TOPIC DISCUSSION: Post Transplant Collapsing FSGS, what role does ischemia play?

A case report of three cases in AJKD this month reports de-novo post transplant collapsing glomerulopathy(PTCG). Rare cases of de novo collapsing glomerulopathy have been reported during the post-transplant course and, in some instances, have been associated with renal graft vascular lesions. This finding raises the important question of whether ischemia could induce podocyte transdifferentiation, a hypothesis supported by evidence of hypoxia-inducible factor–dependent podocyte proliferation in HIV-associated nephropathy.This paper nicely shows the immuno-staining of those patients and positive for VEGF at the podocytic injury suggesting that hypoxia induced increased hypoxia inducible factor is leading to increased VEGF for their survival that ultimately leads to the collapse. Other causes that are commonly associated with Collapsing Glomerulapthy are pamidronate use, interferon use, use of sirolimus, parvovirus B19 virus, CMV infection, Renal artery stenosis, SLE, lymphoma, and recently even use of depakote and dilantin. HIV was negative in all patients? It was unclear if parvo virus was checked as post transplant parvo virus B19 cases of collapsing GN has been noted.

It is a devastating disease and something to keep in the differential diagnosis even post transplant in nephrotic range proteinuria.  Ischemia likely from chronic rejection, chronic calcineurin use might be the culprits.

The same causes that lead to Collapsing FSGS in the non transplanted kidney, should also be ruled out in the transplanted kidney. The important major difference is the ischemia as a cause might be more evident in transplanted kidney.

Image courtesy: design milk

Other references:-

http://www.abstracts2view.com/asn/view.php?nu=ASN09L1_2723a

http://www.ncbi.nlm.nih.gov/pubmed/16705026

http://journals.lww.com/transplantjournal/Abstract/1998/05150/De_Novo_Collapsing_Glomerulopathy_in_Renal.9.aspx

Post Transplant Collapsing FSGS: Is it really all Ischemia?

A case report of three cases in AJKD this month reports de-novo post transplant collapsing glomerulopathy(PTCG). Rare cases of de novo collapsing glomerulopathy have been reported during the post-transplant course and, in some instances, have been associated with renal graft vascular lesions. This finding raises the important question of whether ischemia could induce podocyte transdifferentiation, a hypothesis supported by evidence of hypoxia-inducible factor–dependent podocyte proliferation in HIV-associated nephropathy.This paper nicely shows the immuno-staining of those patients and positive for VEGF at the podocytic injury suggesting that hypoxia induced increased hypoxia inducible factor is leading to increased VEGF for their survival that ultimately leads to the collapse. Other causes that are commonly associated with Collapsing Glomerulapthy are pamidronate use, interferon use, use of sirolimus, parvovirus B19 virus, CMV infection, Renal artery stenosis, SLE, lymphoma, and recently even use of depakote and dilantin. HIV was negative in all patients? It was unclear if parvo virus was checked as post transplant parvo virus B19 cases of collapsing GN has been noted.
It is a devastating disease and something to keep in the differential diagnosis even post transplant in nephrotic range proteinuria.  Ischemia likely from chronic rejection, chronic calcineurin use might be the culprits.
The same causes that lead to Collapsing FSGS in the non transplanted kidney, should also be ruled out in the transplanted kidney. The important major difference is the ischemia as a cause might be more evident in transplanted kidney.
An abstract at ASN showed similar findings as well.


Other references:-
http://www.abstracts2view.com/asn/view.php?nu=ASN09L1_2723a
http://www.ncbi.nlm.nih.gov/pubmed/16705026
http://journals.lww.com/transplantjournal/Abstract/
1998/05150/De_Novo_Collapsing_Glomerulopathy_in_Renal.9.aspx

CLINICAL CASE 6

What is the most sensitive test for detection of paraproteinemia?

A.Serum protein electropheresis (SPEP)	1 (5%)
B.Serum immunofixation	3 (15%)
C.Serum free light chains	2 (10%)
D.Serum free light chains + immunofixation	14 (70%)

Yes. That is correct. Most of you got it right. I think its about time that everyone starts using serum free light chains not only for detection but also for follow up in some of the paraproteinemia patients. The serum immunoglobulin-free light chain (FLC) assay measures levels of free  and  immunoglobulin light chains. Based on the Hematology Associations. there are three major indications for the FLC assay in the evaluation and management of multiple myeloma and related plasma cell disorders (PCD). In the context of screening, the serum FLC assay in combination with serum protein electrophoresis (PEL) and immunofixation yields high sensitivity( just serum free light chains and immunofixation is good enough and you can rule out a lot of your paraproteinemias), and negates the need for 24-h urine studies for diagnoses. 

