Thursday, March 31, 2011

Nephronpower Views

Thanks to Blogger newer techniques
Check out our new views at
http://www.nephronpower.com/view/snapshot
http://www.nephronpower.com/view/flipcard
http://www.nephronpower.com/view/mosaic

and many others
My personal favorite: Snapshot!

HyperKalemia Challenge

35yo Indian male with no PMHx presents to PMD for routine physical and labs. He is found to have a K of 6.8meq/l and sent to hospital for admission and w/u. These results are repeated and verified. The patient has no symptoms or any significant PMHx. He denies use of NSAIDs or any other OTC meds or herbs with the exception a pinch of tamaric powder once or twice daily for a couple of weeks due to inadvertent biting of his tongue. He denies high risk behaviour (HIV risk factors).

Exam is unremarkable as are vitals. Serial labs show HCO3 ranging from 20 - 27 (mostly in low to mid 20s). UA is unremarkable with pH running 5.5. Initial UNa 200meq/l and Uk 30 initially, repeated (for TTKG) shows Una 117 and Uk 12 with TTKG <2. His Cr runs from 0.9 to 1.2. His PRA is 0.12 and Aldo <1 at the time of presentation. Serum cortisol is normal. His medicine team orders MRI abd for some reason and adrenals are remarked as "small".

The nephrologist on the case believes he has Type IV RTA, but etiology is unclear to him. He is treated medically and his K ultimately improves and he is discharged home on fludrocortisone.

He is then seen in the office. It was decided to attempt to see if his renin/aldo levels are inducible through volume depletion and also look for aldo synthase deficiency. His fludrocortisone is stopped for 5 days and he is started on Lasix 20mg BID and subsequent labs only on the lasix for 5 days:

Deoxycorticosterone slightly high and 18-Hydroxycorticosterone high, but 11-deoxycortisol, corticosterone, cortisol all WNL and PRA 1.4 and aldo 27! His BP is not typically more than 130s systolic, however the consideration of Gordon's Syndrome (pseudohypoaldo type 2) is given, and the decision try HCTZ and look for response of K and TTKG.

Differential?

TOPIC DISCUSSION: Residual renal function???

We often associate this term:- residual renal function(RRF) with Peritoneal dialysis and how important that is for fluid management. Why is this not that emphasized in Hemodialysis??? 
Does residual renal function matter in any dialysis modality? The short answer is yes!!

A recent paper in NDT looked at mortality in 1800 haemodialysis (HD) and peritoneal dialysis (PD) patients in 1996-2006.  The investigators estimated a hazard ratio (HR) corresponding to the effect of the full loss of GFR on mortality, as compared to not having fully lost GFR, of 1.50 [95% confidence interval (CI) 1.09-2.07]. The HR corresponding to the effect of GFR when GFR is not (yet) fully lost on mortality was 0.97 (95% CI 0.92-1.02) (per mL/min/1.73m(2)). They found no significant difference in the effect of GFR on mortality between patients starting on PD and HD. They concluded that preventing or delaying the full loss of GFR can improve survival in dialysis patients. This supports the importance that is given to the effect of treatment options for patients with ESRD on the rate of decline of the residual renal function.
Another study found that patients without RRF were older, had lower baseline serum albumin levels and spent 18.6 more days in hospital per year than those with RRF. Mean survival time was significantly lower in patients without RRF (p = 0.027). In a Cox proportional hazards model, only RRF remained as a significant independent predictor. 
Another study in CJASN found a strong relation between RRF and improved phosphate and anemia control in HD patients. 
Given these recent studies, it appears that RRF is very important in HD patients as well. Perhaps holding ACE-inhibitors and/or angiotensin-receptor blockers, limiting the use of nephrotoxic drugs, avoiding dialysis associated hypotension, avoiding contrast media procedures, adequate control of blood pressure might help preserve that RRF. All three studies are listed below!


Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21242677
http://www.ncbi.nlm.nih.gov/pubmed/21317411
http://www.ncbi.nlm.nih.gov/pubmed/21030579

AST Fellows Symposium on Transplantation Medicine

AST Fellows Symposium on Transplantation Medicine

Wednesday, March 30, 2011

CONSULT ROUNDS: Ranolazine and the Kidney?


