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.


Wednesday, October 25, 2017

Consult Rounds: Podocytic infolding glomerulopathy( PIG)

Podocytic infolding glomerulopathy( PIG)

What is PIG? – This is a pathology based finding seen rarely in the EM section of the report. It is a form of  glomerulopathy, in which microspheres or microtubular structure or both are associated with infolding of cytoplasmic processes of podocytes into the glomerular basement membrane.  This type of glomerulopathy is not included in the World Health Organization’s classification of glomerular diseases but has been noticed in few cases reports and large case series from Japan.


Associations: In the largest series from Japan,  most patients might have a subtype of lupus, nephritis  class V, or membranous glomerulonephritis.  MCTD, Sjogren's syndrome and tumor lysis syndrome was also found. Interestingly, hydronephrosis was associated with most patients seen with this entity. There have been cases associated with Myeloma as well. 


Electron micrograph shows cytoplasmic  processes of podocytes infolded into the GBM. At the end of an infolded cytoplasmic process of podocyte, microspheres or microtubular structures or both were found. b The infolded cytoplasmic process of a podocyte went through the middle layer of the GBM, which was accompanied by thickening of the lamina densa.

The pathogenic mechanism of PIG is unknown. Hydronephrosis was found in three of 25 patients.  However, no study has shown that experimental hydronephrosis can induce podocytic infolding.In the large series from Japan, all had GBM thickening, and IF was negative in many, followed by some that had only C1q,c3 and some with a full house pattern.  Membranous GN is the most common light microscopy finding followed by FSGS and MPGN.  In an earlier report, some might have called this entity  Membranous glomerulopathy with spherules.

Some researchers performed an immunohistochemical study of complement C5b-9 complexes in several human kidney diseases and have shown positive reactions on round extracellular particles and on striated membranous structures in the GBM. Therefore, the mechanism of podocytic infolding might be related to the role of special types of complement activation in situ on the microstructure.  We don’t know if infolding of the podocyte cytoplasm may be a pattern of GBM/podocyte disruption rather than a true disease entity. However, the diffuse extent and severity of PIG raise the suspicion of defects in the repair mechanism.

Worth a read as we learn about this new entity!

Here are some interesting references



Sunday, October 1, 2017

In the NEWS: Point of Care ultrasound of the Lungs and the Nephrologists


Typical B-line (left) and the standard definition by Lichtenstein (right).Point of care US is increasingly being used in many medical specialties. Nephrology is catching along swiftly as well.  A recent review by our team led by Ross et al discuss the role of Lung US in the ESRD population.  After a systematic review,  we concluded that lung US can be used to determine volume status in chronic ESRD patients by using the B-line score model( see figure above from paper) as discussed in the paper.


As nephrologists, we should be using this in practice and help diagnose and prognosticate high risk patients and perhaps prevent re-admissions.

The role of lung ultrasonography in nephrology practice requires further research regarding its clinical applications. We stated in our paper the following amazing ways it can be used in clinical practice..
i.            What is the role of lung ultrasonography in the management of AKI in the intensive care unit? Could it be used as an endpoint for continuous renal replacement therapy?
ii.            Given the association of mortality with the presence of B-lines in the chronic dialysis population, what is the role of lung ultrasonography in the management of the patient on chronic HD? Could B-lines be used to guide need for increased ultrafiltration and would this change long-term outcome?
iii.            Could lung ultrasonography be used to guide diuretic therapy in patients with chronic cardiorenal syndrome?
iv.            As B-lines detect subclinical volume expansion, could lung ultrasonography be useful in differentiating hypervolemic from euvolemic hyponatremia?

Where can one learn to get point of care US training?
The Emory US course is the mecca of US training: check out the details here
NKF Spring Clinical Meetings 2017 had a course run by us as a pre-course specifically on point of care US. Similar course will be prepared for 2018
KidneyCon 2018 will also be having a hands on workshop for Point of care US training

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