TOPIC DISCUSSION: Anesthetics and Kidney Disease

Do Anesthetic agents cause Renal Disease?

A recent discussion in a nephrology forum this above question was asked. Evidence on this is scant. On literature review, few cases reports found in 1960-80s and none after that. Perhaps we have not been using these agents anymore.  Some of the older agents might have cause renal disease.  In animal experiments, kidney damage has been reported after low level exposure of halothane.  Few case reports exist of methoxyflurane causing renal dysfunction.  There was a retrospective cohort study and it reported a higher frequency of kidney disease among exposed persons especially women ( in 1968).  Moderate to temporary effect on kidney function has been shown  in patients who got methoxyflurane.  Rats were subjected to chronic exposure to low levels of halothane (10 and 500 ppm for 8 and 4 weeks, respectively). Kidney histology showed proximal tubular changes and mitochondrial injury.

In the 1960s, the widespread use of the inhalational anaesthetic methoxyflurane was associated with a significant occurrence of postoperative renal dysfunction. This was attributed to hepatic biotransformation of methoxyflurane and subsequent release of inorganic fluoride ions into the circulation. It was found that this was more due to the drug containing massive amounts of fluoride and this was all fluoride toxicity. Nowadays, fluoride-related toxicity has been observed neither in animal nor in clinical studies, including prolonged administration and patients with pre-existing renal disease.

Reference:

http://www.ncbi.nlm.nih.gov/pubmed/7001619

http://www.ncbi.nlm.nih.gov/pubmed/5647504

http://www.ncbi.nlm.nih.gov/pubmed/1167217

http://www.ncbi.nlm.nih.gov/pubmed/8775101

http://www.ncbi.nlm.nih.gov/pubmed/8775102

http://www.ncbi.nlm.nih.gov/pubmed/17423691

Concept Map of Hypomagnesemia

A brief overview of Hypomagnesemia using a concept map model
If not complete, help me complete it!

http://www.ncbi.nlm.nih.gov/pubmed/10405219

Quiz 9 Answers

Which drug is paired incorrectly with the target molecule?
Rituximab -- CD20
Alemtuzumab -- CD52
Belatacept -- CD198
Belimumab --- TNFSF13B
Atacicept ---TACI-Ig

The correct answer is Belatacept CD198, that is incorrect pairing. Most of you got it right.
We all are familiar with Rituximab which is a B cell antagonist and since all B cells besides plasma cells are CD20 Positive, its an anti CD20. Alemtuzumab(campath) targets cd52 a protein present on the surface of mature lymphocytes. Atacicept(TACI-Ig) is a human recombinant fusion protein that comprises the binding portion of a receptor for both BLyS (B-Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), two cytokines that have been identified as important regulators of B-cell maturation, function and survival. Atacicept has shown selective effects on cells of the B-cell lineage, acting on mature B cells and blocking plasma cells and late stages of B-cell development while sparing B-cell progenitors and memory cells. The efficacy of atacicept in animal models of autoimmune disease and the biological activity of atacicept in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been demonstrated. The selective inhibitor of T-cell costimulation, belatacept, blocks CD28-mediated T-cell activation by binding CD80 and CD86 on antigen-presenting cells. Understanding the extent to which belatacept binds to its targets in patients may enable correlation of belatacept exposure to receptor saturation as a pharmacodynamic measure of costimulation blockade. Belimumab (registered name Benlysta previously known as LymphoStat-B), is a fully human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-Lymphocyte stimulator (BLyS), also known as B cell activation factor of the TNF family (BAFF).

