The Renal Fellow Network did a nice pocket review of Loin Pain Hematuria Syndrome recently. However they left off an important diagnosis which also presents with hematuria and unilateral pain, Nut Cracker Syndrome. This refers to impingement of the left renal vein between the aorta and superior mesenteric artery.
These patients usually come to the nephrology office with a history of mysterious kidney stones which have been difficult to visualize.
In Nut Cracker Syndrome the pain is always on the left side.
Nice review with imaging studies are found in this NDT article from 1995.
(a) MRI revealed a dilated left renal vein (black arrows) after passing between the aorta (A) and superior mesenteric artery (white arrowhead). (b) MRA showed that the diameter of the left renal vein (black arrow) was larger in the left part adjacent to the aorta (A) compared with the right adjacent part. A prominent left ovarian vein (white arrow), implicating formation of a collateral circulation, was also noted. IVC = inferior vena cava. (c) Digital subtraction MRA found the impingement of the left renal vein (LRV) between the aorta (A) and superior mesenteric artery (white arrowhead).
45 y.o. referred for 4+ proteinuria. Patient is asymptomatic without edema but the FLP shows total cholesterol to be pushing 300. The patient reports for one month he has seen bubbles in his urine. A 24-hour urine showed 2,500 mg of protein on an adequate specimen.
PMHx is significant for gout which has been treated with allopurinol without much improvement. Over the last couple of years he has gone from 100 mg to 300 mg, during this time his uric acid has stayed a midling 7-9 mg/dL. Two months ago he was started on probenecid, a uricosuric agent. This is appropriate as his renal function is great (S Cr of 0.9 in a male who works out).
His physical exam is benign.
No additional relevent data can be gleaned from his labs.
What’s the diagnosis?
Proteinuria due to probenecid. The patient stopped the offending agent and within ten days the U/A showed 1+ proteinuria and the PCR was 0.37.
In the exam room I told him it was a membranous nephropathy but according to this letter to NDT from 2007 the pathology is not typically membranous at all. This jives with the rapid recovery from proteinuria after the medicine is withdrawn.
Here is the mechanism of action of probenecid from UpToDate:
MECHANISM OF ACTION — Competitively inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby promoting its excretion and reducing serum uric acid levels; increases plasma levels of weak organic acids (penicillins, cephalosporins, or other beta-lactam antibiotics) by competitively inhibiting their renal tubular secretion
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.
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.
Frustrating.
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.
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 Chineseinfants who may have been exposed to melamine-contaminated powderedinfant formula? The American Society of Pediatric Nephrologysuggests a conservative approach in asymptomatic infants,PDFsince stones presumed to have been induced by melamine ingestionappear to be passed easily after hydration, and there are currentlyno follow-up reports on the children studied by Guan et al.and Wang et al. Performance of abdominal ultrasonography inall potentially exposed Chinese children living in the UnitedStates would be likely to cost many millions of dollars, anexpenditure difficult to justify, given that both unaffectedand affected children may have no symptoms and that the meaningof 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 primary article is an analysis of 589 children by Na Guan
Methods
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:
High melamine (over 500 ppm)
Moderate melamine (less than 150 pm)
No-melamine.
Ultrasounds were reported as:
Definite stones
Suspected stones (increased sporadic, punctiform echogenicity in the kidneys or pyelocalyceal system)
No stones
Result
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
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.
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.
(a) MRI revealed a dilated left renal vein (black arrows) after passing between the aorta (A) and superior mesenteric artery (white arrowhead). 
