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)

Monday, November 25, 2013

Clinical Case 77 Answers and Summary

A 56 y old on PD presents with PD peritonitis and bacteremia as well likely related to the peritonial infection. How would you treat?

The role of IV antibiotics in PD peritonitis has always been questions. A recent Cochrane review was done on this topic. They identified 36 studies (2089 patients): antimicrobial agents (30); urokinase (4), peritoneal lavage (1) intraperitoneal (IP) immunoglobulin (1). No superior antibiotic agent or combination of agents were identified. Primary response and relapse rates did not differ between IP glycopeptide-based regimens compared to first generation cephalosporin regimens, although glycopeptide regimens were more likely to achieve a complete cure (3 studies, 370 episodes: RR 1.66, 95% CI 1.01 to 3.58). IP antibiotics were superior to IV antibiotics in reducing treatment failure (1 study, 75 patients: RR 3.52, 95% CI 1.26 to 9.81). Based on one study, IP administration of antibiotics is superior to IV dosing for treating PD peritonitis. Intermittent and continuous dosing of antibiotics are equally efficacious.
What about bacteremia in addition to the PD peritonitis?  This is a hard question that hasn’t been looked at. A study did analyze the incidence rates and risks of bacteremia and HD and PD. Placement of a permanent access (fistula, graft, or PD catheter) prior to initiation of dialysis, smoking cessation, and better nutritional status (i.e. higher serum albumin) were associated with a reduced risk of bacteremia in dialysis patients. Higher serum albumin was also associated with a reduced bacteremia-associated mortality.
Two cases reports have looked at treating cases of peritonitis and bacteremia. Most used IP only but some had combo treatment. The jury is still out.

Friday, November 22, 2013

Crizotinib and the Kidney

Does crizotinib cause AKI? and is it reversible?

Crizotinib is a ROS-1 inhibitor and acts on anaplastic lymphoma kinase (ALK) to treat non small cell lung cancer.It also inhibits the hepatocyte growth factor tyrosine kinase. Hence, another angiogenesis inhibitor.
In 2011, it was approved for use in NSCLC with abnormal ALK gene mutation. There was some initial concern regarding this agent and renal function. A biopsy proven case of ATN was published not too long ago from France.

A recent analysis from Univ of Colorado looked at 38 patients with NSCLC who got this agent. The mean GFR decreased by 23.9% compared to baseline and most happened in the first 2 weeks of therapy. Pre renal causes were excluded. 84% of the patients recovered renal function back to baseline after cessation of therapy. The investigators thought that the rapid reversibility raised the possibility that this was a tubular creatinine secretion effect rather than nephrotoxic effect. They didn't have biopsy data.

Here is a commentary on this study.

Thursday, November 21, 2013

HIV associated TMA: Is this an ADAMTS13 mediated entity or CMV related?

HIV associated TMA was more common in the AIDS era. After advent of HAART therapy, this entity is rare.

Traditional Risk factors are:
Low CD4 count, high viral load, concurrent Hep C and AIDS, blacks

Most secondary causes of TMA, treating the underlying cause or removing the underlying medication would treat the TMA(HUS or TTP variant).
Interestingly, one study looked at TMA from HIV in more detail and the use of plasma exchange. They prospectively looked at biological differences and response to the therapy. Response was much better in the HAART + plasma exchange arm versus HAART arm alone.  Interestingly, 80% of the patients that developed TMA , had either low ADAMTS13 levels or antibodies to them-in which case TPE or plasma exchange would offer benefit. Does HIV modulate ADAMTS13 or lead to inhibition?

Another study looked at the role of CMV viremia for causing TMA in HIV patients. They looked at clinical and pathological data for 29 patients with TMA and HIV infection. The diagnosis of TMA was confirmed by histological examination of kidney biopsy specimens (18 cases). Endothelial cytomegalovirus (CMV) inclusions were associated with TMA in nine of 18 cases, whereas histological examination did not detect CMV in any control specimens (P < .001).  This study using a case controlled method demonstrated a link of TMA and clinical systemic CMV infection by an odds ratio of close to 4.

