Tuesday, February 28, 2012

Topic Discussion: Old and New view of "Contraction Alkalosis"

Older View ( traditional taught to us)
Name: Contration Alkalosis
Prevalence: Most common cause of metabolic alkalosis
Primary Insult: Change in Extracellular volume
View Then: increase in sodium absorption in the proximal tubule led to obligatory bicarbonate absorption rather than chloride.
View Then: Correct the volume with expansion of ECF.
Culprit: Volume

Venue to play a major role: Proximal tubule
Dogma: Volume expansion is the key and correct with any volume expander to correct the alkalosis.

Newer View( the new data)
Name: Chloride Depletion Alkalosis
Prevalence: Most common cause of metabolic alkalosis
Primary insult: Chloride depletion
View Now: chloride depletion is the problem and not volume and Na depletion. repeating with Chloride will correct the insult.
View Now: Correct the volume and expand ECF but also make sure it has a Chloride containing fluid as just albumin or Na Bicarbonate will not correct this problem.
Culprit: Chloride depletion

Venue to play a major role: Cortical Collecting Duct
Dogma: Chloride administration without volume expansion is necessary and sufficient to correct this alkalosis.

What happens: There is chloride depletion which leads to reduced Cl delivery to cortical collecting duct(CCD)__>  pendrin activity increases secretion of Hc03 is limited as there isn't much Cl that can be absorbed in exchange.  You deliver more Cl to the CCD, pendrin activity shuts down and Hco3 is released and alkalosis starts resolving. In the principal cell, the K is exchanged for Na and there is kaliuresis.
The urinary Cl is low, Hco3 is low, Ph is low and K is high
The serum Cl is low, Hco3 is high and ph is alkaline

Pendrin is a newly discovered Cl/ HCo3 exchanger on the luminal side of the CCD's intercalated cells.  It is very dependent on the Cl delivery to CCD. So low chloride diet, Chloride depletion alkalosis increase its activity and high chloride diet, met acidosis, resp acidosis and K depletion alkalosis decreases pendrin activity.

Take a look at the recent editorial from JASN and original article:

Dialysis Modality Poll on eAJKD

Take two minutes to complete a dialysis modality poll on Home Hemodialysis and what you would do as a caretaker


Monday, February 27, 2012

A good Nephro Pathology Resource

Check out this excellent Pathology resource

Especially under the meetings- there are good power points uploaded on different Renal Pathology topics since 2009 onwards.

Saturday, February 25, 2012

C3 Glomerular Disease or Post infectious GN?

On kidney biopsy, resolving post infectious can be sometimes a common finding and differentiating it from the novel entity of C3 glomerulonephritis might be necessary. A recent article in KI by Sethi et al nicely summarize the entity of MPGN and how that is going to be linked with C3 glomerular disease(C3GN).  As we have discussed in prior posts and concept maps that MPGN pattern of injury should prompt a secondary cause and this article nicely illustrates that. It also ties in the alternative pathway diseases such as C3GN and dense deposit disease.
In terms of differentiating from Post infectious GN. In light microscopy, once can see exudative neutrophilic endocapillary proliferation compared to C3GN which is usually MPGN pattern of injury but sometimes can be mesangial or proliferative. In PIGN, usually one sees IgG, kappa, lambda and C3 but in C3GN, there should be only C3 primarily.  In electron structure, PIGN is classic subepithelial humps and subendothelial deposits. In C3GN, there are mostly sub endothelial and mesangial deposits and fewer of subepithelial deposits. More common to see double contour in this entity than in PIGN.
Glad to see a better understanding of this entity(MPGN) that is an enigma in glomerular disease world.

Take a look at this mini review in KI.

Friday, February 24, 2012

eAJKD: Advanced age and Kidney Transplantation

Geriatric nephrology is on the rise as the baby boomers age, and more and more patients will encounter nephrologists. Transplant nephrology is facing this challenge as well. Check out the two part interview series in eAJKD with the author of a recent article on transplantation outcomes in the elderly.

Interview Part 1
Interview Part 2

Thursday, February 23, 2012



True 60%
False 40%

Severe alkalemia can cause an increase in anion gap.  Alkalemia leads to glycolysis in the liver and a mild lactic acidosis. In severe volume contracted state, the anion gap can be seen with change in valence of circulating proteins to preserve extracellular volume.  
A prior post had discussed this as well. 

