title: Lipoprotein(a)- and low-density lipoprotein-derived cholesterol in nephrotic syndrome: Impact on lipid-lowering therapy?
abstract: BACKGROUND
  Patients with nephrotic syndrome have the highest lipoprotein(a) [Lp(a)] concentrations known. Lp(a) is an low-density lipoprotein (LDL)-like particle consisting of 45% cholesterol. The usual methods to determine LDL cholesterol do not distinguish between cholesterol derived from LDL and Lp(a) and are thus the net result of cholesterol levels from both lipoproteins. High Lp(a) concentrations therefore significantly contribute to the measured or calculated LDL cholesterol levels. Since statins have no influence on Lp(a) levels, it can be expected that the LDL cholesterol-lowering effect of statins may be diminished in patients who have a pronounced elevation of Lp(a) levels accompanied by only moderate elevations of LDL cholesterol.
  
  
  METHODS
  We investigated 207 patients with nondiabetic nephrotic syndrome in whom Lp(a) concentrations were strikingly elevated when compared to 274 controls (60.4 +/- 85.4 mg/dL vs. 20.0 +/- 32.8 mg/dL, P < 0.0001).
  
  
  RESULTS
  According to National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines for Managing Dyslipidemias, almost 95% of these patients are candidates for a therapeutic intervention to lower LDL cholesterol. LDL cholesterol levels corrected for Lp(a)-derived cholesterol, however, were 27 mg/dL lower than uncorrected concentrations (compared to only 9 mg/dL in controls). If Lp(a)-corrected levels instead of total LDL cholesterol levels were used, 25.7% of patients with low-molecular-weight (LMW) apolipoprotein(a) [apo(a)] isoforms were classified no longer to be in need of LDL cholesterol-lowering therapeutic intervention compared to only 2.3% of patients with high-molecular-weight (HMW) apo(a) phenotypes (P < 0.00001). This ("pseudo") pharmacogenetic effect results in incorrect determination of LDL cholesterol.
  
  
  CONCLUSIONS
  Our observation has an impact on the indication for, and assessment of efficacy of intervention. This potential artifact should be investigated in ongoing large trials in renal patients as well as in nonrenal African American subjects who have on average markedly higher Lp(a) levels. In nonrenal Caucasian subjects with much lower Lp(a) concentrations, this issue will be less relevant.
authors.affiliation: Department of Medical Biology and Human Genetics, Medical University of Innsbruck, Innsbruck, Austria. Florian.Kronenberg@uibk.ac.at
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: Arno
authors.initials: A
authors.lastname: Lingenhel
authors.forename: Karl
authors.initials: K
authors.lastname: Lhotta
authors.forename: Barbara
authors.initials: B
authors.lastname: Rantner
authors.forename: Martina F
authors.initials: MF
authors.lastname: Kronenberg
authors.forename: Paul
authors.initials: P
authors.lastname: König
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
authors.forename: Hans
authors.initials: H
authors.lastname: Dieplinger
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood* / Q000188:drug therapy / Q000628:therapy; D010531:Peritoneal Dialysis, Continuous Ambulatory; D006435:Renal Dialysis
chemical_list: D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D017270:Lipoprotein(a)