So lets revise the risk factors for HIV associated TMA

1. Low CD4, high viral load
3. Blacks
4. Hep C
5. Concurrent CMV viremia
6. ADAMTS13 inhibition or deficiency.

Tuesday, November 19, 2013


The CORAL trial finally has arrived. Stenting the renal vessels has always been a topic of debate.  This is the largest trial to date that directly compared intervention to medical therapy in atherosclerotic renal stenosis.

1. Investigators randomly assigned over 900 patients to either medical therapy or stenting.
2. Cardiovascular or renal events were the end points. - MI, stroke, need for ESRD and or death
3. 43 months of follow up and no different in primary endpoints. No difference in mortality. Blood pressure slight better in stent group
4. Meds that were used in their protocol:- Atacand with or without HCTZ and a combo of CCB and statin.
5. All renal arteries with stenosis >60% or more were treated( prior studies some severe cases were excluded)
6. Close to 50% in both arms had patients with CKD stage 3 or higher( makes it hard to offer stenting already)
7. Looking closely at the data, it appears that there were more strokes in the medical therapy arm but still not statistically significant. Interestingly, more patients reached ESRD in stent arm than medical therapy arm but not statistically significant.
8. Author's recommendation- no significant benefit to stenting in atherosclerotic renal artery disease.

Is this the end of RAS in atherosclerotic renal disease?-I think so!

Monday, November 18, 2013


A new mnemonic has been created in the last few years for anion gap acidosis. 

Glycols( ethylene glycol, propylene glycol)
L- lactate
Renal failure

Two popular mnemonics were often used to remember the major causes of the high-gap metabolic acidoses. The first is KUSMALE which represents Ketoacidosis, Uremia, Salicylate poisoning, Methanol, Aldehyde (paraldehyde), Lactate, and Ethylene glycol. 
The second is MUD PILES( most popular), spells out Methanol, Uremia, Diabetic ketoacidosis, Paraldehyde, Iron (and Isoniazid), Lactate, Ethylene glycol, and Salicylate.

Why GOLDMARK then? The causes have changed in the 21st century. We barely see any more paraldehyde any more, neither we see that much Iron and INH related causes.
Newer causes: D-lactate: seen with short gut syndrome( especially after sugary drinks), diabetes can lead to d-lactate as well. Other new causes is pyroglutamic acid ( oxoproline) seen with chronic Tylenol use. Finally, propylene glycol infusion that is usually found in lorazepam, phenobarb and banana bags.

Tuesday, November 12, 2013

Is BK Virus oncogenic?

EBV virus has been associated with PTLD and many other viruses have oncogenic potential. Does a common urological virus such as BK have oncogenic potential in our transplant patients?    
Given its predilection to lower GU tract, cancers of bladder have been reported with BK( just case reports). In the tumor cells, it is possible to detect fragments of the viral genome that could alter the control mechanisms of the cell cycle and DNA repair.

Besides the correlation between BKVN and graft failure, a small number of case reports suggest an association between BKV infection and the development of renal and bladder cancers in renal transplant recipients. Indeed, for more than 30 years, an oncogenic potential of BKV has been observed in vitro and in animal models. In humans, however, the implication of BKV in tumor development is still unclear.

A table in a recent publication summarizes some of the cases.

Interestingly, Lithium has been associated with collecting duct carcinomas due to the mode of it’s action. At ASN this year, the pathologist presented a case of collecting duct cancer in a transplanted kidney in  a patient who was on Lithium and had persistent BK nephropathy. The biopsy showed a tumor burden as well significant BK virus staining. Talk about second hits!

Monday, November 11, 2013

eAJKD and NOD ASN 2013 coverage

Check out some excellent ASN 2013 coverages of top news and abstracts from ASN 2013 Kidney week'

eAJKD blog :http://ajkdblog.org/tag/kidney-week-2013/
Nephrology on Demand coverage: http://blog.ecu.edu/sites/nephrologyondemand/?p=9224

Monday, November 4, 2013

Clinical Case 76: Answer and Summary

A 35 y old male with BMI of 38 has microalbuminuria. He has hyperlipidemia and no history of DM or HTN. What do you do next?