Just for context, a serum immunofixation might detect 50 fold increase in a specific light chain, the serum free light chains assay detects even a 10 fold increase; hence making it very sensitive test.

Second, the baseline FLC measurement is of major prognostic value in virtually every PCD. Third, the FLC assay allows for quantitative monitoring of patients with oligosecretory PCD, including AL Amyloidosis, oligosecretory myeloma and many patients who had previously been deemed to have non-secretory myeloma. In AL Amyloidosis patients, serial FLC measurements outperform PEL and immunofixation. In myeloma patients, although not formally validated, serial FLC measurements reduce the need for frequent bone marrow biopsies. 

Check out the above linked reference for further reading.

For excellent reading:  Read  the Kidney in Plasma Cell Dyscrasias

The links below are also helpful:-

http://www.mayoclinicproceedings.com/content/81/12/1575.full

http://myeloma.org/pdfs/UnderstandingFreeLight.pdf

Topic Discussion: OUCH!! Should Anesthesia Hurt??

“It will burn for a few seconds, then become numb…” Sound familiar? That’s how I describe the local infiltration of lidocaine to patients. In order to decrease the pain associated with the administration of lidocaine, our interventional radiology department has taught nephrologists to use lidocaine buffered with sodium bicarbonate (1 part NaHCO3 for 9 parts lidocaine) during local anesthesia in preparation for ultrasound guided kidney biopsies. A quick literature search reveals much support for this technique. One hypothesis is that the buffered solution has less protonated molecules which are lipophilic and can more readily enter the myelin sheath resulting in a more rapid onset of action. A second idea is that the buffered solution has less associated discomfort simply because it has a more physiologic pH.

On the other hand, one study showed that the administration rate of lidocaine may have more influence on the perceived pain associated with injection than does buffering. Slow, unbuffered injections were associated with less perceived pain than rapid, buffered injections. (http://www.annemergmed.com/article/S0196-0644(98)70278-1/abstract)

TOPIC DISCUSSION: Alcohol Poisonings, gaps and osmoles

This weeks Kidney International's Whats your diagnosis section discusses a case of Diethylene glycol poisoning. ( image courtesy on left: Precious Body Fluids Blog)
Of all the alcohol poisonings, its important to distinguish which one you are dealing with. The article has a nice table that shows the similarities and differences of them.
Methanol poisoning usually has acute renal failure, met acidosis ( part of MUDPILES), and increased or normal osmolar gap; there is some neurological and visual disturbances.
Propylene glycol is usually seen with ativan drips, is seen with acute renal failure, metabolic acidosis and sometimes an osmolar gap but other findings are negative.
Ethylene glycol, another cause of metabolic acidosis and increased osmolar gap, you see with renal failure and + calcium oxalate crystals.
The Diethylene glycol poisoning is more rare but can happen as in this case. Its usually seen with acute renal failure, + metabolic acidosis and sometimes an osmolar gap but very frequently as noted in this article with neurological facial nerve pals and mild hepatitis.
Isopropyl alcohol is a classic one that has an elevated osmolar gap but no anion gap.
There is always something hiding in the gap. Even a low osmolar gap is abnormal.
take a look at this table I saw in Canadian medical association journal. I think that this table is a nice review.
Says it all.

Belatacept approved by FDA

What is Belatacept and is it going to change the face of transplantation? Its a fusion protein composed of components of  TLA-4, extracellular domain of IgG1.  The drug can selectively block the T cell activation by inhibiting this costimulatory molecule CTLA-4.   From the researchers mainly at UCSF, a landmark paper was published few years ago in NEJM.
They assigned renal tranplant patients to receive an intensive or less intensive of belatacept or cyclosporine. All patients were induced with the same agent of basiliximab. All received steroids and MMF.  At six months, they evaluated that the incidence of acute rejection was no different in two groups. CAN, and decrease in GFR was less common in the belatacept arm.

This drug might show promise. Lets see once more widespread use of it is noted. It might allow us to spare cyclosporine or tacrolimus use in many of our patients. This is important as one of the most common causes of graft loss these days is not rejection but chronic calcineurin toxicity or chronic changes due to medications. The effect on the pancreas by these drugs is also not benign and the most common glomerular disease post transplant still remains to be diabetes.
Lets await and see.

Protocol Biopsies in Renal Allograft Recipients

Please see the link from an excellent website tool: Nephrology on Demand.
I encourage all to use it. It has latest information and classic nephrology articles for everyones use.
Very easy to use and easy access.


Protocol Biopsies in Renal Allograft Recipients