ASN- KSAP First installment

Nephrology Self-Assessment Program (NephSAP) has served for twelve years as a strategy for nephrologists to keep knowledge up-to-date and earn both CME credits.

ASN has recognized a need for material that covers basic principles of clinical nephrology that would be appropriate for individuals who are studying for the In-Training/In-Service examination or preparing for the American Board of Internal Medicine (ABIM) examination in the subspecialty of Nephrology. To this end, the concept of the Kidney Self-Assessment Program (KSAP) was developed.

KSAP is similar to having a Q bank for board preparation and re certification exams.
Please visit and see what you all think

This was must needed and well intended

http://asn-online.org/education/ksap/

Hyponatremia and Edelman equation?

 

Following the simplified Edelman equation: [Na+] = (Nae + Ke)/TBW, hyponatremia can be originated exclusively from a decrease in total exchangeable body sodium (Nae). 

Can you think of clinical scenarios where this might occur and that do not involve patients drinking water or hypotonic fluids ?

What do nephrologists think?

 Please comment with your responses:

Helbert Rondon, MD

Assistant Professor of Medicine

University of Pittsburgh School of Medicine

Wild Nephrology Explored

Last week we had three questions regarding plants that were related to Nephrology.

Wild Nephrology Part 1: Name the " Electrolyte disorder" most commonly associated with this plant.

This is FloxGlove, the plant that is where we get digoxin from. The best-known species is the common foxglove, Digitalis purpurea. This biennial plant has vivid flowers which range in color from various purple tints through various shades of light gray, and to purely white.
Digoxin inhibits Na-K ATPase as a results K remains outside the cells and results in hyperkalemia. Since K and digoxin compete for the same pump, hypokalemia can make digoxin toxicity worse. So, both Kalemias are associated with this agent- one that worsens the toxicity and other as a result of toxicity. 
 http://circ.ahajournals.org/content/48/4/830.full.pdf



Wild Nephrology Part 2: Name the "electrolyte disorder" associated with this plant.

This is Opium Poppy and the most likely disorder is hyponatremia as a result of extreme nausea. 








Wild Nephrology Part 3: The drug from this plant has to be dose adjusted in CKD. Name the plant and the drug

This is Pacific Yew(Taxus brevifolia). The chemotherapy drug paclitaxel (taxol), used in breast, ovarian, and lung cancer treatment, is derived from Taxus brevifolia. Dose adjustment is needed for this chemotherapy in CKD patients. There are no FDA-approved labeling guidelines for dosage adjustment in patients with renal impairment. Experts recommend no dosage adjustment necessary for adults with Cl_cr<50 mL/minute but many do adjust. 

Image Quiz: Wild Nephrology Part 4

Soil samples from this locale provided material for WHAT renal immunosuppressive agent.

eAJKD test your knowledge

Test your knowledge on two topics

Renal Sarcoidosis
ANCA associated Secondary Renal diseases

eAJKD: Test your knowledge on Glomerular Diseases in Sjorgen's syndrome

Check out the latest post on eAJKD re SS and Glomerular Diseases.

TRANSPLANT ROUNDS: Test your knowledge of induction agents!

To test your knowledge of induction agents in kidney transplantation, we invite you to complete the following matching quiz. The answers will be posted early next week.

Match the following induction agents with the description that best matches their profile. One description will not be used.

Alemtuzumab	A. This anti CD25 human/ mouse chimeric antibody is almost devoid of side effects. It does not increase the risk for malignancies or infections.
Rituximab	B. This antibody has been used in a recent trial to facilitate positive crossmatch transplantation in living donors by blocking the effector pathway of antibody mediated allograft injury.
Thymoglobulin	C. This agent is used to treat antibody mediated rejection and as induction in sensitized individuals. It decreased the production of anti-HLA antibodies by targeting the CD 20 receptor on B cells and plasma cells.
Daclizumab	D. This antibody targets CD 52. It is FDA approved for the treatment of CLL. It is often used in minimization protocols for kidney transplantation.
Basiliximab	E. This agent when used as an induction agent may increase the risk of cellular rejection.
Atgam	F. This polyclonal antibody preparation targets many different receptors on T cells. It increases the risk of PTLD, and CMV compared to no induction or anti-CD25 induction. However, it has been shown to be a superior agent in reducing rejection episodes and prolonging graft survival especially in high risk individuals.
OK3T	G. This polyclonal antibody preparation came from horses. It has since been largely replaced by another polyclonal T cell preparation.
Eculizumab	H. This agent was a humanized monoclonal antibody that targeted the alpha chain of the IL-2 receptor of T-cells. The manufacturer discontinued its use in January 2009.
	I. This monoclonal antibody against the T-cell receptor was the first such antibody used for any clinical indication in the United States. Its current use has been minimized due to severe adverse reactions including serum sickness and pulmonary edema.

Answers soon to follow! Stay tuned.

eAJKD: PTLD quiz!

Go test your knowledge of PTLD at the eAJKD blog site

QUIZ:What causes Green urine? Answers

QUIZ : What causes Green urine?

