Tuesday, December 31, 2013

IN the NEWS: Profit or non for profit dialysis units and USRDS data study

Being in dialysis unit that is for profit vs hospital owned or non-for profit- does it matter? Both units provide services that should be beneficial for the patients.  A recent study in CJASN 2013 looked at this specific question using USRDS retrospective data on hospitalization and other outcomes between profit vs non for profit units.

Some key summary points of their evaluation

Patients receiving hemodialysis in for-profit facilities had a 15% higher relative rate of hospitalization compared with those in non-profit facilities.

Among patients receiving peritoneal dialysis, the rate of hospitalization in for-profit versus nonprofit facilities was not significantly different

Patients on hemodialysis receiving care in for-profit dialysis facilities had a 37% higher rate of hospitalization for heart failure or volume overload and a 15% higher rate of hospitalization for vascular access complications.

This is one of the few studies to ever look into this difference. A prior study ( also USRDS study) had looked into length of hospitalizations as well and had found longer stays for profit facility patients. What could be the reasons for the above findings:- training, fellow presence, staffing, medication protocols, checks and balances, length of treatment, patient selection. Etc.

Keeping in mind this is a retrospective outcomes study, one must be cautious in looking at these results. Nephrology community should take necessary steps to try to provide equal care at the both type of dialysis centers.

Tuesday, December 24, 2013

JNC 8: A Nephrology fellow's perspective

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) was released in 2003 and since that time has been an often referenced tool for clinicians seeking to treat hypertension.  From that report we were given useful information such as classification of hypertension along a spectrum of blood pressure ranges , from pre-hypertension to stage 1 and ultimately to stage  2 hypertension.  A goal of <140/90 mmHg should be our target for most of the population, and less than 130/80mmHG for those special populations with increased cardiovascular risk, such as those with diabetes or chronic kidney disease.  Thiazide diuretics were the preferred initial drug for those with uncomplicated stage 1 hypertension.  Multidrug therapy was useful for stage 2 or failure to reach the goal blood pressure.  Simple, straightforward, yet leaving a lot of questions unanswered. Many of us in the nephrology field were awaiting the JNC 8 for years.
So as you can imagine when the JNC 8 came along, just released on December 18, I was anticipating a lot of questions being resolved.  As a nephrology fellow I was looking forward to more specific guidelines and recommendations: what should I do with my elderly hypertensives, my patients with proteinuric CKD?  How about my hemodialysis patients?  Finally, I would get some insightful, specific recommendations on these special populations, or so I thought.
What I did get was a list of 9 recommendations, 9 generic recommendations that do not address my concerns as a budding nephrologist.  In patients over 60 years of age, target a BP of <150/90 mmHg.  However, if they are able to achieve a systolic BP <140 mmHg without adverse effects, than that is fine too.  A goal of <140/90mmHg should be targeted in patients under 60.  If one is over 18 years old and has CKD or diabetes, once again target <140/90mmHg.  An angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) should be used here.   In the black population, those with or without diabetes, a thiazide type diuretic or calcium channel blocker is the preferred initial agent of choice.  In the non black population, a thiazide type diuretic, calcium channel blocker, ACEI, or ARB, can be used. 
While nephrology specific questions were not addressed in detail, these guidelines do serve as the blueprint to help treat those with essential hypertension.  They are a framework for all clinicians to follow to help with all patient types.   They should be succinct, straightforward treatment recommendations that can be quickly applied in the clinic.
 That is exactly what these new guidelines are.  This is very useful information that will benefit many patients.  Tolerating higher blood pressures in elderly patients and avoiding some of the adverse effects of the medications is surely a good thing.  This will help a lot of clinicians realize that attaining a goal blood pressure is oftentimes more important than how it is achieved.  Ultimately, patients and physicians will see positive results.    

The AAFP gives a summary of the guidelines. Also check out the review on BMJ blog on JNC 8

Louis Spiegel, MD
Renal Fellow in training

Monday, December 23, 2013

ACKD Onco-nephrology issue

Check out the latest Jan 2014 issue of ACKD entirely on onco-nephrology.
Dr Yee gives an interesting editorial highlighting the advent of this field in nephrology.
Check out the different reviews in the issue at http://www.ackdjournal.org/issues

Tuesday, December 17, 2013

Consult Rounds: Diabetic Fibrillosis- an entity that is forgotten?

This condition was first described in 1970 by Sohar et al when they observed small sized fibrils in the expanded mesangium of diabetic patients with nodular glomerulosclerosis.

