Monday, February 28, 2011

Geriatric Nephrology

The Feb 2011 issue of ASN Kidney News highlights an important subset of Nephrology- Geriatric Nephrology.
A series of articles are mentioned from ESRD, Transplantation and educational opportunities in this field.
There is a society called the International Society of Geriatric Nephrology that was formed few years ago.
A Journal called Geriatric Nephrology and Urology also exists that caters to articles and studies to this important field in Nephrology.
A nephsap in Jan/Feb 2011 is going to be focused on Geriatric Nephrology as well.
Topics that are included are biology of aging and the kidney, GFR and age, glomerular diseases, geriatric hypertension, Pallative care options are a few topics.
Have a look at this months' very important issue focused on a specific theme
http://onlinedigeditions.com/publication/?m=15191&l=1

TOPIC DISCUSSION: Ageusia and ACEI/ARBS

Has anyone noted any cases of ageusia and ACEI/ARB use? Loss of taste has been reported in few case reports of these classes of agents. How does this work? Zinc depletion leads to taste disturbances. Few other drugs such as thiamazole, penicillamine cause ageusia due to zinc depletion. The active site of binding or ACEI has zinc ions. It is speculated that due to this binding, the zinc availability is decreased (perhaps more in zinc deficient patients from baseline) and leading to taste loss. Stopping the medication usually reverses it. Although when cases were looked at closely, zinc levels were normal and zinc supplementation did not return taste don't support this hypothesis.
Perhaps another mechanism might be at play

Take a look at these references:
http://www.ncbi.nlm.nih.gov/pubmed/394799
http://www.ncbi.nlm.nih.gov/pubmed/8618505
http://www.ncbi.nlm.nih.gov/pubmed/8618505
http://www.ncbi.nlm.nih.gov/pubmed/15185557

Saturday, February 26, 2011

Thursday, February 24, 2011

IN THE NEWS- Idiopathic Membranous GN and HLA-DQA1

The NEJM article just came out showing that Membranous GN has a genetic locus.
Of close to 600 Caucasian studied, two alleles were identified. Chromosome 2q24 contains the gene for the phospholipase A2 receptor, recently identified antibody against in Idiopathic membranous. Chromosome 6p21 contained the gene for HLA complex Class II HLA-DQ alpha chain 1 ( was significant in most patients identified). The PLA2R1 gene was also found to be a associated with the disease in a certain cohort. This supported a prior study that had just come out showing antibodies against phospholipase A2 in idiopathic membranous. Having two copies of the risk alleles in both genes increased the likelihood of the disease by a factor of 78. In all three cohorts studied in their paper, the researchers found a significant association with an HLA-DQA1 allele on chromosome six, while in the Dutch and British groups, they also found a significant link with the gene coding for the M-type phospholipase A2receptor. 
Interestingly, an older study had shown some association with HLA DR3. Look below in the references. As we are learning more and more about this disease, I think that we shall soon have a better treatment option for this enigmatic disease entity.
Ref:

Skin cancer and Transplants

Talking to your patients and just educating them regarding regular skin cancer screening might be just enough to raise awareness and prevent skin cancer. Regular yearly dermatology visits for skin check ups are essential for prevention. Check out this latest healhday article.

http://consumer.healthday.com/Article.asp?AID=650075

Wednesday, February 23, 2011

TOPIC DISCUSSION: Is Veno-occlusive disease associated AKI different from Hepatorenal syndrome?

