1017
NEPHROTIC SYNDROME AND CARDIOVASCULAR DISEASE
SiR,--Considering the vast literature on increased synthesis of lipoproteins in nephrotic patients and animals’I together with the recognised defect in lipoprotein lipase clearing factor2 the paper by Dr Wass and colleagues (Sept. 29, p. 664) strikes a discordant note. Why are nephrotics in SouthEast England so different from those in other areas? Could this paper really represent events in a new era in which steroids are used much less for nephrosis? If we were given lipoprotein profiles we might be able to judge. We are not even given the HDL-cholesterol data nor the method of assay. Patients who came to necropsy did not receive the careful study of the coronary arteries that was performed by Curry and Roberts.3 Perhaps a hasty diagnosis of terminal renal failure meant that atherosclerosis was not adequately assessed. Wass et al. believe that systemic lupus erythematosus (SLE) predisposes to cardiovascular disease but that is not borne out by their table i. Maybe LDL-cholesterol and lipoprotein lipase are normal in SLE neprotics--or perhaps they do not have the increase in unbound free fatty acids/albumin that is the likely explanation for platelet and endothelial cell damage. However, Wass et al. are right to stress the dangers of clofibrate in this situation; carbohydrate restriction will control the hyperlipidaemia.4,5 33 Hawthorn Gardens, Kenton, Newcastle upon
whet his
appetite, we append the HDL cholesterol levels (separated by ultracentrifugation and measured by the method of Levine and Zak8) which were removed at The Lancet’s suggestion (see figure). They are normal. The ratio of HDL:total cholesterol was reduced (datanot shown) because LDL and VLDL levels were raised. Other clinical9 and experimental’° data support the suggestion of normal or even raised HDL levels in the nephrotic syndrome. We agree that the necropsies did not all include careful examination of the coronary vessels, but their series, pre-
dominantly diabetics and patients with lupus, hardly seems relevant. The suggestion that SLE—or some aspect of its management-predisposes to vascular events is supported15 by the data of Urowitz et al.," although not with our own data.12 Despite platelet hyperaggregability,I3,14 platelet serotonin’s and
plasma-p-thromboglobulin
are
normal in
We doubt whether carbohydrate restriction-which would probably aggravate the negative nitrogen balance experienced by nephrotics-would alter cholesterol levels in nephrotic pa-
tients. At least
we can
agree that clofibrate should
not
be used.
J. S. CAMERON
E. N. WARDLE
Tyne NE3 3DE
concentrations
nephrotics without immune complexes in their kidneys, and Futrakup6 noted only minor acceleration of platelet turnover. Thus, the possible role of diminished FFA binding to albumin in promoting vascular damage in vivo remains in doubt.
Clinical Science Laboratories, Guy’s Hospital Medical School, London SE1 9RT
V. WASS
R. J. JARRETT C. CHILVERS
***Professor Cameron and colleagues’ reply follows.-ED. L.
SIR,-Dr Wardle seems to assume that hypercholesterolSEmia (whether accompanied by hypertriglyceridaemia or altered HDL lipoprotein levels or not) is always associated with an increased incidence of accelerated vascular disease; the rational position is to test this hypothesis in unusual groups, such as nephrotic patients. There is no way one can say that nephrotics in South-East England differ from those in the rest of the world when, as we stated, there is no epidemiologically acceptable evidence with which to compare our data. Our patients do not seem to differ from those in San Francisco.6 Our paper was an essay in epidemiology, and Wardle can have all the lipid data in the further paper we mentioned. However, to 1. Shafrir E, Brenner T. Lipoprotein lipid and protein synthesis in experimental nephrosis and plasmapheresis. Lipids 1979; 14: 695-702. 2. Kekki M, Nikkilä EA. Plasma triglyceride metabolism in the adult nephrotic
syndrome. Europ J Clin Invest 1971; 1: 345-51. 3. Curry RC, Roberts WC. Status of the coronary arteries in the
nephrotic syndrome. Am J Med 1977; 63: 183-92. 4. Baxter JH, Goodman HC, Shafrir E. Effect of glucose infusions on serum lipids and lipoproteins in nephrotics. J Clin Invest 1959; 38: 987-7. 5. Bar-On H, Shafrir E. Conversion of glucose into lipids and proteins in experimental nephrotic syndrome. Israel J Med Sci 1965; 1: 365-77. 6. Hopper J, Ryan P, Lee JC, Roseman W. Lipoid nephrosis in 31 adult patients: renal biopsy study by light, electron and immunofluorescence microscopy with experience in treatment. Medicine 1970; 49: 321-41.
