Cholesterol, blood viscosity, chronic kidney disease and statins.
A rather surprising feature of the meta-analysis of the effects of
statins in patients with chronic renal disease by Strippoli et al (1) is
the failure to mention or to recognise the considerable literature which
shows that the major pathogenic feature of hypercholesterolemia is that it
contributes to blood viscosity. In addition, there are many reports which
note that when serum levels of cholesterol are elevated, the cholesterol
content of the red blood cell membrane is increased, with the result that
the cell becomes poorly deformable.
Although statins reduce the blood levels of cholesterol, they may not
influence other blood viscosity factors, and for that reason statin
therapy may have little impact on the kidney dysfunction associated with
increased blood viscosity. Therefore it is not surprising that Strippoli
et al should note that the reno-protective effects of statins are
uncertain.
The effect of blood viscosity on kidney function was a topic for
debate more than 25 years ago. There is general acceptance that
polycythemia is accompanied by raised blood viscosity. In 1981 we found
that the proteinuria of a patient with polycythemia fell by 90% when
venesection lowered his haematocrit from 61% to 45%. That observation was
consistent with the hypothesis that increased blood viscosity was a cause
of proteinuria.(2) Basically, it was proposed that hyperviscous blood in
the afferent glomerular arteriole would influence glomerular filtration so
that the filtrate could be abnormal in both volume and content. But more
importantly, the haemoconcentrating effect of glomerular filtration would
render the blood in the efferent arteriole hyperviscous, and impair blood
flow in the peritubular plexus with consequent impairment of tubular
function.
In 1983 (3) we described the development of hyperproteinemic
proteinuria in mice which were injected i.p. daily with 1ml of saline
containing 250mg of human serum albumin. At 24 hours the mice were
excreting albumin plus a 170,000 dalton protein and at 72 hours this was
joined by a 225,000 protein. By the third day after the last i.p.
injection, only albumin was present in the urine and it vanished on the
fourth day.
Others have commented on the association of blood viscosity and
kidney dysfunction. McGinley et al(4) concluded that, " We suggest that
increased blood viscosity and plasma viscosity may play a role in the
vascular complications of the nephrotic syndrome." The interactions of
central obesity with hyperviscosity and microproteinuria have been
reported (5) and a study of the renal complications of cyanotic heart
disease concluded, " This observation supports the hypothesis that
impaired peritubular blood flow with increased intraglomerular blood
pressure may add to chronic glomerular dysfunction."(6)
Maybe there would be a better outcome if instead of using statins,
fish oil or pentoxifylline was used to reduce blood viscosity in patients
with chronic renal disease.
References.
1. Strippoli GFM,et al. Efects of statins in patients with chronic
kidney disease:meta-analysis of randomised controlled trials.
BMJ.doi.10.1136/bmj.39472.580984 AE.
2. Simpson LO. A hypothesis proposing increased blood viscosity as a
cause of proteinuria and increased glomerular permability. Nephron
1982;31:89-93.
3. Simpson LO, Shand BI. The implications of the changes in the nature
of the urinary proteins whch occur in albumin overload-induced proteinuria
in normal mice. Br J Exp Pathol 1983;64:6-14.
4. McGinley E, Lowe GD, Boulton-Jones M. et al. Blood viscosity and
haemostasis in the nephrotic syndrome. Thromb Haemost 1983;49:155-7.
5. Solerte SB, Fioravanti M, Pezza N, et al. Hyperviscosity and
microproteinuria in central obesity:relevance to cardiovascular risk. Int
J Obes Relat Metab Disord 1997;21:417-23.
6. Dittrich S, Kurschat K, Lange PE. Abnormal rheology in cyanotic
congenital heart disease - a factor in non-immune nephropathy. Scand J
Urol Nephrol 2001;35:411-5.
Rapid Response:
Cholesterol, blood viscosity, chronic kidney disease and statins.
A rather surprising feature of the meta-analysis of the effects of statins in patients with chronic renal disease by Strippoli et al (1) is the failure to mention or to recognise the considerable literature which shows that the major pathogenic feature of hypercholesterolemia is that it contributes to blood viscosity. In addition, there are many reports which note that when serum levels of cholesterol are elevated, the cholesterol content of the red blood cell membrane is increased, with the result that the cell becomes poorly deformable.
Although statins reduce the blood levels of cholesterol, they may not influence other blood viscosity factors, and for that reason statin therapy may have little impact on the kidney dysfunction associated with increased blood viscosity. Therefore it is not surprising that Strippoli et al should note that the reno-protective effects of statins are uncertain.
The effect of blood viscosity on kidney function was a topic for debate more than 25 years ago. There is general acceptance that polycythemia is accompanied by raised blood viscosity. In 1981 we found that the proteinuria of a patient with polycythemia fell by 90% when venesection lowered his haematocrit from 61% to 45%. That observation was consistent with the hypothesis that increased blood viscosity was a cause of proteinuria.(2) Basically, it was proposed that hyperviscous blood in the afferent glomerular arteriole would influence glomerular filtration so that the filtrate could be abnormal in both volume and content. But more importantly, the haemoconcentrating effect of glomerular filtration would render the blood in the efferent arteriole hyperviscous, and impair blood flow in the peritubular plexus with consequent impairment of tubular function.
In 1983 (3) we described the development of hyperproteinemic proteinuria in mice which were injected i.p. daily with 1ml of saline containing 250mg of human serum albumin. At 24 hours the mice were excreting albumin plus a 170,000 dalton protein and at 72 hours this was joined by a 225,000 protein. By the third day after the last i.p. injection, only albumin was present in the urine and it vanished on the fourth day.
Others have commented on the association of blood viscosity and kidney dysfunction. McGinley et al(4) concluded that, " We suggest that increased blood viscosity and plasma viscosity may play a role in the vascular complications of the nephrotic syndrome." The interactions of central obesity with hyperviscosity and microproteinuria have been reported (5) and a study of the renal complications of cyanotic heart disease concluded, " This observation supports the hypothesis that impaired peritubular blood flow with increased intraglomerular blood pressure may add to chronic glomerular dysfunction."(6)
Maybe there would be a better outcome if instead of using statins, fish oil or pentoxifylline was used to reduce blood viscosity in patients with chronic renal disease.
References.
1. Strippoli GFM,et al. Efects of statins in patients with chronic kidney disease:meta-analysis of randomised controlled trials. BMJ.doi.10.1136/bmj.39472.580984 AE.
2. Simpson LO. A hypothesis proposing increased blood viscosity as a cause of proteinuria and increased glomerular permability. Nephron 1982;31:89-93.
3. Simpson LO, Shand BI. The implications of the changes in the nature of the urinary proteins whch occur in albumin overload-induced proteinuria in normal mice. Br J Exp Pathol 1983;64:6-14.
4. McGinley E, Lowe GD, Boulton-Jones M. et al. Blood viscosity and haemostasis in the nephrotic syndrome. Thromb Haemost 1983;49:155-7.
5. Solerte SB, Fioravanti M, Pezza N, et al. Hyperviscosity and microproteinuria in central obesity:relevance to cardiovascular risk. Int J Obes Relat Metab Disord 1997;21:417-23.
6. Dittrich S, Kurschat K, Lange PE. Abnormal rheology in cyanotic congenital heart disease - a factor in non-immune nephropathy. Scand J Urol Nephrol 2001;35:411-5.
Competing interests: None declared
Competing interests: No competing interests