NephMadness Choosing Wisely Campaign: Kidney Donor Risk vs Virally Infected Kidneys (#TransplantRegion)

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The first matchup in the #TransplantRegion leaves us with two tantalizing options: “Kidney Donor Risk” and “Virally Infected Kidneys”. How does one possibly choose between the bold risk one takes when choosing to save a life and the now possible but previously unimaginable transplantation of kidneys infected with Human Immunodeficiency Virus (HIV) the curable Hepatitis C (HCV)?

Let’s take a quick look at team #KidneyDonorRisk. Why should we care about kidney donor risk? Well, even the first kidney donor in 1954 ultimately progressed to end stage renal disease (ESRD)…

Since 1954, we have developed new tools to better quantify a potential kidney donor’s ESKD  risk, like this calculator – which can be used to calculate any donor’s pre-donation 15 year and life time ESKD risk. In addition, 2-time APOL1 champion may easily carry this team to the saturated 16. Would you advise kidney donation to a patient with 2 APOL1 risk alleles, given that 2 out of 19 patients developed ESKD after a median follow up of one year in one small study? If you’re still not convinced, take another look at @KristaLentine’s support of this team as the winner of not only this matchup, but also of the entire #TransplantRegion. She emphasizes the importance of the understanding of donor risk and transparency of communicating this risk.

If #KidneyDonorRisk isn’t your thing, maybe you’re a believer in the #VirallyInfectedKidneys.

And why wouldn’t you be? The THINKER trial showed us that HCV + kidneys can now be transplanted into HCV – recipients, with successful treatment of HCV post transplantation. A limited kidney donor pool may ultimately be significantly expanded, if HCV+ kidneys are no longer discarded.  Similarly, the HOPE (HIV Organ Policy Equity) Act has resulted in the transplantation of HIV+ organs and promising  overall and graft survival rates.

Now what? You’ve read @paulphel‘s comprehensive scouting report and seen enough visual abstracts, but all that really matters is the Blue Ribbon Panel. I predict team #KidneyDonorRisk to win this matchup, and here are the 5 of 9 Blue Ribbon Panelists that I’m most confident will help advance it to the next round:

  1. @FionaCLoud:  She’s a kidney transplant recipient and fierce advocate. It seems likely that she’ll keep #KidneyDonorRisk in her bracket.
  2. @DrDeidraCrews:  She researches the impact of racial disparities on chronic kidney disease, and has published on the disparities in access to kidney transplantation.
  3. @Mike_J_Choi: He’s an author on a 2013 NEJM study describing APOL1 risk variants, race, and progression of CKD. I don’t expect him to forget about APOL1 so quickly.
  4. Tazeen Jafar – She has studied predictors of low eGFR after kidney donation, in a Southeast population from Singapore.
  5. @medicalaxioms –  He probably cares about the #KidneyDonorRisk. The tweet below says it all:

Ready to make your pick? Submit your bracket here.

Samira Farouk, NSMC Intern 2018 @ssfarouk

 

 

#NephMadness Choosing Wisely Campaign (#NCWC) –Women’s Health Region (#WomensHealthRegion)

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From ‘Prematurity’ to ‘Menopause’, life completes a full cycle in the Women’s Health region of Nephmadness 2018. Let it be the glomerular disease (preeclampsia) or dialysis & transplant (reproductive planning) or endocrine disturbances, this region has something for everyone, including our pediatric colleagues. The fact that all of the players in this region are of vital importance makes the choice even more difficult. 

For me, all are champions in their own way, but let’s try to peep into minds of #Blueribbonpanel (BRP) who will have the final word in crowning the champion. The fact that we have 6 wonderful ladies (out of 9 members) on the BRP is a testimony to the fact that this region is going to make it big.

Reproductive planning Vs Menopause in CKD

None of the BRP members have leaked any clues about how they might vote on the Twitter just yet. Therefore, we decided to do a deep dive and search the #WorldkidneyDay chat. This gives us some important clues. Fiona Loud (@FionaCLoud), Policy Director at Kidney Care UK, who is a kidney transplant recipient herself, has talked about Pregnancy in CKD.

She has actively advocated for the patient’s perspective related to pregnancy in CKD during the World Kidney Day chat (#WKDChat).

So it will be not a surprise if she votes for ‘Reproductive Planning’. Also, Eleanor Lederer (@EleanorLederer) had actively participated in the #askASN Chat and discussed reproductive issues in CKD

And she surely advocates pregnancy in glomerular diseases.

Quotes by Roger Rodby (@NephRodby) on reproductive planning are so famous that he was quoted in a presentation in India.

