Nephrology in a Resource Limited Setting, Gaza Edition

Uncategorized

by Nimra Sarfaraz

What did I expect from the healthcare system going into the Gaza strip, seemingly one of the most inaccessible and dangerous places on earth ?

It’s embarrassing to say that media portrayals played a role in my notions. I was expecting to see a lack of physicians in a weak system with destruction all around. What I saw was simultaneously heartbreaking and comforting. I went with a team from MedGlobal, a non profit aimed at providing sustainable health care services to refugees, the most vulnerable in crisis areas and in low resource settings. Through MedGlobal, a diverse team from a professional, ethnic and religious backgrounds formed. Our team consisted of specialists in pulmonary critical care, Ob/Gyn, pediatrics, colorectal surgery, surgical oncology, anesthesia, pediatrics, nephrology, heme/onc and neurology. The team had clinicians from both the UK and the US with members identifying as Hindu, Jewish, Muslim, Catholic, Christian and agnostic; our unity around a common goal was beautiful to be immersed in. Our goal was to provide patient care, teaching and donating direly needed medical supplies, all of us were there on our own time and paid our own expenses.

On our first day there, we met with officials from the Ministry of Health and heard from leaders in the oldest and biggest hospital, Al-Shifa . What I will always remember more so than the jarring statistics was the sense of pleading to be heard, heard by the global community about what is happening. There’s a mingled guilt and helplessness in situations like this and I always come away wondering what sheer dumb luck has led me to such a position of comfort and privilege to sit across from individuals ever capable and exemplifying resilience. Later in the day the clinicians dispersed to meet with their Palestinian counterparts in one of two of the main hospitals we were working at, Al-Shifa Hospital or Nasser Hospital with the purpose of understanding each specialty’s work flow and assessing needs for future missions. I was paired and rounded with Dr. Riad, a bright nephrologist who had studied and trained in Egypt. We rounded on patients together and saw cases that ranged from run of the mill AKI to more complex cases such as steroid resistant childhood nephrotic syndrome that was now worsening, prompting a change in therapy. We visited the dialysis unit where many patients greeted Dr. Riad more as a friend. At the end of the day, when the group reconvened over dinner, all our experiences were similar – the lack wasn’t of human capital or education, the handicap was in a stifling lack of resources and mobility. Half of basic necessary drugs are at zero stock level, meaning there are not enough essential medications to effectively run a hospital to last through the next month. Astounding. The average amount of electricity per day is 7 hours. Dr. Aarti Garg, who did laparoscopic colon surgery on this trip, witnessed firsthand electricity flickering mid operation: luckily, big hospitals have generators but what of regular people?

What was I able to contribute as a nephrologist ?

Honestly the nephrologists there are capable and bright. They are deft at managing complex cases and have access to medications such as tacrolimus, mycophenolate and steroids. Uptodate is a highly cherished resource. Some of the more expensive medications, such as rituximab, are impossible to access because of the blockade. If a patient needs these medications, they need to be transferred out of the Strip. Transfer to more advanced centers is an onerous process, as on average 43 people are given permission to leave per day. Thinking comparatively to Las Vegas, a city of about the same size, to imagine only 43 people allowed to leave Las Vegas per day is mind boggling. People can’t leave to study, to visit family or to get more advanced and necessary medical care. Kidney biopsies that are done are sent across the border to neighboring countries to be analyzed. There is no doubt room for improvement, though it would be remiss to comment without also noting that these limitations will be difficult to overcome unless the prevailing root circumstances change. One notable example was the number of patients in the dialysis unit and the space each patient was allotted. The dialysis unit was full to the brim with one patient able to reach over and touch their neighbor, privacy and space, you see, is a luxury in a densely populated area with limited resources. Medications such as erythropoietin and calcitriol were not available; many patients asked us if we were able to provide these medications on a regular basis. 