See the references below:

Wednesday, February 22, 2012

TOPIC DISCUSSION: A new shift in Minimal Change Disease

As the  Antibodies to phospholipase A2 receptor story goes for Membranous GN, the soluble urokinase for FSGS , there is emerging story about ANGPTL4 overproduction in podocytes leading to minimal change disease.  This abnormal overproduction of this protein leads to podocyte foot process effacement nicely shown in some recent work by Chugh et al.  
Two recent commentaries by clinical Pathologists take a fresh look at this topic. 

An original post by us highlighted the original publication in 2010.

Tuesday, February 21, 2012

TOPIC DISCUSSION: "effective blood volume"

Estimates of blood volume distribution indicates that 85% of blood circulates on the low pressures( venous side) and 15% on the high pressure ( arterial side).  The "effective" arterial volume is the arterial side and the high -pressure circulation.  The major determinant of that is cardiac output and vasodilatation of the vessels. For example, in cardiac heart failure, there is decreased cardiac output leading to decreased forward flow and hence low effective arterial volume. The concept is referring to the over and under filling of the heart and how that leads to volume of the high pressure circulation.
This concept is easy to understand when you have  volume depletion and the blood pressure is low and there is orthostatics leading to effective low blood pressure.  What is decreased effective blood volume in edematous disorders like cirrhosis and CHF? 

What is "effective blood volume"? Cardiac output was initially thought to be the main mediator of this effective blood volume and this makes sense. But if the normal kidney is uniformly responding to decrease in cardiac output in edematous states, then there is a problem as there would be worsening water and Na retention. 
So given the above thoughts, increase in total blood volume could occur, even if there is underfilling of the arterial circulation given most of the blood is in the venous circulation( edematous state).  Underfilling is secondary to decrease cardiac output or increase vasodilatation or diminished splanchnic vascular resistance.

So really, one should think of this as more of “decreased effective arterial blood volume” that drives the flow to the kidney and or “arterial underilling” rather than “effective total blood volume” especially in edematous states.
Dr Schrier describes this concept elegantly in a manuscript in JASN from 2007.


Friday, February 17, 2012

JOURNAL CLUB: Bedtime dosing of anti hypertensives

Studies have shown now that blood pressure follows a circadian rhythm and a normal pattern demonstrates a night time dipping effect.  Some are Non dippers or reverse dippers and have altered BP patterns at night time.  A growing body of literature supports that absence of night time dipping is likely to have high risk of CVD and stroke. There is an increase prevalence of MI in the first several hours after awakening.  A recent study published in JASN examined the effect of administration of BP medications at night time vs daytime (chronotherapy) and ABPM for 48 hours was used.  695 patients with CKD (GFR<60 and some albuminuria for 3 months) were assessed from 2000-2007 and 661 were selected.  One group received night time medication change and other had no change in medications. There was no overlap of medications. It was a PROBE protocol, so prospective, randomized, open label, blinded end point.  The groups were divided into 2 groups: 1 all BP meds in AM and other, 1 or more meds at night.
They should that bedtime dosing of BP meds leads to lower risk of composite CVD events and major CVD events. Bedtime dosing of meds leads to better sleep time BP.  A greater proportion of patients with bedtime dosing had controlled daytime BP.

Is this practice change? Its the first randomized prospective trial to date on this topic with significant outcomes changes.  There was good follow up for 5 years but would the benefit been decreased if followed up for 10years?. It might be not applicable to all CKD patients( especially late stages) but perhaps more general population and early CKD.  The technique was good here and they used 48 hours monitoring.  Is this applicable to the USA population that is a more heterogenous group rather than the investigators in Spain.

Uptodate is listing this study as one of the practice changing study?

Do you agree?


Thursday, February 16, 2012

CONSULT ROUNDS: Primary Polydipsia

Primary polydipsia is an interesting variant of hyponatremia. Its the exact opposite of adipsic hypernatremia.
Classically one might find urine lytes that are very much like so:
Urine Osm 60, Una<10, UK 10 and U Crt 16. 