After reading his paper on “Disease-specific patient reported outcome tools for SLE” we are confident that he will favor reproductive planning. A Twitter and PubMed search for Deidra Crews (@DrDeidraCrews) didn’t reveal any clue directly related to these regions, however she has done some commendable work in the field of disparities in Chronic kidney disease and transplant which makes me believe that she will support reproductive planning in CKD as well.

Thus 4/9 votes for reproductive planning.

None of the PubMed/Twitter accounts of other BRP members had any other clues however, this post by Mark Reid (@medicalaxioms) might be the best clue we can get and is “right” to the point.

Menopause in CKD is an equally important topic addressing harmful effects on cardiovascular risk, bone health and on patients’ quality of life. But we expect ‘reproductive planning’ to be much more popular amongst the BRP. Also, Selection committee member Michelle Hladunewich (@mhladunewich) will try to persuade the BRP in the favour of Reproductive Planning as is evident in her important review on pregnancy in CKD and recently in ESKD.

A battle for the larger Global Impact: Preeclampsia Vs Prematurity

Two of the BRP members Fiona Loud and Mark Reid have a shared their experience with Preeclampsia in these tweets.

Eleanor Lederer has elegantly explained urinary findings is preeclampsia in this paper and she has also addressed this issue on twitter.

Tazeen Jafar’s work on young prehypertensives, on hypertension and cardiovascular health,  and on coronary artery disease in women is likely to make her inclined towards preeclampsia.

This makes it again 4/9 votes for preeclampsia.

The only BRP member who may lean towards ‘Prematurity’ is  Sarah Faubel (@doc_faubel) by the virtue of her work AKI in neonates. Bryan Carmody (@jbcarmody) has made an excellent argument in favor of prematurity in AJKD blog mentioning the long-term kidney outcomes, but unfortunately, he is not on the Blue Ribbon Panel.

Preeclampsia seems to be very popular amongst those who have already filled their brackets.

And that’s my poll for the Women’s Health Region

Bottomline – Women’s health region is here to win. Choose your pick wisely.

Follow #NCWC for daily region updates.

Read the full AJKD blog (and check out the full scouting report for the #Women’s healthregion here).

Submit your NephMadness brackets here.

Do let us know about your choices in the comments.

#NephMadness Choosing Wisely Campaign (#NCWC) – Animal House Region (#AnimalRegion)

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As the submission deadline for picks for #NephMadness 2018 approaches, many of us are wondering how the Blue Ribbon Panel will make its decisions on which teams should advance to the next round. Here we take a look at the Animal House Region (#AnimalRegion) to see who looks like an under-dog and who may come out top dog (animal puns are an added benefit of this region!)

The Battle of Osmolality Regulation: Pee Shark versus Salt-Switching Salmon

It’s tough to get a read from selection committee member Dr. Mark Zeidel and Dr. Timothy Yau’s (@Maximal_Change) great scouting report of this region. This opening battle serving as a clash of the competing osmololar balance mechanisms. Based on popular opinion alone, the shark appears to be somewhat of a fan favorite, judging by the interest garnered by a tweet thread appears in August 2017 about the Greenland shark. While not entirely composed of urine, sharks maintain extremely high urea levels to act as “osmoregulatory ballasts” allowing these predators to maintain osmolality in the range of 1,000mOsm/kg with 30% composed of urea. In addition to their fascinating physiology, sharks also possess fine control of osmoregulation through their rectal glands, with Na/K/2Cl concentrations 50x that of the TAL in humans. Additionally, this discovery has allowed for advances in our understanding of the TAL and diuretic physiology – findings with direct and important consequences for humans.

shark

However, Team Salmon also puts together a convincing team, with a versatility not often matched in this year’s field. As a teleost fish, salmon adapt from freshwater to saltwater and back again to freshwater, a swing of environmental osmolality of 1,000 mOsm/kg without significant changes in serum osmolality. This is due to a combination of osmosensor mediated diffusion and upregulation of transporters in the gills, as well as specialized cells in the GI tract. If adaptability is the key to a team’s success, Salmon may be the sleeper in this region.

 Camel versus Toad: Water, water everywhere or nowhere?

This matchup is the battle of adaption to environmental extremes, and it’s tough to get a read from the selection committee scouting report. This dipsogenic dromedary is the exception rather than the rule with regard to osmolality. Returning to the scouting report, Dr. Zeidel focuses on the physiology of this adaptive response:

Despite these adaptive responses, as camels dehydrate over their 2 weeks without water, their Na rises from 154 to 191 mEq/L, with corresponding serum osmolality rising from 304 to 406 mOsm/kg. When given access to water, they re-hydrate rapidly; they lower their serum Na and osmolality to baseline levels within hours. And again, despite this massive shift, their mentation and neural function remains intact. Remarkably, these large swings in serum osmolality do not alter the camel’s neurological functioning.