This is interesting as in the realm of organized deposits, knowledge of this entity is important as we are embarking on biopsies of diabetics to look for alternate cause of proteinuria. The fibrils may appear to look like Fibrillary GN or Amyloidosis ( although slightly smaller).  To date, no clinical correlation has been noted when these fibrils are seen.

On LM, these fibrils are usually silver stain negative. The degree of decreased argyrophilia depends
on the extent of fibril deposition. The fibrils are only identifiable at the ultrastructural level and can measure from 5-20nm in diameter.  The fibrils are negative for Congo red and Thioflavins T and S.  The pathophysiology might be related to glycosylated expanded diabetic mesangium. Why some get it and some don’t is unclear.
 A nice review comparing organized deposits is presented in the pathology journal.

Amyloidosis is usually Congo red, Thioflavin T or S positive and the fibrils are  7- to 12-nm fibrils, randomly arranged.
Fibrillary GN is usually Congo red, Thioflavin T or S negative, IgG, C3 staining and nonbranching, 15- to 30-nm fibrils, randomly arranged;
Diabetic fibrillosis  is usually nodular GN; Congo red, Thioflavin T or S negative and IF shows linear IgG and albumin  on IF and fibrils are 5–25 nm in nodular mesangial areas
Immunotactoid GN is Congo red, Thioflavin T or S negative with variable microtubules stacked like deposits 10–90 nm

Image source: kidneypathology.com.ar

Saturday, December 14, 2013

HTN emergency: Does it really exist?- An ER physician's perspective

"Level 1 triage coming in to Trauma-B"

Me: "Who's in triage? What are they sending?"

Charge RN: "It's a tachycardic emergency."

Me: "Um, but what is it? What are they here for?"

Charge RN: "I just told you! HR was 146.  EMS gave Lopressor x 2 with no relief."

Me: "..." (head explodes- triaged as a level 3)

Do we HAVE “tachycardic emergencies?” Of course not- it depends what the tachycardia is from, whether it’s physiologic, a primary disorder, a response to stress, pain, fever or hypovolemia, whether it’s sinus or a dysrhythmia, whether it’s causative of other symptoms, in response to those symptoms, or merely coexisting. 

Then WHY do we have hypertensive emergencies?

There have been a number of well reasoned arguments on why hypertensive urgency is a non-entity.  From the time that we stopped using the term "malignant hypertension" we have been moving away from treating a number and bringing therapy back to the symptoms of the patient.  A vague entity like hypertensive urgency is generally indistinguishable from asymptomatic hypertension.

But recently I've had to spend more time discussing hypertensive E-mergency. You'd think I'd be happy about that, wouldn't you?  I mean, Emergency Physician, right? And definitely sicker patients: it's right there in the definition of "end organ damage."  On top of that, it comes with a treatment plan: "25% reduction of MAP within the 1st hour."  Sounds good- ill patients get aggressive care, we save organs, ergo lives, high five and go home.  

Except that the aggressive care of hypertensive emergency may make people worse, not better, and is too often invoked with delusions of benefit.  When I was an intern, there was a tried and true recipe to handle this vital sign when it bothered the nurses.  If the systolic pressure was "too high," the contents of a 25mg nifedipine capsule could be aspirated into a small syringe and delivered sublingually.  The result was a predictable, beautiful lowering of the systolic pressure over the next 30 minutes and at the 1 hour mark we had nearly always achieved the prescribed 25% MAP reduction.  Seen this tried and true method lately?  No, since it was realized that there was a downstream 6% stroke rate. The FDA rejected this use of nifedipine to rapidly lower BP in 1985, but in 1996 it was still a common choice: Today, IV pushes of vasoactive agents for no clinical indication still persist.  I find our collective lack of memory… troubling.  Note the use of the term “pseudoemergency” in the above JAMA abstract and the host of editorial comments that followed.  So what IS hypertensive emergency and what should we do about it then?

Here we go: this one doesn't exist either.  Or rather, it's just as meaningless a definition and entity as urgency.  Try this on for size- Hypertensive emergency isn't a disease.  It is an arbitrary grouping of diseases lumped together so you can remember to treat them similarly.  Oh, except the prescribed treatments are NOT similar and the proposed reduction of MAP should be performed in exactly NONE of those cases.

