Articles that changed the way I practice: Gonzalez and Steroids for AIN

Acute interstitial nephritis (AIN) is a drug induced renal failure.

Patients classically have fever, rash and eosinophilia.

During my fellowship there was little data to support the use of steroids and I came down opposed to steroids. Last year Gonzales Et al. published a retrosprective analysis of 61 patients with biopsy proven AIN. 9 were not given steroids and the remiander were given a hodge-podge of different steroid protocols.

In addition to providing data on the question of steroids the article is a goldmine of data regarding AIN.

The culprit was usually an antibiotic:

  • Antibiotic in 34 cases
  • Cephalosporin in 15 cases
  • Quinolone in 12 cases
  • Penicillin in 7 cases
  • NSAID in 23 cases
  • Allopurinol in 1 case
  • Ranitidine in 1 case
  • Omeprazole in 1 case
  • Pimozide in 1 case

Only 8 patients (13%) had the classic triad of fever, rash and eosinophilia. Table 1:

The key result was a signifigant difference in the need for long-term dialysis and a reduction in the final creatinine with steroids.

The data is not the most compelling (It’s retrospective, the control group was tiny compared to the intervention group) but it is by far best we have on the subject and it changed the way I treat AIN.

Student lecture on Acid-Base

I gave a lecture to the third-year medical students at Providence hospital on Friday. I thought the lecture went well but on saturday I was going over an admit note by one of the students in the class. The patient was admitted with DKA but had a combined metabolic acidosis and respiratory alkalosis. This student didn’t do the Winter’s formula calculation and missed the respiratory disease. Of course so did everyone else on the admitting team.


Here is the handout. I added a couple of things since giving the lecture on Friday.

Update: I corrected a mistake in one of the delta bicarb questions. Sorry.

Acid Base Handout (Student)

Craig Langman’s Editorial on the Melamine Crisis from The Journal

Craig Langman (who has made a previous appearance on PBFluids) wrote an editorial for the Melamine article and pair of letters to The Journal (one from Wang et al. from Taiwan and the other from Ho et al. from Hong Kong).

He recommends the same advice I have been giving for Americans who have adopted Chinese infants:

How should physicians in other parts of the world care for Chinese infants who may have been exposed to melamine-contaminated powdered infant formula? The American Society of Pediatric Nephrology suggests a conservative approach in asymptomatic infants,PDF since stones presumed to have been induced by melamine ingestion appear to be passed easily after hydration, and there are currently no follow-up reports on the children studied by Guan et al. and Wang et al. Performance of abdominal ultrasonography in all potentially exposed Chinese children living in the United States would be likely to cost many millions of dollars, an expenditure difficult to justify, given that both unaffected and affected children may have no symptoms and that the meaning of a stone in an asymptomatic child is uncertain.

Langman emphasizes that each study is unable to estimate a true incidence because the populations studied were not representative of the population at risk.

He also teases the reader by mentioning that stones, which are increasing in frequency among adults, seem to be increasingly common among children. He states that this may be due to dietary and lifestyle issues but doesn’t even entertain the possibility that melamine exposure here in the U.S. and around the world may be responsible. This possibility was first suggested in an insightful article in Slate. We know that melamine is found in the U.S., we don’t know how long it has been here.

My personal sense is that the Slate article is just scaring people unnecessarily. if the increase in stones was do to melamine we would know it. We would know it because stones that are removed by interventions are always analyzed in a stone lab. The stones in China that were due to melamine were made of uric acid and melamine. If even a single stone in the U.S. was found to be melamine the whole medical world would go ape.

The Jounal Delivers a Bumper Crop of Melamine Articles.

The primary article is an analysis of 589 children by Na Guan


All of the children’s parents were given a survey to establish demographic data and judge exposure. The investigators questioned parents on the brand and amount of formula ingested and matched it up to government data on the amount of melamine in each brand. Children were then put through varying degrees of biochemical and ultrasound testing.

All the children were under 36 months of age, the population most at risk of melamine stones.

The primary outcome was the presence of kidney stones.
The General Administration of Quality Supervision and Quarnatine of the PRC analyzed 22 brands of formula and reported the amount of melamine. The researchers then categorized each formula as:
  1. High melamine (over 500 ppm)
  2. Moderate melamine (less than 150 pm)
  3. No-melamine.
Ultrasounds were reported as:
  1. Definite stones
  2. Suspected stones (increased sporadic, punctiform echogenicity in the kidneys or pyelocalyceal system)
  3. No stones
The all important table 1.
In 589 exams they found definite 50 stones, 112 suspected stones and 427 children were stone free.