I have gravitated towards point-of-care ultrasound particularly because of ease of use, rapid diagnostic ability and practicality of use, especially in low resource settings. I’ve previously taken a course with MedGlobal and have been using the Butterfly ultrasound probe on a regular basis. The Intensivists at my home institution have guided and taught me along the way as well. I was tasked with teaching a Point-of-Care Ultrasound workshop to the Internal Medicine and Intensive Care physicians at Nasser and Al-Shifa Hospitals; around 35 med students and attendings attended between two hospital systems. The workshop was well received and we did bedside ultrasound on patients in the Intensive Care Unit there. This part of my time there was likely the most beneficial of contributions to the most amount of people as the clinicians there are going to be using what they’ve learned on an ongoing basis. 

I encourage anyone with even a fleeting curiosity to delve for themselves into the complexities of the situation and with intentional conscience not forget the humanity of people, approach learning about this situation with empathy. Often times the most common narrative is not reflective of reality.

NephMadness Choose Wisely Campaign (#NCWC)

Uncategorized

What to do?  So many good choices, so many ways this can go.  Will your bracket survive past your colleagues and friends or will you have to hear them go on and on how they  pity you or just tell you that you suck.  When the conversation at the next conference turns to NephMadness you don’t want to be the person saying, “Hey I have an early day got to go back to my room”.  Heck this madness is so crazy popular people have literally been kidnapped to prevent entry into the tournament!  

You think to yourself how do I get an edge on the competition.  You google best bets NCAA tournament, there are over 2 million hits.  Oh you meant google best bets NephMadness, first think that shows up is NephMadness for Dummies.  You almost throw your phone/tablet/computer against the wall to show it whose the boss, but wait you remember you will have to buy a new device and who knows if that device will be any smarter.

Then you head to twitter and you see salvation!  You come upon the NephMadness Choose Wisely Campaign #NCWC?  How did this happen? What is this?  Well you see Nephrology Social Media Collaborative (NSMC) Intern Mohamed Elrggal was in a deep sleep when the Knight of NephMadness Past came to him.  He immediately awoke and googled the below image as he needed to know who this Salt Whisperer was.

Image result for gandalf choose wisely

Mohamed thought to himself what does this mean? Suddenly an idea came upon him, what if he led a team to retrospectively analyze the history of the Blue Ribbon Panel, from publications to tweets to choice of coffee and input this data into a simulation model.  He could run the simulation a few thousand times and then be able to accurately predict the winning Teams in NephMadness.  He immediately communicated this idea to his Nephrology Social Media Collaborative (NSMC) co-interns and the team was assembled.  Mohamed’s brainchild became knowns as the Nephrology Choose Wisely Campaign#NCWC.

The first entry was done by the man Mohamed himself.  This was followed in rapid succession by more entries and to totally annihilate the competition check out the wonderful Visual Abstracts!

Image result for rapid fire from destroyer

Below are a list of hyperlinks, first link is to that region’s NCWC entry and then below is the hyperlink to that #specific region (click #NCWC for the whole collection in one spot):

Strong work by @ssfarouk on putting together the infographic summarizing the twitter polls below:

So now you start to feel like you might just win and start to plan a Championship Parade but WAIT WAIT WAIT!  Simply winning is not enough, you feel the need to embarrass your colleagues and walk around like a Boss at the office, to show those other fellowships “Yea we’re bad, What! What!”. Well to honor the idea of FOAMed (Free Open Access Medical education) and to keep your head spinning with content we rolled out the good stuff:

Still don’t know whom to pick, well if all else fails here are some free picks for you. Want free picks in Spanish, no te preocupes we got you covered.

Asking where can I look to find everything mentioned in this blogpost and more coverage of NephMadness click below:

#NephMadness

Shout out to all the contributors to this year’s NephMadness and all the wonderful posts and innovative educational tools used.  A special thanks to our NSMC faculty and the NSMC interns!

And let’s wrap this up with aShooting Starr Moment!

Image result for shooting star

Now let’s win this thing and go cut down some nets!

