Nephsap review: AKI and ICU Nephrology

At Nephsap review of AKI, we came across a question regarding ischemic renal insult and its effect on the rest of the body organs.  AKI induces inflammation and functional changes in many organs and its worth noting the changes that happen in other organs due to AKI.

1. Brain: increased vascular permeability  and disruption of blood brain barrier
2. Lungs: increased vascular permeability and pulmonary edema, increased leukocyte trafficking and altered response to ventilator associated injury
3. Heart:- increased TNF- Alpha and increased apoptosis of heart muscle
4. Bone Marrow:- increased anemia, immune dysfunction and coagulation disorders
5. GI tract:- increased channel inducing factor, and increased k excretion
6. Liver:- increased oxidation products and decreased anti oxidants

Nephrocentric we are!

Minimal Change Disease

Minimal Change Disease

View more presentations from Nephrology, NSLIJ.

IN THE NEWS- CALMAG TRIAL

Calcium acetate/magnesium carbonate (CaMg) is a combination phosphate binder. 

Both can be used separately as binders.

What about using a combined Ca acetate with mg Carbonate binder?

Why ?

1. Less risk of hypercalcemia

2. Increased mg levels have been associated with benefits with vascular calcification and so forth.

A recent paper- nice prospective trial compared using a combination Ca and Mg product vs sevalemer HCL.

The study aim was to show non-inferiority of CaMg in lowering serum phosphorus levels into Kidney Disease Outcome Quality Initiative (K/DOQI) target level range after 24 weeks. Three hundred and twenty-six patients from five European countries were included. After a phosphate binder washout period, 255 patients were randomized in a 1:1 fashion. 204 patients finished the study. 

What did they find?

1. Serum phosphorus levels had decreased significantly with both drugs 25 weeks with equal effects in both arms.

2. Ionized serum calcium did not differ between groups.

3. An asymptomatic increase in serum magnesium occurred in CaMg-treated patients

4. There was no difference in the number of patients with adverse events.

HMM?

1. No cardiovascular risk benefit analysis, not followed long term

2. It seems ca didn't differ, so then why use CaMg combination?

3. Serum magnesium levels are largely dependent on dialysis fluid concentration as the only possibility to eliminate magnesium is via dialysis once residual renal function has disappeared Does that mean we have to monitor for hypermagnesemia more often in this case, the risk is there. 

4. What about the effects of Mg on bone disease? I think there is data that it might be beneficial in lowering pth?But worth a read as it might be important to see long term effects.

Reference: 

http://www.ncbi.nlm.nih.gov/pubmed/20530499

TOPIC DISCUSSION: Management of DKA in hemodialysis Patient

Diabetic patients tend to suffer from ketoacidosis less frequently after starting chronic dialysis than prior to it.The prolonged half life of insulin in advanced renal failure and frequent follow up of patients on chronic dilayis have been identified as reasons for the decreased frequency of ketoacidois in the dialysis population. The usual course leading to ketoacidosis is omission of one or more insulin doses, often due to an intercurrent illness. This is of prime importance as an underlying cause should always be looked for at presentation. The common ones being access related infections and myocardial ischemia.

The absence of osmotic diuresis distinguishes dialysis associated hyperglycemia from hyperglycemia observed in patients with normal renal function.The rise in plasma osmolality that is seen in diabetic ketoacidosis and non ketotic hyperosmolar coma is only in part due to the rise in serum glucose. The marked hyperosmolality is primarily due to the glucose osmotic diuresis that causes water loss in excess of sodium and potassium. The importance of effective plasma osmolality in the development of neurological symptoms are illustrated by observations in diabetic patients with end stage renal disease. These patients can develop severe hyperglycemia, with serum glucose concentrations that exceed 1000 to 1500 mg/dl . However because there is little or no osmotic diuresis, the rise in plasma osmolality is limited , hyponatremia is present, and there are few or no neurological symptoms.

