Thursday, June 30, 2011

Creative Writing to Teach Nephrology

We have designed some interesting tools in teaching renal medicine at our institution. One of them has been creative writing.  Check out the " Call of renin"  It is a creative writing piece that dictates the life of "renin" from "renin's" point of view.

http://www.ncbi.nlm.nih.gov/pubmed/21671849

Monday, June 27, 2011

IN the NEWS: Bardoxolone Methyl and CKD

A new agent called Bardoxolone( anti oxidant) , also called BARD in the prior literature, was studied in a recent NEJM 2011 paper in close to 200 adults with CKD in a randomized, double blinded placebo controlled phase 2 trial. Doses used were 25, 75 or 150mg. The outcomes were change in GFR at 6 months and 1 year.  The results showed that patients who received the agent had statistically more significant GFR increases compared to placebo- all which were maintained at 1 year.  The increases were in the magnitude of 9-10ml.  Low Mg levels and muscle spasms were side effects noted.  
Few years prior, studies had shown that BARD ameliorated ischemic murine AKI as assessed by both renal function and pathology. It is possible that BARD does this by effects on  NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-γ (PPARγ), and heme oxygenase 1 (HO-1).  Studies have shown that BARD regulates PPARγ, not by acting as a ligand but by increasing the amount of PPARγ mRNA and protein.  Prior results  also found that BARD ameliorated cisplatin nephrotoxicity. So it was an inflammation modulator.  Following that there was a shorter study in AJ Nephrology listed below that showed benefit with BARD in CKD stage 3b and 4.


Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21289052
http://www.ncbi.nlm.nih.gov/pubmed/21508635
http://www.nejm.org/doi/full/10.1056/NEJMoa1105351?query=featured_home

In the News- Nephrology on the mobile phone

Use of mobile phone devices in medicine has become increasingly popular.  The editors of nephrology on demand did a study to see if the mobile version of their website was being used a lot.  10% of their major hits were from apple based mobile devices and mostly US based. This allows for further data that a fair amount of physicians and trainees are using these devices to get information and browse useful websites.  More studies and teaching tools using such devices should be needed.




Check out the full article regarding these findings at:
http://www.ncbi.nlm.nih.gov/pubmed/21659443




Also check out touch calc who is making many programs for the phones and devices in nephrology
http://touchcalc.com/

Thursday, June 23, 2011

Negatives of E Learning

A recent letter to the editor in the journal "The Clinical Teacher" reveals some interesting take on e learning from a negative stand point. We all are aware of the good and fun aspects of e learning but this editorial reminds us of a very important point:- practice makes perfect; no podcast or vodcast or blog is going to make one a good physician.  The author says " It may seem a novel way to learn, but as the old Chinese proverb goes:- I hear, and I forget, I see and I remember. I do and I understand.".

Have a look at this interesting thought of the author
Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21585684

Wednesday, June 22, 2011

TOPIC DISCUSSION: Why 3gm of Proteinuria is considered Nephrotic syndrome?


We always think of Nephrotic Syndrome- >3gm of protein loss.  Where did that come from? What is the evidence? Why not 2gm and why not 4gm? A nice post from Nephrohug( in French) discusses this topic in detail. 
It dates as early as 1960s that Dr. Schreiner described in a paper called Glomerular Permeability in the Nephrotic Syndrome.  In that paper, lot has been described but interestingly there is a Figure 4 that( look at first ref below) that shows 184 patients with glomerular diseases and most >3.5gm were considered nephrotic range and had a different pathology compared to <3.5gm. But the range is 2.5-3.5gm. He noted that the clinical parameters ( albumin, lipids, exam) were different in the >3.5 group.  The author notes that the garden variety diseases like pyelonephritis, benign nephroscloerosis, certain lupus nephritis are characterized by daily protein excretion of less than a gram and rarely in excess of >2gm.  When >3gm category was seen, diseases such as MCD, membranous, myeloma, malignant hypertension were noted.( but all had some other clinical features).  From this, a statement was made: "Thus, quantitative proteinuria in excess of 3gm becomes an excellent screening test for the diseases associated with nephrotic syndrome."
In 1980s, another paper by Ginsberg et al, proposed that use of protein/crt ratio in urine samples gave a similar comparison of patients and found >3.5gm to be the cut off for nephrotic syndrome. They studied 46 patients and found excellent correlation of 24 hour urine and spot ratio( where we get our spot ratio from). 
Ref:


Tuesday, June 21, 2011

Cochrane Renal Group

The Cochrane database is well known. There is a Cochrane Renal Group and their latest newsletter is online now as well. Click here for the link. 
Check out the renal group at this link.