Most of the children with stones did not oliguria, dysuria or edema. Only two of 34 stone formers (6%) had hematuria and only 1 had leukoturia (3%). None of the children with suspected stones had hematuria and only one had leukocyturia (1.3%).

Microalbuminuria was found in more of the children with stones (10%) or suspected of having stones (13.6%) compared to the stone free children (5.6%). Symptoms were not helpful in distinguishing stone formers from the stone free.

Fifty-six children had serum creatinine checked (22 with stones, 21 with suspected stones and 13 without). All of the creatinines were normal.

Interestingly 62 of 404 children had a calcium to creatinine ratio that exceeded age based targets. The 15% rate of hypercalciuria was not associated with stone risk in this study (p=0.34).

In multivariate analysis exposure to high-melamine milk (7x as likely) and pre-term birth (4.5x as likely) were significantly associated with stone formation.

The primary conclusion is that the physical and biochemical lab add nothiong to the evaluation of melamine stones. The birth history and the melamine exposure assessment are critical but need to be followed up by an ultra-sound.

The authors note that only 23 of 121 children exposed to high-melamine formula developed stones

NephSAP on the iPhone

Last week on the fellow education day we did the ESRD NephSAP. Dr. Bellovich showed me that the complete text is available through iTunes as a podcast. Sweet. I have started to listen to the NephSAP in the car. Seems like a pretty cool way to get the info.

Buying and selling of Kidneys for transplant: The biggest ethical question in nephrology.

In India kidneys are widely available for purchse. This allows people with the means to get a kidney. The people with the means include Americans and Europeans as transplant tourists. organ tours.

JAMA published an article in 2002 showed that most of the donors are poor people in debt and a few years later they are still or again in debt and have experienced a decline in health. An essay in Lancet the following years details the global organ traffic and some of its negative consequences.

Despite these horrors they abysmal supply of organs makes the concept of buying and selling organs appealing. I have confidence that a well regulated market place for organs could improve the supply and avoid the horrors which result from the under-the-table, unregulated bazaar that currently exists.

Sally Satel outlines the pro argument in a couple of essays.

Kidney stone question

Great question.

I would look at the March 2008 Seminars in Nephrology which is an entire issue devoted to nephrolithiasis.

The issue was guest edited by John Asplin, one of the best teachers I had during my fellowship. We co-authored a chapter on potassium and I tutored medical students for his renal physiology class. He is medical director of Litholink, a independent clinical lab which provides deep clinical information on the metabolic abnormalities found in patients with kidney stones. I use litholink for all of my stone patients and love it.

It also has multiple articles by Fred Coe and Elaine Worcester. Dr. Coe ran a weekly fluid and electrolyte conference that was one of the highlights of my fellowship experience. Every week a fellow would bring a set of electrolytes and Coe would tell you all about the patient simply from the numbers. It was uncanny how good he was.

My favorite quote from Dr. Coe was:

What you do is serious nephrology [he was referring to acute and chronic renal failure]. What I do is just civilian nephrology. [referring to nephrolithiasis]

Elaine and I co-authored a chapter on calcium, magnesium and phosphorous. We had a great collegial relationship during my fellowship and only after I graduated did I realize how large she was in the field of nephrolithiasis.

Craig Langman also wrote one of the articles in this issue of Seminars in Nephrology. He is a pediatric nephrologist and I spent a couple of months with him at Children’s Memorial during my second year of fellowship. He’s a great teacher. He is now on the lecture circuit for Genzyme. If he comes to town, go. He’s one of the great teachers in nephrology.

Update: Dr. Langman sent me a note stating that he is not “on the circuit.” But my advice stands, if he comes to town, don’t miss him.

Kidney Stone Primer

When a patient needs a metabolic evaluation for kidney stones the twnety-four hour urine should include at minimum:

  • Calcium
  • Oxalate
  • Citrate
  • Uric Acid
  • Volume
  • pH
  • Creatinine

A complete evaluation adds:

  • Sodium
  • Potassium
  • Chloride
  • Urea nitrogen
  • Phosphorous
  • Magnesium
  • Ammonia
  • Sulfate

Hypercalciuria is defined as over 300 mg/day in a man and over 250 mg in a woman. Normal urinary calcium is 150-170 mg per day.

Urine oxalate over 90 mg/day should trigger an evaluation for enteric hyperoxaluria or primary hyperoxaluria.

Hypocitraturia is defined as a citrate below 325mg/day. Hypokalemia can trigger hypocitraturia (along with metabolic acidosis) so be careful when prescribing a thiazide for hypercalciuria, the resulting hypokalemia could surpress citrate and increase rather than lower the risk of developing a kidney stone.

While bowel disease is usually associated with calcium oxalate stones, patients often have decreased urine pH which predisposes them to uric acid stones.