The cardiology world has become used to a new kid on the block in the last 5-6 years called Ranolazine or Ranexa. Ranolazine is indicated for the treatment of chronic angina. It has been shown to decrease angina episodes in individuals with coronary artery disease and it has been shown to both decrease angina episodes and increase exercise tolerance in individuals taking concomitant other anti anginal medications. It doesn't affect the blood pressure or heart rate that much. Ranolazine is believed to have its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium level that ranolazine affects the sodium-dependent calcium channels during myocardial ischemia. Thus, ranolazine indirectly prevents the calcium overload that causes cardiac ischemia.  

Why does this agent matter to us?1. It causes an increase in creatinine? Is it real renal injury or a false elevation? Ranexa produces elevations of serum creatinine by 0.1 mg/dL, regardless of previous renal function. The elevation has a rapid onset, shows no signs of progression during long-term therapy, is reversible after discontinuation of Ranexa, and is not accompanied by changes in BUN. In healthy volunteers, Ranexa 1000 mg twice daily had no effect upon the glomerular filtration rate. The elevated creatinine levels are likely due to a blockage of creatinine's tubular secretion by ranolazine or one of its metabolites. 
2. Ranolazine is primarily metabolized by CYP3A and has strong interactions with our transplant drugs calcineurin inhibitors like cyclosporine and tacrolimus. The drug increases the levels of tacrolimus and cyclosporine and could cause renal damage indirectly. Sounds like this is a good agent to use in angina but with caution and possibly in reduction of the CNI doses.
Check out below references:

Tuesday, March 29, 2011

CONSULT ROUNDS: A primer on CVVHDF orders


How does one calculate the prescribed dose on CVVHDF?
Here is an order set:
BFR 150cc/min
DFR  1500cc/hr
Pre pump flow 700cc/hr
Post pump flow 400cc/hr
Ultrafiltration goal 100cc/hr

Our formula for estimated GFR is uv/p ( v=volume, u= urine crt and p= plasma crt). In this case, would be dialysate crt and plasma crt.  We have to make one assumption:- since the rate is so slow, the equilibration of dialysate crt and plasma crt would cancel out and your GFR = Volume.

So then, your diffusive clearance would be your DFR, which in this case would be 1500/60 or 25cc/min
your convective clearance would be your pre +post + UF you ordered= 1200/60 or 20cc/min
Hence, you are getting this person 45cc/min of prescribed GFR. Doesn't mean that is the DELIVERED dose.
One more aspect that might be missing is the residual urine output which might be good and might only add to the GFR.

Just an interesting exercise that we should do all time we do CVVHDF orders.
Also, this helps pharmacy guide your medication prescriptions

Monday, March 28, 2011

CLINICAL CASE 33, ANSWERS and SUMMARY

Which one of the following is NOT related to an elevated PTHrp level and leading to hypercalcemia? What you all answered:

SLE 29% 
Malignancy 6%
HIV associated Lympadenopathy 8%
Massive mammary hyperplasia during pregnancy 6%
Manganese toxicity 23%
During late pregnancy and lactation in hypoparathyrodism 25%

Close race between SLE, Manganese and Late pregnancy. Correct answer is Manganese toxicity. Rest of all are associated with pthrp production.

All above causes mentioned are rare causes of hypercalcemia to begin with.
Lets get to one by one.
We all know that malignancy such as ovary, lung and kidney can be associated with pthrp associated hypercalcemia.  SLE, HIV associated lymphadenopathy has also been associated with pthrp associated hypercalcemia.  Apparently, massive mammary hyperplasia during pregnancy, late pregnancy via placenta production of pthrp and lactation in hypoparathyroidism all have been associated with pthrp associated mechanism of hypercalcemia. The hypercalcemia associated with manganese toxicity is due to an unknown mechanism that we don't know( not pthrp).
Below are few causes that I saw in a very interesting article on rare causes of hypercalcemia.  Take a look.
Ref is below. 