One of the devastating complications of bone marrow transplants is veno occlusive disease(VOD) characterized by weight gain, painful hepatomegaly, ascites, jaundice, bilirubin levels astronomically high.  This usually happens 30 days following the transplant.
VOD associated AKI is clinically not different from Hepato renal syndrome. Patients usually have a a pre renal picture with oliguria, low FENa and clinically appear volume overloaded.  Patients are either hypotensive or normotensive and hyponatremia might be present. Hence looks very similar to a cirrhotic patient with acute renal injury.  Tubular damage can be seen with granular casts in advanced disease and perhaps some component of pigment(bilirubin) nephropathy.  When kidney biopsies are done in the patients, there are no structural damages noted unless ATN has ensued.  Hence, the pathophysiology is similar to hepatorenal syndrome essentially.
Makes the injury mostly volume related or hemodynamic in nature or a "false" permanent activation of renin angiotensin system: like hepato renal syndrome

Ref:
Cancer and the Kidney, Second edition, Eric Cohen

JOURNAL CLUB: ESCAPE TRIAL

Escape
View more presentations from sid.

Courtesy: Pediatric Nephrology blog

Tuesday, February 22, 2011

Nephrology Anagrams

For those of you who love medicine and enjoy it, here is our first installment of Nephrology anagrams: topic is hypokalemia. Check out the March 2011 issue of AJKD quiz page: http://www.ncbi.nlm.nih.gov/pubmed/21335245

Monday, February 21, 2011

TOPIC DISCUSSION: Renal Vein Pressures and Cardio Renal Syndrome!

I was just reading an interesting article regarding cardio renal syndrome (CRS).


Acute Cardio-renal Syndrome: Progression from Congestive Heart Failure to Congestive Kidney Failure in the Journal Curr Heart Fail Rep.
Few interesting points that the article discusses.


1. Creatinine 0.3mg/dl over baseline and BUN greater than 50mg/dl is the strongest predictor of in hospital mortality in cardio renal syndrome( acute kind). The article seems to talk more of the Type I CRS.

2. One potential cause of acute cardio-renal syndrome is worsening intrinsic
kidney disease (eg, diabetic or hypertensive nephropathy) which could trigger the cascade of activation of the  renin–angiotensin-II–aldosterone system, volume retention, and heart failure exacerbation. 
3.Other potential causes for acute cardio-renal syndrome include drugs that can be nephrotoxic or decrease GFR. Prior history of renal dysfunction and/or heart failure is a risk factor for developing acute cardio-renal syndrome.
4. We always think  of acute cardio renal as hypoperfusion of the kidney explained by hypotension or hypovolemia. But majority of the patients are clinically “warm and wet.” Hypervolemia is far more common in these patients then hypovolemia.
5. Hypertension is a more marked predictor of CRS than hypotension
6. If the above are true, what is causing the presumed pre renal like state in the kidney. The article argues that this is due to high central venous pressure transmitted to the renal veins and kidneys.Two prior studies ( one in  mammals in 1931 and another in humans in 1988) are cited as evidence in this review article.
Hypervolemia and acute  increase in renal vein pressure leads to profound azotemia combined with reduced glomerular fitration rate, urine output and sodium retention.
7. Apparently the threshold renal vein pressure before azotemia ensues is 18-20mmHg. 
Many other studies have shown that renal vein constriction results in reduced sodium excretion. This is a possible mechanism in intraabdominal pressure - compartment syndrome associated renal disease perhaps?
8. Congestion of the kidney combined with elevated renal interstitial pressure might be the mechanism by which tubular dysfunction, azotemia and renal failure occurs in CRS rather than presumed hypovolemic state in CRS. 


So is renal venous pressure more important then hypovolemia in decompensated heart failure. The above review thinks so and few recent papers as well. The 1931 paper mentioned above says that you stop making urine after pressure of 20-25mmHg.


Take a look at few recent RFN blog posts on this topic


http://renalfellow.blogspot.com/search?q=abdominal+compartment+
http://www.nephronpower.com/2010/10/in-news-cardiorenal-syndrome-or.html


Ref:
http://www.ncbi.nlm.nih.gov/pubmed/17883988
http://www.ncbi.nlm.nih.gov/pubmed/16994199
http://www.ncbi.nlm.nih.gov/pubmed/2896877
Image source: http://chfc.uk-wuerzburg.de/en/research/projects/project-area-e.html

Thursday, February 17, 2011

CLINICAL CASE 33, ANSWER AND SUMMARY(IMAGE QUIZ)

Image Quiz!!!
What kidney disease do you see the above findings on Electron Microscopy?

