Sunday, July 31, 2011

In the News: CDC recommendations for Prevention and Screening of HIV infection in potential Organ Donors

The most recent CDC recs for the prevention and screening of HIV infection in potential living donors are as follows:
1. Initial screening should be done in all donors.
2. All donors should have repeat testing with a combination of HIV serologic test and HIV NAT as close to organ donation as feasible but no longer than 7 days preceding organ donation.
3. All donors have to be advised on behaviors that could be putting them at risk for HIV infection.
4. For living donors with high risk: specific counseling might be needed one on one basis.
5. Available testing cannot completely eliminate the risk of transmission and all have to be aware.

Ref:

Thursday, July 28, 2011

Live from the consensus conference on "Optimal Testing of Live Donors to Prevent Transmission of Infectious Diseases"

How do we tell a recipient that they are at high risk for a transmissible infectious disease when they are accepting a CDC high Risk Kidney?

Evaluating donors can lead to many ethical decisions. As Dr.Blumberg stated today, there is no real evidence as to what to do with high risk donors. We all agree that recipients should be aware of the increased risk if they are receiving a CDC high risk kidney. But how do we tell them? We can not tell a recipient specifics because we must adhere to hipaa regulations. We are obligated to let the recipient know of their increased risk. They can receive general information that their donor may be at higher risk....
Another important thing we can do is remind donors of their high risk behavior. Remind them of their need to avoid this high risk behavior and also that the recipient can be harmed if they continue the high risk behavior. Perhaps another meeting after the initial visit should be initiated to talk to them about their high risk. If they can not make behavioral modifications they should be given the choice to opt out of the donation process as risk may be greater than the benefit.

Live from the consensus conference on "Optimal Testing of Live Donors to Prevent Transmission of Infectious Diseases"

What is the optimal testing strategy for testing live donors?

In a lecture given by Dr. Michael Ison, we can see that this is an area of great debate. We all agree that potential donors should have serology done for hepatitis b, hepatitis c, and HIV on initial visit. But should we repeat testing? Should we do repeat testing for everyone or should we repeat testing for high risk donors only? And what would this repeat testing mean? When is the optimal time to repeat this testing?
A suggestion was that possibly we can do repeat hepatitis B core and surface antigen testing, and nucleic acid testing for hcv and HIV. 7-14 weeks prior to surgery may be a good time to do these repeat testing.

Again, these tests can result in false positives, more costs, more patient anxiety, more visits and time spent to get blood drawn which can be looked at negatively.
More experience and studies are needed to tell us what exactly should be done. For now we need to follow our instincts and do what is best for the donor and recipient.

Live from the consensus conference on "Optimal Testing of Live Donors to Prevent Transmission of Infectious Diseases

From Dr. Segev's well put lecture:
Perhaps we can stratify Kidney transplant donors into "higher risk" groups. This group can include men who have had sexual relations with other men, hemophiliacs, those who were involved in sex trafficking or received money for it, person who had sexual relations with those high risk for HIV, those who have been incarcerated, and those who use or have used iv or im drugs.
Probably at high risk would be those who use intranasal cocaine or heroin, those with recent STD, those with recent genital herpes, those who traveled to endemic areas where HIV and hepatitis c are prevalent in high numbers, and perhaps natives from endemic areas.

Once we stratify these donors, what further testing should we do? And more importantly how do we inform the recipient that their donor is high risk?  Some things to ponder on!

Saturday, July 23, 2011

TOPIC DISCUSSION: Pure Thin Basement Membrane vs " Hereditary Nephritis with Thin Basement like features"

Classically, Hereditary Nephritis or Alports Syndrome shows the basket weaving appearing or thin and think alternating basement membrane.  Early in the course in some males and almost all females, the only finding on kidney biopsy might be thin basement membrane. The pathologist needs to carefully look for any subtle changes in lamination and change in thickness in other areas as it makes it almost impossible in that stage to differentiate from pure Thin Basement Membrane disease.  When its not possible to differentiate its called " Hereditary Nephritis with thin basement membrane phenotype".  Those cases have to be clinically followed closely in case they develop renal insufficiency.

Ref:
ASN Nephsap July 2011, Pathology

Friday, July 22, 2011

Increasing Interest in Nephrology : Podcast from ASN via Nephrology Bloggers Part 2


http://asn-online.org/publications/kidneynews/podcast.aspx

Check out the reasons of low interest in Nephrology and how to increase Interest in Nephrology

Topic Discussion: Proliferative GN with Monoclonal igG Deposits

Classically the dysproteinemias have glomerular involvement as
1. Light chain or Heavy chain deposition diseaese
2. Cryoglobulenemia
3. Amyloidosis
4. Immunotactoid GN
5. Fibrillary GN