Friday, June 17, 2011

CLINICAL CASE 38, ANSWERS AND SUMMARY

Which of these options are treatment options for management of methotrexate nephrotoxicity?

GI decontamination
  4 (14%)
Aggresive hydration
  8 (28%)
Urinary Alkalinization
  14 (50%)
Leucovorin( IV)
  13 (46%)
Leucovorin (PO)
  5 (17%)
CPDG glucarpidase
  3 (10%)
Recurrent intermittent Hemodialysis
  4 (14%)
Continuous venovenous dialysis
  3 (10%)

MTX ( methotrexate) is a chemo agent that is nephrotoxic.  At high doses, it and its metabolite can accumulate and can cause acute tubular injury.  Dosages higher than 1000mg/m2 are what is associated with renal damage. Most oncologists use prevention strategies with hydration and leucovorin to help combat this side effect.
What helps decrease MTX levels:- all the above listed are right answers. The glucarpidase is a new agent that is experimental but has shown some promise.  

For more information, see:
Ref:

FDA approves Belatacept (NULOJIX) for use in kidney transplantation.



It’s been a long time since the FDA approved a new drug fortransplantation which makes this news very exciting.  On June 16th Bristol-Myers Squibbannounced that the FDA approved the use of NULOJIX (Belatacept) for use inkidney transplantation as an induction and maintenance agent in combinationwith mycophenolate mofetil and corticosteroids. The FDA reviewed the Benefit and Benefit EXT trials prior to coming to theirconclusion. 
Belatacept is a selective T-cell co-stimulation blocker thatis administered IV which offers comparable results to cyclosporine.  Though the acute rejection rate seems to beslightly higher with Belatacept than cyclosporine, trials reveal a higher GFR inthe Belatacept arms at 3 years of follow up. The obvious hope is that the use of Belatacept will avoid calcineurininhibitor nephrotoxicity in kidney transplant recipients improving long termallograft outcome.  The major concern withBelatacept is an increased risk for PTLD seen in many of the trials.  For this reason it is contraindicated in EBVseronegative patients or patients with unknown EBV serostatus.  To address the concern of PTLD Bristol-MyersSquibb established the ENLiST Registry. The registries purpose is to determine the incidence of PTLD, CNS PTLD,and PML in US adult EBV seropositive kidney transplant recipients treated withBelatacept.
Belatacept is administered IV over 30 minutes and the recommendeddosing is 10 mg/kg on the day of transplantation then on day 5, then at the endof weeks 2, 4, 8, and 12. After week 16 it is recommended that the maintenancedose be 5 mg/kg every 4 weeks.


by Dr. Vinay Nair

Thursday, June 16, 2011

IN THE NEWS: The ACT trial

ACT trial is the Acetylcysteine for the prevention of Contrast Induced nephropathy trial. This is the largest randomized trial to date on this concept. Cardiologists and Nephrologists are using acetylcysteine( mucomyst) to prevent contrast nephropathy for the past decade with no real evidence if it really does any benefit. Clearly, there is no harm. But what is the data?
At the recent cardiology meetings at AHA 2010, the primary investigators of this trial showed that the risk of contrast induced nephropathy in patients undergoing coronary or vascular angiography was not reduced using mucomyst.  Close to 2300 patients in a single country were randomized from 2008-2010 and the treatment dose was 1200mg BID for 2 dose prior and 2 doses after procedure.  This was compared to placebo.
There was patients with CKD included close to 15% or so in each arm.  The primary endpoint was Contrast nephropathy as defined by >25% elevation in crt above baseline.  Secondary endpoint was mortality and need for dialysis and side effects. The final conclusions were that the mucomyst does not reduce short term risk of contrast nephropathy and nor did it meet any of the secondary outcomes.
Final publication probably is on its way.  This is probably a final blow on using acetylcysteine in prevention of contrast. At this point, it seems that it was nor harming nor benefiting.  Seems like a well designed study keeping all renal parameters in mind. Not sure if cystatin C was used at all or other novel renal parameters to pick up some minor injuries.  Fluids might be the only alternative. Also, till the paper comes out, we can't know what other causes of renal injury were ruled out.
Comparing bicarbonate based vs normal saline base at a large scale might be necessary as well and might be underway.

A podcast about this can be heard at

A peak at the study can be found at:


ASN Podcast - World Class Nephrologists

http://www.asn-online.org/publications/kidneynews/podcast.aspx
Check out the latest Podcast from ASN on Raheem Brothers - Nephrologists who are doing such great clinical work in rural medicine in Idaho.