#nephmadness #nephforward #NSMC

See the source image

#NephMadness Choosing Wisely Campaign: Trial Outcomes Region #TrialsRegion

Uncategorized

NephMadness.jpg

Welcome to the #TrialsRegion; the region with the greatest potential for generating debate about clinical practice (in my humble opinion). Our ability to distil out the relevant information from the outcomes of trials is paramount in improving the delivery of care to patients with kidney disease. Particularly given the rising prevalence of CKD, there is a clear imperative to develop additional therapies through high-quality trials. Much focus has been placed upon the quality and quantity of RCTs within Nephrology; the overall consensus is that we are lagging behind other specialities. Selection of the correct surrogate marker is fundamental in determining the relevance and wider applicability of trial outcomes.
The first matchup in this region pits the old familiar reliable against the young pretender.Doub

Doubling of creatinine has been used as an endpoint in randomised clinical trials for decades. Long-term changes in serum creatinine are thought to reflect a structural renal function decline and predicts development of ESRD. Doubling of creatinine should reflect a sustained reduction in GFR and represent an important step in progression to ESRD.
Although well established, this venerable contender is far from flawless. Using the CKD-EPI creatinine equation a doubling of serum creatinine level approximately corresponds to a 57% decline in eGFR based on serum creatinine level which is a relatively late outcome in CKD. The variable acute and chronic effects of many drugs on renal function suggest caution should be used when interpreting clinical drug trials using doubling of serum creatinine as outcome.

Enter the challenger 40% reduction in eGFR. There is great interest in considering alternative endpoints to shorten trial duration and reduce sample size. 40% is obvious less than 57%, meaning you hit your clinical endpoint at an earlier stage. This has significant implications for the design and likely successful outcomes of CKD trails. Unfortunately, CKD does not decline in a step-wise manner which is a significant limitation of this approach.  Steady loss of function over time is a relatively late manifestation that reflects physiological factors in remnant nephrons.  The applicability of 40% decline in eGFR is not uniform across all clinical settings, particularly if the treatment effect is not uniform across those who progress rapidly and those who do not progress. The use of different equations for determining eGFR must also be considerGraph.pnged. The NKF-FDA concluded that 40% eGFR decline is broadly acceptable as a kidney end point across a wide baseline of eGFR range, however a minimum follow up of 2-3 years is recommended. The trade-off is between improving power (more events) while increasing type 1 error (i.e. false positives).

It is important to bear in mind that both contenders are based on a biomarker; they do not provide information regarding patient health status. Creatinine itself has limits as a biomarker; changes in serum creatinine can be attributed not only to renal structural changes but may also be reflective of muscle mass, dietary changes, changes in renal tubular secretion of creatinine (particularly in patients with proteinuria and hypoalbuminaemia), and haemodynamic effects (particularly relevant given how many of our “go to” medications in CKD exert their clinical effects).

The chatter so far seems to be leaning towards 40% eGFR decline:

Scouting report @methodsmanmd

Scout.png

Mark’s Bracketology for Trial Outcomes @drpaddymark

Bracket1.png40% eGFR Decrease and Other New Kids on the Block @Badves

New Kid.png

Combing through previous tweets by @NephRodby:

Nephy.pngNeph 22.png

Unfortunately, I was unable to uncover any clues about how the rest of the BRP would be inclined to vote based on their Twitter accounts and PubMed searches; perhaps because these aren’t the easiest of search terms to track.

Prediction—40% reduction in eGFR purely from the point of view of causing a minor upset of an established behemoth and generating discussion. Topf22.png

 

Protein.png

The second match-up in this region is genuinely intriguing—two diametrically opposed surrogate measures.

Proteinuria

Beyond any doubt, proteinuria is predictive of an increased risk of progressive renal function loss over time. This association is found in various pathophysiological conditions, includiPROte.pngng diabetic nephropathy, hypertensive nephropathy, and various primary renal diseases. Difficulties arise with regards to 1. Standardised collection methods (spot vs 24 hr collection) 2. Whether it can be used as a surrogate marker—secondary analysis of the RENAAL study found that reduction of proteinuria was a strong predictor of outcome however there are several studies with conflicting outcomes.

Patient reported outcomes

“The good physician treats the disease. The great physician treats the patient who has the disease” William Osler

PROMS

Given its chronicity and symptom burden, the subjective patient experience is key in understanding the impact of CKD. The success of treatments has been historically assessed by doctors using laboratory measures; incorporation of patient perspective into routine clinical practice has been slow to be incorporated. This is because such measures are thought to be intangible and therefore difficult to replicate across clinical trials.