Camels appear to be drawing strong support on Twitter, with memes in support of this team almost equaling that of Team Shark above. One weakness of the Camel team is the lack (so far at least!) of physiologic understanding of how camels tolerate such dramatic dehydration/rehydration – although some supporters of this team may argue that this makes the feet even more impressive!

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Team Toad’s argument is for the power of the amphibian’s bladder, with the ability to reabsorb water from the bladder as needed depending on evaporative skin losses. First discovered in the 1950s, this physiologically advanced animal (along with others) was responsible for the discovery of aquaporins and essential in our understanding of free water homeostasis. Findings of this advanced physiology in toads and frogs has had direct implications for our understanding of water handling in the human distal tubule. Additionally, the discovery of aquaporins was considered so fundamental that Peter Are won a Nobel Prize for this finding, further strenghting the importance of this team.

Can we gather any information about how the Blue Ribbon Panel will vote? A search of their twitter activity doesn’t reveal any strong preferences, retweets or suggestions of animal preference – in fact all members of the Blue Ribbon Panel have been silent on this region. A quick review of PubMed offers a few clues into how the panelists may vote. Sarah Faubel (@Doc_Faubel), for example, is interested in animal models of AKI, suggesting that she may pick a team from this region to go deep in this year’s tournament. Additionally, Eleanor Lederer (@EleanorLederer) studies regulation of sodium phosphate transporter in proximal renal tubule cells, suggesting that she may be on Team Shark.

#NephMadness Choosing Wisely Campaign (#NCWC) – Pediatric Nephrology Region (#PedsRegion)

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As we head into #NephMadness 2018, many of us are wondering how the Blue Ribbon Panel will make its decisions on which teams they select to advance to the next round. Here we take a look at the Pediatric Nephrology Region (#PedsRegion on Twitter) to see if there is any lean towards one team being victorious over another in each match-up.

Genes in CAKUT vs. Environment in CAKUT:

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of CKD in children. Kidney organogenesis is a precise, multi-step process that begins around 3 weeks gestation with formation of the pronephros and continues through the 36th week of gestation as the final kidneys undergo nephrogenesis. Because of the complexity of kidney development, multiple genetic and environmental insults can influence organogenesis and lead to abnormal formation of kidney and/or urinary tract structures. This #NephMadness rivalry is a battle of “nature vs. nurture” to see which team reigns supreme.

It’s tough to get a read from selection committee member Michelle Rheault’s (@rheault_m) scouting report on this match-up. She touches upon the 50+ genes that have been discovered thus far that are implicated in various congenital anomalies, ranging from renal agenesis to primary vesicoureteral reflux, and how next-generation sequencing could identify a potential cause for CAKUT in 5-10% of cases. Given her research interest in Alport syndrome, a disorder with a clear genetic basis, and her recent comments on Twitter, it may suggest she is trying to sway the Blue Ribbon Panel towards choosing the “Genes in CAKUT” team:

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Then again, in the scouting report she emphasizes the burden of maternal diabetes and obesity in pregnancy and the risks of prematurity, which affect millions of babies born each year. This suggests a possible lean towards environment due to its greater impact on kidney health at a population level.

On a global scale, over 15 million preterm births occur each year. Prematurity leads to the arrest of nephron development and renal hypoplasia although some nephron development may continue after birth. Unfortunately, while premature infants are trying to form a few last nephrons after birth, they are exposed to nephrotoxic medications in the course of their care that may further disrupt this process.

Has the Blue Ribbon Panel leaked any secrets about their thoughts on genes vs. environment in CAKUT? It’s hard to tell as no one on the panel has talked about this match-up on Twitter yet.

A quick PubMed search may offer other clues into how the panelists may vote. Deidra Crews (@DrDeidraCrews), for example, is interested in socioeconomic factors that lead to racial disparities in chronic kidney disease for African Americans. Recognizing the role that environment plays in the risk of kidney disease in this population, it is possible she may vote for “Environment in CAKUT.” Looking at Tazeen Jafar’s research interests in ethnic disparities in the treatment of kidney disease in South Asian countries, this may signal another vote for “environment” as well.