What, in my book, would be a true hypertensive emergency? Well, it should be a case where the blood pressure is physiologically causing the symptom, and rapid lowering should be associated with pt. benefit.  The first part of that sentence is basically addressing the fact that associating a very elevated blood pressure with a disease and calling it "hypertensive emergency" implies that the pathology is caused BY the blood pressure, as opposed to, "happens to be present." (I came across older articles listing epistaxis as a hypertensive emergency.)

Aortic dissection fits the bill nicely.  Eclampsia can be included as a few end organs including the brain are affected and blood pressure lowering is an indicated therapy.  Acute pulmonary edema (not chronic), when presenting with a very high afterload can be included, and this entity has earned the SCAPE acronym from the venerable Dr. Weingart- Sympathetic Crashing Acute Pulmonary Edema. 

All 3 include rapid BP lowering as part of the treatment. 
None of the 3 uses the same preferred agents. 
None of the 3 has the same target blood pressure goals. 
None of the 3 involve tailoring the MAP to become 25% lower than a previously measured pressure- there are hard targets or clinical targets.

Where else does hypertensive emergency get invoked, in my opinion inappropriately?* 


In association with angina and ACS, the assumption would be that the elevated pressure is causing cardiac ischemia.  Yet our therapy is based primarily on antiplatelet agents and not on goal blood pressure.  Interestingly, thisemedicine review: , lists ACS as an entity in which 20-30% reduction in BP is a clinical goal and states, "Treatment is indicated if the SBP is >160 mm Hg and/or the DBP is >100 mm Hg."  I’d love to hear from anyone who thinks it’s a good idea to push these numbers down in pts. going up to cath.  Scary.


Headache is not end organ damage.  That should end the discussion, but let’s go on.  The causal connection is poorly established, and the presence or absence of headache pain correlates poorly with blood pressures.  Studies on the topic are mixed at best.  I recall reading in my dog-eared copy of Tintinalli that this entity classically presents as occipital headache, but only in the presence of diastolics greater than 130.  Hypertension causing headache, if it actually exists, is thought to be uncommon, occurring less than 15% of the time.  Consider that pain may elevate hypertensive pts. blood pressure.  Yet pts and doctors make this connection commonly, prescribing anti-hypertensives when pain control often does the job quite a bit better and more safely.  For an even more complicating point, consider that when the symptom of HA is concerning for SAH, THEN the lack of HTN would be a low risk factor as per Perry’s 2008 BMJ review.  But a benign symptom remains a benign symptom when a pt. with known HTN has an elevated pressure while they are in pain.  Reglan, please.

Now for actual end organ damage:  In association with CVA and brain hemorrhage, there is clear end organ damage related to chronic HTN.  But is the damage caused by the acutely elevated pressure?  Or is that a reactive phenomenon happening after the infarct?  It’s become clear that rapid reduction of MAP may harm these pts. more than help.  From ACEP's Focus on Hypertensive Emergency: "there is little scientific evidence and no clinically established benefit for rapid lowering of blood pressure among persons with acute ischemic stroke."  The 2013 Stroke Guidelines suggest: "the recommendation not to lower the blood pressure during the initial 24 hours of acute ischemic stroke unless the blood pressure is >220/120 mmHg or there is a concomitant specific medical condition that would benefit from blood pressure lowering remains reasonable."  See that really high number there?  No, that’s not my threshold to start IV meds – it’s a suggestion that your pt. should be lower than that at the end of day 1.  Is your guy still in the ED at that point?  Your therapy can be accessed in a committee meeting on hospital boarding, not in your nurse’s PYXIS.

Check out - http://stroke.ahajournals.org/content/early/2013/01/31/STR.0b013e318284056a.full, and if you actually look at this, look at the entry: Induced Hypertension for the Management of Acute Ischemic Stroke.   That’s right, we sometimes push the pressure higher in response to an acute CVA.

Ah, but what if it's a hemorrhagic CVA?  Or if they're getting lytic therapy? (No, I'm not going there.**)  Then it's a different story, and we think BP should be addressed and may improve hematoma size, possibly even outcome.  And we will still ignore the 25% rule, instead opting for a hard goal of treatment.  SBP of <185 is suggested for lytics but you can also check out INTERACT, ATACH or INTERACT 2*** for a treatment discussion of hemorrhage.)  


