Original Investigations: Pathogenesis and Treatment of Kidney Disease and Hypertension
Relationship of renal function to homocysteine and lipoprotein(a) levels: The frequency of the combination of both risk factors in chronic renal impairment*,**

https://doi.org/10.1053/ajkd.2002.36321Get rights and content

Abstract

Background: Total homocysteine (tHcy) and lipoprotein(a) [Lp(a)] levels have been recognized as risk factors for vascular disease. The combination of elevated tHcy and Lp(a) levels may be particularly atherogenic, although no study has examined the prevalence of the combination of both risk factors in patients with chronic renal impairment. Methods: One hundred ninety-seven patients with renal impairment were studied. Patients had glomerular filtration rate (GFR) measured by clearance of chromium 51-labeled EDTA. Blood was obtained for the determination of tHcy, Lp(a), and apolipoprotein(a) [apo(a)] isoform levels. Results: Patients were divided into five groups according to GFR. Mean tHcy levels in the five groups were as follows: GFR less than 10 mL/min, 30.2 ± 9.8 (SD) μmol/L; GFR of 10 to 20 mL/min, 26.6 ± 10.5 μmol/L; GFR of 20 to 30 mL/min, 23.9 ± 8.6 μmol/L; GFR of 30 to 45 mL/min, 22.2 ± 8.6 μmol/L; and GFR of 45 to 75 mL/min, 18.2 ± 9.1 μmol/L compared with control levels of 12.7 ± 4.6 μmol/L. There was a progressive increase in median Lp(a) levels with declining renal function: median Lp(a) levels for those with a GFR less than 10 mL/min were 37.1 mg/dL (range, 0.6 to 156.0 mg/dL); GFR of 10 to 20 mL/min, 30.3 mg/dL (range, 2.6 to 163.7 mg/dL); GFR of 20 to 30 mL/min, 26.1 mg/dL (range, 0.0 to 164.0 mg/dL); GFR of 30 to 45 mL/min, 20.9 mg/dL (range, 0.0 to 99.8 mg/dL), and GFR of 45 to 75 mL/min, 16.8 mg/dL (range, 2.1 to 81.0 mg/dL) compared with control values of 12.5 mg/dL (range, 0.0 to 88.7 mg/dL). Conclusion: Defining hyperhomocysteinemia as tHcy levels greater than the 90th percentile of controls and elevated Lp(a) level as greater than 30 mg/dL, the frequency of the combination increased with declining renal function. Fifty-eight percent of patients with a GFR less than 10 mL/min had both hyperhomocysteinemia and elevated Lp(a) levels, and even in patients with mild renal impairment, 20% of patients had both risk factors present. Am J Kidney Dis 40:916-923. © 2002 by the National Kidney Foundation, Inc.

Section snippets

Subjects and methods

One hundred ninety-seven patients (age range, 27.2 to 86.1 years) with renal impairment (plasma creatinine level, 1.08 to 11.68 mg/dL [96 to 1,033 μmol/L]) were studied, although none had started renal replacement therapy yet. The cause of renal impairment was diabetes mellitus in 30%, hypertensive nephropathy in 13%, chronic glomerulonephritis in 13%, adult polycystic kidney disease in 8%, renovascular in 8%, unknown in 13%, and miscellaneous in 15%. Patients administered folic acid, vitamin B

Results

Table 1 lists patient characteristics for each group of patients, divided by EDTA clearance.

. Patient Characteristics in Five Groups

Empty CellGroups by GFR (mL/min/1.73 m2)
Empty Cell<1010-2020-3030-4545-75
No. of patients5750303426
Age (y)66.5 ± 12.464.8 ± 13.064.2 ± 13.759.5 ± 12.952.5 ± 14.6
Sex (M/F)40/1733/1721/929/821/5
Body mass index24.6 ± 4.127.8 ± 5.426.9 ± 4.527.1 ± 5.127.9 ± 5.4
Plasma creatinine (mg/dL)5.61 ± 1.874.23 ± 1.532.02 ± 0.541.61 ± 0.271.39 ± 1.45
GFR (mL/min)7.6 ± 1.513.5 ± 2.624.9 ± 3.137.5 ±

Discussion

This is the first study to examine both tHcy and Lp(a) levels in a large number of patients with renal impairment using reliable methods of measuring renal function that has included proteinuric patients and those with diabetic nephropathy. Our data for tHcy levels are similar to previous studies that examined tHcy levels in patients with renal impairment measured by isotopic methods.30, 31, 32, 33 In the current study, even in patients with mild renal impairment (GFR, 45 to 75 mL/min/1.73 m2),

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    *

    Address reprint requests to Darren S. Parsons, BM, BS, Department of Renal Medicine, Charing Cross Hospital, Fulham Palace Rd, London W6 8RF, UK. E-mail: [email protected]

    **

    0272-6386/02/4005-0004$35.00/0

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