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.
0.9% normal saline

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
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. 

Monday, August 4, 2014

Tubuloreticular inclusions related nephropathy: Should we look at it that way?

Tubuloreticular inclusions (TRI)s are sub-cellular organelles characterized by small clusters of anastomosing tubule-like structures within cisternae of endoplasmic reticulum and are considered footprints of biological activity of the alpha or beta interferons (IFN-α and INF-β). These structures have been described with collagen vascular diseases (Eg, SLE, systemic sclerosis, MCTD etc.), HIV associated nephropathy and during systemic treatment with interferons. However, the role of TRIs as a reliable indicator of secondary glomerular process with a wide spectrum of etiologies has not been fully studied.

Production of IFNs requires stimulation by viruses, microbial products or specific chemicals via triggering the signaling systems linked to toll-like receptors (TLRs). Both in systemic diseases and viral infections, it’s the IFN-α and INF-β that are most associated with TRI formation. While we have literature supporting some secondary causes that have been associated with TRIs, are we still missing other causes that may lead to a secondary form of GN such as membranous GN, minimal change disease or proliferative GN. 
Does the presence of TRI prompt one to look for a secondary cause? What if the only finding you have is TRI with membranous GN and or TRI with MCD? Should a viral etiology or cancer or systemic lupus be considered?  Or are we dealing with it backwards.  Should we be classifying some of these entities as TRI Nephropathy and then appropriately look for a secondary cause. 

In the literature, only one study has looked at TRIs specifically in reference to this question. It was evaluating Membranous GN with TRIs.  Most of the cases did lead to a secondary cause but 1/3 had no etiology found( or perhaps we don’t know yet about this virus or systemic disease).  Another study did a more wider search and found causes we had already known. Other diverse conditions where TRIs have been described include inclusion body myositis , Kaposi's sarcoma, gliomas and sarcomas. Some of these findings are not in the kidney but in the brain or eye. Perhaps we need to elaborate on disease states that form TRIs and are we missing a bigger entity of TRI related diseases?  Inflammatory myopathies are something to strongly consider. Overall, if there is a high IFN-α and INF-β state in the body from any known or unknown cause- chances that it might lead to TRI formation in the kidney and a podocytopathy which can manifest as MCD, Membranous GN, FSGS or proliferative GN. 

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