Chronic changes can happen.  No IV meds for you.  Sudden bleeds can happen. That ship has sailed. No IV meds for you.  In the rare setting of “malignant” hypertension (yes, the texts still use that word), with acute vision loss and papilledema, ophthalmology textbooks recommend treatment.  They suggest “blood pressure should be lowered in a slow, deliberate, controlled fashion” to - wait for it – prevent end organ damage.****  No IV meds for you.


Renal failure related to blood pressure is exceedingly common in our practice. It is also rarely an acute entity related to sudden elevation in blood pressure.  I'd wager that when we rattle off the list of the 4 end organs we include kidney reflexively and rarely try to describe what that would look like.  Elevated blood pressure? Of course we see very elevated pressures in patients on multiple medications with suffering kidneys.  But this is a chicken and the egg problem akin to the classic "My HTN is causing my H/A" complaint.  Could this be a hypertensive emergency?  I suppose if:

The Cr. was recently better than the current value;
AND there is protein AND blood in the urine;
AND the BP is persistently and impressively elevated despite my earnest attempts to ignore and repeat it.  ("I've tried doin' nothing, and I'm all out of ideas..."*****)

Even then, I'm likely to go the oral medications route than treat with IV medications aggressively as would be prescribed by the "hypertensive emergency" label.  See the above eye discussion for slow, deliberate and controlled.  Oral meds will be just fine here, thank you.

...aaand we're done.  In no medical circumstance that I have encountered has there been an indication to lower MAP by 25% within an hour with powerful IV medication.  When you reach for those meds, you tend to have a hard target defined by the disease you are treating.  The phrase "hypertensive emergency" should join its equally painful brother, "hypertensive urgency" in that place labelled, "stuff we used to say," along with "female hysteria treated with therapeutic internal massage."

P. Mukherji, MD
ER physician at NSLIJ

*Not included: Possible appropriate uses of the term in entities like hypertensive encephalopathy, PRES syndrome, and  IMO especially aneurysmal SAH.  Gimme a break, it’s a rant, not a reference material.

**But if you want to go there, a pithy anti-tPA summation exists at LITFL, here: http://lifeinthefastlane.com/using-clot-busting-drugs-to-treat-acute-strokes/

*** Especially if you like not having patient oriented outcomes, or your pt. is a Chinese male and you're giving urapidil. I recommend we look out for ATACH2 where IV nicardipine is used while looking at death and disability outcomes.  I might be able to generalize that one to my patients.

Thursday, December 12, 2013

Clinical Case 78: Answers and Summary

Which one of the following are items to assess when solute clearance per session in HD is marginal?

Adequacy of the blood flow from the access
  14 (63%)
Dialysate flow rate
  8 (36%)
Dialyzer surface area
  10 (45%)
Duration of dialysis
  18 (81%)
Blood pump speed
  8 (36%)
Serum potassium pre dialysis level
  2 (9%)
Dialysate pathway stagnation
  4 (18%)
Serum sodium pre dialysis concentration
  2 (9%)

All the above need to be assessed to see if the clearance is good for HD session. Serum K and Na pre dialysis has not been evaluated to have any clearance related benefit. Access, dialysis flow rate, blood flow rate, duration of dialysis being the most important followed by blood pump speed, pathway stagnation, fiber bundle clotting, dialyzer surface area are also important components. Check out the free access HD core curriculum in AJKD 2013 for an excellent review on this topic. Watch out for an eAJKD quiz on this topic coming soon as well.

Tuesday, December 10, 2013

Nephron Power: Top Nephrology Stories in 2013: Abatacept for FSGS

Its’ that time of the year- Renal fellow network top 10 nephrology stories of the year .  My pick is Chih-Chuan Yu et al ‘s brief report in NEJM on abatacept in proteinuric kidney diseases.  

Just like belatacept in kidney transplantation, abatacept is an inhibitor of co-stimulatory molecule CD80 or B7-1 in the T cell signaling. It has been approved for use in RA for patients that fail TNF alpha inhibition. What the authors did was show several cases ( mostly post transplant proteinuric diseases) and showed how this agent helped get rid of proteinuria. Taking a step further, they found that post transplant, not all proteinuric FSGS stained for B7-1 in the kidney biopsy. They only treated the B7-1 positive FSGS strain with this agent to show response. 

A table in the NEJM paper shows the 5 patient characteristics. Four patients were post transplant FSGS and had failed rituxan. Two of the four responded to just one dose of 10mg/kg of abatacept and the two remaining needed 2 doses of 10mg/kg.  This is remarkable that just few doses put the disease in remission. They had 36-48 follow up data on all of them and still in remission. The patient 5 was a non transplanted primary FSGS case which was B7 positive and also responded to this agent but required monthly dosages for a year. Given transplant patients are on other agents that are attacking the immune system, one dose might be sufficient compared to non transplanted native FSGS.

