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Proteinuria as a Surrogate Outcome in Chronic Kidney Disease

Proteinuria as a Surrogate Outcome in Chronic Kidney Disease. Early Diabetes – Microalbuminuria (MA) Type 2 Diabetes in American Indians Robert G Nelson, MD, PhD NIDDK, Phoenix. Population. Pima Indians from the Gila River Indian Community in Arizona

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Proteinuria as a Surrogate Outcome in Chronic Kidney Disease

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  1. Proteinuria as a Surrogate Outcome in Chronic Kidney Disease Early Diabetes – Microalbuminuria (MA) Type 2 Diabetes in American Indians Robert G Nelson, MD, PhD NIDDK, Phoenix

  2. Population • Pima Indians from the Gila River Indian Community in Arizona • Biennial examinations since 1965 of all community members ≥5 years old • Medical history/physical examination • Height, weight, blood pressure • Blood and urine tests • Retinal examinations and photographs • ECG • Oral Glucose Tolerance Test • Registries • ESRD • Mortality

  3. Definitions Measure of Albuminuria Collection: Daytime untimed “spot” urine specimens Analyte: Urinary Albumin to Creatinine Ratio (ACR; in mg/g) Analytical methods: Albumin – immunonephelometry (Dade Behring, Inc.); Creatinine – modified Jaffe reaction (Envoy 500) Thresholds: <30 mg/g; normoalbuminuria (NA) 30-299 mg/g; microalbuminuria (MA) ≥300 mg/g; macroalbuminuria Measure of Proteinuria Collection: Daytime untimed “spot” urine specimens Analyte: Urinary Protein to Creatinine Ratio (PCR; in g/g) Analytical methods: Protein – Shevky-Stafford; Creatinine – modified Jaffe reaction (Envoy 500) Thresholds: ≥0.5 g/g (or ≥1.0 g/g in some studies)

  4. Age-Sex-Adjusted Death Ratesin Pima Indians ≥45 Years Old Age-sex-duration adjusted death rate ratio 3.5 (95% CI, 2.8-4.4) Diabetes 37:1499-1504, 1988

  5. Prevalence of Elevated Albuminuria Diabetologia 32:870-876, 1989

  6. Incidence of Proteinuria by Level of Albuminuria Figure.Age-sex-adjusted incidence of proteinuria in diabetic Pima Indians by albuminuria category. Arch Intern Med 151:1761-1765, 1991

  7. Age-Sex-Adjusted Incidence of SCr ≥2.0 mg/dl by Duration of Diabetes and Presence of Proteinuria Age-sex-duration adjusted incidence rate ratio 42 (95% CI, 24-75) Kidney Int 35:681-687, 1989

  8. Cumulative Incidence of ESRDby Duration of Proteinuria 80 Whites with type 1 Pimas with type 2 60 Percent 40 20 0 0 5 10 15 Duration of Proteinuria (years) Diabetologia 36:1087-1093, 1993

  9. Mean (±SE) Change in GFRAccording to Albuminuria at Baseline N Engl J Med 335:1636-1642, 1996

  10. Sequential Measures of Albuminuria Am J Kidney Dis 51:759-766, 2008

  11. Changes in ACR Categories Between Two ACR Measurements Taken Within a 6-year Period Am J Kidney Dis 51:759-766, 2008

  12. Incidence Rate Ratio for Diabetic ESRD (N=89 cases) Relative to Persistently Normal ACR Am J Kidney Dis 51:759-766, 2008

  13. Incidence of Diabetic ESRD Kidney Int 70:1840-1846, 2006

  14. Summary • MA occurs frequently in type 2 diabetes • MA predicts development of overt nephropathy • MA frequently regresses to normoalbuminuria • Low current ACR is associated with a good prognosis regardless of earlier values • Proteinuria strongly predicts progression to renal insufficiency, ESRD, and death • Distribution of albuminuria is changing over time

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