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Tuesday, November 21, 2017

In the News: DNAJB9- a novel autoantigen staining for Fibrillary GN

A new paradigm shift in diagnosis of Fibrillary GN(FGN) has occurred. This rare form of organized deposit related GN might have a pathology staining marker in the making.
Through the use of laser microdissection assisted liquid chromatography tandem mass spectrometry , The Mayo pathologist  recently discovered a novel proteomic biomarker for FGN: DnaJ homolog subfamily B member 9 (DNAJB9), a member of the molecular chaperone gene family. When looking at specific biopsy samples of FGN vs non FGN cases, strong, homogeneous, smudgy DNAJB9 staining of glomerular deposits was seen in all but 2 cases of FGN in one report published in KI-R.

This test had a 98% sensitivity and > 99% specificity. Immunoelectron microscopy showed localization of DNAJB9 to FGN fibrils but not to amyloid fibrils or immunotactoid glomerulopathy microtubules. (http://www.kireports.org/article/S2468-0249(17)30341-8/pdf)

Another similar manuscript in JASN showed the same finding. 






Looks like we may have a diagnostic test and catch more cases of FGN 

Saturday, November 18, 2017

TOPIC DISCUSSION: Diuresis in CHF

An amazing article this month in NEJM discusses Diuretic use in CHF- a must read for Cardiologist and Nephrologists.

Some interesting take home points:

1. Diuretic resistance causes: Non adherence, gut edema, impaired diuretic secretion due to CKD or aging, hypoproteinemia, hypotension, nephrotic syndrome, use of NSAIDS, low renal blood flow, nephron remodeling and neurohormonal activation.

2. Bumetanide and torsemide have higher and more consistent oral bioavailability over furosemide and make oral and IV doses kinetics similar( often under utilized by many)

3. Torsemide has the longest half life of all loop diuretics-- 6 hours.

4. Two forms of adaptations: a) A dose of loop diuretic increases urinary Na loss for few hours but then is followed by a period of very low sodium excretion often called " post diuretic Na retention". When dietary Na intake is high, the post diuretic Na retention effect will offset the initial natriuresis. 
The second is braking phenomenon.  When diuresis happens and fluid volume declines, this activates the SNS and RAS leading to nephron remodeling( distal nephron hypertrophy). This is a helpful thing to put brakes on the severe contraction of the ECF. But when this occurs in a patient that is volume overloaded, it's causing harm.

5. Treatment should aim for daily urine volume of 3-5L till euvolemia.  A stepped wise approach is suggested in bolus of furosemide followed by drip if needed. Metolazone or HCTZ( high dose) can be used as additional agents.

6. Tolvaptan: Data is mixed and can be used in some especially if Na issues are also a concern
7. Dopamine and Nesirtide - no data to support use
8. Aldactone didn't improve outcomes in acute CHF patients that require aggressive diuresis
9. Diuretic Resistance: Failure of diuretics to achieve decongestion, so with max doses you still get a a urine Na<10.
10. Use of amiloride and carbonic anhydrase inhibitors may be beneficial in diuretic resistant patients.
11. UF in CHF appears to be indicated primarily when dialytic therapy is also indicated for worsening cardiorenal syndrome.
12. Hypertonic saline with diuresis might be an interesting option -- robust trials still pending.
13. Skillful use of diuretics is the bottom line on how to succeed in treating CHF with renal dysfunction.

I had hoped the authors had commented on use of lung US in this disease. Diuretic use guided by Lung US findings might be more useful in many cases than later exam findings of edema( personal observation). 

Monday, November 6, 2017

TOPIC Discussion: LVAD and the Kidney



Left ventricular assist devices (LVADs) are common and implantation carries risk of AKI. LVADs are used as a bridge to heart transplantation or as destination therapy. Patients with refractory heart failure that develop chronic cardiorenal syndrome and CKD often improve after LVAD placement. Nevertheless, reversibility of CKD is hard to predict. After LVAD placement, significant GFR increases may be followed by a late return to near baseline GFR levels, and in some patients, a decline in GFR.
In a recent review in CJASN, we discuss changes in GFR after LVAD placement, the incidence of AKI and associated mortality after LVAD placement, the management of AKI requiring RRT, and lastly, we review salient features about cardiorenal syndrome learned from the LVAD experience.


Salient points   

Most of the AKI and CKD post LVAD is related to right ventricular failure. Identifying that and providing aggressive diuresis and or UF might be important.
Long term CKD related to LVAD might be related to hemolysis and R-CHF.
Hemodialysis and PD – both can be successfully be done in outpatient setting with LVADs
AVF should be still the first choice for LVAD patients in the outpatient settings that require dialysis e
The most important of all, interdisciplinary teams including cardiologist, surgeons, and nephrologists are critical in the success of an LVAD program.

Sunday, November 5, 2017

Nephrology on the rise, Positive trials, Positive job market!!

Nephrology really took an amazing turn this Kidney week in 2017. Positive trials, positive news and amazing things are happening for everyone involved in renal care.

First and foremost, the high impact clinical trials in 2017 ASN Kidney week revealed several positive trials.

The REPRISE study showed the impressive promise of use of tolvaptan in late stage ADPKD.  The liver related side effects were minimal. Hope to see this in clinical practice soon

The MENTOR trial that compared cyclosporine to rituximab for PLA2R membranous GN showed rituximab to be non inferior with lower rate of adverse effects. Looks like rituximab will be changing the treatment paradigm in membranous GN treatment.

Is contrast nephropathy dead? No not really. A randomized controlled trial showed that intra arterial contrast studies are more likely to cause contrast nephropathy compared to intra-venous, but both did have a incidence of contrast nephropathy.

A novel agent called QPI-1002 showed significant promise in decreasing AKI post CABG in high risk population.

Bardoxolone Methyl Improved GFR Measured by Standard Inulin Clearance: The TSUBAKI Study in Japan. The return of Bard!!

Another positive note: The GW-ASN fellows survey showed an upswing in job opportunities for our fellows in training. https://www.asn-online.org/education/training/workforce/

Finally, social media nephrology Guru Joel Topf wins Robert Narins award with an amazing video presentation done by ASN.