Nephropathy Due to Chinese Herbal Medicines

July 29, 2008

In 1992 a cohort of women with a rapidly progressive interstitial nephritis was identified in Belgium. The cause of this nephropathy was subsequently traced to the use of Chinese herbal medicines designed to encourage weight loss. The offending herbs were banned. Nevertheless more than 100 cases of the disease had been reported in Belgium by 1998. The herb blamed for most of the cases was Aristolochia fangchi which is rich in aristolochic acid (AA); this compound seemed to be the cause of the disease.

Debelle and colleagues review this disorder in a paper in Kidney International. Their in depth review exhaustively covers the subject. They believe that the disorder is seriously under reported. The disease may be quite widespread in India, China, and other Asian nations. Debelle, et al list many botanicals that are suspected to contain AA. The list is so long that you might be tempted to cancel your trip to the Beijing Olympics. These authors favor the less colorful name for this disorder of aristolochic acid nephropathy (AAN) as opposed to Chinese Herbal Nephropathy.

Balkan endemic nephropathy (BEN) was a disease reported, not surprisingly, in the Balkans about 50 years ago. It closely resembles AAN.

Proposed relationship of AAN and BEN - Debelle, et al

Proposed relationship of AAN and BEN - Debelle, et al

Though its pathogenesis is unknown is may be due to wheat contaminated with seeds of Aristolochia clemaditis and thus may be an earlier incarnation of AAN. AA exposure is also strongly linked to urothelial malignancies. The take away message here is to avoid AA. AA containing herbal medicines are widely available in many countries and can easily be obtained over the internet. Caveat emptor.

Dermal Deposits of Gadolinium in NSF

July 25, 2008

The gadolinium and NSF story continues to become clearer. A paper in the July issue of the Clinical Journal of the ASN shows deposition of gadolinium in the skin of a patient who developed Nephrogenic Systemic Fibrosis (NSF). Traces of iron were also found. NSF is seen exclusively in patients with renal failure; most of these patients have received gadolinium based MRI contrast agents. The half life of gadolinium is a little more than one hour in patients with normal renal function, but rises to 120 hours in dialysis patients. It appears that accumulation of gadolinium in the skin and other organs is the trigger for the development of this syndrome. The current study in CJASN provides further support for this view. As stated in an earlier post here, nobody with a glomerular filtration rate of less than 30 ml/min should receive gadolinium unless the indication is stronger than the fear of inducing NSF.

The study’s abstract is reproduced below.

Background and objectives: The pathogenesis of acquired nephrogenic systemic fibrosis recently described for patients with renal insufficiency and a history of exposition to gadolinium-based magnetic resonance contrast agents is not completely understood. A role for circulating fibroblasts in the fibrosing tissue is hypothetical, and the mechanism of the assumed trigger function of gadolinium remains elusive.

Design, setting, participants, & measurements: A skin lesion on a 76-yr-old man with symptoms of nephrogenic systemic fibrosis lasting 5 mo was studied at the ultrastructural level. After confirmation of he diagnosis by histopathologic methods, the presence and distribution of gadolinium, iron, calcium, and magnesium by energy filtering transmission electron microscopy was also examined.

Results: The performed electron spectroscopic imaging and electron energy loss spectroscopic analyses on deparaffinized samples revealed deposition of gadolinium in irregular small aggregates that adhered to cell profiles and collagen fibers of the connective tissue, forming a perivascular “gadolinium-deposit zone” in the skin. Traces of iron signal were demonstrated in singular gadolinium-positive deposits, and iron presence was found in adjacent connective tissue. The ultrastructural cell analysis of the lesion showed among numerous poorly differentiated fibrocytes also higher differentiated cells with myofibroblastic characteristics, including bundles of intermediate filaments and attachment plaques in the cell periphery, indicating an ability of lesional fibroblasts to differentiate into myofibroblastic cells.

Conclusions: These findings support the pivotal role of gadolinium chelates in the development of nephrogenic systemic fibrosis.