  • Patient Reported Outcome Measures (PROMs)—any metric assessing health, illness or health care benefits from the patient’s perspective; in general they take the form of a questionnaire. PROMs have the potential to highlight relevant symptoms and changes in symptoms, promote patient engagement in their treatment. They include the Kidney Disease Quality of Life Short Form and the Dialysis Symptom Index.
  • Patient-reported experience measures (PREMs) capture information about the healthcare experience as perceived by the patient. They can refer to a variety of issues ranging from cleanliness of facilities to waiting times and how HCPs deliver information.

Of the two, proteinuria has certainly generated the most discussion to date

 

Oates 2.png

Protein 2

Proteinpost.png

 

Swqap post

Rodby.png

The rest of the BRP

Given the extensive patient advocacy work by @FionaCLoud I would imagine she would lean towards PROs.

During her time as ASN President @EleanorLederer has spoken about patient engagement and its role in clinical decision making.

Lederer.png

@DrDeidraCrews was involved in a study examining patient related outcomes and has done extensive work on social determinants of health.

Reid.png

Scouting report @methodsmanmd

Scouting

Mark’s Bracketology for Trial Outcomes @drpaddymark

Mark 2.png

My prediction: Although proteinuria remains the more controversial of the two, Patient Related Outcomes by a narrow margin (5 to 4).

Final winner: 40% reduction in GFR. This could be the dark horse of the competition.

NephMadness Choosing Wisely Campaign (#NCWC): Pathogenic DSAs vs The Untransplantables (#TransplantRegion)

Uncategorized

man-couple-people-woman.jpg

The fight to come out of the Transplant Region is like a sibling rivalry.  Truly all four competitors relate to each other under the umbrella (aka family) of access to transplantfor various patient populations.  Get ready because you know in sibling battles there is no “illegal” weapon.  It is time to get down and dirty.  We are going to discuss Pathogenic Donor Specific Antibodies (DSA’s) versus The Untransplantables.  Please check out my NSMC co-intern Dr. Samira Farouk’s amazing game preview of Kidney Donor Risk versus VirallyInfected Kidneys.

Let us first take a look at Team Pathogenic DSA’s.  They have been scouted before with excellent reviews and concerns.  If one word describes this team as Dr. Dorry Segev mentioned in his overview of the Transplant Region it is “Enigma”. The detection of Pathogenic DSA’s allows for more appropriate matching between donors and recipients and avoiding acute antibody mediated rejection (ABMR). However, how do you know how significant the DSA is?   This brings us to the team leader Antibody Strength or his streetball name “Da MFI” (Mean Fluorescence Intensity).  A team’s leader can reflect both a team’s strength and weaknesses all at once.  “Da MFI” shows good game with great defensive MONITORING on the court, but has limitations such as getting caught out of position or not finishing at the basket.

Ideally the HLA antibodies bind proportionately to a standard amount of target antigen and high antibody levels will develop.  But what if using single antigen bead assays that give us the “Da MFI” the following happens?

1. There is a lower antigen density and despite high levels of antibodies produced there is a falsely low MFI

2.There are high antibody levels and complement activation leading to soluble C1q that blocks HLA antibody binding to the selected antigen, resulting in a falsely low MFI

3. Two different antigen beads have different HLA antigens but the same epitopes diluting the serum antibody resulting in a lower MFI

4. The patient had a sensitizing event leading to production of DSA after antibody testing

5. If you take the same samples with the same beads and do the same test over a course of a week you could end up with varying MFI’s

So Yes we can detect Pathogenic DSA’s but we definitively do not always know what it clinically means.

In 1968 the World Health Organization established criteria for screening practices and it was said that yes in theory was a good practice but there will be “snags”.