Mainly because of the absence of the osmotic diuresis a dialysis patient in DKA may be less likley to be volume depleted and in most cases the extracellular volume is expanded from its baseline, and only if it is deemed clinically necessary should small aliquots of fluid be administered with continuous evaluation

Total body concentrations of potassium is unchanged, and they frequently have a high serum potassium level. Hyperglycemia has muliple effects on serum potassium: lack of insulin causes translocation of intracellular potassium to the extracellular compartment, a second hyperkalemic effect of hyperglycemia is the consequence of associated hypertonicity, which also leads to egress of potassium from the cells to the extracellular compartment

Insulin infusion is the only treatment required in majority of the patients. Emergency hemodialyis may be considered in severe pulmonary edema, profound metabolic acidosis and severe hyperkalemia with EKG mainfestations

http://www.ncbi.nlm.nih.gov/pubmed/18945331

 by

RIMDA WANCHOO, MD

Nephrology Fellows do better with online training!

The creator of Nephrology on Demand Dr Tejas Desai has performed a nice study that showed that nephrology fellows who used an online educational module did better in terms of test scores and so forth.  Nephrology fellows from Emory University, from the Classes of 2008-2010, were the primary subjects asked to use this instrument. We tracked their use of every teaching resource for 20 months. In addition we tested their knowledge of nephrolithiasis before and after using our interactive teaching module.  Eight of 10 renal fellows showed increases in postmodule test scores. Check out the full study in The recent issue of Journal of Nephrology.


Reference:
http://www.ncbi.nlm.nih.gov/pubmed/20954135

IN THE NEWS- Barbershop BP management is better than MD Office

A fascinating study in Archives of Internal Medicine shows that barbershop based HTN outreach programs controlled HTN better in black men then MD office visits. The investigators evaluated continuous HTN monitoring and referral program conducted by barbers in motivating patients with HTN to pursue physician care.  It was called the BARBER-1 Trial.  So the two groups were either receiving just a pamphlet for HTN control by the barber or a BP check and suggested physician follow up. The follow up was for 10 months and goal was HTN Control rate.  The intervention arm(2nd arm) did much better and absolute difference of 2.5mm HG in the SBP.


People are very loyal to their barbers and they like to see the same barber for many years. This long lasting relationship can lead to good benefits for their health and in this study, it did show that. The blood pressure was lower in the first arm as well but the second arm did even better.
So just having a lot of the health conversations in a non MD office setting might be a better target as well. 

Further studies on programs like these should be performed. This is fascinating!! 
Also check out a nice review by nephronline
http://nephronline.com/news.asp?N_ID=4187&ref=nf


Reference:
http://www.ncbi.nlm.nih.gov/pubmed/20975012

Outcomes of kidney transplantation from HCV positive donors

Given the global organ shortage for transplantation, use of expanded criteria donors and donors with potentially transmissible diseases has been established as a way to mitigate this problem somewhat. While there is universal consensus on rejecting kidneys from HCV antibody positive donors for transplantation in HCV antibody negative recipients, there is controversy regarding the use of these kidneys for HCV antibody positive recipients. Well, we have the first study that reported the long-term experience in this area (Morales et al, Am J Transplant. Nov 2010). This study was done in Spain. Outcomes of 162 HCV antibody positive recipients (97% of them are HCV RNA positive as well) that received a kidney from HCV antibody positive donors were compared with outcomes of 306 HCV antibody positive recipients that recieved kidney from HCV antibody negative donors. Mean follow-up was 74.5 months. There was no difference in patient survial and decompensated liver disease between the two groups. 5-year and 10-year graft survival was 58.9% and 34.4% versus 65.5% and 47.6% respectively (p = 0.006) while death-censored graft survival was 69% and 47% versus 72.7% and 58.5% (p = 0.055). Cox-regression analysis could not identify the donor's HCV serology as a significant risk factor for death, graft failure and severe liver disease in HCV antibody positive recipients. These findings prove that use of this strategy is safe and helps the problem of severe organ shortage that we are facing now.