**Rare causes of hypercalcemia associated with elevated 1,25-dihydroxyvitamin D
1. Wegener’s granulomatosis 
2. Cat scratch fever 
3. Crohn’s disease 
4. Acute granulomatous pneumonia 
5. Hepatic granulomatosis in chronic dialysis 
6. Talc granulomatosis 
7. Silicone granulomatosis 
8. BCG therapy 
9. 8-Cl-cAMP therapy 
10. Lipoid pneumonia 
11. Subcutaneous fat necrosis of the newborn 

**Rare presentations of the milk-alkali( calcium alkali) syndrome
1. Oyster shell calcium in betel nut chewing 
2. Overdose with buffered aspirin 
3. Massive cheese ingestion ( tofu perhaps as well)?
4. Munchausen’s syndrome 

**Unusual PTHrP-mediated hypercalcemic conditions
1. SLE 
2. HIV-associated lymphadenopathy 
3. Lymphedema of chest and pleural cavities 
4. Massive mammary hyperplasia during pregnancy 
5. During late pregnancy and lactation in hypoparathyroidism
6. With benign tumors of ovary and kidney, and in benign pheochromocytoma

** Medications that have been unusually associated with hypercalcemia
1. Omeprazole in acute interstitial nephritis 
2. Theophylline toxicity 
3. GH in intensive care unit patients 
4. Parenteral nutrition 
5. Foscarnet 
6. Hepatitis B vaccination 
7. 8-Cl-cAMP chemotherapy 
8. Manganese toxicity 

**Rare causes of hypercalcemia in which the mechanism is not known
1. Eosinophilic granuloma 
2. Leprosy in rheumatoid arthritis 
3. Mycobacterium avium complicating AIDS 
4. Cytomegalic virus infection in AIDS
5. Chronic berylliosis 
6. Nocardia asteroides pericarditis 
7. Diffuse octeoclastosis 
8. Paraffin granulomatosis 
9. Brucellosis 
10. Isolated ACTH deficiency 
11. Glucocorticoid withdrawal 
12. Hypocaloric diet in hypoparathyroidism 
13. Advanced chronic liver disease 
14. Type I Gaucher’s disease with acute pneumonia 
15. Lymphedema in SLE 
16. Juvenile rheumatoid arthritis 
17. Lymphadenopathy with high IL-6 

**Causes of Pseudohypercalcemia
1. High serum albumin 
2. Thrombocythemia 
3. Calcium binding to M-proteins 

Ref: 

Who gets kidney first?- the thoughts in 2011

Organ allocation system always has been going down the list on a first come first basis. A discussion has been ongoing in the transplant circles and organizations on age based distribution of organs. Hence, someone who is young getting a "better" kidney then someone "older".  Is that reasonable or is that age based discrimination?

Take a look at the reactions of many below. There must be a better way!

http://onpoint.wbur.org/2011/03/01/allocating-kidney-organs

Then look at this opinion
http://www.azcentral.com/arizonarepublic/opinions/articles/2011/03/06/20110306newcomb-transplants-07.html

Sunday, March 27, 2011

IN THE NEWS- E Nephrology

The WWW has emerged as an important player in nephrology education of patients and physicians
This article in the Indian Journal of Nephrology echoes that statement.
Have a look


http://indianjnephrol.org/article.asp?issn=0971-4065;year=2011;volume=21;issue=1;spage=1;epage=9;aulast=Manchanda

Friday, March 25, 2011

Concept Map of Viruses and the diseases in the kidney( summary)

Here is a summary of the Powerpoint on Viruses and the Kidney using a concept map
Its busy concept map- you can zoom in for details.

Thursday, March 24, 2011

TOPIC DISCUSSION: What causes Foamy Urine?

Foamy urine
Besides albuminuria, proteinuria and infection, what else can cause foamy urine??? ever wondered?
Here is a list of causes other than above
1. Bilirubinemia
2. Pneumaturia
3. Retrograde ejaculation
4. Fast urination, or increased velocity
5. Vesicocolic fistula
6. New onset of prostatitis