Interferon associated FSGS
  5 (7%)
 
HIV
  4 (5%)
 
HTLV
  1 (1%)
 
Fabry's Disease
  54 (79%)
 
Adenovirus Nephritis
  4 (5%)
 


The vast majority of you said Fabry's Disease.
That is correct.
In HIV, HTLV and Interferon FSGS, one would see Tubular reticular inclusions. In Adenovirus Nephritis, sometimes, you can catch the virus in the cell on EM that might be looking like above.
The above is a Zebra body classically seen in Fabry's Disease. It is an X linked disease that is a lysosomal storage disease and deficiency in activity of alpha galactosidase.
The RFN has a nice recent blog on the disease inheritance.
What does one see on Kidney Biopsy?
1 Light Microscopy: foamy visceral epithelial cells. vacuoles in podocytes, mesangial widening, most of this lipid material deposits in the podocytes and some in epithelial and then endothelial cells. Advanced disease can show FSGS as well.
2. Electron microscopy: enlarged secondary lysosomes (zebra bodies as shown above) packed with lamellated membrane structures.  As diseases advances, fusion of foot processes and proteinuria. 
A nice paper on pathology in the kidney is in JASN. look below

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/12068025

Wednesday, February 16, 2011

Suggest and Vote for New Ideas in Nephrology

The NIDDK has come up with a very novel tool to discuss new ideas to conduct research in Nephrology.
The Kidney Research National Dialogue (KRND) website offers this to everyone around the globe.
Please take a moment to suggest ideas, or support ideas that have been proposed. This is a great way to see what might be new in the field of research.

http://krnd.ideascale.com/

Tuesday, February 15, 2011

Risk factors for post transplant Hypertension

Here are a list of factors that contribute to post kidney transplant development of Hypertension.
1. Pre existing HTN
2. Body Mass Index
3. Native Kidney disease
4. Donor age
5. Donor sex
6. Donor Hypertension
7. Longer Cold Ischemia time
8. Delayed graft function
9. Steroids
10. CNI( cyclosporine>tacrolimus)
11. Acute rejection
12. Anti body mediated rejection
13. Chronic Allograft Nephropathy
14. TMA
15. Recurrent glomerular disease
16. Transplant renal artery stenosis
17. Lymphocele leading to obstruction
18. Ureteric stenosis

Take a look at the more comprehensive article in AJKD
http://www.ncbi.nlm.nih.gov/pubmed/21251543

Monday, February 14, 2011

TOPIC DISCUSSION: Pseudohyperphosphatemia

What are the causes of spurious hyperphosphatemia?
1. Paraproteinemia
2. Hyper builirubinemia
3. Hyperlipidemia
4. Liposomal Amp B preparation
5. Blood sample contamination with tpa or heparin
6. Thrombocythemia

Lot of these errors are due to the type of measurement used in labs- especially the colorimetric assay

A nice case has been discussed in AJKD of a MGUS with pseudohyperphosphatemia.
http://www.ncbi.nlm.nih.gov/pubmed/20951488