IN THE NEWS- Permeability Factor and FSGS

Permeability factor in FSGS has been in debate all along. A recent CJASN review summarizes the role of permeability factors in many nephrotic syndromes. 
New things I learned:
1. Minimal Change disease :- there is some research that a there is a vascular permeability factor called VPF.
Injecting rats with this factor, increased urinary protease and hemopexin in active nephrotic syndrome rats.
2. FSGS disease:- increased glomerular permeability factor has been described in case reports and experimental animal models.  There is also another glomerular permeability factor called CLC-1 that decreases nephrin and apparently this factor is blocked by anti CLC-1.
A nice strategy is proposed by the authors on attacking different aspects of the podocyte.
1. Decreasing the circulating levels of this factor or factors:- could use cytotoxic agents, antibody blocking agents.
2. Protect the podocytes by immunosuppresive agents:- steoids, CNIS, Anti CD20 etc.
3. Protect the endothelium:- perhaps VEGF inhibitors
4. Protect the kidney from fibrosis:- ACEI, ARBS, Anti TGF , fibrates and lipid lowering agents.
References:

http://www.ncbi.nlm.nih.gov/pubmed/20966123

http://www.ncbi.nlm.nih.gov/pubmed/19700061

Salivary Prograf levels

Check out this interesting post from Pediatric Nephrology on salivary tacrolimus  levels

https://www.pediatric-nephrology.com/daily-updates/2010/10/26/329-salivatac.html

U 002 Nierentransplantation / kidney transplant

A nice you tube video ( cartoon) of a transplant surgery

TOPIC DISCUSSION: Green Urine

A nice letter to the editor in AJKD talks about a rare cause of Green urine.
What is nice is a summary of causes they show that could cause Green urine.
This specific case was a benzo which displaced flupirtine that caused green urine

Other more common causes of green urine are:
Amitriptyline,Cimetidine,Indomethacin,Methylene blue
Metoclopramide,Propofol,Ingestion of Asparagus officinalis (a spring vegetable)
Meconium aspiration syndrome in newborns,Urinary tract infection with Pseudomonas species
and Vitamin B tablets.

Check out the article at AJKD
http://www.ajkd.org/article/S0272-6386(10)01261-8/fulltext

FGF-23 and PTH and Bone Disease post transplant

Patients with ESRD have bone disease of various types. The three that are commonly seen are adynamic bone disease, increased bone turnover related or a combination of both.
BMD loss is common complication following kidney transplantation.
Few points to take home from a recent paper published in CJASN 2010, October edition.

1. The bone loss is accelerated in the post transplant period- why? Steroids and perhaps CNI worsen the rate.
2. Other risk factors are pre existing renal disease, hypogonadism, and metabolic acidosis.
3. 90% of post transplant patients have hypophosphatemia( CNI related and or tertiary hyperparathyroidism)
4. Renal phosphate wasting has bad effects  on bone
5. The renal phosphate wasting in part might be caused by elevated FGF23 levels or phosphatonin hormone.
6. PTH levels don't return completely to normal in most transplant patients post transplant
7. FGF 23 levels usually return to normal after one year post transplant
8. A recent study found that a high FGF23 level and low pth at time of transplant are the highest risk of developing bone disease post transplant
9. The most common bone biopsy finding post transplant is adynamic bone disease.

Image source: clipartheaven.com
References:
http://www.ncbi.nlm.nih.gov/pubmed/20634326
http://www.ncbi.nlm.nih.gov/pubmed/17359508
http://www.ncbi.nlm.nih.gov/pubmed/16941023

IN THE NEWS- Bilirubin might be protective

A recent article in Kidney International shows that in rats who had hereditary hyperbilirubnemia had lower incidence of diabetic nephropathy.
This might be news to some but mild indirect hyperbilirubenemia has been associated with decreased cardio vascular disease, decreased kidney disease and cancer risk as well.
Why is that? It is because bilirubin is an antioxidant. 30% of the world's population has an entity we call Gibert's Syndrome( mild indirect hyperbilirubenemia, its a defect in an enzyme that helps conjugate bilirubin, UGT1A1). Hence, those people should be protected. Few studies have shown this with diabetes.

I think its about time we started studying the benefits of having Gilbert's syndrome in terms of protection against kidney disease. perhaps it was a genetic selection! or the next wave!

