Consult Rounds: Cryoglobulins and the Kidney

Cryoglobulins and the Kidney

Cryoglobulins are Igs that reversibilly precipitate at temperatures <37C.  This results in symptoms that can lead to rashes, vasculitis, ulcers, ischemia, joint pains, and eventually in 25% cases – renal injury.

Two mechanisms: immune complex GN vs high viscosity related.  All have nephritic/nephrotic syndrome with various levels of kidney function.

1/3 with purpura and arthralgia
¾ with low C4 and ½ with low C3

All 3 types of cryoglobulins reported with renal disease

Most commonly it occurs in settings of type II (“mixed”) cryo secondary to hepatitis C virus.  Most patients with type II or III cryoglobulins have a positive rheumatoid factor.  The pathology pattern of injury is either membranoproliferative or diffuse proliferative GN.

•          Type 1 Cryo( monoclonal IgM or IgG) – MM, MGUS, WM, lymphomas and CLL

•          Type 2 Cryo(monoclonal IgM + polyclonal IgG)- CLL, lymphoma, SLE, Hep C

•          Type 3 Cryo(polyclonal)- lymphoproliferative diseases, SLE

Treatment

Treatment of underlying cause- Hep, SLE, Myeloma

Steroids

Alkylating Agents

Anti CD-20 agents( good response in some cases)

Plasmapheresis ( adjunct) if skin involved and early renal
involvement

Topic Discussion: Baclofen and ESRD

Baclofen is often used as a muscle relaxant in many patients. It has a half life of 3-7 hours and 80% excreted by the kidneys.  It is extremely important to dose adjust in CKD and avoid use in ESRD patients. Dialysis is a good mechanism to remove the agent as well in-case of ingestions and overdoses.

A recent case published in AJKD highlights this important drug related interaction in CKD and ESRD patients. 

The authors describe two excellent clinical algorithms.

The first algorithm discusses dose adjustments.
If GFR>90, no dose adjustment necessary
If GFR 60-90, decrease initial dose by 1/3
If GFR 30-60, decrease dose by ½ and watch for mental status changes
If on RRT or GFR<30, avoid use

The second algorithm discusses if there is a known baclofen toxicity( seizures, hypotenia, encephalopathy, etc.)

If severe AKI, CKD or ESRD- start daily HD or CRRT
If normal renal function or mild AKI but with respiratory depression or seizures- start daily HD or CRRT
If normal renal function or mild AKI and no severe symptoms- no dialysis

Consult Rounds: Tamoxifen induced hypercalcemia

A forgotten cause of hypercalcemia we need to remember is the drug- tamoxifen

This chemotherapy agent used in breast cancer has had a track record of causing hypercalcemia.
It was first described in 1980s.  In that large study, 470 patients with metastatic breast cancer treated with tamoxifen, ten patients (2.3%) developed hypercalcemia. All patients with hypercalcemia had osteolytic or mixed lytic and blastic bone metastases. Hypercalcemia developed after a median period of seven days (range 4-11 days) of tamoxifen administration. Hypercalcemia was treated with conventional measures and serum calcium levels normalized in nine patients, either with a brief interruption of tamoxifen therapy or in spite of continued treatment. Four patients experienced partial remissions with continued tamoxifen therapy. These results indicate that hypercalcemia is a potentially serious complication of tamoxifen therapy but is generally short-lived, and can be controlled with supportive measures, thus allowing continued tamoxifen administration.

Other published reports are

https://www.ncbi.nlm.nih.gov/pubmed/8241000

http://annals.org/aim/article/692303/tamoxifen-hypercalcemia

http://www.sciencedirect.com/science/article/pii/0002961081901744

One recent study looked at a large series of breast cancer patients who were hypercalcemic post tamoxifen- happened within 9 days of start and peaked at a level of 13. All patients also had bone lesions as well.  Gallium nitrate was used to reverse the abnormality while keeping tamoxifen on.

https://link.springer.com/article/10.1007%2Fs00774-005-0678-4

No mention of this in any renal literature. Unclear mechanism of this entity. 

Topic discussion: Downsizing in Nephrology

A timely editorial just got published in CJASN. 

http://cjasn.asnjournals.org/content/early/2017/08/23/CJN.04740517.full

Three large NYC related programs give their thoughts on downsizing in nephrology fellowship spots. A comparison is made with anesthesiology that helped revert their trend of decrease supply in the 1990s.  The authors bring up few major concerns

1.       The debt burden of recent graduates and the compensation that nephrologists receive is not attractive. But the authors make a good point that while the starting salaries are low, there is room for growth and potential that other fields might not have. This is speculative and might depend on coast to coast in the US. While certain parts of the country, nephrologist make a lucrative salary, there are others where hospitalists make much more than nephrologists.

2.       The authors make an interesting suggestion of broadening our certification. This is an excellent thought. I urge the nephrology community to try to do this in the 2-3 year time frame of a fellowship. There are a minority of candidates who would do an extra year given their debt burden but incorporating something extra in your fellowship might help that candidate get that certificate along with Nephrology- be it glomerular disease, onconephrology or critical care.

3.       Chronic disease models have done well with PA and NP based teams in certain parts of the country. Examples are oncology, BMT, renal transplant, CT surgery. Nephrology should learn from these models. As the authors suggest, perhaps cautious downsizing might help reverse trend of supply/demand and help get outstanding candidates back in Nephrology.  A formula was suggested back few years ago by Desai and perhaps can be considered if need be.

4.       Overnight call is part of being a nephrologist. While authors suggest that the fellows might be called in a lot- one cannot ignore a K of 8 and wait till the 8AM fellow/attending comes in. Remote management might be possible but we have to be cautious in those methods.  Transplant overnight call should be reduced and can be the most helpful. A DDRT call should really not involve the nephrology fellow unless dialysis is required pre transplant. 

5.       Regardless of number of applicants a program is getting- the dependence on fellows for day to day work should be abolished.  This makes the applicant feel that the program is “fellow” centric and not “fellow” dependent. Attending directed services, NP, and PA based practice can help foster this environment. The flip side is loss of intensive education.  Given the rounding in the dialysis unit to only an NP or PA and relieving the fellow might lead to long term loss of education that we may regret. If planning this, would careful involve fellow in some of the rounding as well.  In addition, taking care of certain volume of patients and putting a cap on consults can also lead to “inefficient” graduates and unable to handle the volume when in private practice.  Fellows also have to learn how to manage and prioritize sick vs not that sick patients and how to manage a long and busy list. Nephrologists are smart physicians. We also want our fellows to be effective communicators, and efficient doctors.

I commend the authors on this very provocative essay and hoping this dialogue continues in making nephrology more attractive as it was many years ago.  

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