Villazon Before the Fall

July 23, 2008

Rolando Villazon’s new recital disc Cielo e Mar, his first for DGG, was recorded in March of last year before the tenor’s cancellation of five month’s of engagements. The cause of Villazon’s disappearance was attributed to exhaustion. He has returned this year with a less intensive schedule than the manic pace he had moved at the preceding few years.

There’s no sign of the collapse that was to occur shortly after this recording was made. The Mexican tenor sounds in fine voice which makes his subsequent vocal problems all the more poignant. Reviews of his 2008 performances suggest that his voice is still beautiful, but that it tires easily and that his high notes sometimes crack. Voices are as evanescent as shadows; often when they go they go for good or never get back to their previous best. Consider Ben Heppner who started to crack during his Otello run in Chicago in 2001. I was there and it was painful to see a great artist in so much trouble. He took time off and and has returned, but he’s not the same singer he was before encountering Iago. What will happen to the much younger Villazon is uncertain.

All of the arias on the new disc are from roles the tenor has yet to sing. There is no reason that given luck, discipline, and hard work that he shouldn’t eventually sing a spinto role like Adorno in Boccanegra. After all it is these three characteristics that have enabled Placido Domingo to build an amazing career full of roles he shouldn’t have sung. But Domingo seems to made of extraterrestrial protoplasm. In addition to more or less standard stuff there are five selections that are rarely heard and which Villazon makes a good case for hearing more often.

The two arias from Saverio Mercadante’s Il Giuramento sound beautiful when you hear them though they don’t seem to stick in your brain after they’re over. They’re six bands apart on the disc for no apparent reason. The same is true of “Intenditi con Dio” from Fosca by the Brazilian composer Carlos Gomes. The Gomes piece is quite beautifully sung. Villazon easily makes you interested in hearing more by both composers.

I’ve always wanted to hear more by Ponchielli than La Gioconda which is commonly dismissed solely because it’s popular. I Lituani has much fine music in it. “Il Padre” from Il Figliuol Prodigo reinforces my wish to hear more of Ponchielli’s work. Interestingly Antonio Ghislanzoni of Aida fame wrote the librettos for both Gomes’s Fosca and Ponchielli’s I Lituani. The scena from Donizetti’s Poliuto is given a vigorous and idiomatic performance,

But the main reason to buy a recital CD by a singer his to hear his voice and see how he realizes his interpretations. Villazon is first rate on both counts. His beautiful ‘creamy’ voice shows no sign of strain. He sings with feeling and conviction and phrases with sensitivity and finesse. His high notes are easily produced and have ping. If you’ve liked his previous work you’ll want to have this disc. I can only hope that this is not farewell recital. A voice this rare would be tragic to lose so prematurely.

The conductor of all the selections is Danielle Callegari leading the Orchestra Sinfonica Di Milano Giuseppe Verdi.

The full program is listed below.

More on Gadolinium and NSF

July 2, 2008

More evidence mounts supporting the causal role of gadolinium containing MRI contrast agents and nephrogenic systemic fibrosis (NSF) in patients on dialysis. Two papers in the June 2008 issue of the American Journal of Kidney Diseases examine the issue.

Kallen, et all report that “Receipt of gadolinium-containing MRI contrast is associated with NSF in a dose-dependent manner. The risk associated with gadolinium may differ by contrast agent and dialysis modality. Use of gadolinium-based contrast agents should be avoided when possible in patients with renal failure.”

Schieren, et al in the same issue of the journal observe that Gd-diethylenenitramine penta-acetic acid, but not gadubutrol cause an increase in the acute phase reactant CRP and was associated with more adverse clinical events.

These observations suggest that some gadolinium preparations may be more likely than others to induce untoward events. They further suggest that NSF may be an inflammatory disease induced by the contrast agent. Good practice dictates that the agent be avoided in patients with reduced renal function. If its use is unavoidable the smallest dose possible should be employed.