Take a look at these interesting references

http://www.ncbi.nlm.nih.gov/pubmed/17895455
http://www.ncbi.nlm.nih.gov/pubmed/20686447
http://www.fedprac.com/asp/archive/article.asp?ArticleID=2209&DeptID=

Aspergilloma in the transplant kidney

A recent issue of AJKD talks about a case of aspergilloma in the transplanted kidney. The fact that it affected the kidney is the novelty of the case and the also they used a novel way of treating this patient. Please see the link below.


http://www.ajkd.org/article/S0272-6386(10)01257-6/fulltext

Racial Disparities in CKD, a presentation

Check out this nice presentation from Dr.Calderon

Racial disparaties in Chronic Kidney Diseases

View more presentations from Nephrology, NSLIJ.

CONSULT ROUNDS: Page Kidney

What is a page kidney?
Page kidney is the external compression of a kidney. The condition is usually caused by a subcapsular haematoma, associated with high blood pressure and occasional renal injury, as described by Irwin Page in an animal model with cellophane papers wrapped round the kidney in 1939 and, subsequently, clinically in 1955. Its not from external abdominal compression like seen in abdominal compartment syndrome. Its rather a bleed within the confines of the kidney that can cause compression of renal vasculature and ultimately HTN and renal injury.
What do you do? Previously, the treatment of Page kidney has been exclusively surgical, but recently, laparoscopy- and radiology-assisted drainage has been used successfully. Management of hypertension is tough and sometimes requires nephrectomy as well.


Few good references:
http://www.nejm.org/doi/full/10.1056/NEJMicm020037
http://www.ncbi.nlm.nih.gov/pubmed/20694451
http://www.ncbi.nlm.nih.gov/pubmed/20535256

Renal Fellow Network: Pancreas transplant pearls

Renal Fellow Network: Pancreas transplant pearls: "Pancreas transplantation is considered the treatment of choice for patients with refractory Type I Diabetes Mellitus. The first pancreas tr..."

TOPIC DISCUSSION: Different ARBS

When we look at different angiotensin receptor blockers. All of them have different half lives and apparently different excretion means.
Which ARB is longest acting:- Telmisartan has the longest half life of 24 hours; followed by Irbesartan which is 15 hours, Olmesartan is 13 hours and then comes valsartan at 9 hours, eprosartan at 7hours, candesartan at 4hours, and losartan is the shortest acting at 2 hours.
Which ARB is cleared by the liver? All of them are. Valsartan, Irbesartan and Eprosartan are >80 cleared by liver. Olmesartan, losartan and candesartan have significant renal clearance( >30%) hence making it a tough choice in someone with CKD perhaps?
Which ARB gets affected by diet? Only valsartan can be modified due to diet, rest are not.
Which ARB is most bioavailable? Irbesartan is the most at 70%, rest of them are around 30-40%


All ARBS are protein bound.

TOPIC DISCUSSION: Urinary Diversions

When someone has a bladder surgery and complete removal of the bladder, there are three ways a new bladder can be created. Its important to know this information as nephrologist so that we understand what the anatomy is.

1. Neobladder(urethera diversion): a new bladder is created using the intestines and connected directly to the urethera and patient can urinate like they normally do. It sits in the body.
2. Ileal Conduit. a segment of the intestine is linked up to the ureters creating a diversion that directs urine through a stoma into a bag sitting outside the body.
3. Indiana Pouch : a pouch is made from parts of the intestine that hooks up to the ureters in the abdomen and connected to a stoma outside and a catheter needs to be inserted to drain the urine.

Wait list and desensitization?

Two landmark papers have discussed using potential agents for potential patients who are on wait list for a kidney but have a very high PRA or now one might use a cPRA. 

The first paper is from 2004 titled was using IVIG.  A rare treat to find a randomized double blind placebo controlled trial in transplant literature, this is one of them. 101 patients ESRD with PRA>50% randomized to getting placebo vs 2g/kg monthly for 4 months of IVIG. If transplanted, additional infusions were given monthly for 4 mo. Baseline PRA levels were similar in both groups. Sixteen IVIG patients (35%) and eight placebo patients (17%) were transplanted. Rejection episodes occurred in 9 of 17 IVIG and 1 of 10 placebo subjects. Both groups had equal 2 year graft survival.  

