title: Body mass index modifies the risk of cardiovascular death in proteinuric chronic kidney disease.
abstract: BACKGROUND
  In subjects with end-stage renal disease, a high body mass index (BMI) is inversely related to overall mortality, which has been coined reverse epidemiology phenomenon. This study sought to investigate this paradox as well as a possible risk modification by proteinuria on the relationship of BMI with earlier stages of chronic kidney disease (CKD) concerning cardiovascular mortality.
  
  
  METHODS
  We used the Vienna Health Screening Initiative, a longitudinal cohort study from 1990 to 2006, including 49 398 volunteers (49.9% women, age 20-89 years): n = 2487 showed mild CKD (proteinuria and GFR >60 ml/min/1.73 m(2)) and n = 392 showed moderate CKD (GFR = 30-59 ml/min/1.73 m(2)). The follow-up period was 5.5 +/- 4.2 years; n = 148 cardiovascular deaths occurred. Exposure variables were BMI, glomerular filtration rate (GFR) and proteinuria. Cox regression models on cardiovascular mortality with adjustment for age, sex, log(cholesterol/HDL), uric acid, smoking, glucose, diabetes, mean blood pressure, hypertension and antihypertensive drug use were fitted.
  
  
  RESULTS
  The risk factor paradox is shown in moderate CKD (GFR = 45 ml/min/1.73 m(2)): hazard ratios (HR) of BMI contrasts decreased consistently from 1.28 (95% CI 0.33-5.82) at BMI 20 kg/m(2) versus 25 kg/m(2) to 0.76 (95% CI 0.38-1.50) at BMI 30 kg/m(2) versus 25 kg/m(2) and to 0.58 (95% CI 0.13-2.64) at BMI 35 kg/m(2) versus 25 kg/m(2), thus showing an inverse relationship compared to mild CKD/healthy participants. Examining proteinuria as an effect modifier in this context showed that in moderate CKD (contrast: proteinuria versus no proteinuria) HR decreased more profoundly from 9.43 (95% CI 2.66-27.40) at BMI 25 kg/m(2) to 3.74 (95% CI 0.93-15.70) at BMI 30 kg/m(2) and to 1.95 (95% CI 0.37-22.30) at BMI 35 kg/m(2), and conversely in non-proteinuric subjects, hazards for cardiovascular mortality increased in underweight as well as in overweight/obese subjects in a U-shaped manner.
  
  
  CONCLUSIONS
  Our results suggest that obese subjects with proteinuric CKD may not be counselled for weight reduction since a higher BMI was associated with a remarkably reduced risk of death.
authors.affiliation: 3rd Medical Department, Donauspital im SMZ-OST, Medical Research Society DC Vienna, Medical University Vienna, Vienna, Austria.
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Obermayr
authors.forename: Christian
authors.initials: C
authors.lastname: Temml
authors.forename: Georg
authors.initials: G
authors.lastname: Gutjahr
authors.forename: Alexander
authors.initials: A
authors.lastname: Kainz
authors.forename: Renate
authors.initials: R
authors.lastname: Klauser-Braun
authors.forename: Reinhold
authors.initials: R
authors.lastname: Függer
authors.forename: Rainer
authors.initials: R
authors.lastname: Oberbauer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000401:mortality*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011507:Proteinuria / Q000150:complications*; D012307:Risk Factors; D012907:Smoking; D015996:Survival Rate; D055815:Young Adult