Wednesday, November 13, 2019

Topic Discussion: Interferons and kidney disease

Interferons usually have been linked with kidney damage with forms of podocytopathies. CJASN paper from 2010 from CUMC described these lesions. Collapsing FSGS may occur after treatment with IFN-alpha, -beta, or -gamma and is typically accompanied by the ultrastructural finding of endothelial tubuloreticular inclusions.
Following that series of 11 patients showing Collapsing GN, few cases reports were published in 2016 showing FSGS as well. Another large series by Markowitz et al in 2015 of 32 patients also showed podocytopathies but this time also MCD and FSGS along with collapsing GN. The MCD patients had complete and partial remission but the FSGS and collapsing GN had <50% complete or partial remissions.

But the most common lesion that is hidden in the heme literature is TMA but many being renal limited. There are now over 80 cases described of TMA , AKI and HTN related to interferons. Outcome analysis revealed complete remission in 27 (40%), persistent chronic kidney disease (CKD) in 28 (42%) and fatality in 12 patients (18%). (10) Treatment with corticosteroids, plasma exchange and rituximab resulted in durable responses.

In an elegant experiment by a group published in 2016 in Blood showed that type 1 interferon can induced TMA. They showed that the clinical phenotype of cases referred to a national center is uniformly consistent with a direct dose-dependent drug-induced TMA with interferon. They then showed that dose-dependent microvascular disease is seen in a transgenic mouse model of IFN toxicity. This includes specific microvascular pathological changes seen in patient biopsies and is dependent on transcriptional activation of the IFN response through the type I interferon α/β receptor. Together their clinical and experimental findings provide evidence of a causal link between type I IFN and TMA. So, this experiment showed that from bedside to bench the clear relationship of interferon and TMA development.
So in summary, the renal lesions seen with Interferon should really be TMA, and podocytopathies such as FSGS, collapsing GN and MCD.

Friday, November 1, 2019

In the NEWS: NephSim as an educational tool

Nephrology education related published work is sparse. NephSim, a mobile optimized website tool with cases and interactive approach was developed in 2018. Over 24 cases have been presented and discussed in this tool. Case contents have been amazing. But what the creators of this tool now did is- validate it with a peer reviewed publication. Recently published in JGME, a med ed journal, Farouk et al showcase the NephSim tool and discuss the results of their outreach of this tool and a survey that showed high rate of satisfaction and usability.

Innovation in Nephrology education is extremely important. Case discussions leading to differential diagnosis and then pathology and diagnosis helps in creating and making a Nephrologist a better diagnostician. The NephSim project also showcases the use of website, social media platforms such as twitter and other ways to share information.

This tool can easily be replicated in other fields in internal medicine or medicine. The ease of using and doing the cases makes it very accessible and able to be transformed in all fields in medicine. The drawbacks- survey response was low but enough to make major conclusions. But like most med-ed studies, it touches the first tier of outcomes- medical knowledge (self-assessed) and not addressing other ways of medical knowledge. We hope to see using some of these tools used( perhaps in combo)- such as NephSim, Nephmadness, Whatsapp, blogs, NephJC. Etc—to change practice patterns, behaviors and ultimately effect patient outcomes.

Saturday, October 12, 2019

Topic Discussion: HSCT associated TMA, a renal endothelial variant of GVHD

Kidney injury post HSCT is a mystery. While the initial AKI is from multiple causes, the chronic damage we see in the survivors of HSCT is not well understood. In a recent review in AJKD, we did consider this to be mostly TMA related. But is TMA a form of GVHD ( renal limited) is what some including us have proposed. When one looks at the literature from GVHD and links to the kidney- one thinks of secondary membranous, but perhaps this is a rare finding- endothelial glomerular damage might be more common(TMA).

In a recent mice study, the authors looked at HSCT effect on kidney in various murine models of GVHD. The most common finding was glomerular with classic mesangiolysis, mesangial proliferation and edema with subendothelial widening and microthombi. These are features of HSCT- associated TMA. So, it is very possible that getting a HSCT might be a second hit to several folks who might carry a complement deficiency and perhaps there is some activation of complement system.

Some of the literature proposes that TMA and GVHD are not related but both affect the complement cascade. As clinicians we have seen several cases of TMA and concurrent GVHD and a recent reported case series confirms this. It is intriguing and possible that renal-limited TMA might be a variant of GVHD.  GVHD is usually an epithelial cell disease but having an “endothelial” target might be possible in the kidney. In most cases, when TMA is diagnosed in a patient with HSCT, the knee jerk response is to discontinue CNIs. Whether this is of potential benefit or harm is not clear.

Tuesday, September 17, 2019

Concept Map: Polyuria

A solute diuresis is defined -- urine osmolality >600 mosmol/kg and a total daily osmolar output >1000 mosmol (calculated as the urine osmolality multiplied by the 24-hour urine output).

A water diuresis is defined with a urine osmolality <600 mosmol/kg and often <300 mosmol/kg and a total daily osmolar output <900 mosmol.

Another way to look at it from pure Uosm perspective is U osm <100mOsm/kg is generally a water diuresis from polydipsia or DI.  