The second was  in 2009, the use of rituximab and IVIG  for desensitization during renal transplantation. A total of 20 highly sensitized patients with known DSA + this time were enrolled and received treatment with intravenous immune globulin and rituximab. The authors noted the rates of transplantation, panel-reactive antibody levels, cross-matching results at the time of transplantation, survival of patients and grafts, acute rejection episodes, The PRA decreased post treatment, significantly. Time to transplant also decreased to 5-6months.  Sixteen of the 20 patients (80%) received a transplant. At 12 months, the mean survival rates of patients and grafts were 100% and 94%, respectively. 

So the only data we have on what to use in highly sensitized DSA+ patients on the WAITING list is IVIG and rituximab perhaps? ( smaller study).

References:

http://www.ncbi.nlm.nih.gov/pubmed/15579530

http://www.ncbi.nlm.nih.gov/pubmed/18635429 

CLINICAL CASE 27, ANSWERS and SUMMARY

Which one of the following components has a gain of function mutation to lead to atypical HUS?

CFH (23%)
CFI (0%)
MCP (19%)
C3 (34%)
THRB (23%)

Most of you said C3 mutation is a gain of function mutation followed by THRB and CFH. Again, this is a fairly new field when it comes to describing atypical HUS. There is new and emerging data all the time.  When one sees a patient and you are suspecting atypical HUS, the protein levels, you should check are: Factor H, I, B and C3, antibody for Factor H as well.  Mutation screenings are usually for Complement Factor H(CFH), Complement Factor I(CFI), Membrane co factor protein (MCP), C3, Complement Factor B(CFB) and Thrombomodulin (THRB). This is usually the workup. The complement system can be culprit. In this syndrome, due to impaired regulation of the complement system, it damages the renal endothelium.  This can occur due to loss of function mutations or gain of function mutations.  If you get a loss of function of the "regulators" such as CFI, THRB, CFH, and MCP, you get a HUS.  If you get a gain of function of the "activators" such as C3 and CFB, you get aHUS as well. So the correct answer is C3. 

Here is a nice review:-

http://www.ncbi.nlm.nih.gov/pubmed/20865638

http://www.ncbi.nlm.nih.gov/pubmed/20736981

http://www.ncbi.nlm.nih.gov/pubmed/20526633

Sirolimus and Male Fertility

I just came across an interesting paper published couple of years ago. Zuber et al (Am J Transplantion,July 2008) carried out an observational study in male patients aged 20-40 years who received a kidney transplant during 1995-2005 in France. Patients on sirolimus based immunosuppression had a significantly reduced total sperm count and a decreased proportion of motile spermatozoa compared to patients who did not receive sirolimus. Also, it was found that the fathered pregnancy rate (pregnancies/1000 patient years) was 5.9 and 92.9 in patients receiving sirolimus-based and sirolimus-free regimens, respectively. Of those patients in whom sirolimus treatment was interrupted, only half of the patients showed a significant improvement in sperm parameters. The authors concluded that sirolimus is associated with impaired spermatogenesis and may reduce male fertility. So, if you have a male transplant patient on sirolimus presenting with fertility issues, switching sirolimus to another agent like tacrolimus may help.

IN THE NEWS:- Tiger on Dialysis

Check out this latest news from India.
Dialysis saves the tiger's life
http://sify.com/news/tiger-undergoes-dialysis-in-bhopal-for-the-first-time-news-national-kkoukmbjehe.html

IN THE NEWS:- Cardiorenal syndrome or renocardiac syndromes?

We do see a lot of times dysfunction of one organ affecting the function of the other.
Hepato renal was a perfect example of this type of entity
The triad of decreased kidney function, therapy resistant heart failure and diuretic resistance has been termed now cardiorenal syndrome.
According to the experts, there are several types:
1. Acute cardiorenal syndrome ( CRS type 1):- acute cardiac failure leading to kidney injury
2. Chronic cardiorenal syndrome ( CRS type 2):- long term ckd from long term cardiac failure
3. Acute renocardiac syndrome ( CRS type 3):- acute worsening of cardiac function due to kidney disease( perhaps Nephrotic syndrome would fit this best)
4. Chronic renocardiac syndrome ( CRS type 4):- long term cardiac changes due to long term CKD( wouldn't this be most of our CKD patients)
5. Secondary cardiorenal syndrome(CRS type 5):- systemic diseases that cause both kidney and heart to fail( amyloid comes to mind)

Check out a nice review in AJKD and the last references is a nice one that summarizes the five types of cardio renal syndromes

http://www.ncbi.nlm.nih.gov/pubmed/20557988
http://www.ncbi.nlm.nih.gov/pubmed/19554920
http://www.ncbi.nlm.nih.gov/pubmed/20427956

NEJM Case

Check out this week's NEJM educational case!
Its all about Nephrology!
http://www.nejm.org/doi/full/10.1056/NEJMimc1004455#figure=preview.jpg

CONSULT ROUNDS: renal disease

An interesting discussion took place yesterday.