Image source: http://www.urinecolors.com/foamy_urine.php

Monday, March 21, 2011

CONSULT ROUNDS: Preparing For a Pheochromocytoma Removal

Once a diagnosis of Pheochromocytoma or paraganglioma is made, removal of the tumor requires medical management that involves Nephrology involvement heavily.
There are basically two arms to the preparation. One is controlling the hypertension and second is making their blood pressure salt dependent and responding to fluids when they are post op. No trials have been ever conducted on any of these approaches but from years of experience of many physicians, this works.
What agents to use for controlling the BP? - Alpha blockade first, followed by beta blockaded. Never do the reverse as it will lead to unopposed alpha and more HTN. Usually this can be started 7-12 days prior to surgery and then towards the date of the surgery, recommended high salt diet to ensure good dependence and response to fluids as the longer you have alpha blocked them, the less they will respond to pressors once the tumor is removed.
The alpha blockers of choice are:- non specific alpha blocker and longer acting Phenoxybenzamine, or specific short actings like doxazosin or terazosin.  The Beta blockers used are propranolol or atenolol. Sometimes, metyrosine is used, which inhibits the catecholamine synthesis( the side effect profile- not great).
Some patients with persistent HTN, might need IV phentolamine as well pre op for 24-48 hours followed by IVF at high rates prior to surgery and very close monitoring of the HTN during surgery via anesthesia.
Two most commonly feared post op complications are:
Hypotension:- hence we try to make them fluid dependent.
Hypoglycemia:- Due to fall of catecholamine secretion and may need glucose infusion.

Kidney Transplant Recipient Infected With HIV From Live Donor - Procedure Needs Reviewing

Kidney Transplant Recipient Infected With HIV From Live Donor - Procedure Needs Reviewing

Friday, March 18, 2011

TOPIC DISCUSSION: Contraction Alkalosis or CDMA?

Contraction alkalosis has been associated with volume contraction and we throw that term out all the time.
This issue of Nephsap has an interesting editorial about the nomenclature of this entity and the pathophysiology behind it.  Most of the time, severe volume contraction, leads to lactic acidosis, and not metabolic alkalosis unless you have a selective chloride depletion.  Hence, the authors feel that this entity should be really called Chloride Depletion Metabolic Alkalsois (CDMA).
Studies summarized showed that such alkalosis corrected more when Na or any other cation was supplemental Cl rather than any other anion. CDMA was produced by gastric aspiration, chloruretic diuretics , NaNo3 infusions, and post hypercapnia and all got better with Cl- repletion and not Na or K replacements.
So CDMA is corrected by selective Cl repletion despite maintained or increasingly negative Na or K balance, continued Hc03 loading and high levels of Ang II.
It was not corrected by Na or K repletion without Cl-. It was hard to correct with Cl- alone in abnormal renal function. What happens is the distal nephron in the collecting duct ensures a bicarbonate diuresis in response to Cl repletion.

Take a look in more detail at Nephsap March 2011
Also other good ref:
http://www.ncbi.nlm.nih.gov/pubmed/4875677

Thursday, March 17, 2011

TOPIC DISCUSSION: Lactate levels and B2 agonists? any connection



Lactic acidosis has been reported in many cases in severe asthma due to production by over worked respiratory muscles. However, there is some thought that the b2 agonist agents might induce lactic acidosis or just elevated lactate levels. Even patients who are not asthmatics who get these agents have had similar reports. So far, lactic acidosis occurring in association with β-2 agonist treatments such as salbutamol, ritodrine,  meta-proterenol,  and albuterol have been reported, and its mechanism remains poorly understood. In one study, healthy volunteers without respiratory distress who were given intravenous infusions of either salbutamol or rimiterol had dose-related increases in lactic acid levels. In the absence of any clinical signs of circulatory shock or severe hypoxia , this would be considered a type B acidosis.  β-2 Receptor activation produces excess glycogenolysis and lipolysis. Increased glycogenolysis eventually leads to increased concentrations of pyruvate. Pyruvate is converted to acetyl CoA, which enters the citric acid cycle. If pyruvate does not enter this aerobic pathway, it is converted to lactate instead, thereby potentially causing lactic acidosis. 
An emergency medicine evaluation of this event was done prospectively. In total, 18 subjects who presented to an emergency department were enrolled in the study.  All patients were treated with albuterol; four puffs (100 microg/puff) at 10 minute intervals, delivered by a pressurised metered dose inhaler into a spacer device over a 2 hour period. At the end of treatment, mean plasma lactate level 2.94 mmol/l was significantly higher (p = 0.001) than baseline. Of the 18 patients, nine (50%) showed lactate levels > or = 2.5 mmol/l (four patients presented values > 4 mmol/l); however, there were no significant differences in the airway response between groups. Their conclusions: "This study confirmed previous observations that high lactate concentrations can develop during the first hours of inhaled beta agonist treatment. The presence of a previous hyperadrenergic state may predispose to the development of this condition. A significant improvement in lung function was associated with elevated lactate levels."


