Topic Discussion: HSCT associated TMA

Recently, we wrote an article on Bone marrow transplant or HSCT related TMA for AJKD.
Few things that we have seen in our experience and also what we learnt while writing on this topic is important for Nephrologists to understand.

1.       Diagnosis of TMA related to HSCT that effects the kidney is hard to diagnosis. It is likely the most common kidney biopsy finding post HSCT.  Besides the lab parameters of kidney injury, TRENDING the LDH, haptoglobin, platelets and hemoglobin is critical. In addition, HTN might be the first and most important sign of impending TMA. If the patient requires more than 2 meds for HTN control, one for CNI and other for steroids, it is possible that there is a smoldering TMA . Perhaps we miss some of these cases due to this. Early Nephrology referral might be key as urinalysis is not uniformly done in most centers years post HSCT.

2.       Once infections such as parvo, BK and CMV have been ruled out, a complement mediated process is the likely cause.

3.       CNIs are usually portrayed as the most likely culprit but not all allogenic HSCTS are on CNI and none of the autologous HSCT are on CNIs, yet TMA ensues. In many instances, TMA still gets worse.

4.       Based on some recent findings in the basic science world and few case reports, we propose that TMA following HSCT in many cases might be an “endothelial” variant of GVHD. Treating the underlying GVHD might be the best option in these cases. This might open certain treatment avenues that we haven’t really encountered.

5.       If the TMA is not a ADAMTS13 process, or a “antibody” being removed, TPE doesn’t really help in most cases. Rituximab can be a potential option as this might also help treat GVHD. Alternatively, in many pediatric patients, eculizumab has been used with some success to halt the activated complement  process.

Topic Discussion: Pseudoporphyria

If a dialysis patient presents with a recurrent, sun-sensitive, bullous, and scarring rash on their hands, think of an entity called “pseudoporphyria”.

Patients with ESRD have a limited capability to excrete porphyrins. If there is history of recurrent PRBCS transfusions and/or liver disease, accumulation of iron pigments happens, which in turn provoke pseudoporphyria, characterized by a photosensitive, vesiculobullous skin eruption. Skin fragility and scarring are also observed.

See this reference

https://www.ncbi.nlm.nih.gov/pubmed?term=643142

https://www.ncbi.nlm.nih.gov/pubmed/10401031

Pseudoporphyria is clinically indistinguishable from porphyria cutanea tarda , and both conditions will be associated with elevated serum levels of porphyrins. In the case of pseudoporphyria, the elevated porphyrin levels result from lack of renal excretion. There is no enzyme problem here like in true porphyria cutanea tarda. 

In addition to dialysis, a wide range of drugs are associated with pseudoporphyria. It was first identified in patients taking quinolones. NSAIDS, retinoids, diuretics and some anti neoplastic agents such as TKIs have been associated with pseudoporphyria.

An entity to monitor in our ESRD patients.

Picture courtesy: From an article in JAMA on cyclosporine induced pseudoporphyria. 

Concept Map: Distal Renal Tubular Acidosis

Distal RTA is the true Nephrogenic RTA and can be truly divided into two variants- the hypokalemic and the hyperkalemic types. Here is a concept map of the topic

Concept Map: Low Anion Gap

Here is a summary of various causes and mechanisms of a Low Anion Gap

Clinical Case 91: Answer and Discussion

A twitter poll question I had asked


https://twitter.com/kdjhaveri/status/1033699053043949568

Which one of these interferes with plasma and urine catecholamines assay?

— Kenar Jhaveri (@kdjhaveri) August 26, 2018

The answer is all of the above. There are several agents that interfere the workup for pheochromocytoma and can interfere with the catecholamine and dopamine pathway. The comprehensive list is listed below.

Tricyclic antidepressants, phenoxybenzamine, labetelol can affect the measurement of both catecholamines and metanpehrines

Monoamine oxidase inhibitors and buspirone affects mainly the metanephrine measurements

Caffeine, L-Dopa, Carbidopa mainly affect the catecholamine assays

Concept Map: OSA and HTN

 

Reference: http://cjasn.asnjournals.org/content/6/5/954.full

 http://cjasn.asnjournals.org/content/6/5/986.abstract

Topic Discussion: Phosphorus content of prescription Medications

There is a source of dietary phosphorus that has been noted but is largely unrecognized and unquantified—the phosphorus content of prescription medications. That drugs may contain phosphorus is clear, as it is indicated on the list of inert ingredients reported on their package label. Sherman et al few years back did an amazing study that showcased that medication preservatives might have phosphorus content that we don’t recognize. This might be also causing some phosphorus rises in our patients and need for increased binders.

Medication and dose	Manufacturer	Phosphorus content	Amt of Phos binders required additional
Lisinopril 10mg	Qualitest	40.1mg	2
Lisinopril 10mg	Blue Point labs	32.6mg	1.5
Amlodipine 10mg	Greenstone	27.8mg	1
Amlodipine 10mg	Lupin	8.6mg	-
Paroxetine	Glaxosmith Kline	111.5mg	5
Paroxetine	Cadila	22.7mg	1
Renavite	Cypress	37.7mg	1
Renocaps	Nnodum	1.7mg	-

How do we help our patients with this information? Better would be some way of making prescribers aware that their prescribed medications may be high in phosphorus—they are not ‘dialysis safe’. 

Perhaps creating a database of all drugs and their phosphorus content might be useful.  Or is this not consequential to our patients as diet is the biggest factors… the above is just the sample of drugs the author had inquired.. imagine the rest of the medications and other chemotherapy and other anitbiotics we give our patients.