Clinical Case 59: Answers and Summary

WHICH OF THE FOLLOWING STATEMENTS REGARDING CHOLESTEROL IN NEPHROTIC SYNDROME ARE TRUE?

In nephrotic syndrome(albumin 2-3 range), VLDL produced by the liver are rapidly metabolized so that the LDL concentrations rise whereas VLDL remain normal (13%)

Cholesterol increases but TG remain normal(30%)

With severe nephrotic syndrome, < albumin 1.0g/dl, VLDL accumulate and LDL decline and TG start rising (21%)

When proteinuria is massive, the apoprotein CII are lost and contribute to accumulation of VLDL as well (43%)

No consistent pattern of HDL serum conceontrations has been identified in nephrotic syndromes(26%)

Under normal circumstances, VLDL produced by the liver is hydrolyzed to IDL and HDL by lipoprotein lipases situated in a number of extrahepatic sites including endothelium and adipose tissue.  IDL then gets converted to LDL by the liver. In nephrotic syndromes with moderate hypoalbuminemia (2-3g/dl), VLDL produced by the liver is rapidly metabolized so that the LDL concentrations rise whereas VLDL remain relatively normal.  Cholesterol increases and TG might stay normal.  With severe hypoalbuminemia(<1g/dl), VLDL accumulate and LDL concentrations fall and hence TG rise higher.  This might be because inhibition of lipoprotein lipase is seen by free fatty acids that normally bind to albumin and accumulate in adipose tissue as albumin falls. When there is massive amounts of proteinuria, apoprotein CII, a normal component of VLDL and stimulator of lipoprotein lipase may also contribute in accumulation of VLDL. 

What about HDL? Since HDL have molecular sizes comparable to albumin, it may be reduced in nephrotic syndrome due to urinary losses. Also, accumulation of unbound lysolecithin may decrease the synthesis of HDL. Even with these two mechanisms, one would predict low HDL levels but mixed patterns have been noted in nephrotic syndromes. 

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/191663

http://www.ncbi.nlm.nih.gov/pubmed/184367

http://www.ncbi.nlm.nih.gov/pubmed/2747006

ABG vs. VBG

Arterial blood gas is gold standard to get the oxygenation and acid base information. Venous blood gas has been tried for patient comfort. How does VBG compare to ABG?
Check out the a post by a NYU resident on this topic. Very informative.

http://www.clinicalcorrelations.org/?p=5608

eAJKD updates- Nephrology education issue

Training of Nephrology fellows
Structure of Renal electives for Medicine Residents

IN the News: Phosphate binders and CKD

A recent publication in JASN by Block et al compared >100 patients head to head on placebo, lanthanum, sevelamer and calcium acetate and looked at few end points:- Change in mean serum phosphorus, urinary phos, pth, 1,25 vitamin D levels, FGF23 levels and vascular calcifications and bone density scores in CKD patients. The study proposes that although the parameters in above all improved, there was a concern that binders might progress vascular calcifications.

Few take home points
1. Mean phos levels did decline in all groups compared to placebo.
2. Urinary phos levels were also different in active vs placebo group.
3. PTH levels increased with placebo and remained stable with active therapy
4. FGF-23 were elevated at baseline and didn't change much in both active and placebo groups
5. Bone mineral density improved in active patients
6. Active therapy resulted in significant increases in median annual percent change in coronary artery and abdominal aorta.

Few inferences and discussion points
1. Although randomized and controlled, this study has a small n and once distributed had only few patients <50 per group.
2. Baseline phos levels to begin with were in 4.0 range suggesting good control already
3. There were less patients with CHF and HTN in the placebo group ( perhaps effecting the results?)
4. Vascular calcifications noted in coronary and abdominal aorta might not truly reflect cardiac events.
5. Commendable work but more larger studies need to be done to confirm these findings.
6. Just like anemia story, perhaps the Phos study might have the same ending.

Is Iron The answer?

As restrictions have arose in using of erythropoietin agents in dialysis patients, the use of IV iron has risen in the nephrology community. What are the rates of iron overload in such instances?
Studies have shown that excessive use of iron can intensify the oxidative stress associated with chronic kidney disease, and promote endothelial dysfunction and cardiac disease. Excessive iron reduces iron utilization and is involved in the generation of intracellular reactive oxygen species, which induce cell injury; the risk of subtle toxicity from iron excess exists. Unnecessary iron supplementation accelerates hepcidin  production. This effect on ferroportin 1 (FP-1), keeps intracellular iron from being carried even if the iron storage is adequate; it also decreases iron absorption from the intestine.In the most recent issue of the Am J of Medicine, an editorial to a  study done prospectively found that there was iron overload in 84% of a 119 stable HD patients. Some of the amount of iron reached the levels found in hemochromotosis. A prior study had shown that the risk factors were ferritin >500.   The Japanese Society for Dialysis Therapy Guidelines has proposed that a minimal amount of iron should be given to chronic kidney disease patients. Japanese clinicians believe that the risk/benefit ratio for iron supplementation is higher than that accepted in Western countries. So now what?
A proper attention to body's individual iron stores and ferritin levels along with perhaps hepcidin information might be a more prudent way to decide iron treatment. More robust guidelines might be needed.

IN THE NEWS: Walking and Hypertension assessment

Hypertension is tough to manage in the elderly as no one really knows what the target blood pressures should be in the age >80.  The standard guidelines might not really be correct in the very elderly population.
Perhaps a slightly higher blood pressure might be more prudent in the very elderly. Prior studies have shown increase mortality in over management of HTN in the elderly.
A recent study has an interesting way to look at HTN. Using walking speeds to assess the risk of HTN management in the elderly is a novel concept.  The association between BP and mortality varied by walking speed.  The fast walkers(≥0.8 m/s for a 20ft walk) with with elevated systolic BP (≥140 mm Hg) had a greater adjusted risk of mortality compared with those without.  Among slower walkers, neither elevated systolic nor diastolic BP (≥90 mm Hg) was associated with mortality. Interestingly, they also found elevated systolic and diastolic BP was strongly and independently associated with a lower mortality  in people who didn't complete the walking test. These findings are consistent with prior studies that have found that the association of BP and mortality diminishes with age. HTN management might change as frailty increases with age. 
Testing walking speeds for the hypertension management and assessing risk might be an easy tool to use.
Any comments?

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