In addition, the RFN did a nice post that also discusses the role of this agent in lupus nephritis and diabetic nephropathy. Take a look at these links

Why do I think that compared to other great stories in nephrology, this makes the number 1 contender in 2014?  Besides my love for podocyte and glomerular diseases?
1.      The authors have now identified another APOL1 like characteristic of FSGS- B7 + FSGS( perhaps should become a new category in FSGS- as they will respond to abatacept)
2.      Novel therapies for FSGS and other glomerular diseases are lacking.  While rituximab, IVIG, galactose, ACTH have come to the market, nothing has shown this dramatic of a difference.
3.      The authors took the transplantation literature and applied it to glomerular diseases. This is what is needed more and more. In addition, let’s take it to the next level- apply rheumatology and oncology literature and look for agents that will apply to glomerular diseases.
4.      This excites young minds about nephrology.  This is a positive step forward in the “sexiest” part of the kidney( glomerulus) and hope to excite many residents to take on the field of nephrology.

Go to Renal Fellow Network and vote for your top nephrology story of 2013!

Thursday, December 5, 2013

Does IgA nephropathy have lambda pre dominance?

IgA nephropathy is the most common GN in the world.  Does IgA molecule in this disease have a light chain predominance? Yes it does.

In early 1990s, Lai K ( 30 patients) et al evaluated this concept.  Compared to kappa staining, the lambda staining was higher in IgA nephritic patients and in addition there was pre dominance of IgA lambda chains in circulation.  Interestingly the same authors published the same results in AJKD in 1998 showing the same concept.  In the same year, the same group of authors showed that IgA had strong lambda mesangial binding in another journal.  Interestingly, a JASN review later refers to the Lai studies as well regarding the lambda dominance of IgA.

A more thorough study done recently is more intriguing. The pattern of light chain IF and light microscopic diagnosis in 306 cases of various nephropathies was reviewed in one center in India. Light chain deposits were seen in 240 (78.43%) cases. In IgA nephropathy, lupus nephritis and post-infectious glomerulonephritis (PIGN), lambda positivity was more as compared to kappa. Light chain deposits in LCDD and membranous nephropathy were more kappa type.

In other words, there is some lambda predominance of kappa in IgA nephropathy but we have to keep in mind the number of patients that the first 1990s this was evaluated in. It was interesting to see that the retrospective review confirmed this from India and it also showed that PIGN and lupus also had a more lambda predominance.  There is also IgA myeloma which is important to keep in the differential if the pathologist says there is significant more dominance( but the light microscopy and EM findings will be much different in myeloma related disease)

Monday, December 2, 2013

IN THE NEWS: New guidelines for Hypertension in Pregnancy

A recent task force from ACOG ( included high risk OB, anesthesiologists, nephrologists) in 2013 re-evaluated the definition and concept of using proteinuria in the diagnosis of pre-eclampsia. Proteinuria is not going to be considered a hard finding anymore for the diagnosis of pre-eclampsia. The ACOG felt that this would delay diagnosis in many cases. The entire report is found here.
Proteinuria seemed to have been down graded in many instances in the report. 


BP criteria remained
Proteinuria over 5gm has been eliminated from the term of severe preclampsia.
Severe features of pre-eclampsia now include: BP changes, SBP>160mmHg, low platelets, impaired liver function, AKI, pul edema and new onset cerebral disturbances.

Some other changes:

  • Screening to predict preeclampsia beyond taking an appropriate medical history to evaluate for risk factors is not recommended.
  • Vitamin C or vitamin E to prevent preeclampsia is not recommended.
  • Daily low-dose aspirin to help prevent preeclampsia is suggested in very high-risk women with a history of preeclampsia and preterm delivery.
  • Antihypertensive medication is recommended for severe hypertension during pregnancy.
  • A decision to deliver should not be based on the amount of proteinuria or change in the amount of proteinuria.
  • The use of magnesium sulfate is recommended for severe preeclampsia, eclampsia, or HELLP syndrome.

Risk factors the task force came up with for pre-eclampsia:

Prior pre eclampsia
Chronic HTN
Thrombophilia history
Multi-fetal pregnancy
Family history
DM I or II
Advanced maternal age ( >40)

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