This doesn't suggest volume depletion but suggests water intoxication. In the setting of a low Serum osm, the ADH is shut off but thirst is not shut off here and as a result the person keeps drinking water.  This is classically seen in psychogenic variants but cases have been described with CNS trauma as well.  It should be taken very seriously, as the amount of water ingested exceeds the amount that can be excreted by the kidneys,and can on rare occasions be life-threatening as the body's serum sodium level is diluted ( in other words dilutional hyponatremia ) to an extent that seizures and cardiac arrest can occur.
The excessive levels of fluid intake may result in a false diagnosis of diabetes insipidus since the chronic ingestion of excessive water can produce diagnostic results that closely mimic those of mild diabetes insipidus. However, in Diabetes Insipidus patients urinate excessive amounts because of a lack of ADH (central DI) or a lack of sensitivity (Nephrogenic DI). 
One can differentiate between the two patients in an by a water deprivation test. In a patient with primary polydipsia, water deprivation should cause the patient patient to urinate less (because water intake was the cause of the excessive urination). In someone with primary polydipsia, once their water intake were restricted, their normal kidneys would begin to concentrate the urine again. 
In someone with DI, the urine would remain dilute even in the absence of water intake.

Besides free water restriction and increase solute diet, bio feedback might show some promise.

Another interesting take on treatment was a paper that described using azetazolamide for treatment. The authors reported 5 patients in whom acetazolamide was trialed for this symptom. Acetazolamide improved polydipsia and/or hyponatremia in 4 of the 5 cases. This treatment was well tolerated and allowed 3 of the patients to permanently leave isolation. 


Monday, February 13, 2012

History Lesson: from the "Gray's Anatomy"

" the kidney has, of late years, been frequently the seat of surgical interference. It may be exposed for exploration or the evacuation of pus( nephrotomy); it may be incised for the removal of stone (nephro-lithotomy); it may be sutured when movable or floating (nephrorraphy); or it may be removed (nephrectomy)."  - The Urinary Organs, Book: Gray's Anatomy( collector's edition)

Interesting language from historical books. We don't use "nephrotomy" any more. When you google that term, you don't get anything back much except pages of "nephrostomy". Evacuation of pus is now mostly an interventional radiology procedure. Nephrolithotomy is now the realms of the urologist.   Floating kidney is now called "nephroptosis". How often do we see nephrectomies being done now for non transplant related reasons? Very little.

Friday, February 10, 2012

Insufficient Medicare Drug Coverage for Immunosuppression in Transplant Patients – The Chance to Right a Wrong

Current Medicare coverage for immunosuppressive drugs in transplant patients stops 3 years after kidney transplantation for all patients except those over the age of 65, or who have work related disabilities. This policy is based on the premise that once transplanted all patients should be able to join the work force and afford private insurance – therefore saving money for the healthcare system. Unfortunately this idea is wrong both financially and morally.

A recent publication in the New England Journal of Medicine by Gill and Tonelli highlights this problem beautifully. They point out that the U.S. is the only industrialized country that does not cover lifelong immunosuppression costs; and that long term transplant outcome in the United States is inferior to countries such as Australia, the UK and Canada that do provide lifelong coverage. In addition, an analysis of the USRDS registry revealed that Medicare insured patients have worse transplant outcome then non-Medicare insured patients, and that the discrepancy was amplified after 3 years post transplantation. Finally they point out that by improving transplant outcome by paying for lifelong immunosuppression, our healthcare system would actually save money, by virtue of having patients avoid more costly dialysis.

In addition we have all witnessed many transplant patients with complex medical problems, and significant chronic kidney disease that are unable to work. Not to mention that with the current unemployment rate even healthy people cannot find jobs!

There is currently a proposal before congress titled “The Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act of 2011,” that would reverse the prior provision and provide lifelong coverage for kidney transplant recipients. As nephrologists we should all rally behind this act, as we have all seen patients lose transplants due to the tremendous financial burden of immunosuppressive agents. Our participation is of utmost importance as a prior attempt at the same policy in 2009 failed.

So how can we help? The AST recently sent out an email that makes it pretty simple. I have attached the email below. Lets rally behind this act and set right a deadly policy that that has gone on for too long! Please comment on this post to show your support!

Please ask your:

2 Members of the U.S. Senate to Co-Sponsor:

S. 1454, Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act

1 Member of the U.S. House of Representatives to Co-Sponsor:

H.R. 2969, Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act

How Do I Do This?

1.) Call the U.S. Capitol Switchboard at (202) 224-3121;

2.) Ask to be transferred to the offices of your Members of Congress

(You have 3 of them);

3.) Once you are transferred, ask to speak with the Congressional office's Health Care Legislative Assistant;

4.) Request or leave a message indicating that as a transplant professional, from the Member's Congressional district or state, that you strongly urge the Member of Congress to co-sponsor House bill H.R. 2969 or Senate Bill S. 1454.

If you do not know the names of your 1 member of the U.S. House of Representatives or 2 U.S. Senators, you may go online to www.congress.org and there will be a site for you to enter your zip code and secure the names of your elected officials.

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