So yes there is a lot of science and fascination with Team Pathogenic DSA’s but I have to agree with Dr. Segev, the Team are a group of freshman with their “snags” that will grow together and change with new teammates over time, this is likely not the year but a title run might not be that far in the future

Also Pubmed articles by the Blue Ribbon Panel mentioning “Antibody”: 0

Our opposing team are the Untransplantables One easy rule in picking the winner in NephMadness is where is the most ready prime time player aka look for a relevant intervention with a significant transparent effect on diagnosis, treatment, or patient outcomes.  Well the Untransplantables were once a ragtag group that heard the words, “too sensitized”, “can’t go against nature”, “no student would ever EXCHANGE over to this team”, and “can’t land a hot shot recruit”, maybe not anymore.  They have a superstar in my opinion that would make the all tournament team, overcoming HLA incompatibility in transplantation.  The superstar has two primary offensive weapons, the paired kidney donor exchange (PKDE) and desensitization.  Let us focus on PKDE.  The National Kidney Registry (NKR) is a national registry in the USA of listing living kidney donors and recipients in need of a kidney transplant.  The NKR was founded in 2007 and as of early 2018 has resulted in 2598 transplants(https://www.kidneyregistry.org/index.php).  This goes beyond a patient being untransplantable with a potential donor, it also allows for a better match in terms of other factors such as age.  PKDE can be used in concert with desensitization via an  algorithmic approach.

See the source image

But do not forget there are a few other players that have given new hope to patients.  One of them is ABO incompatibility transplantation which is becoming more mainstream in particular with specific type B blood recipients receiving organs from donors with A2/A2B blood type.

Simply put, the Team Pathogenic DSA’s has plenty of team Defense and Monitoring.  However it is questionable how much this will lead them to a win.  On the other hand we have The Untransplantables whom have a great defense (since technically DSA monitoring is used in these patients) but can score in both natural and unnatural ways.

Plus if you ask who is the most prime time ready player that has made an impact measured by number of transplants, then it becomes an even easier decision.

Yep HLA typing and checking for DSA is a pillar of transplantation, but think about it if I find an issue using my DEFENSIVE MONITORING but then how do I SCORE off it?  Use one of the methods mentioned with the Untransplantables like desensitization or PKDE.

Plus if you think health care providers and patients aka our Blue Ribbon Panel want to overcome barriers not just hear they exist which way do you think they will sway?

Pick: The Untransplantables    

#NephMadness Choosing Wisely Campaign (#NCWC) – #HyponatremiaRegion

Uncategorized

(aka What Did I Get Myself Into?)

Welcome to the #HyponatremiaRegion of #NephMadness – where everything’s somewhat made up and the only the points from the #BlueRibbonPanel matter!

European VS US Hyponatremia Guidelines

Hyponatremia strikes a frisson of anxiety in me, especially when receiving phone calls from colleagues who regard me (as a representative of the nephrology team) as the ultimate authority in the matter. After going through the patients’ medications and history, I generally weakly advise mostly fluid restricting, occasionally fluid resuscitating and, when the mood strikes – investigating for SIADH. For anything else – there is always 3% hypertonic saline (which I have never been successful at obtaining)

This is why I leapt at the chance of learning more about how the experts approach this nebulous entity – enter the Battle of the Continents: the European vs US Guidelines! Reading this excellent and concise scouting report by Swapnil Hiremath (@hswapnil) will make navigating the guidelines less daunting.

In addition, here is an infographic that attempts to simplify things further:

HypoNa infographic v6

As Swap points out, there are similiarities in the guidelines:

Perhaps the most important part is that both guidelines agree on a limited daily increase in serum sodium even in severely symptomatic hyponatremia (unlike in the 1980s, when the target was to bring sodium up to 128 mmol/L in a day)! And hypertonic saline is the fastest way to fix it on both sides of the Atlantic, as it has been since 1938.

However, he also points out some significant differences:

Do you prefer the Europeans with their streamlined and graded algorithmic advice or the Americans with detailed explanations and ungraded boxes of advice? Do you agree with trials of tolvaptan that results in a recommendation against their use and case series driving a urea recommendation or do you think the funding source and a tolvaptan recommendation are uncomfortably aligned?