On the genetics side, Michael Choi (@Mike_J_Choi) has a research interest in APOL1 risk alleles. Fiona Loud (@FionaCLoud), the Policy Director at Kidney Care UK, is a renal transplant recipient herself and has tuberous sclerosis, a genetic disorder of tumor growth associated with renal manifestations including angiomyolipomas, cysts, and renal cell carcinoma. This may signal two votes from these panelists for “Genes in CAKUT.”

So where does this leave us? Two Blue Ribbon Panel members with possible votes for “Environment in CAKUT” and two potential votes for “Genes in CAKUT,” but it’s anybody’s game.

GN Diagnosis vs. HTN Diagnosis:

Glomerular diseases comprise the second most common cause of pediatric chronic kidney disease, just behind CAKUT. However, they are arguably the most challenging cases we see in our practice and come with plenty of co-morbidities and complications. Many of us have had that experience of a patient with steroid-resistant nephrotic syndrome that has gone through our limited arsenal of immunosuppression down the path to ESKD, or that challenging lupus nephritis patient with multiple lupus flares while on oral steroids and MMF. Hypertension, on the other hand, is also a tough team to beat. There is a known association of high BP in childhood with adult hypertension, yet many children go undiagnosed. Furthermore, obtaining accurate BP readings in children can be a challenge (older studies have shown that infants who cry raise their BP by 30-50 mmHg on average!) and BP targets are different based on the child’s age, gender, and stature.

Going back again to the selection committee member for the #PedsRegion, Michelle Rheault’s research interest in Alport syndrome may suggest she could be setting up the Blue Ribbon Panel to vote for “GN Diagnosis.” However, again looking at kidney disease from a population-level standpoint, she makes the following argument about the burden of pediatric HTN and the consequences of us not identifying it early:

Unfortunately, children with high blood pressure grow up to be adults with high blood pressure. In the Childhood Determinants of Adult Health study, children with blood pressure >90th percentile had a 35% increased risk of elevated blood pressure or hypertension in adulthood. Children with hypertension also demonstrate increased intermediate markers of cardiovascular disease including increased LV mass, carotid intimal media thickness, and pulse wave velocity. By putting in a little effort early to diagnose and treat childhood hypertension, a lifetime of cardiovascular disease risk can be minimized. From a potential health system impact standpoint, this team has a clear leg up on the competition.

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This, in addition to the hype surrounding the newly released AAP Pediatric Hypertension guidelines, make it seem like “HTN Diagnosis” has a home court advantage.

But what does the Blue Ribbon Panel have to say? A quick Twitter search has not revealed any clear bias from panelists towards one particular team. When looking at PubMed, Michael Choi’s research interests in APOL1 and glomerular disease as a whole suggests a vote for “GN Diagnosis.” Tazeen Jafar’s research on BP control in rural South Asian communities and involvement in the Control of Blood Pressure and Risk Attentuation (COBRA) trial suggests a lean towards “HTN Diagnosis” with her vote.

Like the CAKUT bracket, “GN Diagnosis” vs. “HTN Diagnosis” remains a toss-up. Glomerular diseases, though relatively uncommon in the whole pediatric population, is a more common cause of CKD and ESKD in children than in adults and fraught with management challenges. However, given the long-term risks of not identifying elevated BP in childhood and the rising prevalence of HTN in this age group, particularly due to the obesity epidemic, I would lean towards “HTN Diagnosis” as claiming victory but not by a big margin.

Follow #NCWC for daily region updates.

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

Submit your NephMadness brackets here.

 

#NephMadness Choosing Wisely Campaign – (#ContrastRegion)

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Contrast is Nephrotoxic vs Contrast is NOT Nephrotoxic

Contrast Induced Nephropathy (CIN) or Contrast Induced AKI (CI-AKI) or may be Contrast Associated AKI (CA-AKI) surely exists. It may be wrongly diagnosed using the serum creatinine elevation definition, or it may be over-diagnosed with lots of associations and comorbidities. However, it does exist and we all saw patients, even “dialyzed” patients with CI-AKI. As written on the AJKD blog:

Raise your hand if you have seen a patient with AKI due to contrast administration (and if you didn’t raise your hand, either you are not a nephrologist, or, ahem, you need to brush up on your diagnostic acumen!).

Even the writer of “Contrast is NOT nephrotoxic” section still has some doubts:

We repeat, association is not causation. To call AKI in a patient with vascular disease, sepsis, underlying CKD, who, by the way, has had a recent contrast-enhanced computed tomography (CT) scan, as contrast-induced is just plain lazy! Hence there has been a move afoot to replace CI-AKI to contrast associated AKI (CA-AKI), or even post-contrast AKI. But with so many associations, surely there is fire beneath the smoke?