We were comparing renal and other diseases.  When we have someone with cardiac disease, or stroke, the goal is usually to Increase perfusion and increase blood flow the other organ at stake.

Its interesting as in kidney disease, particularly glomerular or proteinuric kidney diseases, what we do is to decreases the flow to the kidney or decrease perfusion so that the Kidney has to do LESS work and hence less loss of protein. Interesting way to look at it.
This is one of the reasons why in some cases of Unilateral renal artery stenosis and Diabetic Nephropathy, the kidney with the side of stenosis is spared of diabetic changes! 
But then again, if you have ischemic nephropathy, the problem is low blood flow and you need to fix that.

The kidneys always want to be exclusive and different from rest of the body!

TOPIC DISCUSSION: Chronic Hyponatremia

A recent case based review in AJKD talks about correction of profound hyponatremia.
What is always more concerning is correction of chronic hyponatremia?
The article mentions a nice rule of sixes:
check it out

If the case is of chronic hyponatremia:- six meq/l per 24 hours and if severely having symptoms then use six meq/l in 6 hours.

Rule of sixes!

Reference:
http://www.ncbi.nlm.nih.gov/pubmed/20709440

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

New Transplant Information website

Check out this excellent website on information on transplantation
http://www.kidneylink.org/
It has medical news, patient stories, webinars and useful links to all transplant readership

CONSULT ROUNDS: Free water excretion

Someone has a urine Osm of 90? Can you calculate the free water loss?

Yes!

Total Volume of Urine = Clearance of Solute + Clearance of Water

So your Free water Clearance of Water = Total Volume of urine - Clearance of solute

So Free water Clearance = Total volume - ( uosm/sosm * total volume)

Something simple but often forgotten!

TOPIC DISCUSSION: SECONDARY VS PRIMARY FSGS

FSGS can be broadly divided into genetic causes, primary or secondary causes. Leaving genetic aside, how does one differentiate between primary FSGS vs Secondary FSGS ( say from hyperfilatration, Obesity or Anabolic steroids use)?

Clinically and pathologically?
Some clues
1. Obviously, a good history might help you guide this differentiation.
2. Usually, its a slower increase in proteinuria in secondary cause usually Obesity or hyperfiltration related
3. The proteinuria amount is much much lower in a secondary cause. Someone with 30gm of proteinuria, think more primary
4. The progression to ESRD is also slower in the secondary cause unless probably a drug that is toxic like pamidronate induced collapsing FSGS
5. The pathology usually shows more glomerulomegaly in secondary causes.
6. The pathology usually shows more spotty and irregular foot process effacement in secondary cause and more diffuse in primary cause.
7. Absence of hypoalbumenemia might suggest a secondary cause as well
8. Normal blood pressure and no edema on exam might also suggest a secondary cause( classically seen in HIVAN)
9. Foot process width over 1500nm usually more points towards idiopathic form of FSGS.

Some interesting references:
http://www.ncbi.nlm.nih.gov/pubmed/17059996
http://www.ncbi.nlm.nih.gov/pubmed/18813290
http://www.ncbi.nlm.nih.gov/pubmed/11260414

TOPIC DISCUSSION: Maintenance of Metabolic Alkalosis

When there is vomiting: we get metabolic alkalosis due to H loss, we all know that!
What maintains that alkalosis and what causes the hypokalemia that we see with it? Often it's confused that there is K loss via GI track. Its not true

1. Hypovolemia continues to cause more Bicarbonate absorption
2. You have just activated the RENIN, angiotensin system leading to more met alkalosis
3. Activation of the system, leads to K loss in the urine.
4. Loss of Cl in the GI track allows for more Hco3 absorption

All these above methods lead to Maintenance of the Met Alkalosis in vomiting.

