Tuesday, September 2, 2014

Friday, August 29, 2014

In the NEWS: LCDD without proteinuria: A challenge for nephrologist


Classically Light chain deposition disease(LCDD) presents with proteinuria ( almost in the nephrotic range). A recent article in NDT looks at a small cohort of patients that presented with LCDD with <0.5gm of proteinuria.  They present 14 cases, average proteinuria was 0.3g/day. Most had CKD at baseline.  IgG kappa was the most common light chain followed by IgM kappa.  Only 3 patients had diagnostic myeloma, 2 had WM.  Interestingly 5 had MGUS and 4 had smoldering myeloma.  Serum creatinine decreased in most cases after chemotherapy was introduced. Proteinuria never became nephrotic range.   This is thus far the largest series of such LCDD without proteinuria. Early identification of this atypical variant of LCDD is important.  It seems also that it’s a smoldering form just like the hematologic counterpart and most of these patients had either MGUS or SM and not full blown MM.  

What did the pathology show?-  diffuse tubular basement membrane thickening; some with duplication.  Rare casts were noted.  Nodular sclerosis of GN lesions only in 2 cases and others did have some mesangial hypertrophy and ischemic lesions.  No amyloidosis was noted in any cases. 


Classically thought to be a proteinuric variant of myeloma, LCDD can also present as a non proteinuric disease mainly involving tubules. 

Saturday, August 23, 2014

Ipilimumab and renal disease


Ipilimumab is a human monoclonal antibody that targets T lymphocytes antigen-4 or CTLA-4 and it’s used in clinical practice to treat melanoma.  Does this agent lead to nephrotoxicity?

Where do we encounter CTLA-4 in the renal literature?

Agonists to reduce immune activity using CTLA-4 Ig are available such as Orencia( abatacept) for SLE and RA.  Belatacept is a similar agent used in transplantation literature for treatment and prevention of rejection.  How are they different from ipilimumab that is used to treat cancer?  This antibody binds to human CD152 and enhances T cell response especially against tumor cells. It basically boosts the immune response against the tumor cells.  So invitation of the T cells into the kidney could be possible- and renal injury a potential side effect.

Literature search revealed three published cases.
And a NEJM case report on the drug causing lupus like nephritis.

It seems that the treatment of this leads to activation of T cells that can stimulate a classic vasculitis or interstitial nephritis. 

As the cancer literature grows,  we have to be mindful of the nephrotoxicites of such agents.




Tuesday, August 19, 2014

Concept Map: Thrombotic microangiopathies













This is based on a recent review by George and Nester in NEJM on TMA syndromes. Looking and classifying TMA in this format is much more pathophysiologic than using terms such as HUS and TTP

Out with HUS and TTP and let's use more CAUSE based TMA as the term to help understand pathophysiology and then use the appropriate treatment

**( complement mediated TMA) is a better term then using atypical HUS as it gives more information regarding pathophysiology and not confuse us.

Click on the image for a larger/readable view.


Sunday, August 10, 2014

IN the NEWS: Balanced solutions all the way- do we need more studies?

Balanced fluids such as lactate ringers have made it to the medicine literature finally.
This week in Annals of Internal Medicine, a meta analysis showed that balanced fluids trumped normal saline in sepsis treatment.  Normal saline, initially invented during the cholera epidemic has come a long way in medicine literature.
Solution
pH
Na+
Cl-
K+
Ca++
Lactate
Glucose
Osmolality
Other
0.9% normal saline
5.0
154
154
0
0
0
0
308
0
LR
6.5
130
109
4
3
28
0
275
0

A landmark trial in JAMA in 2012 showed that chloride based fluids might not have that great of renal outcomes.  Another one showed increased renal blood flow.

In addition, this year in Nephmadness 2014, balanced solutions was a top match. 

Wednesday, August 6, 2014

Clinical Case 84: Answers and Summary

What is the pathology seen in the kidney in Mesoamerican nephropathy?

Chronic glomerular damage
  1 (5%)
 
Chronic tubulo interstitial damage
  13 (72%)
 
Chronic thrombotic microangiopathy
  0 (0%)
Chronic nodular sclerosis
  4
The correct answer is tubulo interstitial disease.  The best summary of this entity was recently discussed in the online nephrology journal club ( NephJC).  

This link also goes over the discussion re this entity on twitter. 


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