly for declines in kidney function. A cohort of 1617 adult (>20 years) patients with at least 12 months of follow-up and two or more primary care visits, but without recorded creatinine measurements, was randomly selected within the San Francisco Department of Public Health Community Health Network (a consortium of >30 clinics delivering care to underserved patients) , starting in January 2005. ICD-9 diagnostic coding in outpatient, inpatient, and emergency department records defined diagnosed diabetes (250.x, 249.x) and hypertension (401.x-404.x, 997.91). The majority of this untested cohort had neither diabetes nor hypertension (93.9%); however, while only 1.1% had diabetes, 5.5% had hypertension (6.1% with either condition). With adjustment for age, race/ethnicity, gender, poverty, insurance, and language, both middle (45-64 years) vs. younger (20-44 years) age [OR=2.22, 95% CI (1.25-3.94)] and black vs. white race/ethnicity [3.18 (1.54-6.55)] were statistically significantly associated with higher odds of having either diagnosed risk factor in this cohort. Medicare vs. Medicaid insurance was also marginally associated with higher odds of having these conditions [2.72 (0.90-8.22)]. Similarly, middle age and black race were associated with higher risk of having hypertension alone; for diabetes, the associations were similar but not statistically significant. Other insurance vs. Medicaid was associated with decreased odds of having diabetes alone [0.17 (0.04-0.84)]. Up to 6% of underserved patients who have not had creatinine measured may have powerful, diagnosed risk factors for CKD (hypertension and diabetes) that are not recognized by providers. Provider education regarding appropriate creatinine testing in the setting of known CKD risk factors may be warranted to optimize preventive care.
Am J Kidney Dis. 2011;57(4):A1-A108