Lenalidomide and its renal toxicities?

Lenalidomide and renal toxicity, can this occur? Most chemotherapy drugs used to treat paraproteinemias are not nephrotoxic. But with renal toxicities such as electrolyte disorders, AIN and perhaps some GNs, anything might be possible. While cause and association cannot always be ruled out, knowing some associations is helpful. Lenalidomide usually is not associated with any nephrotoxic capabilities. In most cases, it has been studied now in patients with severe renal failure as well. In a recent letter to the editor in AJKD, a case of minimal change disease is reported. Interestingly, NSAIDS were also confounding factors but no AIN was found. Prior to this, a case of fanconi syndrome has been reported with lenalidomide as well. When paraproteins itself can cause GN and fanconi syndromes and other electrolyte disorders, sometimes its hard to make a case for the chemotherapy causing the renal damage.

Topic Discussion: Hypercalcemia and leukemias..( not lymphomas)

Classically, one associates hypercalecmia of malignancy with solid tumors such as breast cancer, kidney cancer and so forth. In regards to hematologic cancers, the lymphomas, and myelomas are the two disease states that have shown to have hypercalcemia.

Does AML, ALL and other leukemias have associated hypercalcemia? It’s rare. T cell leukemia classically associated with HTLV-1 has been widely reported and is the most common leukemia to have hypercalcemia. Besides that, the rest of them are 1-2 case reports. NEJM had one of the earlier cases of this association. Recently, childhood ALL was reported with hypercalcemia of malignancy as a result of parathyroid hormone-related peptide and E2A-HLF from translocation 17; 19.  Shu et al discuss the mechanism involved in leukemias and hypercalcemia. Cancer type T cell leukemia has a 50-90% incidence of hypercalcemia and its pthrp mediated or interleukin mediated or perhaps RANKL mediated. Acute non lymphocytic leukemia has a rare incidence but its pthrp and or 1,25 Vitamin D mediated.

International Update on Glomerular Diseases 2013 Talks

This April we had an update on glomerular diseases at our division. The international society of nephrology graciously has displayed few of the talks on their ISN Education website for all for viewing. Have a look at most of the talks from that day.

http://www.theisn.org/glomerular-disease/tags/course-update-on-glomerular-disease/itemid-916

In The News: Androgen deprivation therapy and AKI

Androgen deprivation therapy (ADT) is one of the mainstay treatments for prostate cancer. A recent study in JAMA2013, via a nested case control study show that these agents might be leading to or may be associated with acute kidney injury. Total of over 10,000 patients were looked at and comparing to matched controls, found these agents to be associated with AKI.

What are the different hormone therapies for prostate cancer?

Orchiectomy (surgical castration)

Luteinizing hormone-releasing hormone (LHRH) analogs

These drugs lower the amount of testosterone made by the testicles. Treatment with these drugs is sometimes called chemical castration because they lower androgen levels just as well as orchiectomy.

The LHRH analogs available in the United States include leuprolide (Lupron^, Eligard), goserelin (Zoladex) to name a few.

Luteinizing hormone-releasing hormone (LHRH) antagonists

LHRH antagonists work like LHRH agonists, but they reduce testosterone levels more quickly and do not cause tumor flare like the LHRH agonists do. Degarelix (Firmagon) is an LHRH antagonist used to treat advanced prostate cancer.

Anti-androgens

Anti-androgens block(ADT) the body's ability to use any androgens. Even after orchiectomy or during treatment with LHRH analogs, the adrenal glands still make small amounts of androgens.Drugs of this type, such as flutamide (Eulexin), bicalutamide (Casodex), and nilutamide (Nilandron), are taken daily as pills.

Other androgen-suppressing drugs

Estrogens , Ketoconazole (Nizoral)

The report in JAMA focuses on ADT and its anti androgen effects. During follow-up, the investigators identified 232 cases with a first-ever AKI admission. These cases were compared with controls matched for age, one year since prostate cancer diagnosis, and duration of follow-up. Compared with never use, current use of ADT was significantly associated with a 2.5 times increased odds of AKI.

The association was mainly driven by a combined androgen blockade, estrogen only, and other combination therapies, which were associated with a 4.5 times, 4.0 times, and 4.0 times increased odds of AKI, respectively, in adjusted analyses. Oral antiandrogens only, gonadotropin-releasing hormone agonists only, and bilateral orchiectomy each was associated with about a twofold increased odds. There might be a combined effect as stated by the authors.

One case report of flutamide associated AKI does exists. The case had shown temporal association in a patient with metastatic prostate cancer. No biopsy was done.

Few questions remain?

1.       How come we don’t see this as frequently then? ( or perhaps we are missing it)

2.       What is the biopsy findings of these patients? Is it tubular damage, glomerular damage, - no mention of that anywhere. There might be protective benefits of androgens to the kidneys but there are basic science papers that have shown the opposite as well.

3.       Looking closely at cases vs cohorts in this manuscript, while no p values are provided, there were more percentages of cases with HTN, CAD, CHF, on NSAIDs, antibiotics, Given complex statistical analysis and more sensitive analysis, they were able to still show an association.

4.       Repeat study to confirm this association needs to be done. This is an observational data from outcomes type of research. This deserves a well designed trial to replicate this and see if this clinical holds true.

Teaching resources page

Please see update teaching resources page
http://www.nephronpower.com/p/nephrology-teaching-resources.html

Please comment on any other resources you know

CONSULT ROUNDS: PRES in Pregnancy

                

Posterior reversible encephalopathy syndrome (PRES) is a clinic-neuroradiological syndrome associated with various clinical conditions, presenting with headache, encephalopathy, seizures,
cortical visual disturbances or blindness. Imaging predominantly shows parieto-occipital white matter changes, with vasogenic edema being the most accepted pathophysiology.
Common clinical conditions include hypertensive encephalopathy, renal failure, autoimmune disorders and treatment with immunosuppressant or cytotoxic medications.
Uncommon clinical conditions include acute intermittent porphyria and cryoglobulinemia.

Some of the earlier cases of PRES were seen with SLE patients and in kidney transplant patients the classic association is with CNIs in rare circumstances. Preeclampsia and eclampsia may be the most common  causes of PRES during pregnancy and most cases are managed without neuroimaging, and the incidence remains unknown.  However, it is uncertain whether a cause and effect relationship truly exists between the two or if these represent independent processes with some element of clinical overlap.
By definition, all patients with posterior reversible encephalopathy syndrome have a characteristic MRI pattern with bilateral hemispheric boundary zones of hyperintensities on T2 and FLAIR imaging, with increased apparent diffusion coefficient values, affecting the cortex and subcortical and deep white matter to varying degrees. The pathogenesis of PRES remains unclear, but it appears to be related to disordered cerebral autoregulation and endothelial dysfunction. Cerebral venous and sinus thrombosis (CVST) in the postpartum period is also a common cerebrovascular incident during the puerperium. Clinical manifestations consist of headache, vomiting, focal or generalized seizures, confusion, blurred vision, focal neurologic deficits, and altered level of consciousness. It is in the differential diagnosis when considering PRES in pregnancy in the post partum period.

                                                                               

Image source: radiopaedia.org           

Nephrology Fellows Jeopardy

Check out the above banner for upcoming Mt Sinai Nephrology sponsored  Fellows Nephro-pardy. More details to follow!!