Wednesday, December 30, 2009


A great case of hyponatremia that is in a patient with CNS disease and leading to a Cerebral Salt Wasting vs SIADH picture. Hard to differentiate both when the patient is already on 3% saline. Usually the volume status can give the clue if seen initially before the treatment is started.

Main topic of discussion was an approach to deal with this via a tonicity balance method.
A nice paper by Dr. Mitch Halperin et al in Intensive Care Medicine in 2001 reviewed this topic with a nice example.
When we treat someone with natremias, we account for mostly either free water excess or free water loss and adjust our rate of fluid choices accordingly. A different approach is of using the simple WHAT IS GOING IN ( salt and water) and WHAT IS COMING OUT( salt and water) and calculate the total net NA excess or loss and free water excess and loss and adjust based on that.
Take a look at that paper: Its titled Tonicity Balance and not electrolyte free water calculations guides therapy for acute changes in natremias. A must read!

Monday, December 28, 2009


There has been a lot of debate regarding renovascular hypertension/kidney disease and the benefits of revascularization vs. medical therapy. The much anticipated ASTRAL trial has just been published in the NEJM November 12, 2009. However, many questions remain unanswered.

Briefly, this was a randomized, multi-center, unblinded trial of 806 patients with atherosclerotic renovascular disease assigned to either medical therapy or revascularization with medical therapy (403 in each arm) followed over an average of 34months. Primary outcome was renal function as measured by reciprocal of creatinine and secondary outcomes were BP, time to renal and CV events, an mortality. No significant difference was found between the two arms in any outcomes, but 23 patients had complications associated with revascularization, including 2 deaths and 3 amputations.

The study design was based on "equipoise", or true uncertainty about which arm would do better. This, of course, is very subjective. Those thought to benefit from revascularization were excluded. The problem with this is that no one clearly knows who would benefit. Such assumptions are based on small studies looking at such things as degree of stenosis, resistive indices on duplex, hypertension control, renin/aldo levels, degree and rate of decline of renal function, and so forth. To have these patients undergo revascularization may therefore be considered "standard of care", and perhaps this is why a design of this nature was performed (ie. to include these patients would be "unethical").

It should also be noted that ~40% of patients had stenosis less than 70% in both arms, and unilateral RAS was included in a study where the primary outcome looked at renal function (although their posthoc analysis of severe bilateral stenosis or severe unilateral stenosis of solitary kidney also showed no difference).

We must be careful on how we interpret studies. This is a step in the right direction to draw a conclusion, but by no means should this be seen as anything definitive...

TOPIC DISCUSSION: NSF post transplant. theraputic challenge

A patient with history of Minimal Change disease and lupus nephritis who had renal transplant few years back. unfortunately immediately before transplant she had MRI with Gad. for years she had been complaining of a taught skin and immobility in her joints. recently she was seen by rhem and a skin biopsy showed NSF. her Cr 1.0. she is on prograf, cellcept prednison, what could we do to treat NSF? since we're able to diagnose it.

so NSF has been recently recognized as potentially a fatal disease. it is characterized by myofibroblasts depositions in internal organs such as liver, heart, kidneys etc as well as externally mainly the skin. it presents as painful,symmetrical thickening of the skin and the joints that can be misdiagnosed as scleroderma and alike,calciphylaxis, cellulitis. it follows a progressive unremitting coarse. major risk identified is exposure to gadolinium in dialysis patients or CKD patients with GFR<30. it maybe dose related.
all cases are retrospective, and all have been exposed to gad by history.

how?Free Gd3+ is poorly soluble, highly toxic, and can form precipitates with anions that tend to be elevated in renal failure. This has led to the hypothesis that excess exposure to free Gd3+ in patients with kidney disease leads to tissue damage.PD patient maybe at higher risk. Gad half life is dramatically increased to 1.3hrs in healthy to over 15 hours in CKD 5 patients.

Initiation of recombinant human erythropoietin (EPO) therapy or an increase in dose may be associated with NSF, but the true nature of the relationship between EPO and NSF remains incompletely understood.A case report described two patients without a history of exposure to gadolinium who developed NSF post-kidney transplantation ;the authors postulated that vascular manipulation or endothelial injury was a possible trigger.

treatment:case series. transplantation, Extracorporeal photopheresis ,Ultraviolet A1 (UV-A1) phototherapy, Plasmapheresis and more recently rapamune and gleevac have been proposed. all of these therapies have been inconsistent and disappointing.

back to the above case: options are either switching to rapamune based regimen. or addition to gleevac with special attention to infectious risks and significant edema developing in these patients.