IN THE NEWS- Meta-analysis in Nephrology

A recent article in Kidney International reviews the role of meta analysis in Nephrology world. Based on the survey this group did in NYC area, most physicians viewed meta analysis in nephrology useful and influenced their patient care.
What are the limitations of meta analyses?( from the article- refer to article for details)
1. Publication bias
2.Mixing apples and oranges
3. Garbage In, Garbage Out
4. Outcome selection bias
5. Patient exclusion bias
6. Truncated study bias
7. data collection errors
What are the strengths  of meta analyses?
1. Power
2. Highlights areas that need work
3. More transparent form of review- and not just a review article
4. Sounder bias offered
Even with all these meta analyses happening in our literature, many of our guidelines are still "opinion" based.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/20827259

TOPIC DISCUSSION: Camels and their Kidney!

Ever wondered what the camel does differently than us to survive in the hot environment? The camel does have a special kidney and a special GI tract.The camel's kidney actually can concentrate the urine more than sea water but less than a dessert rat.  Since the camel can concentrate the urine more than sea water, salty water intake won't harm the animal. Investigators have studied the  structure of the camelian kidney to discover whether or not the anatomical features necessary for producing a highly concentrated urine were present or not. The relative thickness of the medulla was calculated in the camelian kidney as it has been demonstrated that this thickness has a direct relationship with the ability to produce a highly concentrated urine.  A relative thickness of the medulla is a good measure of the length of the loop of Henle which is an indicator of urine concentration. The thickness reported in camels was 7.89 in comparison to the value of 8.5 in kangaroo rats, much more than humans.
Also, what happens if you haven't drunk water in 5 days and all of a sudden you re hydrate. A dehydrated camel can replace water within minutes of drinking, and some of this water is quickly absorbed into the bloodstream. With water in the bloodstream, ADH declines and the kidney will return to normal renal function within 30 minutes of drinking. Not only does the camel adopt to scarce water but the kidney can also adopt to rapid dehydration and not lead to demylination of the brain.
What are some other features this animal has to store water for long periods of time?
Another interesting part of the camel physiology is that they have 3 stomachs, acting as storage( 1.5 gallons per stomach) for the water and hence when water is not available, they can slowly replenish the system. The camel stores water in its blood stream, an interesting physiological process. Capable of losing forty percent of its body's weight before becoming distressed, it is able to go five to seven days before having to drink. The amount it drinks when water is available would cause severe problems in most animals, up to 21 gallons in about 10 minutes.The camel's mouth, stomach, and teeth have all developed to allow it to eat plants that are not palatable to other desert animals.Contrary to popular myth, the camels don't store water in their humps, its full of fat for food storage.
Some of the rodents in the dessert can actually concentrate up to 7500mOsm.
Fun things you can learn from other animals who adopt better to water problems

http://www.ncbi.nlm.nih.gov/pubmed/511770
http://www.ncbi.nlm.nih.gov/pubmed/407772
http://www.ncbi.nlm.nih.gov/pubmed/475010

Sirolimus- the Positive aspects

The same issue of KI shares another view- the positive aspects of sirolimus
As we mentioned earlier that this agent was discovered as a cancer drug and has antiproliferative properties

Recent animal data and human data have shown it to be beneficial in preventing cancer post transplant
So the benefits of this agents are:

1. Prevention of cancer, as mTOR is responsible for transcription and translation for cell growth.  Definite evidence against Kaposi, Skin cancers and renal cancers.
2. Increase in T regs
3. Anti viral effects - CMV, BK and EBV viral infections ( still not sure- conflicting data)
4. Tolerance inducing potential
5. Control of fibrotic process - conflicting data when compared to CNI alone

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/20981120

Nephsap review: Fluids Electrolytes

Another interesting Nephsap teaching point by a question was an under recognized cause of acquired apparent mineralcoritcoid access.
Liver cirrhotic patients with elevated bilirubins and sickle cell crisis patients who have elevated bilirubins have this happen to them.  When total bilirubin levels are very high, it is hypothesized that worsening cholestasis led to greater bile acid inhibition of 11B - HSDH type II in the distal nephron and this allows for K wasting via cortisol mediation and HTN as well.
Case reports have been reported in liver cirrhosis and sickle cell crisis patients?
Wonder if we see this or its noticed in Post BMT - VOD syndrome?