title: Nephrinuria associates with multiple renal traits in type 2 diabetes.
abstract: BACKGROUND
  The involvement of nephrin in controlling renal function is unclear with the literature only emphasizing its role in albuminuria. We therefore investigated the potential association between nephrinuria as evidenced by the appearance of urinary immunopositive nephrin fragments, with multiple renal traits.
  
  
  METHODS
  Western blot analysis of the urine samples from a cross-sectional study of 381 Chinese type 2 diabetic patients revealed four distinct protein fragments, indicative of nephrinuria. Albuminuria was measured in random spot urine samples using the albumin/creatinine ratio (ACR), while estimated glomerular filtration rate (eGFR) was calculated using the creatinine-based Modification of Diet in Renal Disease formula.
  
  
  RESULTS
  Each nephrin fragment was associated with a decline in eGFR (smallest P = 0.001). Even with the inclusion of logarithmic form of ACR (ln ACR) in the multivariate model, nephrinuria still remained significantly associated with lower eGFR (smallest P < 0.05). Nephrinuria was also strongly associated with lnACR and this finding was independent of eGFR (smallest P < 0.001). Thus, nephrinuria was independently associated with both renal traits in the form of lnACR and eGFR. Furthermore, nephrinuria was significantly associated with lower eGFR even among normoalbuminuric patients (ACR ≤ 30 mg/g) (smallest P = 0.002), potentially implicating nephrinuria in the development of normoalbuminuric renal insufficiency. Apart from the renal traits under investigation, the presence of nephrinuria did not associate with other patient clinical characteristics.
  
  
  CONCLUSIONS
  Nephrinuria was associated with multiple renal traits in type 2 diabetes even in normoalbuminuric patients who are traditionally perceived as having a low risk of chronic kidney disease.
authors.affiliation: Department of Epidemiology and Public Health, National University of Singapore.
authors.forename: Daniel P K
authors.initials: DP
authors.lastname: Ng
authors.forename: Bee-Choo
authors.initials: BC
authors.lastname: Tai
authors.forename: Elaine
authors.initials: E
authors.lastname: Tan
authors.forename: Helen
authors.initials: H
authors.lastname: Leong
authors.forename: Siti
authors.initials: S
authors.lastname: Nurbaya
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Lim
authors.forename: Kee-Seng
authors.initials: KS
authors.lastname: Chia
authors.forename: Chia-Siong
authors.initials: CS
authors.lastname: Wong
authors.forename: Wei-Yen
authors.initials: WY
authors.lastname: Lim
authors.forename: Harry
authors.initials: H
authors.lastname: Holthöfer
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000209:etiology*; D015153:Blotting, Western; D003404:Creatinine / Q000378:metabolism; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D008565:Membrane Proteins; C113267:nephrin; D003404:Creatinine