Interesting:
take a look:
Ref:
http://www.ncbi.nlm.nih.gov/pubmed/15911945
http://www.ncbi.nlm.nih.gov/pubmed/18410827
http://www.ncbi.nlm.nih.gov/pubmed/12883427
http://www.ncbi.nlm.nih.gov/pubmed/1299986

Wednesday, March 16, 2011

CONSULT ROUNDS: Cefepime Neuro-toxicity and the Nephrologist

Cefepime-induced neurotoxicity: an underestimated complication of antibiotherapy in patients with acute renal failure that we cannot forget. Often, we suggest to change the dose of this antibiotic but someone with fluctuating renal function, this agent can lead to neurological side effects that sometimes can mimic uremia.

The classical symptoms are myoclonus, confusion, aphasia and ultimately seizures.  EEG will be abnormal.
Stopping the agent or using dialysis as a saving modality might help. In one study in an ICU, Five patients had been treated with cefepime, admitted for seizures and coma. All suffered from acute renal failure, induced by sepsis and other causes. All patients underwent hemodialysis, which led to complete neurological improvement in four of them. 
Dialysis can help in this toxicity and should be used early if possible to avoid seizures and other long term neurological complications. Dosing adjustments are a must in someone with suboptimal renal function.

Take a look


More Pediatric Grand Rounds from www.pediatric-nephrology.com

Check out the latest pediatric grand rounds from Dr.Sethi's blog.

https://www.pediatric-nephrology.com/index.php?view=entry&year=2011&month=03&day=10&id=428:pgrxvi

For the entire series, check it out at this link
https://www.pediatric-nephrology.com/index.php?option=com_content&view=article&id=70&Itemid=69

Olmesartan for Patients with Diabetes

Olmesartan for Patients with Diabetes

Tuesday, March 15, 2011

Sunday, March 13, 2011

Saturday, March 12, 2011

Friday, March 11, 2011

TOPIC DISCUSSION: TB and the Kidney

What is the role of the kidney in Tuberculosis(TB).  A recent paper in KI March 2011 issue deals with this disease entity. The most common finding on the kidney biopsy with TB is Tubular interstitial disease.
A few take home points from the article that is the largest case series of TB associated renal disease.

1. It is still rare to have kidney involvement
2. Kidney involvement is usually late and with chronic TB more than acute TB
3. Most common finding is chronic granulamatous tubular interstitial disease
4. In this series, 9/25 patients became ESRD
5. Treatment includes anti TB regimen +/- steroids as well
6. 36 month follow up of remaining non ESRD patients was dismal as well and worsening CKD
7. Earlier diagnosis and preservation of renal function might be important

Virtual Library ( the Welch Library) Part 2

The Evolution of Library Services
Blair Anton, Hamid Robb, MD, FASN, and Stella Seal discuss the changing role of librarians and the services they provide to physicians and scientists.
Courtesy ASN Media Center