Wednesday, June 15, 2011

Human Herpes Virus – 6: An uncommon but potentially treatable infectious agent in transplant recipients


HHV-6 is a DNA virus part of the beta-herpesvirus family andcan be divided into HHV-6 A and B. Primary infection is mild and occurs usually in childhood; therefore themajority of healthy adults have serologic evidence of prior infection.  HHV-6 can re-activate in theimmunocompromised transplant recipient leading to asymptomatic viralreplication or less commonly active infection. The highest prevalence by pcr has been shown to occur in bone marrowtransplant recipients (28% to 75%) but viral replication has also been shown tooccur in liver (28% to 32%) and renal transplant recipients (23% to 36%).  Although asymptomatic viremia is common,clinically active infection carries a high mortality and may be susceptible tospecific antiviral treatments.   
How does HHV-6infection present?
HHV-6 infection commonly presents with high fever oftenassociated with leukopenia, and encephalitis between 2-4 weeks posttransplantation.  Other clinicalmanifestations include pneumonitis, hepatitis, colitis and bone marrowsuppression.  Rash typical of a leukocytoclasticvasculitis can also be seen. Encephalitis may be associated with seizure activity andhyponatremia.  Encephalitis is morecommonly seen in BMT patients but has been described in solid organ transplantpatients as well.  HHV-6 infectionscommonly co-exist with other viral infections including CMV. 
HHV-6 reactivation has also been associated with druginduced hypersensitivity syndromes, malignancies, multiple sclerosis, fulminanthepatitis and mycocarditis though causality has not been demonstrated.
What are theassociated laboratory and imaging findings?
CBC: Bone marrow suppression, leucopenia, thrombocytopenia
Chemistry: Transaminitis, hyponatremia
CSF:  High lymphocytecell count with elevated protein.  HHV-6can be detected in CSF by pcr. 
MRI of brain: Symmetric non-enhancing white matter lesions.  MRI may be normal in patients infected withHHV-6.
How can youdiagnose active infection?
Serologic testing: Sensitivity varies and most tests cross react with HHV-7.  A fourfold increase in titers orseroconversion is considered diagnostic.
Virus culture from affected tissue or blood can be done butare difficult to perform.
Viral detection: Virus may be present in PMBC’s of patients with latent infection leadingto a “false” positive pcr.   ThereforeHHV-6 should be identified in affected tissue or acellular plasma orserum. 
What are thetreatment options?
No therapy has been clearly documented to treat HHV-6although several agents with in-vitro activity have been tried.  Ganciclovir is effective against HHV-6B butmay not be active against HHV-6A (minority of infections).  Foscarnet has activity against both A and Bhowever; its use is complicated by nephrotoxicity.  In severe cases both agents can be tried andwhenever possible a reduction in immunosuppression should be considered.

References:
http://www.ncbi.nlm.nih.gov/pubmed/11241800                     

By
Dr. Vinay Nair

TOPIC DISCUSSION: BIOMARKERS

A recent article in AJKD June 2011 issue reviews the up and coming bio markers to replace creatinine in renal injury.
Lets summarize what they have to say:
1. In the differential diagnosis of AKI, currently we use FeNa to help distinguish renal vs pre renal and if  need be urinalysis and biopsy.  Proposal is to eventually use: IL-18, Kim -1, NgAL, NAG

2. In early detection of renal injury, currently we use crt and GFR, would would help is cystatin C and perhaps GST, IL18, KIM-1, NGAL, NAG and L-FABP.

3. In prognosis, we currently use AKIN and RIFLE criteria based on crt.  What might help is cystatin C and above ones as well.

So far, I continue to use only and only one marker, Creatinine- the best marker to date for renal disease; and perhaps proteinuria for progression of kidney disease.  I have ordered cystatin C sometimes, but never really helped me clinically.  So hoping some of these markers or PANEL of markers might be more helpful than what we currently use in renal disease.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21411200

Monday, June 13, 2011

Friday, June 10, 2011

TOPIC DISCUSSION: Light chains and the Kidney- traveling the nephron


Light chains can be toxic to the kidney when they are over produced. The types of pathology one finds are: Cast Nephropathy( usually light chain + uromodulin mediated), AL Amyloidosis( more lambda than kappa mediated), Monoclonal Ig Deposition disease ( LCDD, HCDD, LHCDD)- usually kappa more than lambda.  Light Chain Fanconi Syndrome (kappa more than lambda), Cryoglobulinemic GN( polyclonal), Waldenstroms ( IgM kappa or lambda), Immunotactoid GN( igG kappa or lambda), Proliferative GN with monoclonal IgG deposits ( kappa or lambda).
Some key points:
1. 40% more light chains are produced than heavy chains
2. Around 500mg/day of there FLC are in circulation daily
3. 80% are extravascular
4. 2/3 are kappa and 1/3 are lambda hence a ratio of 1.8:1 ratio in the serum.( function of production and clearance)
5. That ratio showed be the same when in renal injury from other causes to have more kappa than lambda always.
6. FLC are mostly removed by proximal tubule epithelial cells, Kappa is 40% per hour and lambda is 20% per hour, so half lives come out to be 2-4 hours and 3-6 hours respectively.
7.  If in renal failure, what gets rid of these FLCS? the reticuloendothelial system does try to do it but the half life can increase to 32 hours
8. Mice injected with FLC from patients with renal lesions developed the SAME renal lesion in those patients suggesting each FLC might act differently in different patients.  Hence the primary structure of molecule might be important. A nice article in Kidney International 2011 June summarizes the newest research in LC biology.
image source: aafp.org
Ref:



