The first round results of NephMadness 2018 are in! Who’s up? Who’s down? Who’s out? Check out the Current Standings. What was your bracket buster? Where did the Blue Ribbon Panel go wrong? Tweet your reaction with hashtag: #Saturated16

Women’s Health Region

Right out of the gate, Reproductive Planning took an early lead against Menopause in CKD and never decreased the pressure, leading to a major blow-out.

Reproductive Planning wins 9-0.

Comments from the BRP:

Families may be making decisions right now and need the best information there is; using International Women’s Day to bring out this topic which is not well and consistently attended to is really important.

It seems like the default response to reproductive planning for nephrologists is “Avoid pregnancy.” We need to make this more nuanced.

Preeclampsia’s Global Impact came in strong and the Prematurity’s Global Impact shots just weren’t falling for them leading to an easy win for team Preeclampsia.

Preeclampsia’s Global Impact wins 7-2.

Comments from the BRP:

This is a tough one. I know that nephron number based on low birth weight is all the rage. An increased SNGFR as being potentially harmful in the setting of a reduction in renal mass was the basis for the Brenner hypothesis. This work led to ACEi use in 5/6 nephrectomy rats and eventually to ACEi (and all RAAS blockade) trials in humans providing one of the major clinically useful offering the nephrologist has to slow the progression of proteinuric CKD. But preeclampsia is fascinating…something so normal (not a pathologic state) and common as pregnancy going so wrong. Just seems like evolution could have done a better job that to have this condition affect “4-8%” of pregnancies. And if they get through it, women still are at risk of more episodes and even CKD. I just love this topic. a-Flit went far a couple NephMadnesses ago. Love preeclampsia.

Preeclampsia in the context of kidney disease deserves real attention, for both long and short term outcomes.

Preeclampsia: Such a common problem. We are finally beginning to make headway.

In low and middle income countries (LMICs) where up to 50% of births are attended by traditional (non-physician) birth attendants (TBA), preeclampsia is grossly underdetected and complications including acute kidney injury are common, often resulting in death. Strategies to raise awareness and training of TBAs in screening and managing preeclampsia should be an essential component of obstetric care services in LMICs.

Preeclampsia more interesting pathophysiology

Animal House Region

Shark Osmolarity and Salmon Osmolarity kept it close throughout the game but a last minute three-pointer by Salmon Osmolarity wins it.

Salmon Osmolarity wins 5-4.

Comments from the BRP:

Major kudos to the next 4 topics: shark, salmon, camel, and toad. What is cooler than osmolar renal evolution and who is cooler than Homer Smith? How does one possibly pick between the pee shark and the amazingly adaptive salmon? A shark rectal gland that has the NaK2Cl transporters on the opposite side of the kidney? One to reabsorb NA and ione to excrete it. Seriously, how can that even happen? Did they really evolve independently? But the salmon’s ability to adapt to salt and fresh water is even more amazing. Imagine if humans could excrete Na through a rectal gland or gills! No HTN?

Sharks are scarier than salmon.

Sharks are boring.

Team Toad Water Storage was asleep for most of the game letting Team Camel Water Storage run the court and win in a landslide.

Camel Water Storage wins 8-1.

Comments from the BRP:

What is not cool about a toad? They are cute as hell, can have poison skin, beautiful colors, and now they drink water and store it in their bladder for the opposite of a rainy day? And that the Aborigines knew to drink their bladder water in times of need? Did somebody make that up? But the camel being able to tolerate a Na range from 154 to 191, Hgb doubles? This makes the pee shark seem like a rookie. And the alliterative phrase “dipsogenic as a dromedary,” nicely played. Camel wins.

Always been fascinated by the idea that the camel stores water in its humps. OK, so that is not true…

World’s getting drier.

Peritoneal Dialysis Region

Solute Issues in PD looked like a 16-seed and not the kind that busts brackets. Volume Issues in PD won in a landslide.

Volume Issues in PD wins 8-1

Comments from the BRP:

I tell the fellows volume is the new uremia and in PD it is both insidious and pernicious (I’m well aware how pathetic it is that I try to show off using big words). Solute in PD, BORING. PET testing is totally overrated for PD prescription, survival is way more about RRT than the therapy itself (maybe that is the real “pee-value”).

A good opportunity to highlight common challenges which we can now use technology to assist with – and it is time to do that as these are not new issues. Patients need reliable PD as an option, and help with managing their own fluid status. A focus on this is a patient-centered choice.

It seems like every PD patient I see has edema.

Culture-Negative Peritonitis was able to keep up with Catheter Dysfunction in PD throughout the first half of the game but came out asleep in the second half leading to an easy win by Catheter Dysfunction in PD.