Thursday, March 10, 2011

IN THE NEWS: Belimumab and Lupus


Benlysta(belimumab) is an investigational human monoclonal antibody drug and the first in a new class of drugs called BLyS-specific inhibitors. These drugs prevent b-cell proliferation and development in to mature plasma cells with a resulting drop in antibody production. This mechanism of action is very well-suited to Lupus whose pathophysiology is widely thought to involve autoantibody formation. As of March 10, 2011, This agent is now approved for treatment of SLE.  This was mainly based on a 52-week study, also known as BLISS-52, enrolled 865 patients in 13 countries outside North America and randomized active lupus patients to 10mg/kg active drug (Belimumab, also known as Benlysta), 1 mg/kg active drug, or placebo (not containing active drug) in addition to their standard lupus medications.
Patients had to fulfill the American College of Rheumatology lupus criteria, have active lupus, and remain on a stable treatment regimen (excluding other biologic therapies or cyclophosphamide) in order to be eligible for the trial. Patients with severe lupus kidney disease and lupus-related neurologic problems were excluded. The study medication was given intravenously (through the veins) two weeks apart for the first two doses, and then every four weeks. The study met primary end point and the the response rates were 57.6%, 51.7% and 43.6% for Benlysta 10mg/kg, 1 mg/kg, and placebo, respectively (the response rates were significantly better in the active drug arms). In addition to improvement in various clinical measurements of disease activity, patients were also able to reduce steroid dosages. Notably, the drug was tolerated well and the safety profile, including the infection rate, was comparable to the placebo arm. Another trial was similar and also excluded patients kidney and CNS involvement. African American patients and patients of African heritage participating in the two studies did not appear to respond to treatment with Benlysta. The studies lacked sufficient numbers to establish a definite conclusion. The most common side effects in the studies included nausea, diarrhea, and fever (pyrexia). Patients also commonly experienced infusion reactions, so pre-treatment with an antihistamine should be considered.
Again, a nice step forward towards treatment of LUPUS in general but Patients with Severe kidney disease were excluded. At this point, lets see what the renal community feels about this novel agent. 
Ref:

Top Ten Reasons to Love you Kidneys

10. They are the best "Shaped" organ in our body 
9. If it wasn't for them, you wouldn't be able to get rid of your body's wastes.
8. They are the "Smartest" organ in our body
7. If it wasn't for them, you wouldn't be able to get rid of your excess water
6. They are the " most complex" organ in our body( even more than the brain)
5. If it wasn't for them, you wouldn't be able to live just on bananas ( some people do)- very well engineered!
4. They are the "most successful" organ in our body( one might ask why:- born smart, has an objective, can go into pre- renal success all the time and has long term plans set from before)
3. If it wasn't for them, you wouldn't have healthy bones.
2. If it wasn't for them, you wouldn't have healthy blood.
1. They are the "HAPPIEST" organ in our body! A smiling kidney is a working kidney.

Keep everyone's kidney happy! Happy World Kidney Day Everyone!


http://www.worldkidneyday.org/

Wednesday, March 9, 2011

Virtual Library ( the Welch Library) Part 1

A virtual Library. Take a look at this Youtube video-courtesy ASN
Nancy Roderer and Sue Woodson discuss the shift to a virtual library and how faculty and the library collection will benefit from this change.  


Elimination of anti rejection medicaitons

ASN news recently reported a study that is ongoing using specially processed stem cells from the same kidney donor being transplanted along with the kidney to that recipient, allowing that to continue in chimerism leading to an early presumed tolerance and hence no anti rejection medications for long term.
This concept is not new and has been attempted in the recent past. In 2008, NEJM paper by David Sachs et al showed that 5 patients could come off all immunosuppresion after a combined stem cell and kidney transplantation. This theory is used in myeloma treatment as well when patients get an allogenic and kidney transplant at the same time allowing to help both the organs of treatment.
A similar concept was presented recently in CJASN Feb 2011 issue about using autologous  mesanchymal stromal cells during kidney transplants. They showed that in two patients, this allowed engraftment of T regs in the peripheral blood and control memory CD8 T cells function.  In vitro studies have shown that mesenchymal stromal cells abrogate allo immune response  and could function as anti T cell agents in a "different" manner.


here is some older data on this topic:
http://www.ncbi.nlm.nih.gov/pubmed/18216355
http://www.ncbi.nlm.nih.gov/pubmed/20605588
http://www.ncbi.nlm.nih.gov/pubmed/20930086

Smoldering vs Active Myeloma

Here's a simple way to differentiate from smoldering or inactive Myeloma from active( borrowed from our Heme/onc doctors)

C alcemia (hyper)
R enal failure
A nemia
B ony mets and pain
I nfections or immunoparesis(is defined as a reduction (below the lower normal limit) in the levels of 1 or 2 immunoglobulin (Ig), with respect to the values of the corresponding uninvolved Ig.)