JOURNAL CLUB: Is there anything we can do to prevent Contrast induced nephropathy?

Few weeks ago we discussed a new item on the many disappointing items that have been proposed to mitigate the risk for contrast nephropathy. the article in the Circulation 2009;120:1793-19-799, Iloprost-a prostacyclin analog- a vasodilator was noted in rat studies to attenuate the ischemic effects of contrast media. so a randomised, double blinded, placebo-controlled trial to see if Iloprost is up to the challenge. 208 patients, Cr 1.4 or more, cardiac angiograms were done +/- intervention. results: ??it may protect CIN.

obviously this is a small study, their placebo CIN rate was much higher than usual(23% vs 5-15%) which may have helped improve the data for the study drug. other issues were the inappropriate use of eGFR in a dynamic situation, the significant hypotention in the Iloprost arm is a concern, the bleeding tendencies from the platelet-inhibition property of Iloprost.

what do we know about CIN: 3-13% depending on definitions and patient populations, most significant risk factor is CKD, you can multiply Cr by ten and get an estimated risk score, it rarly leeds to dialysis, hyperosmolar contrast and >150cc increase the risk. other soft risk factors like low ef, anemia, diuretic use, chf, Htn, ?ace.
best treatment is prevention; Normal saline vs 0.5%saline 12 hours prior.
etilogies proposed: vasoconstriction, upregulation of the RAS system, dowenregulation of the vasodilators signaling, PH acidemic being worse.
??ischemic-reperfusion injury.


A nice review on this topic is in this month's issues of Nature Reviews Nephrology.

After renal transplantation, a large percentage of patients lose bone. This loss of bone results from a combination of factors that include pre-existing renal osteodystrophy, immunosuppressive therapy, and the effects of chronically reduced renal function after transplantation. Many studies have found that the type of bone disease that pre dominates in the post transplantation world is Low turnover disease.  Low bone volume and low bone turnover has been associated with cardiovascular calcifications.  Do we use less Vitamin D in these patients, more of cinacalcet, the data is scant? This review might help answer few questions and stem more for further research. 

Wednesday, December 23, 2009


We believe that the lesion in HIVAN is collapsing glomerulopathy. Collapsing FSGS is believed to be a podocyte proliferation disease based on multiple studies done in rats and humans staining for podocyte proliferation markers and dedifferentiation markers.
A recent study in Am J of Physiology Renal Physiology is showing a novel concept. The investigators did a basic science study on role of epithelial mesanchymal transdifferentiation (EMT) in the development of HIVAN phenotype.  Their data showed that in mice, it appears that myofibroblasts are migrating from either glomerular or tubular sites and then proliferating. Series of stainings confirmed that EMT was happening and was contributing to the proliferative phenotype in HIVAN mice.
So its likely that in collapsing FSGS there is proliferation, but not of podocytes as once thought. So it still might be a podocytopenic process due to proliferation of other types of cells and leading to EMT causing this change.  Its a start of an out of box thinking of this process.
Hopefully this might shed some light and perhaps help in treatment of HIVAN in addition to HAART when it occurs.


TMA in Lupus. This is a controversial topic and evidence is not really present on what to do.  The topic was about using plasmapheresis for such patients.

Key Points
1. Lupus Nephritis and plasmapheresis --> the evidence is negative for use of it.
2. TMA in Lupus( evidence of schistocytes, LDH , low haptoglobin, thrombocytopenia, renal failure, proteinuria, hemolytic anemia) ---> plasmapheresis has shown some benefit if given early to reverse the TMA process and or renal function improvement( its all based on case series and case reports)

3. In prior cases, acute renal failure and MAHA resolved with use of pheresis, steroids or heparin. The cases reported provided further evidence that a TMA can cause acute renal failure independent of lupus nephritis. TMA should be distinguished from other forms of renal vascular disease, particularly a noninflammatory lupus microangiopathy, which is probably mediated by subendothelial immune-complex deposits. The absence of immunoglobulin deposits in vessels involved by a TMA indicates that microvascular thrombosis is promoted by mechanisms other than those usually attributed to immune-complex disease. Phospholipid reactive antibodies may be pathogenetic in some cases. ADAMTS-13 Antibodies might play a role in lupus TMA or possible role of anti endothelial antibodies. Removal of these antibodies with pheresis is the goal.
Anti CD20 agents might be helpful as well given their role in decreasing production of those antibodies!

