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Renal Week 2008: CVD and CKD: Case 7

66 yo woman with ESRD due to analgesic nephropathy. Hx of Crohn’s Disease. Extended criteria deceased donor allograft transplant 1.5 yrs ago.

Now SBP of 160.

Next Speaker Ojo. Greatest name in Nephrology.

CVD and CKD in Transplantation

Progressive reduction of acute rejection since 2000 from 17.4 to 10.3% at one year. This should improve outcome of graft and patient; however post-transplant life-span has decreased from 14 in 1995 to 12.7 in ’06.

CVD is the explanation for this conundrum.

After the first year the most common cause of loss of graft is: death with a functioning graft (56%). This is twice as common as number 2, chronic rejection (21%).

43.5% die of CVD.

Hypertension, DM, hypercholesterolemia, obesity, and anemia are all more prevalent in transplant patients than transplant candidates or prevalent dialysis patients.

Focus on immunosupressant drugs

  • In HIV patients with lower cd4 have higher higher CVD death rate
  • Same relationship of CD4 to CVD is seen in patients with radiation exposure (Hiroshima) causing lower cd4 counts
  • also seen in transplant patients.

Rabbit data showing that increased cholesterol plaques with concurrent CSA, without change in lipid profile. Roselaar jci 1995 96 1389.

Steroids are dangerous even at low doses in the normal population.

CSA increase BP.

CSA also causes endothelial dysfunction.

Sirolimus is antiatherogenic, as seen in cardiac stents.
MMF also appears to reduce cholesterol plaque Romero Atherosclerosis 2000: 152:127-133.

Cr alone is a predictor of CVD independent of immunosupression and traditional risk factors.

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Renal Week 2008: CKD and CVD: Antihypertensive therapy

Case report of a patient with HTN
Ray Townsend is the MC (sweet). He presnts a patient with HTN and modest CKD. Cr 1.4 up from 0.9 in 2001.

Ray passes off to Domenic Sica.

Antihypertensive Drug Therapy in patients with HTN and CKD.

Volume expansion

  • Patient was on 25 mg of HCTZ. No need to change to loop if the patient is euvolemic. Chlorathalidone vs hctz
  • Ernst HTN 2006. chlorathalidone reduced 24hr mean bp more (7 vs 12) non-ckd patients. night time bp drop was even more pronounced 6 vs 13 mmHg.
  • Recommends switch within class from hctz to chlorthalidone
  • the increase in calcium may help with PTH. interesting.
  • elison JCI 83: 113; 1989 images of hypertrophy of DCT with loop diuretics
  • He’s pushing torsemide
  • Using FeNa to determine if patient is responding to loops (look for fena>3%)
  • Why is there variability in bioavailability of furosemide: floculation of pills stops some absorption. Use of liquid furosemide doesn’t help because of only a limited area of absorbtion: early duodenum only.
  • He likes the torsemide

Drug accumulation

At gfr 30-50 need to think about dose adjustment.
Renally cleared: atenolol, nadolol, betaxolol

Hepatically cleared
propanolol, metoprolol, carvedilol

Dose response to beta-blockers is flat in CKD.

Don’t titrate atenolol. It is renally cleared and patients are already retaining the drug before you increase the dose. Though the BP effect is not dose dependent, the adverse effects are.

Aldosteronism

  • 20% of patients with CKD.
  • Likely this patient will have aldo level of 14-20 and renin less than 1
  • Aldosterone antagonists (AA) reduce proteinuria
  • Need diuretic on board to get much BP effect
  • Half-life of spironolactone is 24 hours, in liver disease 120 hours, and in CKD multiple days. These figures include active metabolites. He feels eplerenone is safer because you won’t get accumulation.
  • Consider qod dosing of spironolactone. Consider 12.5 mg qd
  • beware of heparin causing hyperkalemia with AA
  • Similar warning for ACEi, ARB, TMP/SMX

Clonidine

  • in CKD clonidine is renally cleared. This decreases rebound htn by extending the half life
  • initially clonidine has a steep dose responce at low doses but then flattens
  • causes dose dependent volume retension. this is worse with TTS
  • at higher doses the peripheral alpha stimulation will overcome the central reduction in alpha activity so patients get increase in BP. This is seen in clonidine OD or with autonomic dysfunction.

