Lipoprotein(a)- and low-density lipoprotein-derived cholesterol in nephrotic syndrome: Impact on lipid-lowering therapy?
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.
Kronenberg
Florian
F
Department of Medical Biology and Human Genetics, Medical University of Innsbruck, Innsbruck, Austria. Florian.Kronenberg@uibk.ac.at
Lingenhel
Arno
A
Lhotta
Karl
K
Rantner
Barbara
B
Kronenberg
Martina F
MF
König
Paul
P
Thiery
Joachim
J
Koch
Michael
M
von Eckardstein
Arnold
A
Dieplinger
Hans
H
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
D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D017270:Lipoprotein(a)