Funny Stuff

Top 10 reasons fellows went into nephrology: ( Courtesy Dr.Alan Perlman of Weill Cornell/Rogosin Institute)

10.       You can see more psychiatric patients in 30 minutes rounding in the dialysis unit than you will see in an entire year doing psychiatry.
9.         “My therapist told me it was a good way to control my nephromania”
8.         You can cheer up a patient with a failing transplant by telling them it’s just a good humoral rejection.
7.         When our patients are pissed, we take it as a sign of success.
6.         “Dialysis gives me the tickles.”
5.         The feeling of superiority you get the first time you urinate after rounding in the dialysis unit
4.         Dialysis patients love jokes about metabolic bone disease
3.         “I find that stabbing a stranger multiple times with a sharp stainless steel instrument helps me to relax.”
2.         “I thought finding an organ swapping program would enhance my lovelife”
1.           To channel a lifelong love of urine into a golden stream

Monday, December 21, 2009

IN THE NEWS-Balamuthia mandrillaris and Kidney Transplants

The New York Times just reported that two transplant patients had a rare brain infection that was transmitted to them by kidneys taken from a donor at the University of Mississippi Medical Center  This might be the first human-to-human transfer of the amoeba Balamuthia mandrillaris....What is Balamuthia mandrillaris: - Its a leptomyxid Amoeba which can cause amoebiasis in humans. The most common thing it causes is the meningoencephalitis.  It will enter our body via the lower respiratory tract or open wounds. The granulamotous ameobic encephalitis it causes is usually fatal. The patient might present with neurological symptoms of siezures, headaches and frank paralysis. There are so few cases in the word, that only two have been successfully treated with antibiotics and antiparasitics but all had permanent neurological defecits. Only a  total of 10 encephalitis cases were known to have been caused by the amoeba between 1997 and 2007. This is scary!!!

Sunday, December 20, 2009


Lets discuss Renal Vein Thrombosis in a Membranous GN .
What to we do? Some points that were discussed!
1. Anticoagulation with warfarin vs Lovenox
2. Sometimes surgery is required and thrombectomy is done. Rarely!
3. When do we use thrombolytics?  Apparently based on few case series and case reports, to use it when there is active clot, flank pain, and no contra indication of recent bleeding and there is a worsening renal function.
4. If their proteinuria is controlled well with ACEI or ARBS, and if they still get a pulmonary embolism, deep venous thrombosis or renal vein thrombosis, do you start treating the Membranous glomerulopathy  with immunosuppresive therapy? No evidence for that? But perhaps we should be or should perhaps look for a secondary cause of that membranous, perhaps a cancer!!

Friday, December 18, 2009


The first mentions of HTN were in 6th Century BC. Scientists coined the term ESSENTIAL HTN, as they thought that the BP elevation was essential for survival when some patients had vascular disease. The first ever elevated blood pressure in a patient without kidney disease was reported by Frederick Mahomed in late 1800s.
The most interesting fact is that the keeping your BP<140/90 has no evidence basis. It came from an insurance agent representative who noticed that patients with BP >140/90 were dying earlier.  

Wednesday, December 16, 2009


A recent article in CJASN from the University of Utah Health Sciences sheds an important issue in our field.
Using a faculty roster of the American Medical Colleges, they studied the number of full time nephrology facutly over the years.  There were 1315 full time faculty in 2008, this was 4.9% lower than 1998.  Importantly, there were more and more senior faculty but not an increase in junior faculty.  There was a decrease in tenured academic nephrologist and an increase in non tenured academic nephrologists.  Majority of the faculty comprised of an increase in international medical school graduates and fewer american graduates.

This data is interesting and worrisome as there will be a shortage of academic nephrologists in the future.
The monetary payback, the current economy and the lifestyle are likely major players in the decision making of residents going into nephrology and then fellows going into more private practice settings.  Perhaps, as a community , we have to encourage more fellows to take on the road for academia ( clinical, basic science researcher or a clinician educator).  The task is tough.