Blue or green urine may be caused by:

1.    Dyes such as methylene blue, indigo carmine

2.    Bladder irritation decreasing meds:- pyridium(usually orange but also green), uroblue, trac tabs

3.    The infamous propofol, has also been reported to cause green coloration of the urine

4.    Amitriptyline, indomethacin, resorcinol, triamterine, cimetidine, Phenergan, rifampin

5.    B vitamins especially.

6.    An inherited form of high calcium (called "familial hypercalcemia") can result in blue urine, which has lent this disease the nickname "blue diaper syndrome"

7.    Indicanuria,

8.    Pseudomonas  infection

9.    Pneumaturia: can be caused by bile when there is a fistula between the urinary tract the intestines.

Some good references:

Slawson M. Thirty-three drugs that discolor urine and/or stools. RN. 1980 8. 9.

Blakey SA, Hixson-Wallace JA. Clinical significance of rare and benign side effects: propofol and green urine. Pharmacotherapy. 2000 Sep;20(9):1120-2.

http://urology.stanford.edu/about/articles/abnormal_urine.html

http://www.mayoclinic.com/health/urine-color/DS01026/DSECTION=causes

Image Quiz: What causes this color?

What is your differential diagnosis for "green urine"?

Complement Component Quiz Answers

Question:

Match the following complement components with their function in the complement cascade

C5a	Membrane attack complex
DAF	Initiates the alternative complement pathway
C5b-9	Initiates the classical complement pathway
Factor H	Byproduct of the classical complement pathway
C5	Potent inflammatory mediator
C1q	Membrane bound complement regulatory protein
C4d	Blockade of this complement component is the treatment for PNF
C3b	Deficiency results in atypical HUS

Answers:

C5a – Potent inflammatory mediator

DAF (decay accelerating factor) – membrane bound complement regulatory protein

C5b-9 – membrane attack complex (MAC)

Factor H – Deficiency results in atypical HUS (hemolytic uremic syndrome)

C5 - Blockade of this complement component is the treatment for PNF (paroxysmal nocturnal hematuria)

C1q – Initiates the classical complement pathway

C4d - Byproduct of the classical complement pathway

C3b - Initiates the alternative complement pathway

Post by

Vinay Nair 

Complement Component Quiz

Match the following complement components with their function in the complement cascade

C5a	Membrane attack complex
DAF	Initiates the alternative complement pathway
C5b-9	Initiates the classical complement pathway
Factor H	Byproduct of the classical complement pathway
C5	Potent inflammatory mediator
C1q	Membrane bound complement regulatory protein
C4d	Blockade of this complement component is the treatment for PNF
C3b	Deficiency results in atypical HUS

Good Luck
Answers provided in 1 week

Questions by Dr. Vinay Nair
Mt Sinai, Transplant Division
New York, USA

Hypokalemia quiz answer

Labs on presentation: Na 117, K 1.5, Normal renal function. Exam consistent with volume depletion. EKG changes consistent with hypokalemia. Hyponatremia is asymptomatic

Treatment?

A. Treat hyponatremia first and then hypokalemia

B. Treat hyponatremia and hypokalemia simultaneously

C. Treat hypokalemia first and then hyponatremia  

Any thoughts? What would you do?
Here is what you all said:

" C,  but I believe that, in practice, we'd probably end up doing B."

"I would think treat both. As you improve distal tubular flow with saline , hypokalemia can worsen"

"How about KCl, NaCl and DDAVP with water restriction."

"Treat hypokalemia first.”

”In this case the hyponatremia may be at least partly explained by the huge deficit in total body potassium stores, thus causing intracellular shift of sodium in exchange for potassium. Given that this patient is asymptomatic, option C is probably the safest. Aggressive repletion of K w/150-200 mEq daily for 2-3 days will be necessary to replete his K and the patient's Na may slowly improve as well."


"Treat hypokalemia with IV KCL (ECG abnormalities make it urgent). Repleting volume would probably take care of hyponatremia."

"Patient should only be treated for Hypokalemia first as hypokalemia correction itself will cause improvement in hyponatremia. The theory behind it is with K repletion, there is translocation of K in the cell and Na will move out. Mich. Halperin book has an excellent article on this."

I think all responded practically the right answer. Correction of hypokalemia is very important in setting of hyponatremia and one has to be watchful of not over correcting Na too fast in this setting as correcting the K will correct the Na as one of the commenters pointed out. There have been cases reported of osmotic demyelination from just aggressive correction of K leading to fast Na correction.

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/20338465

http://www.ncbi.nlm.nih.gov/pubmed/8192171

Quiz 9 Answers

Which of these statements is TRUE regarding living donor related transplantation in Fabry's Disease?

Renal Transplantation from a heterozygote female relative into a patient with Fabry is risky as globotriaosylceramide accumulation might be present in this donor, without clinical symptoms ( is a true statement)

The measurement of Alpha galactosidase A activity in a potential female living related donor for a patient with Fabry's is not sufficient as a normal value cannot exclude a random X chromosome inactivation( is a true statement as well)
Living related transplantation is possible in donors who do not have the mutation.( this is true)

One has to be careful with male donors as late onset Fabry's disease exists in males and they 

develop proteinuria and renal failure after age of 25 years.( this is true)

Demonstration that the recipient's gene mutation is absent in the potential female relative donor is required before living related transplantation is performed in a patient with Fabry's ( also true)

Hence the answer is all of the above

Check out the Nature Review Nephrology Dec 2010 edition for Kidney Transplantation evals in Hereditary Nephropathies

http://www.ncbi.nlm.nih.gov/pubmed/20877305

http://www.ncbi.nlm.nih.gov/pubmed/3120588

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).