Recently, a new entity has been identified called Proliferative GN with dysproteinemias or monoclonal igG deposits ( PGNMID)
Some features
1. MPGN pattern of injury, with endocapilary proliferation.  (Now if we look back at the original papers of secondary MPGN pattern of injury one of the classic causes is dysproteinemias, so unclear why this is a new category)
2. Interestingly, only 50% ended up having a bone marrow proven lymphoma or myeloma diagnosis( so now what do we do?)
3. All had proteinuria
4. 75% or more had hematuria
5. Treatment in this one study with immunomodulators showed no benefit
6.Type 1 Cyro MPGN pattern has to be ruled out.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/14675039
NephSap July 2011

Thursday, July 21, 2011

T regulatory Cells: A short review


T regulatory cells have now come out and made a splash in the transplant world but also in the immunology and glomerular disease world.  Treg are usually CD4+, CD25+, CTLA4+.
A common misconception is that all are Foxp3 positive.  
There are many types of Tregs.
Natural kind that do express Foxp3 and CD25 and they usually are IL-2 dependent
Induced Tregs are induced in the periphery and can express Foxp3 but after development
Regulatory Tregs do not express Foxp3 and CD25. They depend on IL-10 on development.

IL-10 has always been associated with regulatory function.
Now given above information, immunology always is evolving and who knows what will be new in 2011.



Wednesday, July 20, 2011

TOPIC DISCUSSION; Stages of Membranous GN

On Electron microscopy, Membranous is defined by electron dense deposits in the sub epithelial region.

Classically there are 4 stages:
Stage 1:- sparse deposits, LM can even look normal.
Stage 2:- most commonly noted finding, the classic Spikes appearance
Stage 3:- deposits with overlying membrane formation, looks like a chain like formation
Stage 4:- disappearance of the deposits.

Interestingly, these stages don't correlate clinically
Progression from one to another could even mean improvement or worsening of proteinuria
We usually encounter Stage 2 most of the times
But just in one glomerulus, you can find multiple stages!

Ref: Neph Sap July 2011

Tuesday, July 19, 2011

TOPIC DISCUSSION: Renal Function in Pregnancy

A recent review in ASN Kidney News nicely summarizes the renal function in pregnancy- By Dr.August.

Here are some summary points:
1. GFR will increase by 50%, practical pointers:- crt of 0.4mg/dl is not abnormal and going up to 1.0mg/dl might be a sign of renal dysfunction.
2. Renal Blood Flow increases by 80%
3. There is early decrease in blood pressure to the extent of 5-10mmhg SBP and 2-5mmhg in DBP even letting people come off BP medications
4. There is little evidence that the increased GFR is leading to increased intraglomerular pressures and there is hyperfiltration injury.
5. RR, Tidal Volume and Alveolar ventilation increases in pregnancy
6. Partly compensated resp alkalosis ensues
7. There is a decreased osmotic threshold for thirst and ADH release. Hence, there is a decrease in Serum Osm and plasma Na.
8. Increase 1,25 Vitamin D levels have been observed in Pregnancy and pth is decreased, urinary Ca excretion is decreased.

The last concept is interesting and why these levels increase and perhaps that's the reason we might encounter a slight hypercalcemic state.  There is some data that placenta can make pthrp as well.

Interesting physiologic changes

Ref:
ASN KIDNEY NEWS 2011:-Page 7-9
http://www.ncbi.nlm.nih.gov/pubmed/8588110
http://www.ncbi.nlm.nih.gov/pubmed/1992673

Monday, July 18, 2011

Advagraf Study

There has been talk about using prograf once a day for quite sometime now.  When it is used once a day its a tacrolimus prolonged use and its called Advagraf.  A recent  multicenter, 1:1-randomized, parallel-group, noninferiority study compared the efficacy of twice a day tacrolimus to advagraf.; combined with steroids and low-dose mycophenolate mofetil without antibody induction, in 667 de novo kidney transplant recipients. 
Per paper:


Biopsy-proven acute rejection rate at 24 weeks  was 15.8% for Tacrolimus BID versus 20.4% for Tacrolimus QD (p = 0.182; treatment ).
Kaplan-Meier 12-month patient and graft survival rates were 97.5% and 92.8% for Tacrolimus BID and 96.9% and 91.5% for QD. 
Both treatment groups showed equally well-maintained renal function at 12 months  by GFR
Overall, it was not inferior to twice a day dosing.


The original Ref is at:
http://www.ncbi.nlm.nih.gov/pubmed/20840480

Women in Nephrology From the ASN Media Center


Sunday, July 17, 2011

New Informative Transplant News Website

please check out www.transplantnow.com.
This is similar to Nephrology now and compiles latest articles in Transplantation from major journals and will allow for good compilation.

Saturday, July 16, 2011

TOPIC DISCUSSION: MPGN Type III


Membrano Proliferative Type III is a rarely discussed entity.  What is that and when do you usually see it?