REJECTION and TOLERANCE

This week is a transplant week in the journals.

The NEJM has a nice review on Rejection of the Kidney Allograft. Have a look. its very well written and combines the latest information on all concepts of rejection(with excellent visual portrayals)
Antibody Mediated and Cellular Mediated are discussed. It even goes into details of T cell activation and co stimulation and is a simple read for all.
It ends with a nice summary on even Late Acute rejection and Chronic Rejection

Another treat this week is the Nephrology Nature Review Journal- features an entire issue on Transplantation Tolerance, the holy grail of Transplantation. It reviews nice articles on Tolerance review, T Regs, Tregs and B cell interactions, Mixed chimerism and Biomarkers and proteonomics in transplant tolerance.

The references are below:
http://www.nejm.org/doi/full/10.1056/NEJMra0902927
http://www.ncbi.nlm.nih.gov/pubmed/20717099

KIDNEY WEBSITES IN my languages!

https://www.pediatric-nephrology.com/daily-updates/2010/10/08/312-kidneyhindi.html

This is fascinating!

Renal Fellow Network: Key to angiotensin formation solved? Preeclampsia ...

Check out this nice post from the RFN on new concept in Pre eclampsia!

Renal Fellow Network: Key to angiotensin formation solved? Preeclampsia ...: "Researchers from the UK published a new and exciting article exploring one of the fundamental mechanisms of blood pressure regulation by the..."

JOURNAL CLUB: AASK TRIAL 2010

A recent journal club presentation by Dr.Kellie Calderon

AASK  about Hypertension- JOURNAL CLUB

View more presentations from Nephrology, NSLIJ.

TOPIC DISCUSSION: An uncommon consult:-OHSS!

Here is a case: someone with elevated serum creatinine, hyponatermia, marked edema and hypoalbuminemia --> 6 weeks into pregancy induce by in vitro fertilization.

We will pause here to recognize British researcher Robert Edwards who was just awarded the 2010 Nobel Prize in Medicine...

Ovarian Hyperstimulation Syndrome(OHSS) typically presents as volume overload and elevated serum creatinine early in the course of IVF. Hormonal therapy (appropriately) stimulates the ovaries, but occasionaly "hyper"-stimulated ovaries enlarge, become cycstic and large fluid shifts can occur in a capillary-leak like syndrome. It is believed that Vascular Endothelial Growth Factor plays a role by increasing sensitivity to nitric oxide and promoting neoangiogenesis.

Cases range from mild to life-threatening and are graded in severity from 1-3. Mild cases are treated with observation and discontinuation of hormonal therapy, whereas severe cases can have marked electrolyte disorders (hyponatremia, hyperkalemia), severe ascites, pericarial/pleural effusions and thromboembolic phenomenon from hemoconcentration.

IN THE NEWS- Nephrology Workfore

The latest issues of ASN Kidney News talks about a very important issue being the nephrology workforce.
Given the rise in population and the aging nephrologists, along with decline in medical residents applying for nephrology, there is going to be a big shortage of Nephrologists in the coming few years!

What can be done to help decrease this burden that we might all be faced with?
The article mentions some good ideas and wanted to add a few more:-
Lobbying for more support for our fellowship programs
Perhaps having more fellowships
Getting medical students interested and residents interested in nephrology early on
Innovative tools of passing down nephrology knowledge will attract more applicants
Removing the "fear" of renal medicine that many residents and medical students carry.
ASN and NKF doing more medical and resident oriented talks

What we need to do as a community is to "package" and "sell" Nephrology as a FUN, CHALLENGING and EXCITING field to our students and residents. It is !!! and we just have to do a better job with promoting our field!

http://www.asn-online.org/publications/kidneynews/archives/2010/oct/KN_oct2010.pdf

Basic concepts in Immunology

Concept 1
Think of Innate immune system as "non antigen presenting mediated". it can get activated without antigen presentation. Cells that are major players: NK cell and Macrophage
Adaptive immune system is " antigen presentation mediated". Needs that extra help.
Cells that play role here:- B cells, T cells, DC