  8 (10%)
Weight loss and observe microalbuminuria
  63 (79%)
Observer microalbuminuria
  6 (7%)
Kidney biopsy
  2 (2%)

With 79 responses, most of you would just recommend weight loss( given BMI) and observe the microalbuminuria. Close second was starting ACEI/ARB.  Given no DMII or HTN, many thinkers in nephrology on "microalbuminuria" say that observing might be a better option. Chronic illnesses such as obesity, hyperlipidemia, rheumactic illnesses, etc. all can lead to microalbuminuria. In other words, it can thought of as "ESR" test rather than real renal disease. Observing is important as if rises to significant proteinuria, then certain action might be needed ( as new disease might have developed or meds might be indicated). Data on this is still skim and perhaps we shall hear about this soon in the literature.

Wednesday, October 30, 2013

Sweet hydrothorax: A PD complication

Acute hydrothorax is an uncommon but a well-recognized complication of peritoneal dialysis. No single test is definitive for diagnosis. Diagnosis becomes a challenge.
Peritoneal dialysis-(PD) related hydrothorax was first reported in 1967 by Edward and Unger in JAMA( see attached). Transudative pleural effusion develops, more commonly involving the right side, and usually occurs immediately after starting PD or a few days later. The patients may remain asymptomatic or have sudden dyspnea, decrease in ultrafiltration, or pleuritic chest pain.
How do we diagnose it?
Presence of high pleural-fluid glucose concentration.
Pleural fluid concentration of glucose >300mg/dl might be diagnostic.
Others have hypothesized that, given dynamic movement of dialysate, an absolute glucose-concentration level cannot be used to diagnose PD-related hydrothorax. The pleural fluid-to-serum glucose concentration gradient of greater than 2.77 mmol/L (50 mg/dl) was proposed as the cut-off to diagnose the condition.
In general, any pleural-fluid glucose concentration greater than serum is considered to be highly supportive of PD-related hydrothorax.
1.Radionuclide scan (for example, Tc-99 m DTPA) is associated with sensitivity of 40% to 50%.
2.The methylene blue test has been used where its injected and dye is traced from the peritoneum to the pleura. In one study showed no sensitivity and is associated with a risk of chemical peritonitis.

Some case report examples in literature

Check out this powershow that reviews the management of this entity.

Tuesday, October 29, 2013


This year ASN is doing a Fellows In Training( FIT) Bowl again and we shall be doing a mystery case based debate with two fellow teams.
Case based debates are a fun challenging debate sessions that we have invented at our institution that has been a monthly event at our fellowship. Fellows get a brief discussion of a case and then have to choose tests from the power point slide on the left( sample example) and get closer to the diagnosis. Each tests comes with positive and negative points and can get you closer or far from the diagnosis. Costs and what the tests entails have to be known. Finally, the team with the most points reads the kidney biopsy findings. A pathologist will then discuss the case.
This is going to be held on Nov 8th 2013 from 2-4PM at Rm B311 hosted by myself and Dr Hitesh H Shah. Following case debate, there is going to be fellows jeopardy competition.
All fellows in training should try to attend as this will be a fun event.

Thursday, October 17, 2013

Promoting Palliative care in ESRD

A recent article in CJASN promotes 5 policies that are essential to provide good palliative care in ESRD.

1. Universal screening for palliative care(PC) needs:  How can this be done? Questionnaires and screening tools. One such example is the surprise question tool.

2. Incorporate PC measures in ESRD QIP: The advance care planning and documentation of code status can be a start. What has been done thus far has not touched PC.

3. Train the nephrology workforce to deliver PC: This is the most essential piece. With the current fellowship structure, is this possible? Are the faculty in major academic centers even comfortable? Lot of work to be done in this area. A recent study showed that PC experience of renal fellows is very poor.

4. Payment reform for PC services: Incentive always works

5. Fund PC research: Hope this will also happen as well.

The last two policies will only work when big health systems and medical schools promote the science of palliative care. It's about time sub specialists train in PC irrespective of their specialty- cardiology, GI, heme/onc, critical care or renal.

Wednesday, October 16, 2013

TOPIC DISCUSSION: Renal biopsy findings in Diabetics

A recent study looked at patients who had diabetes and had a biopsy at Columbia Univ path registry.
They wanted to see what other findings are seen besides diabetes. Most of these patients had atleast 10 years of diabetes. Prior reports have suggested IgA and Membranous GN as the most common non diabetic findings in these patients.