..I. V
u
c"JU
"%.U
Plasma albumin
uV
SiR,—In the study by Dr Eykyn and her colleagues (Oct. 13, p. 761) the incidence of anaerobic sepsis in the metronidazole treated patients seems unexpectedly high. In a paper given to the Surgical Research Society in Dundee in June, 1978, we reported the results of a double blind prospective trial of metronidazole and kanamycin given orally, preoperatively, in which one group received metronidasole alone. In some respects, therefore, the results are comparable. All patients undergoing elective colonic resections were admitted to the trial. The principal exclusions were patients with ulcerative colitis or Crohn’s disease and those requiring additional antibiotic cover (i.e., patients with valvular heart-disease). Three surgical groups were identified : (A) right colon resection (to splenic flexure), (B) left colon resection, and (C) abdominoperineal resection. Patients received metronidazole 400 mg orally 6 hourly and kanamycin 600 mg orally 6 hourly for 3 days up to the time of surgery, or an identical placebo, in one of the following combinations of treatment: metronidazole and kanamycin (MK), metronidazole and placebo kanamycin (MP), or placebo metronidazole and placebo kanamycin (PP). 67 patients entered the trial. The antimicrobial combinations were randomised for each surgi7. Carlson K. Lipoprotein fractionation. J Clin Path 1973; 26: suppl 5, 32-7. 8. Levine J, Zak B. Automated determination of serum total cholesterol. Clin Chim Acta 1964; 10: 381-84. 9. Lopes-Virella M, Virella G, Debeukelaer M, Owens CJ, Colwell JA. Urinary high density lipoprotein in minimal change glomerular disease and chronic glomerulonephritis. Clin Chim Acta, 1979; 94: 73-81. 10. de Mendoza SG, Kashyorp ML, Chen CY, Lutmer RF. High density lipoproteinuria in nephrotic syndrome. Metabolism 1976; 25: 1143-49. 11. Urowitz MB, Bockman AAM, Koehler BE, Gordon DA, Smythe HA, Ogryzlo MA. The bimodal mortality pattern of systemic lupus erythematosus Am J Med 1976; 61: 221-25 12. Cameron JS, Turner DR, Ogg CS, Williams DG, Lessof MH, Chantler C, Leibowitz S. Systemic lupus with nephritis: a long-term study. Quart J Med 1979; 48: 1-24. 13. Bang NU, Trygstad CW, Schroeder JE, Heidenreich RO, Ciscko BM. Enhanced platelet function in glomerular disease. J Lab Clin Med 1973; 81: 651-60. 14. Reumuzzi G, Marchesi D, Mecca G, de Gaetano G, Silver MJ. Platelet hypersensitivity in the nephrotic syndrome. European Dialysis and Trans-
plant Association, Amsterdam, June, 1979: abstr p. 78. JS. Platelet and plasma serotonin concentrations in glomerulonephritis. I. Thromb Res 1979; 15: 109-25. 16. Futrakul P, Poshyschinda M. Kinetic evaluation of hemostasis in the steroidsensitive nephrotic syndrome. J Singapore Pædiat Soc 1977; 19: 273-76.
15. Parbtani A, Cameron
g/1
Plasma HDL cholesterol levels in male adult-onset nephrotic patients.
ANTIMICROBIAL PROPHYLAXIS IN ELECTIVE COLONIC SURGERY
(8)
and female
(0)
1018 cal group, and the supervision of tablets and their issue, was performed by the hospital pharmacist. All patients received the same mechanical preparation and all received subcutaneous heparin as prophylaxis against venous thromboembolism. The presence or absence of postoperative sepsis was recorded. Trivial wound erythema and stitch abscesses without systemic disturbance, were disregarded. Subsequent analysis showed that the surgical groups were well matched for age, sex, drug groups, and underlying disease (there were 62 cases of malignancy, 3 of diverticular disease, 1 of familial polyposis coli, and 1 of intusussception secondary to leiomyoma).