Moreover, the selection committee member Prof. Paul M. Palevsky, one of the co-authors of the famous recent PRESERVE trial, still think that IV contrast has a risk for nephrotoxicity

However, neither Dr Palevsky, nor others who wrote this excellent AJKD blog post; Swapnil Hiremath (@hswapnil), Anitha Vijayan (@VijayanMD), Natasha Dave (@NatashaNDave), and Rajeev Raghavan (@jeevsmd), will choose which of the 2 brackets will win.

Let’s dig deeper into the actual #BlueRibbonPanel (BRPs) Twitter feeds/PubMed searches to see if that reveals the possible picks:

Doing a Twitter search with (each of their account names + contrast) gave positive results for 2 of the BRP; Roger Rodby @NephRodby and Mark Reid @medicalaxioms

Dr Rodby tweeted something about CIN deniers:

The Mark Reid Twitter search didn’t bring up a clear statement about nephrotoxicity, but in general he seems an advocate for nephrotoxicity.

This is 2/9 for Contrast Nephrotoxicity.

Searching Pub ed for other BPR members:

Dr Sarah Faubel, is an expert in AKI, her PubMed search identified many articles about deleterious effects of AKI including CI-AKI. So, she probably would also vote for Contrast nephrotoxicity. Dr Fiona Loud is one of the contributors to the NICE AKI guidelines in 2014, which clearly discusses the CI-AKI issue.

No clear statement about contrast being non-nephrotoxic from any of the BRP members.

This leaves us with 4 (out of 9) members possibly voting for Contrast is Nephrotoxic, with the 5 others also will probably do the same!

A follow up AJKD blog post by Dr. Michael Rudnick confirmed our results, when he stated clearly that:

Verdict: Contrast IS nephrotoxic among high-risk patients. We would consider it a technical foul against the nephron if the threat of CI-AKI is not considered in patients with an eGFR < 30 mL/min and in patients with eGFR 30-44 mL/min, especially if coupled with high risk features such as diabetes

Gadolinium in CKD4 vs Iodinated Contrast in CKD4

If you choose to go with contrast is not nephrotoxic, you would probably choose Iodinated contrast in CKD4, however, as we concluded above, Contrast is Nephrotoxic, so we will argue for Gad in CKD4.

The AJKD blog post is killing it with some straightforward statements we are highlighting here:

What about doing a contrast-enhanced CT scan, using iodinated agents instead? Even the most avowed obituarist of CA-AKI will still accept that there is a risk of AKI after contrast when the eGFR is already so low. A small rise of 25%-50% in Scr may be all you need to push the CKD stage 4 patient over the edge. The resultant oliguria and fluid overload will quite often necessitate starting dialysis. Immediately. Weigh that against the very small (likely <<<1%) lifetime, long-term risk of NSF with the lower risk group II agents. The choice will light up brighter than any contrast agent.

Also:

In conclusion, to quote the European guidelines, “An unfortunate result of anxieties about NSF has been that enhancement during MRI may be avoided inappropriately and important disease overlooked. In a patient with mild or moderate renal impairment, the risk of NSF from an MR examination enhanced with one of the most stable gadolinium-based agents is likely to be less than the risk of nephrotoxicity from a CT examination enhanced with an iodine-based agent.

Even when arguing for iodinated contrast in CKD4, they ….

Estimates of contrast use, from 2003, were 80 million doses, corresponding to 8 million liters of iodinated contrast in humanity. If you are a strong believer in contrast causing kidney failure, this volume of contrast could explain the entire CKD epidemic!

Probably it is Swapnil (@hswapnil), who seems not convinced at all with the non-nephrotoxic contrast!

So, how about the BPRs thoughts (I mean that is what we all want to know anyway?

A rapid look at Twitter and PubMed, will not result in much info, except for Roger Rodby, who wrote an opinion paper about the use of Gad in HD concluding clearly that:

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And those of you who are following ASN Communities, will know his opinion regarding this issue.

We presume that other BRP member who will vote for Contrast is Nephrotoxic, will also vote for Gad in CKD4 (or maybe not). But these are the available data currently.

See you in another region.

Follow #NCWC for daily region updates.

Read the full AJKD blog (Contrast region) here .

Submit your NephMadness brackets here.

How to organize your PDF library?

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My second blog post is about “How to organize your PDF library” in a way that you can easily retrieve papers you need without being in a mess. Despite it is not so easy, but these ways can facilitate your work. Try it!

https://renalfellow.blogspot.com.eg/2018/02/how-to-organize-your-scientific-pdf.html