Uosm between 100-300 mosm/kg is usually a mixed polyuria( either a central and nephrogenic partial DI and maybe simultaneous water and solute intake and CKD)

U Osm >300 is generally solute diuresis 

Thursday, September 12, 2019

Topic Discussion: Do Renal consultations matter in surgical and cardiac ICU patients

AHA moment arrived when I saw this article in AJKD on interdisciplinary collaboration of nephrology with surgical and cardiac surgery ICUs. It was a qualitative study highlighting some of the conversations that happen in the CTICU with the nephrologists and what is “felt” about renal consultations.
This is an important topic that we encounter as consultants. Often, we get urgent calls from the ICU, for example CTICU , “ Doc, we need an urgent consult, this patient post CABG is oliguric now and crt rose from 1 to 1.4mg/dl and we need urgent CRRT, and we placed the dialysis catheter already for you…”
Now this situation is not uncommon… how does one respond to that..
Either you say, “ gee. Thanks for that and I will come evaluate and decide if I even need to use that catheter as they might not need dialysis..”  What is the role of the Nephrologist in some of the surgical run ICUs.? Are we seen merely as technicians or truly thoughtful physicians that make decisions that will or not alter the care of the patient..
The article really highlights this very important issue. Some of the major themes highlighted are listed below
1.      There was almost an absent influence of renal decisions in some of the surgical and CTICUs; this stemmed from many surgeons and intensivists not sure of the renal fellows decisions not going along with attending nephrologists decisions. In my opinion, many times and at many centers-they bypass fellow based consult services and call attendings only for that reason.
2.      Nephrology fellows and attendings found it hard to communicate to CTICU staff as the PA or NP would not really be making that decision and the final decision came from the surgical head of that patient ( who often is not in the unit)
3.      Nephrology fellows might not realize the hierarchy noted in some of the surgically based ICUs compared to MICUs.  This is interesting as the first time we encounter surgical culture in depth is during renal fellowship( 3 years in medicine- we usually are kept away from SICU, CTICU and NSICU)
4.      What I found totally astonishing was one of the comments made in box 2 by an NP that was interviewed is that “renal was the only service we had to call to get something done as We can’t just order dialysis” – and hence making us seem like just a dialysis ordering physician
5.      It also goes into details on who manages the fluid removal once CRRT has been started. It is an ongoing battle. Often this leads to conflict and at many centers, Nephrologists have given up CRRT ordering and management to ICU intensivists( sad but true)
6.      Due to our consult note and recommendations have no value- many times- there was early signing off of the consult- as “ if they are not listening to our recommendations anyway – why bother writing a note everyday…” Not uncommon to see in this unit.
7.      While Nephrologists thought they were best valued to understand AKI and noted a good nephrologist is a good internist. Meanwhile, surgical staff didn’t believe that and felt nephrologists were mostly dialysis gatekeepers and didn’t feel we understood AKI in the overall ICU status and ordering tests of diagnostic significance were not very valuable.
8.      The role of nephrologists being dialysis proceduralist clashed nephrologists value of preventive medicine mainly in the CTICU. From a surgical perspective, a consultation that doesn’t offer any valuable intervention such as dialysis to help the acutely ill patient is useless. – heard that one before many times
9.      The most common disagreements were on when to do dialysis, timing of initiation and managing fluids—the most common we see in practice anyway. It is not uncommon where I have written “ stop diuretics” but they are continued and then days later I am starting them on RRT.  But there have been also times where I have said “ stop diuretics” and they continued and they did better by not listening to me.  So in general, does our opinion matter?
10.   Interesting, surgical and CT ICU staff viewed dialysis as a tool to get rid of the kidney problem whereas we see it as a last resort before trying all medical maneuvers.  One comment was really funny, In box 3, one of the nephrologists interviewed said “ they view most of us as technicians. Just like anesthesia can just put the person to sleep, just put a tube and no big deal- anyone can do it, you can slap someone on dialysis, no big deal.”.  My favorite one I get called is “ can you come and spin him”
11.   Finally, due to history of these interactions, nephrologists and nephrology fellows avoided the controversial issues. Many times, this led to resignations from the case.
12.   Lot of these changes are due to different medicine vs surgical cultures.

How do we fix this? Can we fix this? The authors describe this is discipline siloing leading to ineffective collaboration amongst fields of medicine. This is important to break and learn. This will be critical as it can harm patients if gets escalated and neglect ensues. We need to understand the other persons perspective and realize that all physicians have one medical school, residency and fellowship—we all bring in some value to the patient. We need to respect and honor each other’s fields of medicine.
When I showed this article to one of our CT surgeons, his/her reaction was merely to dismiss it. My fellow and I were hoping for more of a conversation to improve this encounter.
Then the next day, in the CTICU, we see that the curtains are closed and one of the rooms was having open heart surgery happening in the middle of the ICU – for an urgent mater.  We were just amazed at the life saving nature of their field in medicine… it is just amazing what they can do. And I told my fellow, “ if they can make the ICU bed an OR instantly, their assumption is that dialysis can happen instantly and at any place- even in the OR..” We have to understand that they come from a different perspective.  Once we start understanding that, we may be more welcoming of their way of thinking. Similarly, at some point, perhaps they can understand our physiological approach to certain things and preventive nature of AKI and that dialysis is a procedure and not the first thing we should be doing..”

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