1. 37% had Diabetic nephropathy
2. 36% had non diabetic renal disease alone
3. 27% had diabetic neph and another disease
4. In the non diabetic renal disease alone:- FSGS , HTN, ATN, IgA neph, membranous GN, Anca disease comprised most of the diagnosis in that order of frequency.
5. ATN was the surprise finding that had not been reported prior reports.

Interesting and useful data. This is probably lower than expected as most that get a biopsy had a clue for an alternate illness in the kidney. The ones that don't get a biopsy also might have dual disease states that often get missed.


Monday, October 14, 2013

ANIO-ASN Dinner evite

The American Nephrologists of Indian Origin (ANIO) invite you to join
us for a reception and dinner at the American Society of Nephrology
Meeting 2013 in Atlanta.
Date:  11/8/2013 at the Peachtree special events and conference center
200 Peachtree Street, Suite 206, Atlanta, GA 30303
7:00 pm  onwards
RSVP  at  anio.asn@gmail.com to attend.

Friday, October 11, 2013

Clinical Case Answers and Summary 75

What is the mechanism of injury of carfilzomib induced renal injury?

Carfilzomib (Kyprolis, Onyx) is a next-generation epoxyketone proteasome inhibitor that is approved for the treatment of relapsed refractory multiple myeloma. The phase 2 trial  that initially raised interest in this agent was a single-arm study of patients with refractory multiple myeloma who received carfilzomib 20 mg/m2 intravenously twice weekly for 3 weeks in cycle 1 and  then 27 mg/m2 for subsequent cycles. Increased serum creatinine was the most frequently reported renal adverse event, affecting 25% of the 266 patients in this study.
Case report and discussions with experts suggests its more likely to be a pre-renal insult. Glomerular disease is less likely the cause of the renal toxicity. In a patient who has multiple myeloma with renal involvement, nephrotoxicity caused by the disease can be hard to distinguish from nephrotoxicity caused by an agent. 

Thursday, October 10, 2013

Non renal causes of microalbuminuria

Non renal causes of Microalbuminuria

Non specific Inflammation
Prolonged elevation in blood pressure


Courtesy of Dr George Bakris.

Wednesday, October 9, 2013

ROADMAP: Did we forget to use this map?

Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease( so we think). Some people might argue its a word that needs to be taken away from the medical dictionary. In 2011, NEJM published the ROADMAP trial.  They wanted to show if the use of ARB would delay the onset of microalbuminuria or albuminuria in patients with Type 2 DM. In a randomized trial, over 4000 patients were either in olmesartan arm or placebo for close to 3 years. The primary outcome was the time to the first onset of microalbuminuria. 

Interesting results:
1. The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; 
2. Microalbuminuria developed in 8.2% of the patients in the olmesartan group  and 9.8% in the placebo group 
3. The serum creatinine level doubled in 1% of the patients in each group. 
4. Greater number had fatal cardiovascular events in the treatment arm — 15 patients (0.7%) as compared with 3 patients in the placebo arm (0.1%) (P=0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes.

This is striking. Causes:- was it hyperkalemia? was it lower blood pressure than we think should be for DMII. This was reviewed by FDA as well. Other renal blogs had mentioned this trial as well.

Monday, October 7, 2013

IN THE NEWS: Conservative management in CKD, and no dialysis

A recent study published in a non nephrology journal highlights a critical point that is often missed by nephrologists. Although there is data coming out from prior studies that conservative management might be better for certain groups of patients then offering dialysis, more studies need to confirm this. This study is a retrospective observational study that looked at conservative management vs offering dialysis.

Some key points

1. The renal replacement therapy group survived for longer when survival was taken from the time estimated glomerular filtration rate at different GFRs.
2. When factors influencing survival were stratified for both groups independently, renal replacement therapy failed to show a survival advantage over conservative management, in patients older than 80 years or with a World Health Organization performance score of 3 or more. 
3. Acute hospitalizations were more in the RRT arm
4.Seventy-six percent of the conservative management group accessed community palliative care services compared to 0% of renal replacement therapy patients ( THIS is a striking number).

ASN had a series of videos on this topic as well.
Finally, a nice blog post on GeriPal on this topic on HD patients.
Image source: www.gloryhpc.com

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