Catheter Dysfunction in PD wins 6-3

Comments from the BRP:

Peritonitis is problematic, but a bad catheter means no PD. They either work or they don’t, really nothing in the middle, cause the middle always fails.

There are avoidable errors here and getting better at catheter placement and avoiding an unnecessary swap to hemodialysis is a winner.

Trial Outcomes Region

40% Reduction in eGFR got an early lead right out of the gate and despite a strong finish and a full course press, Doubling of Creatinine couldn’t close the gap.

40% Reduction in eGFR wins 6-3

Comments from the BRP:

Anyone that knows me knows that I cut my teeth on clinical trials with the captopril T1DM trail. The MDRD and the captopril trial were both going on at the same time in the late 80s early 90s. The MDRD (NIH) used GFR slopes with GFRs from iothalamate clearances for an endpoint, while the captopril trial (Collaborative Study Group) used doubling of serum creatinine. Ed Lewis, my mentor and PI of the captopril trial, tells the story of how he was discussing outcome measures with either Ray Bain or John Lachin (I cannot remember if it was Ray or John…), biostatisticians from GWU, in a cab one day and wanting a hard end-point, came up with TIME TO doubling of serum creatinine. That end-point served the captopril trial well and others to follow. The MDRD was a negative trial, as the GFR slope differences may have been lost by the acute reduction in GFR seen in protein restriction (also seen in RAAS inhibition, but not enough to double the creatinine). Doubling was also good because it predicted halving of renal function (the captopril trial also did iothalamate GFRs but was not primary endpoint) and predicted ESRD. A 40% change in eGFR, a creatinine based measurement, follows the same principle, just happens sooner and could increase study power.

“In a meta-analysis of 37 randomized trials in CKD, more than 80% showed that the use of a 40% endpoint in most cases would improve statistical power while only minimally inflating the type 1 error rate.”

This makes sense to me and I don’t feel like a traitor voting for 40% since it really is a kinder, gentle doubling. 40% it is.

All of our surrogate markers are inadequate. How do diet and weight changes affect this marker?

Stop making new things.

Proteinuria played strong defense but in the end Patient-Reported Outcomes offense and inability to miss a shot led to a close win.

Patient-Reported Outcomes wins 5-4.

Comments from the BRP:

As we have been so successful slowing GFR loss with BP management, RAAS administration, etc, it becomes harder to prove something new works. You cannot not use RAAS inhibition (an arm without RAAS) – that would be unethical. But as we slow GFR loss, you need greater n and longer follow-up! What about the surrogate of proteinuria, something that seems to predict renal outcome? It varies a lot day to day, hour to hour, but it is EASY to measure and with enough measurements, you should be able to tease out a trend that may predict GFR outcome. I really believe that if your proteinuria goes down you will do much better than if it goes up. How easy is that? I know PROMS are popular, but I just can’t feel the love…couldn’t in prior NephMadnesses and still cannot. Maybe as a nephrologist I only trust “harder” data? Proteinuria is the future of trials.

Bring back PROMS, or in other words what patients think and report on their care and treatments as a driver for improvement is a must.

Patient-reported outcomes relevant only in advanced kidney disease and not in earlier stages which are generally asymptomatic. Proteinuria relevant in both.

Hyponatremia Region

This game was predicted to be a close matchup but in the end the crowd favorite European Guidelines just couldn’t keep up with US Guidelines.

US Guidelines wins 6-3.

Comments from the BRP:

US v Europe? I LOVE hypoNa. Few things are harder to treat well and nearly impossible to teach. Europe: They have 7 figures, 10 tables and 18 boxes of recommendations ugh ugh ugh, how can that help? But I love the 3% bolus approach. I also love urea for chronic cases. The Americans also like 3% bolus. I also love vaptans, although the response can be very unpredictable. The tie breaker here is the US pre-emptive use of DDAVP (“DDAVP clamp”). This is the way to go.

European Guidelines: I confess to a local prejudice 🙂 but if both are trying to do the same thing then let’s look at the simpler set in more detail.

US Guidelines: You have to wonder how differences in the populations served influence the perception of problems with hyponatremia correction.

European Guidelines: Easier

Cerebral Salt Wasting looked like a DIII team that accidentally got invited to the big dance. SIADH won this matchup handily.

SIADH wins 7-2.

Comments from the BRP:

CSW? Seriously?

Simple. SIADH is the more convincing argument and highlighting it may educate more nephrologists.

SIADH: Such an exciting topic. What about that fractional excretion of urate?

It’s all SIADH.