Quiz 8 answers

Immunology Quiz: There are two types of Tregs:- the natural kind and the induced kind. Which of these statements is FALSE?

1.The natural T regs are thymus derived   0 (0%)

2.The induced T regs are generated in the periphery   0 (0%)

3.The natural T regs are derived from T effector cells  5 (50%)

4.The natural T regs suppress autoimmunity  2 (20%)

5. The induced T regs induction requires CD28 signalling, and possibly TGF-B and other cytokines

  1 (10%)

6.The natural T regs are selected by autoantigens

  2 (20%)

There are two types of T regulatory cells, one that is natural Tregs and the other that is induced T regs.

But are Foxpe+T reg cells.

Natural T regs: are Thymus derived, selected by autoantigens and could be autoreactive.

They cross react to alloantigens and suppress autoimmunity.

Induced T regs: are generated in the periphery, derived from T effector cells.  Their induction requires cytokine activation and CD28 signialling.  They are positively and negatively regulated by many pathways.

Hence, the choice number 3 is wrong.

Nice review below:

http://www.ncbi.nlm.nih.gov/pubmed/20683480

Quiz 7 Answers

What is the most common glomerular disease following Liver Transplantation?

Ig A Nephropathy	7 (46%)
Minimal Change Disease	0 (0%)
Membranous GN	4 (26%)
MPGN Type 1	4 (26%)

When 105 renal biopsies were studied in patients with non renal transplants for causes of glomerular disease, the most common transplant where glomerular disease was seen was liver transplantation. If you exclude, Thrombotic microangiopathy over glomerular disease, the most common was IgA Nephropathy followed by MPGN type 1 ( likely secondary to Hepatitis C).

In Bone marrow transplantation:- the most common finding was Thrombotic Microangiopathy( likely drug related or bone marrow transplant nephropathy or radiation related) followed by minimal change disease and membranous GN( which is usually seen with GvHD)

In Heart transplantation, IgA topped the list again.  

A nice review can be found below:

http://www.ncbi.nlm.nih.gov/pubmed/20883535

Quiz 6 answers

Which is true? 1.The incidence of Kaposi Sarcoma is most highest in liver transplants of all solid organ transplants
2.Females are more of risk than males get Kaposi Sarcoma in Renal transplant patients
3.It is caused by Human Herpes virus 6 4.Most cases of Kaposi's Sarcoma occur in individuals of Mediterranean or Arabic origin 5.Most cases of Kaposi Sarcoma are visceral in nature in Transplant recipients. The correct answer is 4. Kaposi Sarcome- can be seen in transplant patients. In general few observational findings It is three times more common in males than females It is caused by HHV 8, not 6 Most cases of this virus occur in individuals of Mediterranean or Arabic origin Risk factors are usually levels of CNIs Usually presents as a cutaneous lesion in legs and lymphedema.  Skin involvement is most common Visceral involvement is rare in transplant patients, <10 % Most cases of HHV 8 related KS have been seen in cardiac and renal transplants.

Quiz 5 Answers

Which one of the following is not a risk factor for PTLD
EBV status of donor/recipient 2 (16%)
Prior malignancy 1 (8%)
"Net" immunosuppresion 1 (8%)
Prior BK Virus infection 6 (50%)
Age 2 (16%)

Most of you got this one right away!
All except Prior BK infection has been associated to be a risk factor for PTLD In kidney transplant recipients
Please review the recent updated PTLD presentation by Arun Chawla for further clarification

http://onlinetransplantcenter.blogspot.com/search/label/presentations

Quiz 4 Answers

What is the most common cause of Denovo Thrombotic Microangiopathy post renal transplant?

Calcineurin inhibitor toxicity 5 (55%)
Antibody mediated rejection 3 (33%)
MPGN 0 (0%)
Malignancy 0 (0%)
Infections 1 (11%)

Denovo TMA post transplant is defined as happening in the early post transplant period.( 6 months). All of the above can cause de novo TMA in post transplant patients. The most common cause as most of you got it is CNI toxicity. Although, Antibody mediated rejection closely follows it and should always be considered. Another cause not listed here is ischemic repefusion injury as well leading to a TMA.
A recent study in AJT August 2010 showed in a retrospective fashion that TMA can be very strongly associated with C4D positive Biopsies showing ABMR as well. 14% with CD4 positive patients had TMA compared to only 3% with C4D negative biopsies. Treatment changes - Plasmapheresis might help in this case as you will remove the donor specific antibodies and also help the process of TMA treatment.

Regardless in any case of TMA, treat the underlying cause if found! CNI induced TMA doesn't NEED to be treated with plasmapheresis

References:
http://www.ncbi.nlm.nih.gov/pubmed/20659088