Tuesday, March 8, 2011

Tissue Engineering Renal Tissue

The Regenerative Division at Wake Forrest University has been doing some ground breaking work.
One study done there allowed for some initial work regarding re generation of kidney cells.  This system involves the cultivation of expanded primary renal cells in a three-dimensional collagen-based culture system. After one week of growth, individual renal cells began to form renal structures resembling tubules and glomeruli. Histologically, these structures show phenotypic resemblance to native kidney structures. The reconstituted tubules stained positively for Tamm-Horsfall protein, which is expressed in the thick ascending limb of Henle's Loop and distal convoluted tubules. These results show that renal structures can be reconstituted in a three-dimensional culture system, which may eventually be used for renal cell therapy applications. The article listed below presents a three-dimensional culture system that allows for reconstituting single renal cells into kidney structures in vitro, thus providing a controlled platform for renal tissue formation in vivo.

ref:
http://www.ncbi.nlm.nih.gov/pubmed/18845258

Concept Map of Hyponatremia

A concept map of Hyponatremia created by a mind of a medical student. By Grace La Torre, MS IV

Sunday, March 6, 2011

Bortezomib for desensitization!

Donor specific alloantibody producing plasma cells might be a good target for proteosomic inhibition by bortezomib. Bortezomib has some data in case series and reports of treating antibody mediated rejection. A recent study published in Transplantation 2011 discussed case series of 4 patients with extremely high DSA and couldn't just get apheresis alone.  They received 4 doses of bortezomib alone in one group and other 4 received 16 doses and  plasma exchange.  The response of these 8 patients was compared to 8 patients with plasma exchange alone.  Bortezomib alone didn't do much but bortezomib + plasma exchange did better than just plasma exchange alone in terms of DSA decrease.  This might lead to more protocols that might develop using this agent for treatment of desensitization.
This study is small and not well designed. IVIG has been used in many centers and Anti CD20 agents as well. Is it bortezomib alone that is doing the magic or is it that we just need two agents along with plasma exchange.  So plasma exchange + IVIG pr plasma exchange + rituximab or plasma exchange + bortezomib.

Have a look


Friday, March 4, 2011

Complications of Peritoneal Dialysis

TOPIC DISCUSSION: Amyloidosis and Factor X deficiency

Whats the relation of the above two? AL Amyloidosis can present with Nephrotic syndrome and cardiac dysfunction that we are very aware of. Hepatic and splenic involvement cause organomegaly but little functional impairment.  Hemorrhagic manifestations are primarily due to sub-endothelial deposition of amyloid leading to capillary fragility and hemorrhage.  The bleeding time is typically prolonged but platelet aggregation and von Willebrand functional activity are normal. A rare complication is an acquired factor X deficiency state resulting from factor X adsorption to the amyloid fibrils in the vasculature. Residual factor X levels range from 2% to 50%. As a result, both the PT and aPTT are prolonged but the thrombin time and fibrinogen concentration are normal. Mixing studies of the patient's plasma and normal plasma correct the abnormal PT and aPTT, suggesting a factor deficiency state; but infusion of factor X results in a rapid loss of factor X activity. Factor IX deficiency has been reported as well.
So if someone has Factor X def and unexplained: Amyloidosis can be in the differential diagnosis. The thought was that factor X deficiency associated with systemic amyloidosis is due to binding of factor X to body tissue, probably within the circulatory system.

The NEJM article from 1977 first was to note this association in Amyloidosis. 

http://www.nejm.org/doi/full/10.1056/NEJM197707142970203
http://bloodjournal.hematologylibrary.org/cgi/content/full/97/6/1885

Thursday, March 3, 2011

CLINICAL CASE 34, ANSWER AND SUMMARY

Which of these genes are linked with diabetic nephropathy?
Angiotensin I Converting Enzyme gene
  3 (11%)
 
Endothelial nitric oxide synthase gene
  0 (0%)
Erythropoietin gene
  0 (0%)
Gremlin 1 gene
  2 (7%)
 
Protein Kinase C-B1 gene
  5 (18%)
 
Superoxide dismutase 1 gene
  2 (7%)
 
All of the above
  15 (55%)
 
Most of you got this one right. its all of the above. 
A recent literature search and a meta analysis published in Diabetologia
34 replicated genetic variants were identified Of these, 21 remained significantly associated with diabetic nephropathy in a random-effects meta-analysis.  Many were identified and sub divided in different race groups. All the ones mentioned above were important. Please look below at the ref for more data.