Wednesday, June 8, 2011

TOPIC DISCUSSION: Urinary Snapshot of Lupus Nephritis does not equal what you see on the Kidney Biopsy


What degree of Class IV lupus nephritis presents with just hematuria?
What degree of Class I lupus nephritis presents with just hematuria?

Take a look at this data from a recent paper in 2009 by Seshan et al.

Of 541 patients studied for classification of lupus nephritis,
40% of Class I, 19% of Class II, 22% of Class III, 4% of Class IV and 6% of Class V presented with asymptomatic hematuria.
40% of Class I, 42% of Class II, 25% of Class III, 7% of Class IV and 13% of Class V present with asymptomatic proteinuria
20% of Class I, 15% of Class II, 17% of Class III, 40% class IV and 65% of Class V presented with Nephrotic Syndrome.
20% of Class II, 34% of Class III, 27% of Class IV and 7% of Class V presented with Nephritic Syndrome
4% of Class II, 2% of Class III, 18% of Class IV and 2% of Class V presented with Acute renal failure
4% of Class IV and 8% of Class V had presented with Chronic renal injury.

So in summary: Lupus can present on kidney biopsy much more differently than clinically.  Look at the wide spectrum of just hematuria and proteinuria.


Ref:

Monday, June 6, 2011

BanFF 2011 Presentations By Dr.Kim Solez

TOPIC DISCUSSION: ADH and Pain?

The relationship of pain and SIADH is well documented. Severe pain can lead to inappropriate ADH production.  Why is that? Why does pain cause ADH release? Looking into the literature, not much has been studied regarding this specific question.
A single paper in 1977 from UCLA describes the effect of pain on plasma ADH concentrations. They studied patients with pain after surgery and compared to controls. Age, smoking and pain came out factors associated with increase in ADH levels. It was a nice and small study but showed that pain led to ADH increase.
Stress might not be the case, might be pain directly. Some studies have shown that stress itself without pain did not led to increase ADH.  Pain has two components:- readily localizable specific sensation that is mediated by the spinothalamic tracts and the second is the arousal of the Reticular formation , ventral thalamus and hypothalamus and perhaps ADH connection might be in this latter portion. Stimulation of the brain stem reticular formation has shown to increase ADH in animals.
When asking few academicians: some responses I got was : Flight and Fight state from an evolutionary standpoint perhaps that wants ADH to be elevated in that state and allow for the beneficial effects.
Also, ADH is produced naturally perhaps in wound healing and in these pain flight and fight situations, leads to such a response.
Interesting , not well defined and studied

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/630725
http://www.ncbi.nlm.nih.gov/pubmed/6399311

BANFF 2011 Updates

Thursday, June 2, 2011

TOPIC DISCUSSION: Hemoperfusion vs Hemodialysis for poisons?

Hemoperfusion is the passage of anticoagulated blood through a column containing activated charcoal or resins that helps remove lipid bound and water bound drugs. Drug removal using this form might be superior to hemodialysis.  If the drug is water soluble, and has significant metablic complications  and rebound properties, hemodialysis might be better. If the drug is lipid soluble like barbiturates, hypnotics, sedatives and digitalis might work better with hemoperfusion.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21531322
http://www.ncbi.nlm.nih.gov/pubmed/20692080

Wednesday, June 1, 2011

IN THE NEWS: EXRTIP

What is EXTRIP?  It is a workforce in extracorporeal treatments in poisoning that is comprised of nephrologists and toxicologists to come up with evidence based data to treat common poisonings.  There are no randomized trials in poisonings to define the role of dialysis properly. Most of the data out there is based on opinions and hence there is always disagreements.
Randomized trials in poisonings are hard to design. Few reasons are consenting, rare disease category, heterogeneous patients, mortality is low. The workforce will address how to even conduct proper trials in poisonings.  Hemodialysis is a valuable tool used in it but indications are very often based on perhaps erroneous toxicokinetics or clinical assumptions.  An entire journal of ACKD was recently dedicated to this topic
A must read for all for a topic that has lost it's flavour amongsts nephrologists

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21531321

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