Friday, February 11, 2011

TOPIC DISCUSSION: Hypercalcemia of Malignancy

Few tips on Hypercalcemia of Malignancy.
1.Occurs in 20-30% of patients with cancer
2. Usually the cancer is evident 90% of the time before the calcium problem arises.
3. Highest risk is Renal Cell Cancer, followed by Non small cell lung, Myeloma and then leukemia and breast cancer
4. 3 main mechanisms:- replacement of normal bone structure by metastatic cells and destruction via IL-6, IL-1 and TNF-alph stimulating osteoclastic activity; pthRp production by the tumor leading to binding to pth receptors in kidney and bone and causing similar effects as pth would; 1,25 0h vitamin D production mainly by lymphomas leading to increased intestinal absorption.
5. pth production (ectopic) is rare but can be seen. Primary hyperparathyroidism can occur in cancer patients as well.
6. Vitamin D(25-0H) can be elevated if there is excessive Vitamin D intake.
7. IV fluids, furosemide, calcitonin are few initial drugs to be used. Dialysis might be needed in some serious cases.
8. Pamidronate is safe in patients with CKD and hypercalcemia. It does cause Collapsing glomerulopathy. Zolendronate is to be used with caution in CKD as it can cause ATN.
9. Based on ASO guidelines, patients with moderate CrCl 30-60ml/min require no dose adjustment for pamidronate but require it for zolendronate.  For severe disease <30cc.min, zolendronate is contraindicated and pamidronate infusion time is increased to 4-6 hours and dose decreased.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/8706358
http://www.ncbi.nlm.nih.gov/pubmed/15673803
Cancer and the Kidney, Eric Cohen, 2nd Edition.

Monday, February 7, 2011

TOPIC DISCUSSION: Lactic acidosis and Dialysis?

What is the data on Hemodialysis or CRRT on lactic acidosis?
The above mentioned treatments are mentioned in the literature for severe lactic acidosis Type A.  In one paper, the lactic acidosis resolved during treatment with bicarb based hemofiltration.  Few case reports exist about using CRRT do successfully treat lactic acidosis.
However, there is a lot of doubt about the clearance of lactate.  One paper studied 10 patients that were in AKI and lactic acidosis and checked stable lactate levels pre and post CRRT.  They concluded that the mean lactate concentration actually increased despite renal replacement therapy.  He medial total plasma lactate clearance was 1379ml/min(range 754-1881) and the median filter lactate clearance was 24ml/min suggesting that the filter lactate clearance accounted for only <3% of total lactate clearance.  Hence CRRT doesn't compete with lactate overproduction. If the cause is Type B lactic acidosis and a drug induced nature or ethanol induced, removing the offending agents via dialysis might be beneficial. There are case reports of metformin induced lactic acidosis being treated with dialysis, all met with some form of skepticism.
A prior post described metformin induced lactic acidosis and role of dialysis.
http://www.nephronpower.com/2010/03/metformin-toxicity-lactic-acidosis-and.html

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/10560814
http://www.ncbi.nlm.nih.gov/pubmed/9666950
http://www.ncbi.nlm.nih.gov/pubmed/8989177
http://www.ncbi.nlm.nih.gov/pubmed/11251027

Male Fertility and Transplantation

Male fertility has not been studied in detail in transplantation.  Does immunosuppresive therapy have impact on sperm production or motility?
Most reports suggest that male transplant recipients have successfully fathered healthy kids.
The one drug that might have led to problems is sirolimus: On observational study showed that sperm count was decreased in the sirolimus arm of the study and that could affect pregnancy outcomes.  No data exists on other agents at this point.

Ref
http://www.ncbi.nlm.nih.gov/pubmed/18510638
http://www.ncbi.nlm.nih.gov/pubmed/17714220
http://www.ncbi.nlm.nih.gov/pubmed/19601935

Sunday, February 6, 2011

TOPIC DISCUSSION: Membranous and Class Type IgG

Membranous GN can be idiopathic or secondary. Idiopathic has been associated with IgG4 subtype noted on IF which activates complement alternatively. The secondary forms usually are either IgG1, 2 or 3 and don't activate complement alternate pathway but do classical pathway. When lupus or hepatitis patients have membranous, the IF usually shows IgG1,2 or 3 and possibly full house and TRIs as well( in lupus). The patients with MPGN have granular glomerular deposits of all four IgG subclasses, with a predominance of IgGl and IgG3. These data suggest that the IgG4 subclass may play an important role in the pathogenesis of idiopathic membranous.
Another distinguishing feature at least now available is the antibodies to the human phospholipase
A2 receptor (PLA2R) found in many patients with idiopathic membranous.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1576972/pdf/clinexpimmunol00139-0066.pdf
http://www.nephronpower.com/2010/06/topic-discussion-primary-vs-secondary.html