Wednesday, March 2, 2011

IN THE NEWS--> DOSE TRIAL

This Week at NEJM.org March 3, 2011
In this issue of the Journal, Felker and colleagues report the results of the Diuretic Optimization Strategies Evaluation trial (DOSE; ClinicalTrials.gov number, NCT00577135).
look at this for details.
basically they compaired high dose lasix vs. low dose. also compared intermittent q12 vs. continues.
high dose was not better. intermittentjust as good, transient Renal injury with high dose group

this is a direct qoute from the link below
"What are the implications of this trial? The DOSE trial has importantly identified a lack of greater benefit with the diuretic regimen of continuous infusion — a regimen that is used frequently — than with a regimen of intermittent boluses. It also showed that, despite theoretical concerns and the findings of prior observational studies, a high dose of loop diuretics, as compared with a low dose, did not substantially worsen renal function. Both of these findings should change current practice. Since a high-dose regimen may relieve dyspnea more quickly without adverse effects on renal function, that regimen is preferable to a low-dose regimen. Administration of boluses may be more convenient than continuous infusion and equally effective.
Editorial


Comparative Effectiveness of Diuretic Regimens
G.C. Fonarow N Engl J Med 2011

ANCA VASCULITIS

A nice discussion on ANCA vasculitis by Dr.Peter Schrier

Tuesday, March 1, 2011

CONSULT ROUNDS: An approach to orthostatic hypotension with supine hypertension

This is not uncommon; but can happen in the elderly. The cause is usually autonomic failure.
These patients can have supine BP of 200 systolic and decrease to 70 systolic upon standing.
Goals of therapy are to prevent the supine HTN and decrease the drop in SBP while they are standing up.
1-non-medicinal interventions:
So basically increase salt intake to decrease the hypotensive episodes, standing up slowly to mitigate the hypotensive symptoms and prevent sycope and falls, High Ted stocking and has to be high up to groin to increase venous return and increase CO and BP upon standing, crossing legs while standing for the same reason. and finally sleeping in 30-40 degree angle; avoiding warm drinks and meals : these above measures decreases renal flow and activates renin-angiotension system and mitigate hypotension upon standing.
2-Nitropaste at night and to be removed in AM may be helpful.  Acytelcholinsterase inhibitors and there are thought to work through catacholamine surge(norepinephrine usually) and pressors activity and increase in BP during standing; and the advantage is that there no hypertensive sides effects.
Erythropoietin has been tried but hypertensive side effects do limit its use.
Clonidine may be helpful(case reports and series only); my personal experince it worked 2/3 patients. it increases upright BP through the postsynaptic effects on alpha 1 receptors agonist. and it decrease supine BP through the alpha2 receptors cenrtaly; the fact that these patients have discoordination between their central and peripheral nervous systems due to the autonomic failure, clonidine is able to perform both functions and actually narrows the orthostatic gap.

In the News: Transplant rules changing

Proposed Kidney Transplant Rules Favor Younger, Healthier Recipients
Kidney transplants would be given preferentially to younger, healthier patients, under rules being considered by the United Network for Organ Sharing (UNOS), according to the Washington Post.
Current rules favor recipients who have been on waiting lists longest, but the shift is an attempt "to get the most out of a scarce resource," according to Dr. Kenneth Andreoni, the chair of the UNOS committee considering the changes, as quoted in the Post.
Bioethicist Arthur Caplan, also quoted in the article, says that the change has implications for other areas of medicine: "This is moving it away from a save-the-sickest strategy to trying to get a greater yield in terms of years of life saved."
UNOS has circulated a document describing the proposal and is seeking comments. We link to it below.
Washington Post article (Free)

Concept Map of Kidney Injury in hematopoietic Stem Cell transplants

Here is a concept map of different types of kidney injuries noted in hematopoietic stem cell transplants patients. this does not supplement in depth knowledge of the subject. This is an introduction to the topic.
Any updates are welcome and if something is missing, let me know to add it on.




Growing Kidneys

Check out this excellent post on Growing Kidneys

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