Concept 2
Think of the immune system as : Effector system and Regulatory system
Effector systems play a role in causing inflammation and damage and " doing their job" best!!! CD4+T, CD8+T cells, NK cells, B effector cells are all major players
Regulators are the "policemen". They are the Tregs and Bregs. They are out there trying to shut out fires and inflammation and try to "tone down" the reaction.  Having more police around makes for a more robust and more "Controlled" immune system

Concept 3
The adaptive immune response has two arms
Afferent arm:-Antigen presentation
Efferent arm:- T cell activation

Concept 4
Two types of destruction:- cell mediated via Cd4 and Cd8 cells- granzyme and perforin and killing the cell
or antibody mediated via B cell-- leading to complement activation killing

Role Playing exercise in Transplant Education

We did another session of role playing with the fellows and transplant medicine
Each fellow was assigned a "cell" that is an active playing in Immunology. Then they were asked to describe themselves in Homeostasis and then a state of Immunosuppression. A nice discussion and arguments ensued and a live display of the immune reaction was done.  The teaching of basic immunology for transplantation was mediated via this teaching method.
The cells the fellows' role played were: NK cell, macrophage, CD4+ T cell, CD8+T cell, DC, B effector cell, T Reg cell, B reg Cell.

TOPIC DISCUSSION

A recent quiz page in Kidney International Oct 2010 issue talks about a very interesting case of someone with hypophosphatemia and hyperphosphaturia, with normal calcium and Vitamin D levels.
A nice table shows the breakdown of someone with hypophosphetemia and loss of Phos via urine

If there is hypercalcemia along with it:- think of primary parathyroidism and post transplant parathyroid disease or pthrp production or hypocalciuric hypercalcemia.

If there is normocalcemia along with it:- only acquired disease is oncogenic osteomalacia. genetic causes are FGF23 mutation or PHEX mutation.  Usually all of them are associated with elevated FGF23 levels.
If the FGF23 are low think HHRH

If there is hypocalcemia think Barter's, Fanconi syndrome or other RTAs.

It is interesting that people are now measuring FGF23 levels to help dilenate different disorders of calcium and phosphate.  Take a look at this case in KI.

http://www.ncbi.nlm.nih.gov/pubmed/20877382

CLINICAL CASE 26 , ANSWER and SUMMARY

Which Statement regarding " Milk Alkali Syndrome" is False? The "true" Milk Alkali syndrome incidence declined in the 1980s due to the advent of H2 blockers	0 (0%)
Currently, the cases of this entity are more accurately termed Calcium Alkali syndrome	1 (5%)
It is NOT a common cause of hospital admissions for hypercalcemia	5 (29%)
It classically presents with hypercalcemia, hypophosphatemia, metabolic alkalosis and acute renal injury	4 (23%)
Levels of 1,25 hydroxy vitamin D are usually low in majority of these cases, but not all.	2 (11%)
It affects post menopausal women and pregnant women the most	5 (29%)

Lets take it one by one.  In the early 1900s, due to excessive milk intake and Sippy method - there were many cases of Milk Alkali syndrome. It did decline in 1980s due to the advent of H2 Blockers and also the decrease intake of Milk in general.  There are now cases started in 1990s in large part seen in post menopausal women due to increase intake of Calcium and Vitamin D medications and the new term for this entity might be " Calcium Alkali syndrome".  It is the 3rd most common cause of hospital admissions for hypercalcemia in the US, following hyperparathyrodisim and malignancy induced hypercalcemia.
It classically presents with Increased ca, low phos and met alk and acute kidney injury.  "Tums" might be most common culprit.  The earlier cases of "Milk-Alkali" syndrome usually presented with hypercalcemia and hyperphosphatemia due to MILK ingestion.  Levels of 1,25 Vitamin D in patients with this syndrome are usually low due to suppression but there can be few cases of normal to inappropriately high as well( due to possible prior exposure to Vitamin D supplements).

In summary, its a disorder that we have to keep in our differential if the incidence is too high. The correct answer hence is 3 as it is a common cause of hospital admissions, perhaps not diagnosed right away!

take a look at a recent JASN reference
http://www.ncbi.nlm.nih.gov/pubmed/20413609