Contrast Region

Coming in to this game Contrast is NOT Nephrotoxic had been hot from the 3-point line making them the early favorite. However, the 3-pointers just weren’t falling and Contrast is Nephrotoxic came up with the big win.

Contrast is Nephrotoxic wins 7-2.

Comments from the BRP:

Contrast is not nephrotoxic and the moon landing was staged. Granted it may not be as common or risky as we have been led to believe, but CIN exists.

Kidney people, we need to be clear on our messages and if this, on balance, is the case, then don’t confuse the world, and especially patients.

A million case reports can’t be wrong.

Gadolinium in CKD4 tried to keep up but their free throws just wouldn’t fall, giving Iodinated Contrast in CKD4 the easy win.

Iodinated Contrast in CKD 4 wins 6-3.

Comments from the BRP:

When NSF was first being reported, Mark Perazella (he is at Yale where dermatopathologist, Shawn Cooper, developed the NFD and then the NSF registry) and I (thanks to Mark) wrote a lot on this topic. I opined in a piece in Seminars in Dialysis that if you avoided the original Gad preparations, avoided the typical angio double dose, and dialyzed immediately thereafter and daily for 3 treatments, that you should be able to give Gad to ESRD. That was sticking my neck out a bit, but I seemed to have gotten away with it. There have been few cases (even with the original Gad) of NSF in CKD4. So while I avoid Gad whenever possible, I still think there was an overly conservative approach by avoiding it in even in CKD3 or greater! My bias all along is that we should ease up and I agree with the radiologists. I realize there is a new movement at hand describing “gadolinium storage condition” and “gadolinium deposition disease” relating to brain gadolinium findings, even in patients with decent GFRs. I am not convinced.

If patients need the scans, they should not be disadvantaged by anxieties induced by the noise in this topic; rather, they should be offered informed decisions and the well-evidenced prophylactic measures.

Both teams put up a good case but iodinated had the most convincing edge here.

Iodinated contrast: Apparently all we need to do is give saline.

Pediatric Nephrology Region

Genes in CAKUT came out strong and played like the 2 seed they are, easily beating Environment in CAKUT.

Genes in CAKUT wins 7-2.

Comments from the BRP:

In nature vs nurture, I am going for nature. Both need deeper understanding and both have merit but if genetic testing can help with them why then maybe it can help more families planning their children.

Such exciting developments. We need to now look at how mutations in genes result in specific CAKUT phenotypes.

DNA is fancy.

I voted against nephron number the first time around (preeclampsia v prematurity) so I’ll flip it here.

Hypertension Diagnosis got out to an early lead in the first half but GN Diagnosis came out strong in the second half and were able to pull out a 2-point win.

GN Diagnosis wins 5-4.

Comments from the BRP:

HTN boring, GN exciting. Sorry, Swapnil Hiremath, I am glad I have you as my HTN resource, but it is just the way I feel.

HTN diagnosis: Tough to deal with, lifelong in its deleterious effects – and relatively common, this one needs more attention and education on the interventions.

HTN diagnosis: The influence of the obesity comes to the fore.

Transplantation Region

Pathogenic DSAs could not keep up with The Untransplantables’ fast-paced offense and strong defense. Easy win for the Untransplantables.

The Untransplantables wins 7-2.

Comments from the BRP:

Give me your tired, your poor, your huddled masses yearning to breathe free, your untransplantables. Few professions have to think outside the box like transplantation, most of where we are today in this field is because of some real “idea cowboys.” I think this is a big deal. Nothing changes a life like a renal transplant and to be deprived of that is devastating. Yes, a very big deal when you can reverse that.

The Untransplantables: Well done to both teams but with pathogenic DSAs having further to go and the use of the paired pool exchange showing hope for highly sensitized patients, my vote goes to that team and to encourage further study and awareness of this possibility for the long waiters.

The Untransplantables: Is this really a possibility?

Virally Infected Kidneys and Kidney Donor Risk played a close game going in to double over time. In the end, Virally Infected Kidneys won out with a last second layup.

Virally Infected Kidneys wins 5-4

Comments from the BRP:

Primum non nocere. Blah blah blah. Finding ways to use previously rejected kidneys will improve so many more lives than the harm done in donating a kidney. A numbers game for me. Once again, not accepting conventional wisdom can lead to a paradigm shift.

A close decision with special commendation for virally infected kidneys. However, kidney donor risk wins my vote, having a wider potential impact in guiding decision-making in potential donors and recipients.

Kidney Donor Risk: We have identified some risks but not all.

Ladies and Gentleman, your Saturated 16!

Current Standings | NephMadness 2018 | #NephMadness | @NephMadness