Tuesday, December 15, 2009

TOPIC DISCUSSION: Cerebral Salt Wasting

Now whether you believe in this entity or not, it's quite interesting. In the literature there appears to be a debate that goes back and forth, mainly between two groups: one lead by Richard H. Sterns from University of Rochester School of Medicine and Dentistry, and the other from John K. Maesaka from Winthrop (supporting). The diagnosis appears to be heavily reliant on clinical hypovolemia. There have been several studies published indicating that clinicians (nephrologists, cardiologists, intensive care) are lousy at this determination, when compared to invasive or semi-invasive monitoring. Therefore, unless hypovolemia is obvious (hypotension, tachycardia, orthostasis), it is difficult to make this distinction from euvolemia.

To make this diagnosis, the patient should have substantial urine sodium excretion in the setting of hypovolemia. This is ofter suggested by having a negative sodium balance, more so than would normally be seen in "SIADH" which tends to be mild. The other absolute must in this diagnosis is that adrenal insufficiency (both glucocorticoid and mineralocorticoid) must be ruled out, since it presents similarly. CSW has been mostly implicated in patients that have subarachnoid hemorrages, but many have described this phenomenon without any neurological features. Proponents of this entity (Maesaka, et al) also describe a method to distinguish CSW from SIADH, and that involves looking at the FeUric Acid. This is high in both states, but the distinction comes with treatment (with FeUric Acid becoming normal in SIADH and remaining elevated in CSW after correction). Opponents feel the negative salt balance often reflects the high rate of Na infusion that is given to patients when they first present, and when seen days later by nephrologist, the physiologic excretion of this is then seen. They also propose that the water retention and catecholamine release result in a physiologic excretion rather than true "salt wasting".

I write about this due to a patient who presented similarly as described in the papers of CSW. I only recently discovered that CSW was described before SIADH, and that once SIADH had been described, CSW reports had virtually vanished, only to resurface decades later in the neurosurgical literature. I don't know if I believe it or not, but until this is absolutely proven or disproven, we need to keep our differential open. Whether you believe in CSW or not, optimal therapy in the setting of SAH is hypertonic saline, so it may not matter what you call it.. Ultimately it's a beast that probably will continue to be debated without definative answers.

Monday, December 14, 2009


13 patient kidney swap was performed at Georgetown University and Washington Hospital Center last week making it the largest kidney swap till date. Way to go!!!
This new swap idea is excellent as it provides certain people who have been on the waiting list with a chance of possible getting an excellent matched kidney from a live donor. 
A good review of the swap is in the recent review in AJT

Saturday, December 12, 2009

IN THE NEWS --->KDIGO guidelines for Transplant Care

Finally they are here. A list of recommendations and some suggestions for every aspect of transplant care:
induction to post transplant malignancy to cardiac disease and lifestyle of patients.

Its a detailed document with good references and overall gives some general guidelines to follow for screening, and overall care of the patients. It is available for free at the AJT website.

Friday, December 11, 2009

IN THE NEWS --->Pre eclampsia as hyponatremia

We reported in the current Clinical Nephrology about pre eclampsia presenting as hyponatremia and resolving only after delivery. Classically the syndrome presents with hypertension and proteinuria; the presumed pathophysiologic mechanisms involve both maternal and placental factors resulting in endothelial damage and placental hypoperfusion. Multiple gestations are a known risk factor for development of preeclampsia.  Hyponatremia in preeclamtic pregnancy has been described in few cases, many of which were twin pregnancies.  We believe the physiology of non-singleton pregnancies causes a hepato-renal like syndrome and the development of hyponatremia occurs in the setting of increased free water intake.  Because of this physiology, patients are at risk for developing azotemia and preeclampsia.  Awareness of this potential entity in non-singleton pregnancies is key for prenatal care and frequent monitoring of serum Na should be routine.


The COOPERATE study had looked at combination ACE inhibitor and ARB therapy in proteinuric patients with non-diabetic kidney disease. The journal Lancet has retracted the paper after the results of an academic investigation indicating some concern regarding the validitiy and ethical issues with the study. Along with the recent ON-TARGET data, its going to be hard to use a combination of ACE and ARB till we get more data. 

Is some proteinuria really bad for the kidney? Or is the kidney doing the right thing to protect itself? No answers!!