Friday, February 4, 2011

Renal Blog in finalist for Best Medical Blog( Clinical)

Renal Fellow NetworkAll Nephro centric people out there and all who support blogging as an educational tool for the renal community go online and support the Renal Fellow Network as it has entered the final five in the 2010 Medgaget Awards!!
Go and vote below
http://www.medgadget.com/2010bestclinical.html
More information on Medgadget awards can be found on http://www.medgadget.com/

TOPIC DISCUSSION: Spontaneous Perinephric Hemorrhage

If you have someone who presents to you with a spontaneous renal hemorrhage, what causes come to your mind? Things to keep in your mind are:


Renal Cell Cancer
Angiomyolipoma
Abscess
Hemorrhagic cyst
Arteriovenous Malformations
Idiopathic



The above list was based on a radiology study of 18 patients where a cause was discovered ultimately by CT scan rather than Ultrasound.

http://www.ncbi.nlm.nih.gov/pubmed/2672096
http://www.ncbi.nlm.nih.gov/pubmed/2300864
http://www.ncbi.nlm.nih.gov/pubmed/11517829
Image source: http://www.catscanman.net/blog/

Nephsap review: Transplantation

A question encountered on our recent Nephsap review on transplantation:
What regimen would be the safest in pregnancy? If one had to choose between CNI + prednisone or CNI+ azathioprine. The groups were divided.
What is the data?
As you go down the list in immunosuppresive medications: most are C and below and no medication is a Risk category A or B.  Cyclosporine has the most data with tacrolimus with extrapolated data. Aza and MMF would be close to category D compared to CNIs which are more of a category C. Steroids would also fall in category C.  From a clinical prespective, the safest immunosuppression for a woman who wishes to get pregnant seems to be a combination of controlled CNI and prednisione. MMF should be discontinued.
What if you were on a steroid sparing protocol? Would you add steroids or AZA instead of MMF?
Azathioprine is teratogenic in animal studies.  It does cross the placenta/ and hematologic toxicities can happen to the fetus.  But a lot of pregnancies have been documented successfully at many transplant centers with AZA.  So some centers would choose to add AZA in this case but some might just do steroids and CNI. Due to lack of data, there is really no right answer. Risks and benefits of all agents have to be discussed and decisions made on an individual basis.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21266268
http://www.ncbi.nlm.nih.gov/pubmed/20685549
http://www.ncbi.nlm.nih.gov/pubmed/18368705
http://www.ncbi.nlm.nih.gov/pubmed/16095516

Thursday, February 3, 2011

Tuesday, February 1, 2011

CLINICAL CASE 32, ANSWERS AND SUMMARY

Which infectious agent is the most common cause of Post infectious Glomerulonephritis in the elderly?


Streptococus 48%
Staphlylococcus 30%
E Coli 11%
Pseudomonas 1%
Candida 2%
Viral Cause 4%

Hmm. Most of you got this answer wrong. The correct answer is Staph.
Post infections GN ( PIGN) is usually a childhood illness following a Streptococcus infection.  In the Elderly, the disease is not as well defined. The question above is asking about the most common organism in the elderly leading to PIGN.  The correct answer is Staph. There is a large series of patients close to 110 cases of >65 years of age and biopsy showing PIGN.  Mostly males more than females and diabetes or malignancy on the background in 60%of the patients.  The most common infection was Staphylococcus 46% and followed by Streptococcus at 16% and then gram negative organisms.  Low c3 was present in 70% of patients and most common site of infection was skin and then lung and then UTI.  Prognosis is poorer compared to childhood PIGN and only 25% had full renal recovery. Check out the full reference below.



Ref:

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