Few pointers:
1. Simplistic way to look at it:- MPGN III = MPGN type I + Membranous GN
2. So, you see sub endothelial deposits, double contouring and sub epithelial deposits
3. IF usually shows C3, IgG and IgM
4. Clinically, features are similar to MPGN 1
5. Some renal pathologists will consider this as a variant of MPGN I with increase subepithilial deposits
6. Complements are low only in 50% of patients
7. One of the first cases described was in a patients ( child) with hepatitis B surface and e antigenemia.
8. Other cases have been seen in tropical diseases and autoimmune disease associated or idiopathic as well.
9. Degree of relapse is more. Steroids can be tried. Treating underlying secondary cause might be crucial

image source: medscape.com

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/15012698
http://www.ncbi.nlm.nih.gov/pubmed/12042898
http://www.ncbi.nlm.nih.gov/pubmed/9669425
http://www.ncbi.nlm.nih.gov/pubmed/6363317

Thursday, July 14, 2011

CLINICAL CASE 39: ANSWERS AND SUMMARY


Which one of the following is NOT associated with Hepatitis B virus?
Membranous Glomerulopathy
  5 (5%)
Membrano proliferative GN
  1 (1%)
Mesangio proliferative GN
  6 (7%)
IgA nephropathy
  37 (43%)
Poly Arteritis Nadosa
  8 (9%)
All above are associated with Hepatitis B
  28 (32%)



Tough battle between All above and IgA Nephropathy. Traditionally, we think of Hep B and kidney disease as classically as Membranous GN.  So the most common finding is that.  MPGN, Mesangioproliferative and PAN have been also noted with Hep B.  Ig A has some rare associations with Hep B as well.  So the most probable answer should be All above are associated with Hep B.  The presence of immune complexes in the kidney suggests an immune complex basis for the disease like in MPGN sometimes, but a direct antigenic effect is the most likely cause of the proteinuria. Studies have shown that clearance of HBV antigens, either spontaneous or following antiviral treatments results in improvement in proteinuria. Thus, prompt recognition and specific antiviral treatment are critical in managing patients with HBV and renal involvement. Check out ref 1 and 2 for oldest literature on this topic. The last few references are linking IgA nephropathy and Hep B in endemic areas.

Here are some references:
http://www.ncbi.nlm.nih.gov/pubmed/605896
http://www.ncbi.nlm.nih.gov/pubmed/2023605
http://www.ncbi.nlm.nih.gov/pubmed/14988643
http://www.ncbi.nlm.nih.gov/pubmed/21677438
http://www.ncbi.nlm.nih.gov/pubmed/3293854
http://www.ncbi.nlm.nih.gov/pubmed/12970894

Tuesday, July 12, 2011

New Nephrology teaching website

http://www.gkaonlineacademy.com/
Check out the nice and well designed GKA Online Academy to learn renal medicine.

In the NEWS:-Pregnancy and the Kidney

http://onlinedigeditions.com/publication/?m=15191&l=1
ASN Kidney News July 2011 has an entire issue on Pregnancy and Kidney Disease from basics to transplant related issues.


Friday, July 8, 2011

TOPIC DISCUSSION: Methotrexate in the urine

Methotrexate can cause renal damage is well known but precipitation in the urine and appearance in urine analysis is unique.  Tubular obstruction damage and urine precipitation noted in a recent picture in Kidney International highlights this toxicity.  Check it out below

Ref:
http://www.nature.com/ki/journal/v80/n2/abs/ki201197a.html

Wednesday, July 6, 2011

TOPIC DISCUSSION: Dendritic Cells and Renal disease

Dendritic cells(DC) are traditional thought to be anti infectious and a link between the innate and the adaptive immune system.  A nice breakdown of DC role in kidney disease recently discusses its role in homeostatic, anti inflammatory and pro inflammatory roles in kidney diseases.
In terms of homeostatic roles: there is evidence that DCs can do some immune tolerance in renal allografts, and small molecular weight antigens.  The anti inflammatory roles have been in mostly nephrotoxic nephritis(drug induced) especially cisplatin nephrotoxicity. Some data is also present in suppressing pro inflammatory cytokines in ischemic reperfusion injury. Most of the data is in being pro inflammatory in nature and that is in causing proteinuria, promoting ANCA through Th cells, IL-12 secretion in lupus and Th1 response in tubular insterstitial disease.
This leads us to believe that there might be many types of DC and there are.  CD11B like DC due immune surveillance and activate Th cells and are present in kidney in certain glomerular diseases.  CD8 like DC are found in renal lymph nodes and have some T cell activation role.  Inflammatory DC regulate Th cells and Plasmacytoid DC may have some role in lupus nephritis.