RESULTS* I
i
I
I
i
i
*No.
infections/no. cases. MK reduced the incidence of sepsis
significantly compared
with PP (Fisher’s exact test p
NEPHROTIC SYNDROME AND CARDIOVASCULAR DISEASE
SiR,--Considering the vast literature on increased synthesis of lipoproteins in nephrotic patients and animals’I together with the recognised defect in lipoprotein lipase clearing factor2 the paper by Dr Wass and colleagues (Sept. 29, p. 664) strikes a discordant note. Why are nephrotics in SouthEast England so different from those in other areas? Could this paper really represent events in a new era in which steroids are used much less for nephrosis? If we were given lipoprotein profiles we might be able to judge. We are not even given the HDL-cholesterol data nor the method of assay. Patients who came to necropsy did not receive the careful study of the coronary arteries that was performed by Curry and Roberts.3 Perhaps a hasty diagnosis of terminal renal failure meant that atherosclerosis was not adequately assessed. Wass et al. believe that systemic lupus erythematosus (SLE) predisposes to cardiovascular disease but that is not borne out by their table i. Maybe LDL-cholesterol and lipoprotein lipase are normal in SLE neprotics--or perhaps they do not have the increase in unbound free fatty acids/albumin that is the likely explanation for platelet and endothelial cell damage. However, Wass et al. are right to stress the dangers of clofibrate in this situation; carbohydrate restriction will control the hyperlipidaemia.4,5 33 Hawthorn Gardens, Kenton, Newcastle upon
whet his
appetite, we append the HDL cholesterol levels (separated by ultracentrifugation and measured by the method of Levine and Zak8) which were removed at The Lancet’s suggestion (see figure). They are normal. The ratio of HDL:total cholesterol was reduced (datanot shown) because LDL and VLDL levels were raised. Other clinical9 and experimental’° data support the suggestion of normal or even raised HDL levels in the nephrotic syndrome. We agree that the necropsies did not all include careful examination of the coronary vessels, but their series, pre-
dominantly diabetics and patients with lupus, hardly seems relevant. The suggestion that SLE—or some aspect of its management-predisposes to vascular events is supported15 by the data of Urowitz et al.," although not with our own data.12 Despite platelet hyperaggregability,I3,14 platelet serotonin’s and
plasma-p-thromboglobulin
are
normal in
We doubt whether carbohydrate restriction-which would probably aggravate the negative nitrogen balance experienced by nephrotics-would alter cholesterol levels in nephrotic pa-
tients. At least
we can
agree that clofibrate should
not
be used.
J. S. CAMERON
E. N. WARDLE
Tyne NE3 3DE
concentrations
nephrotics without immune complexes in their kidneys, and Futrakup6 noted only minor acceleration of platelet turnover. Thus, the possible role of diminished FFA binding to albumin in promoting vascular damage in vivo remains in doubt.
Clinical Science Laboratories, Guy’s Hospital Medical School, London SE1 9RT
V. WASS
R. J. JARRETT C. CHILVERS
***Professor Cameron and colleagues’ reply follows.-ED. L.
SIR,-Dr Wardle seems to assume that hypercholesterolSEmia (whether accompanied by hypertriglyceridaemia or altered HDL lipoprotein levels or not) is always associated with an increased incidence of accelerated vascular disease; the rational position is to test this hypothesis in unusual groups, such as nephrotic patients. There is no way one can say that nephrotics in South-East England differ from those in the rest of the world when, as we stated, there is no epidemiologically acceptable evidence with which to compare our data. Our patients do not seem to differ from those in San Francisco.6 Our paper was an essay in epidemiology, and Wardle can have all the lipid data in the further paper we mentioned. However, to 1. Shafrir E, Brenner T. Lipoprotein lipid and protein synthesis in experimental nephrosis and plasmapheresis. Lipids 1979; 14: 695-702. 2. Kekki M, Nikkilä EA. Plasma triglyceride metabolism in the adult nephrotic
syndrome. Europ J Clin Invest 1971; 1: 345-51. 3. Curry RC, Roberts WC. Status of the coronary arteries in the
nephrotic syndrome. Am J Med 1977; 63: 183-92. 4. Baxter JH, Goodman HC, Shafrir E. Effect of glucose infusions on serum lipids and lipoproteins in nephrotics. J Clin Invest 1959; 38: 987-7. 5. Bar-On H, Shafrir E. Conversion of glucose into lipids and proteins in experimental nephrotic syndrome. Israel J Med Sci 1965; 1: 365-77. 6. Hopper J, Ryan P, Lee JC, Roseman W. Lipoid nephrosis in 31 adult patients: renal biopsy study by light, electron and immunofluorescence microscopy with experience in treatment. Medicine 1970; 49: 321-41.