The current issue of ASN Kidney News reviews a presentation that was at ASN this year.  ASN San Diego 2009, a presentation showed that recurrent lupus nephritis is uncommon in lupus patients who receive a kidney transplant, but the condition often leads to rejection and loss of transplant  with an increased risk of death after transplantation.
The study group analyzed 6850 patients with a history of lupus who received kidney transplants between 1987 and 2006. The researchers found that lupus nephritis occurred in 2.44 percent of individuals in the study and that it led to a fourfold increased risk of kidney transplant
failure. Also, death occurred in approximately 16 percent of affected transplant recipients. African Americans, younger women, were certain risk factors.
This comes as a no surprise to me. Another presentation I went to in the ATC 2009 from Europe had mentioned that when they did protocol biopsies in lupus transplanted patients, they did find low grade Lupus Class II in many of these patients. Likely what is happening is they are heavily immunosuppresed, so what drugs we are using for rejection is also helping the lupus to be under control. Perhaps, the Steroids, Cellcept , CNI combination might be a good treatment for lupus then? rather than just cellcept or cytoxan with steroids. Perhaps lupus requires three tier treatment like transplant patients do.
Things we can learn from transplant patients!

Thursday, December 10, 2009


Here is a case of BUN of 260 and creatinine of 14 on presentation and K of 7.5.
Dialysis disequilibrium syndrome (DDS) was the main focus of discussion.

1. The initial dialyses should be gentle, but repeated frequently. 
2. Two hours of hemodialysis with BFR of 150-250ml/min 
3. Use small surface dialyzer
4. Prophylactic benzodiazepines
5. Prophylactic phenytoin 
6. Administration of mannitol IV every hour of dialysis 
7. High Na bath
8. Severe DDS with seizures can be reversed more rapidly by raising the plasma osmolality with either 5 mL of 23 percent saline or 12.5 g of hypertonic mannitol.

Wednesday, December 9, 2009


The first descriptions of henoch schonlein purpura

IN THE NEWS --->Infection in the kidney

A recent study published online in the Journal of Infectious Diseases quotes that the WEST NILE virus can survive in the kidney for many years. The group followed 100 patients with severe West Nile infections, who were tested for seven years after their initial infection and more than 50%continued to have infection-related symptoms, and five eventually died of kidney failure. This is interesting as this might have implications for West Nile as a cause of ? collapsing FSGS that is idiopathic.
It might be interesting to see what type of renal disease these patients died of.  This might be extremely important in transplant patients as they are more prone to different types of infections!!

Tuesday, December 8, 2009

IN THE NEWS --->Model predicting likelihood of survival on dialysis

A new model can help physicians determine if a kidney disease patient on dialysis is likely to die within the next few months, according to a study just mentioned in (CJASN). This clinical tool could help medical professionals initiate discussions with patients about end of life care. Five simple factors: a 'no' answer to the surprise question, older age, decreased serum albumin, presence of dementia, and presence of peripheral vascular disease (blockage of an artery that leads to an arm or a leg), could be mathematically combined to accurately predict that a patient is unlikely to survive past six months. When comparing a patient who died within six months with one who remained alive, 87% of the time the model accurately predicted that the former patient had a higher risk of dying within that timeframe than the latter. The researchers validated their model by testing its accuracy in another 514 kidney disease patients on dialysis, where the model's predictive accuracy was only slightly lower (80%).
This is fascinating and hopefully we can have this tool available to be used in clinical practice. Nutrition has again and again shown to be an important predicting variable for survival on dialysis.

IN THE NEWS ---> Anti CD 20 everywhere

Rituximab is becoming a popular drug among nephrologists. Starting with lupus in the LUNAR trial. Now the RAVE trial showing it working well with ANCA vasculitis, and its trade of mark in antibody mediated rejection has made it a household name in the nephrology home.

Interesting article in NEJM last month showed the use of Rituximab for Type I DM. It showed decrease in antibody production and patients required less insulin. This is fascinating and its good to see that people are thinking out of the box.

What's next -- Rituximab in Hashimoto's Thyroid disease?

But want everyone to be ware as we use this drug more and more. There are B regulatory cells and we might be doing some small harm slowly and hope we don't see any long term side effects years from now!!! Just as the T regs act as policemen to mediate inflammation, there are B regs as well that might be doing some policing that we might be vanishing away with Rituximab!!!

Monday, December 7, 2009


The first documented kidney transplant in the United States was performed June 17, 1950, on Ruth Tucker, a 44-year-old woman with polycystic kidneys, in Evergreen Park, Illinois. Due to no immunosuppresive therapy, the kidney rejected right away. The first successful human kidney transplant took place at Brigham and Women's Hospital in Boston, USA, with identical twins.

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