Check out these recent references.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21613986
http://www.ncbi.nlm.nih.gov/pubmed/19276627
http://www.ncbi.nlm.nih.gov/pubmed/19381017

Saturday, July 2, 2011

Many guidelines equal no guildelines for cardiac evaluation before renal tranplantation

The degree of cardiac testing for potential transplant recipients is highly variable and depends on the practices of the particular transplant center. Multiple guidelines have been proposed by experts in the field however there is a huge variability between each guideline. At the two ends of the spectrum are the KDOQI guidelines which suggest universal testing for CAD at regular intervals depending on risk, and the ACC/ AHA who recommend testing only for symptomatic patients or patients who can not achieve 4 mets of activity. A recent article in cJASN by Friedman et al. demonstrates this beautifully(1). The authors had performed cardiac testing in 87% of their patients then retrospectively applied the KDOQI, AST, Lisbon and ACC/AHA criteria to thier patients to assess how many would have been tested. Turns out that 100%, 92%, 68% and 20% would have been screened respectively. The authors discovered ischemic disease in 17 (10%) of their patients and 10 of them underwent revascularization (7 had single vessel PCI). KDOQI and AST guidelines would have picked up all of the cases, Lisbon criteria would have picked up 16 patients and ACC/AHA would have picked up 4 of the patients with ischemia. The problem is that it is not clear whether identifying ischemia or performing revascularization in such patients is of any benefit in reducing cardiovascular event rates! In fact there are well designed studies that show pre-surgical revascularization in all patients with ischemic heart disease does not reduce cardiovascular morbidity and mortality in patients undergoing major vascular surgery(2) - but of course these studies were not in dialysis patients...

What we need is a large multicenter randomized controlled trial to evaluate the potential benefit in pre-transplant cardiac testing +/- revascularization in reducing cardiac morbidity and mortality in patients undergoing renal transplantation - to settle the question once and for all.

Reference:
1. Friedman et al. A Call to Action: Variability in Guidelines for Cardiac Evaluation before Renal Transplantation. cJASN 2011;6:1185
2. McFalls et al. Coronary-artery revascularization before elective major vascular surgery. N Engl J Med 2004;351: 2795
2804, 2004

Topic Discussion: Warfarin Related Nephropathy


A commonly used agent is warfarin for anticoagulation.  Recently there have been some published case reports of warfarin induced nephropathy(WRN). More recent, an original article on the incidence and prevalence of this entity in CKD has also been mentioned.

What is this entity? High INR was associated with a rise in crt in biopsy of patients showed glomerular hemorrahge and renal tubular obstruction with red blood cell casts.  A recent retrospective review of over 15000 patients who were on warfarin and had an INR >3 and creatinine at the same time were reviewed.  A presumptive diagnosis of warfarin induced toxicity in the kidney was made if crt increased by 0.3mg/dl in 1 week after INR was >3.  WRN occurred in 20.5%,and 33% of the patients with CKD.  The mortality was also higher with people with this entity.  Other diagnosis that could have cause an acute renal injury were considered in those 4006 patients and carefully ruled out by looking at the chart.

The study highlighted few important points:
1. This entity should be considered in the differential diagnosis with AKI on warfarin
2. The risk factors to make this risk higher were age, DM, HTN and CVD but most important risk factor that doubled the risk was CKD.
3. Average INR to show this entity was only 4
4. The higher risk of WRN in CKD patients maybe be more likely due to having a sub therapeutic INR
5. There is no correlation of WRN and level of INR
6. WRN has substantial decreased survival rate but unclear if this is purely from WRN or other co morbid conditions.
7. Glomerular hemorrhage leading to tubular cast obstruction leading to ATN is the most likely mechanism
RFN also blogged about this in 2010 at
http://renalfellow.blogspot.com/2010/08/warfarin-induced-aki.html
Read more at the following references:
http://www.ncbi.nlm.nih.gov/pubmed/21389969
http://www.ncbi.nlm.nih.gov/pubmed/20413993
http://www.ncbi.nlm.nih.gov/pubmed/19577348

Friday, July 1, 2011

TOPIC DISCUSSION: Wunderlich Syndrome


Wunderlich syndrome can be seen in dialysis patients.  It is spontaneous non traumatic renal hemorrhage.  Usually this is seen in angiomyolipomas and sometimes even in urothelial cell cancers. Some cancers are common in dialysis patients, renal cell or urothelial can be seen.  Usually the syndrome presents with back pain, flank pain or hip pain.  CT scan can diagnosis it. If they are not making urine, blood in the urine might not be noted.  A high index of suspicion in at-risk patients therefore is important to timely identify and manage this disease.
A recent AJKD article describes this entity.

Ref:

ASN Podcast on Nephrology Blogging Part 1


Check out the Nephrology Blogging world get interviewed by ASN Kidney News: It features Blogging world of Nephrology via discussions with Renal Fellow Network and Nephronpower editors.

http://www.asn-online.org/publications/kidneynews/podcast.aspx

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