..I. V
u
c"JU
"%.U
Plasma albumin
uV
SiR,—In the study by Dr Eykyn and her colleagues (Oct. 13, p. 761) the incidence of anaerobic sepsis in the metronidazole treated patients seems unexpectedly high. In a paper given to the Surgical Research Society in Dundee in June, 1978, we reported the results of a double blind prospective trial of metronidazole and kanamycin given orally, preoperatively, in which one group received metronidasole alone. In some respects, therefore, the results are comparable. All patients undergoing elective colonic resections were admitted to the trial. The principal exclusions were patients with ulcerative colitis or Crohn’s disease and those requiring additional antibiotic cover (i.e., patients with valvular heart-disease). Three surgical groups were identified : (A) right colon resection (to splenic flexure), (B) left colon resection, and (C) abdominoperineal resection. Patients received metronidazole 400 mg orally 6 hourly and kanamycin 600 mg orally 6 hourly for 3 days up to the time of surgery, or an identical placebo, in one of the following combinations of treatment: metronidazole and kanamycin (MK), metronidazole and placebo kanamycin (MP), or placebo metronidazole and placebo kanamycin (PP). 67 patients entered the trial. The antimicrobial combinations were randomised for each surgi7. Carlson K. Lipoprotein fractionation. J Clin Path 1973; 26: suppl 5, 32-7. 8. Levine J, Zak B. Automated determination of serum total cholesterol. Clin Chim Acta 1964; 10: 381-84. 9. Lopes-Virella M, Virella G, Debeukelaer M, Owens CJ, Colwell JA. Urinary high density lipoprotein in minimal change glomerular disease and chronic glomerulonephritis. Clin Chim Acta, 1979; 94: 73-81. 10. de Mendoza SG, Kashyorp ML, Chen CY, Lutmer RF. High density lipoproteinuria in nephrotic syndrome. Metabolism 1976; 25: 1143-49. 11. Urowitz MB, Bockman AAM, Koehler BE, Gordon DA, Smythe HA, Ogryzlo MA. The bimodal mortality pattern of systemic lupus erythematosus Am J Med 1976; 61: 221-25 12. Cameron JS, Turner DR, Ogg CS, Williams DG, Lessof MH, Chantler C, Leibowitz S. Systemic lupus with nephritis: a long-term study. Quart J Med 1979; 48: 1-24. 13. Bang NU, Trygstad CW, Schroeder JE, Heidenreich RO, Ciscko BM. Enhanced platelet function in glomerular disease. J Lab Clin Med 1973; 81: 651-60. 14. Reumuzzi G, Marchesi D, Mecca G, de Gaetano G, Silver MJ. Platelet hypersensitivity in the nephrotic syndrome. European Dialysis and Trans-
plant Association, Amsterdam, June, 1979: abstr p. 78. JS. Platelet and plasma serotonin concentrations in glomerulonephritis. I. Thromb Res 1979; 15: 109-25. 16. Futrakul P, Poshyschinda M. Kinetic evaluation of hemostasis in the steroidsensitive nephrotic syndrome. J Singapore Pædiat Soc 1977; 19: 273-76.
15. Parbtani A, Cameron
g/1
Plasma HDL cholesterol levels in male adult-onset nephrotic patients.
ANTIMICROBIAL PROPHYLAXIS IN ELECTIVE COLONIC SURGERY
(8)
and female
(0)
1018 cal group, and the supervision of tablets and their issue, was performed by the hospital pharmacist. All patients received the same mechanical preparation and all received subcutaneous heparin as prophylaxis against venous thromboembolism. The presence or absence of postoperative sepsis was recorded. Trivial wound erythema and stitch abscesses without systemic disturbance, were disregarded. Subsequent analysis showed that the surgical groups were well matched for age, sex, drug groups, and underlying disease (there were 62 cases of malignancy, 3 of diverticular disease, 1 of familial polyposis coli, and 1 of intusussception secondary to leiomyoma).
RESULTS* I
i
I
I
i
i
*No.
infections/no. cases. MK reduced the incidence of sepsis
significantly compared
with PP (Fisher’s exact test p
