IN the NEWS: A transplant like multi target protocol for Lupus Nephritis

A transplant type protocol for treating Lupus nephritis has arrived. This makes a lot of sense as recurrence post transplant of Lupus nephritis is very low.
If we had just used MMF alone with steroids, most lupus might have recurred in transplant but we use CNI + MMF in most cases or some equivalent of those agents.  In addition, transplant patients get induction with thymoglobulin like agents and perhaps’ it those agents that keep lupus under control.  A new study in Annals of internal medicine used this multitarget approach to attack lupus nephritis and directly compared to IV cytoxan given monthly.

To summarize:

It was a 24 week randomized open label multicenter trial in China in adults with biopsy proven lupus nephritis.  One arm received tacrolimus and MMF and the other got monthly IV cytoxan for 6 months. Both got pulse steroids and PO steroids.  After 6 months, more patients in the tacro+MMF group showed complete remission and there was a higher response rate in a shorter period of time.  In addition, less adverse events were noted in the MMF+tacro arm as well. 

Few things to ponder on:

1.       This worked in a cohort of Chinese patients; will this work in AA, whites and others?

2.       Most of our patients present sometimes with rising creatinine and it might be concerning to place them on CNIs as well in that setting, but we do in many transplant cases..

3.       Most of these studies include the prior ALMS and so forth never include the sick of the sickest with crescentic GN.  Those might still require IV cytoxan.

4.       Also, this study had a 6 month follow up.  Long term data might be needed for toxicity profile as well.

Overall, encouraging and worth considering in US based population.  A transplant like multi drug protocol for lupus nephritis makes sense.  What’s next? Thymo for lupus nephritis?

Topic Discussion: Proximal Tubulopathies with monoclonal light chains

Proximal tubule is a commonly involved part of the kidney in myeloma.  Classically, they are noted more with light chains compared to heavy chains.  A recent article sheds light on the four mechanisms on how they might impact the proximal tubule and lead to four distinct clinical settings. I have summarized the four types in a table format here.

Type	Proximal tubulopathy without cytoplasmic inclusions	Proximal tubulopathy with interstitial inflammation(AIN variant)	Proximal tubulopathy with cytoplasmic inclusions	Proxmial tubulopathy with lysosomal indigestion
Pathology	Vacuolization of tubular cells and perhaps some necrosis	Vacuolization but AIN as well. Lymphocytes mainly	Swollen proximal tubular cells and EM shows rectangular or angulated inclusions in cytoplasm appear crystalline in nature	Enlarged proximal cells, EM shows lysosome was occupied by substance.
Predominant light chain	Kappa more than lambda	Kappa more than lambda	Kappa and one case of lambda	All kappa
Seen with MGUS	Yes	Yes	Yes	Yes
Clinical	Slowly progressive renal failure, some non nephrotic proteinuria	ARF, more patients requiring dialysis, non nephrotic proteinuria	Slowly progressive renal failure,glucosuria, phosphaturia and non nephrotic range proteinuria	Slowly progressive, glucosuria and phosphaturia
Unique features	Second most prevalent, older age	Most prevalent, older age	Younger age	Least prevalent, younger age

In the NEWS: Nephrology Social Media Collective (NSMC) Internship

Social Media internships are  new to the medical community. There is a short course that some schools offer to their medical students. We don't really know what the outcome of those courses have been on the students that take it. 

The Nephrology social media community leaders starting planning an internship in nephrology social media in Dec 2014 under the leadership of Joel Topf from PB fluids.  We feel that social media will not only enhance their skills as a nephrologists, but help spark some interest in budding nephrologists. This will be the first of it's kind in Nephrology. Check out the website at http://www.nephjc.com/internship

The internship is open for fellows, attendings, residents and our first class just got announced as well on the website. The projects they shall be working on are doing posts, tweets, and various projects.  Nephmadness would be a part of their training, with blog posts for PBfluids, RFN, Nephronpower, eAJKD, Ukidney.com and also being part of the rising online journal club( www.nephjc.com)



Please welcome Nikhil Shah, Chi Chu, Scherly Leon and Hector Madariaga as the first class of the first nephrology social media internship.

CONSULT ROUNDS: Acute Kidney Injury following TAVR

There is increase data now that patients undergoing transcatheter aortic valve replacement (TAVR) are at increased risk for acute kidney injury (AKI). The procedure usually involves contrast dye being used. 

Looking back to 2010, one of the earlier studies found that AKI occurred in 11.7% of the patients following TAVR and was associated with a greater than four-fold increase in the risk of postoperative mortality. Hypertension, chronic obstructive pulmonary disease, and blood transfusion were predictive factors of AKI. In those patients with pre-procedural CKD, TAVR was associated with a significant reduction of AKI compared with surgical AVR. In addition, studies have shown that renal function is a predictor of mortality post TAVR.

An Italian registry abstract found similar results.  Females and patients receiving >3 RBCS units after the TAVR where more likely to develop AKI. Another study done in 2010 published in NDT showed that transapical access, number of blood transfusions, post-interventional thrombocytopenia and severe inflammatory response syndrome (SIRS) were risk factors for AKI post TAVR.

The Valve Academic Research Consortium (VARC) recently published criteria for AKI after TAVR. The main findings of the another study indicate that AKI after TAVR is a frequent complication, which occurs in >10% of patients. These patients have significantly worse outcome. In agreement with previous studies, they found that the transapical approach was associated with an increased risk for AKI. A probable explanation for this observation may be associated with patient selection. Usually patients with high vascular burden of disease are selected for the transapical approach and risk of embolization post TAVR leading to AKI might be higher.  Another interesting risk factor is blood transfusion. A similar association was also identified in patients undergoing cardiac surgery.  PRBCS transfusion might serve as a surrogate for hypotension and bleeding or it might lead to a pro inflammatory state peri-op leading to free iron and hemoglobin.

A more recent analysis by Columbia University Medical Center found that  peri-procedural life-threatening bleeding was the strongest predictor of AKI after TAVR; high white count and low platelets were also noted in the AKI group. Finally, another abstract found that male gender and urgent need for TAVR was associated with more risk of AKI.

So in summary, what I could come up with that are risk factors for AKI post TAVR that are fairly common in  most studies

Contrast use( debatable) as might be the most obvious

Transapical approach

Number of Blood transfusion peri procedure( Bleeding related), the more- the higher risk?

Post intervention thrombocytopenia

Urgent need for TAVR                                       

Concept Map: Glomerular diseases seen with cancer

Click on the figure for larger view
Based on review article in Kidney International

Top 10 eAJKD posts from 2014

Top 10 eAJKD posts from 2014 (courtesy Matt Sparks) in reverse order with contributor names

10. Kidney Week 2014: New Drug for Hyperkalemia –Dena Rifkin

9. Welcome to Nephmadness 2014- Matt Sparks, Joel Topf, Kenar D. Jhaveri, Warren Kupin, Edgar Lerma

8. Recovery time from dialysis session? Does it Matter?- Veeraish Chauhan

7. An update on Glomerular diseases 2014- Jean Francis

6 .It’s finally here- the New US kidney allocation- Vinay Nair

5. Lupus Nephritis: A treatment update 2014-Craig Gordon

4. Test Your Knowledge: Acid-Base Disturbances in the Hemodialysis Patient- Ritu Soni

3. Drug Abusers and Kidney Disease: A Pathologist Perspective-Tibor Nadasdy

2. Test Your Knowledge: Hemodialysis- Rimda Wanchoo
1. A New Nephrologic Syndrome: Acute Fellowship Insufficiency- Warren Kupin