Below are screenshots from both guidelines detailing their funding and COI of the authors:

Screen Shot 2018-03-25 at 00.33.29 Screen Shot 2018-03-25 at 00.34.18

The European Guidelines

Screen Shot 2018-03-21 at 9.20.37 PM

The US guidelines

Make of them what you will.

A very timely poll by fellow NSMC co-intern Mya Hwte Nge (@mhtwenge) shows what the general public think… but will this reflect the decision of the BRP?

I started by going through the Twitter accounts of the BRP, and found these from Roger Rodby (@NephRodby) and Mark Reid (@medicalaxioms):

Unfortunately, I was unable to uncover any other telling clues about how the rest of the BRP would be inclined to vote based on their Twitter accounts and PubMed searches (I did, however, manage to get distracted by quite a few interesting abstracts, so it’s a win-win for me!)

I then decided to change my tactic by attempting to dig through the archives of a few other notable salt whisperers and electrolyte gurus who might influence the choices of the BRP: Joel Topf (@kidney_boy – I had to limit myself to tweets from the past 5 years), David Goldfarb (@weddelite), Rush Nephrology (@Rush_Nephrology) , and Bill Whittier (@TWhittier_RUSH). Although not much was found after searches of most of these accounts, the treasure trove of tweets from Joel did not disappoint – it’s safe to say that he is a proponent of vaptans! 

(and he loves a bit of hyponatremia!)

(check out the rest of the thread in which he stated Ure-Na worked for him)

Disappointingly, I was also unable to clarify Swap‘s stance on these guidelines – unsurprising, as the scouting report was very balanced and neutral.

My last ditch attempt at trying to get somewhere with this ended with me going through some open forum posts at ASN communities. I get the feeling that both tolvaptan and urea are favoured by nephrologists, but with the caveats that:

  • Tolvaptan costs a lot more, and there are a few articles that highlight the possibility of osmotic demyelination syndrome with overly rapid correction of hyponatremia (here, here and here) – hence the need for very close monitoring and careful dosing
  • Urea is potentially unpalatable – although this might be debunked with this viral tweet of Roger trying some Ure-Na:

I feel that the BRP (maybe besides Mark) will be inclined to vote for the US guidelines – why not have two weapons in your arsenal, rather than be limited to just one? Does it matter greatly that Otsuka funded the US guidelines when other prominent nephrologists who don’t seem to have conflicts of interest swear by vaptans?

SIADH VS Cerebral Salt Wasting (CSW)

Swap succinctly explains why these two entities are important to distinguish in his scouting report:

In SIADH, the first-line intervention is fluid restriction, which will make matters worse in the volume-contracted patient with salt wasting. Conversely, salt wasting syndromes can be easily fixed with intravenous normal saline, which would make hyponatremia worse if the patient has SIADH instead.

He tries his best to stay impartial throughout the description of cerebral salt wasting, but then ends the section with this:

Regardless of what you think about the reality of cerebral salt wasting, SIADH is a condition that every nephrologist worth their salt needs to know how to manage. It is not an easy condition to deal with. Clinicians need to use all their cerebral capacity to recognize symptoms, correct the sodium level with the appropriate level of aggressiveness, and not spend too much time chasing the salt-wasting hobgoblins.

I struggled to find any opinions on cerebral salt wasting by the BRP bar this one by Roger

But then this impassioned thread by David in response to Mitch Rosner’s picks for the #HyponatremiaRegion dropped – and it looked like the final word on CSW had been said! @weddellite for CSW!

I did not think that this would have gone unchallenged – what did the rest of NephTwitter think? Check this thread out!

(tl;dr – Joel and Matt Sparks, @Nephro_Sparks are decidedly not backing CSW)

I therefore predict that this will actually be an upset and the BRP will vote for CSW (with the possible exception of Roger who might not take the outcome without a fight – might this herald internal disharmony among the BRP?!)

In conclusion, I feel that the two winners of this unassumingly controversial bracket will be the US guidelines and cerebral salt wasting!

Follow #NCWC for region updates.

Read the full AJKD blog (and check out the full scouting report for the #HyponatremiaRegion here).

Submit your NephMadness brackets here.