Nice job by Justin, class of 2018. Podcast on sickle cell anemia.
Nice job by Justin, class of 2018. Podcast on sickle cell anemia.
Made for the #NephMadness #TransplantRegion, here’s a nice way to spend any Sunday morning (answers below, try not to cheat…):
What are the beliefs of patients with Chronic kidney disease about Pregnancy?
What do they want to know from their doctors?
This study throws some light on this important yet neglected subject.
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.
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!
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:
Asking where can I look to find everything mentioned in this blogpost and more coverage of NephMadness click below:
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!
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.
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 considered. 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
Mark’s Bracketology for Trial Outcomes @drpaddymark
40% eGFR Decrease and Other New Kids on the Block @Badves
Combing through previous tweets by @NephRodby:
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.
The second match-up in this region is genuinely intriguing—two diametrically opposed surrogate measures.
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, including 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
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.
Of the two, proteinuria has certainly generated the most discussion to date
The rest of the BRP
Given the extensive patient advocacy work by @FionaCLoud I would imagine she would lean towards PROs.
@DrDeidraCrews was involved in a study examining patient related outcomes and has done extensive work on social determinants of health.
Scouting report @methodsmanmd
Mark’s Bracketology for Trial Outcomes @drpaddymark
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.
Check out this fun crossword about transplantation. Let us know if you get all correct in the comments below.
Hint: For all the answers visit the #Transplantation region of #Nephmadness
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.
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
(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!
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:
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:
The European Guidelines
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?
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:
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?
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!
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.
The PD region is an interesting one. As a commonly used dialysis modality worldwide it has historically remained under utilised in the US. However its popularity has increased over the last 2 years.
This region pits 2 common PD issues – ‘Volume Issues’ and ‘Solute Issues’ against each other and 2 less common, but important, issues ‘Culture Negative Peritonitis’ and ‘Catheter Dysfunction’ against each other.
The battle between Volume Issues and Solute Issues
Volume issues come up daily, or multiple time a day in all PD units. The patient’s’ volume status, often expressed in relation to their target weight, is usually recorded daily. This then decides what PD bags they’ll use that day and can influence their symptoms, the amount of input they need from PD nurses and Nephrologists, how often they need to come to the PD unit as well as the frequency of hospitalisations
Although some tools exist to help guide fluid balance such as bioimpedance and lung US the mainstay of volume assessment is daily weights, measurement of drain out volumes, and longitudinal follow up with clinical fluid assessment
In contrast to the low-tech volume issue, solute issues are higher tech and understanding the ins and outs of the three-pore model, PET testing and the ideal peritoneal dialysis prescription for high, average, and low transporters takes a bit more time and reading. Understanding the patients transport status does allow us to ensure the patient is on an appropriate type of PD(i.e. short exchanges usually using overnight APD ±
Daytime exchanges or longer exchanges most suited to CAPD) for them which ultimately allows the patient to get the most of PD and stay in euvolemic with no uremic.
For true PD bliss it is imperative to get both of these issues right.
However, I would argue that in terms of patients’ symptoms, hospitalisations and day to day management volume issues are much more important than solute issues. But what will the Blue Ribbon Panel think?
The showdown between team Catheter Dysfunction and team Culture Negative Peritonitis
These are less frequent problems than teams Volume V Solute but can cause a lot of trouble when they occur. Culture Negative Peritonitis is often a regular peritonitis (e.g. staph epi) that won’t grow in culture because of prior antibiotic use or incorrect sampling. However sometimes it can be from a non-infectious source e.g. ‘collection from a dry abdomen’ or from an organism that’s hard to grow. TB peritonitis can be a difficult to find and difficult to treat etiology of infectious peritonitis.
Catheter Dysfunction is frequently encountered with different degrees of severity. Fortunately, the most common cause of catheter dysfunction is constipation. This is often dealt with expertly by the PD nurse and may not even find its way to the nephrologist. However, some causes of catheter dysfunction are harder to deal with. For example, the PD catheter can change position in the abdomen or can be wrapped in the omental. This can be addressed by Interventional Radiology or occasionally repeat surgery warranted. Unfortunately this could mean the end for that particular catheter.
I would argue that catheter dysfunction has a bigger impact on patients and on technique survival than culture negative peritonitis
What I think doesn’t matter so can we gain any clues on what the Blue Ribbon Panel may think? All of the panel members have kept quiet on social media about their possible preferences forcing some further digging to try find out their thoughts or biases to further inform your #NephMadness choices. This is what has come up from PubMed searching and a quick view of their social media postings.
Roger Rodby (@NephRodby) has tweeted a few times about PD
I tell my Fellows if a patient has been on PD for more than a couple years, anything funny is a clue for EPS until proven otherwise #nephjc
— Roger Rodby (@NephRodby) July 12, 2017
In your cases the pooper was also the patient? In my case the peritonitis patient was the parent of the pooper; to politely paraphrase #plz
— Roger Rodby (@NephRodby) June 14, 2017
Rodby has mentioned encapsulating peritoneal sclerosis (EPS) which could cause volume issues, solute issues, catheter dysfunction, and culture negative peritonitis. He has also tweeted about PD Peritonitis secondary to baby poo. I imagine that isn’t culture negative… Its a coin toss for Rodby
Fiona Loud(@FionaCLoud) is an enthusiastic advocate for Home Therapies, meaning the PD region is right up her street. She has also tweeted about the difficulties of maintaining a strict fluid balance on dialysis. Maybe relevant… Volumes Issues??
— Fiona Loud (@FionaCLoud) June 21, 2017
Mark Reid (@medicalaxioms) has also tweeted about PD. He has commented on the PD survival advantage
Looking at the numbers agains this morning it still looks like PD results in longer survival than HD. Sending up a prayer for you!
— Mark Reid, MD (@medicalaxioms) December 12, 2017
He has also tweeted this…
Is it really dialysis if it’s peritoneal? Asking for a friend…
— Mark Reid, MD (@medicalaxioms) July 8, 2016
So there you have it. Although the blue ribbon panel are keeping their choices close to their chest as to their preferences within the PD region, its clear PD is an important issue to many of them. The PD region is likely to go far!
In the absence of any failsafe Blue Ribbon predictions i’ll give you mine:
The battle between Volume Issues and Solute Issues:
The showdown between team Catheter Dysfunction and team Culture Negative Peritonitis:
Follow #NCWC for daily region updates.
Read the full AJKD blog (and check out the full scouting report for the #PDRegion Region here).
Submit your NephMadness brackets here.