CCB

  • Amlodipine has half-life of 40 hours
  • nifedipine’s half-life goes from 2 to 4 hours in renal failure
  • Edema with CCB is worse in patients with CKD because they already have increased volume

ACEi

  • 10 in the US
  • fosinopril and trandolopril have significant hepatic clearance
  • ARB are not renally excreted
  • dialyzable: captopril, enalepril, lisinopril. Use in overdose.

Statin

  • AUC of simva increases 4 fold with diltiazem
  • Cool case report of a patient on 80 of simva who was admitted for A-fib with RVR and gets started on a diltiazem gtt. He developed rhabdo a few days later.

That’s it. Question time.

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Melamine in the eggs, melamine in pesticide

Hong Kong discovers high levels of melamine in chinese eggs:

Hong Kong said last week it would test meat, vegetables and processed food for melamine, a move that underlines concerns about food safety in the former British colony which returned to Chinese rule in 1997.

It imposed a cap on melamine in September, restricting it to no more than 2.5 milligrams per kilogram, while melamine found in food meant for children under three and lactating mothers should be no higher than one mg per kg.
The level of melamine found in the eggs was 4.7 mg per kg, the newspapers said.

The newest revelations on melamine toxicity involves vegetables that are sprayed with the insecticide cyromazine. This derivative of melamine degrades back into melamine resulting in the contamination.

Recently, experts have investigated and confirmed that melamine has also been found in lettuce, water cress, tomatoes, mushrooms, potatoes and other agricultural products. There is 17 milligrams (0.000037 lbs) of melamine per kilogram (2.20 lbs) of mushrooms.

Cyromazine itself apparently has very little toxicity:

Cyromazine is practically nontoxic (acutely) to mammals and birds. Exposure estimates for these organisms are 0.05 ppm. Acute toxicity for birds is 1785 ppm maximum. Safety factor is 105-106 for birds. Acute toxicity for mammals is 1000 ppm maximum. Safety factor is again 105 – 106.

Cyromazine

melamine

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Journal Club: Campath and ACE/ARB and AKI in CABG

The first article was an analysis of campath for induction with tacrolimus.

Patients were randomized to either

  • Methylpred 250 mg and Campath 20 mg immediately following surgery followed by Tacrolimus Group
  • Tacrolimus, prednisone, and MMF (no induction therapy)

Primary outcome was biopsy proven rejection at 6 months.
Secondary outcome was biopsy-proven rejection at 12 months, time to first rejection, patient and graft survival, incidence of corticosteroid resistant rejection.

n= 131 deceased donor, kidney transplant in patients with PRA ≤ 25%. All patients were receiving their first kidney. Age 18-65.


No episodes of humoral rejection was found in either group.

The figure above I think is particularly informative as it becomes obvious that all the difference is in the first month. This is a study of induction vs. no induction and they demonstrate a huge reduction in early rejection with induction.

Big picture: large reduction early reduction but no difference in serum creatinine at one year.

The second article was a retrospective analysis of the risk of acute kidney injury based the presence or absence of ACEi/ARB.

A VA study looking at chronic use of ACEi or ARB and the risk of acute kidney injury following cardiovascular surgery. SUNY Buffalo looked at 1,358 patients with CV surgery from 2001-2005. 50% were on ACE/ARB

  • 40% had AKI (essentialy all Modified RIFLE: Stage 1, Cr rise ≥0.3 or 50-100%)
  • 7 patients Stage 2 (Cr rise 2-3x the baseline)
  • 2 patients Stage 3 (Cr greater than 4 or >3x the baseline)

They found that use of ACEi/ARB had a 27.6% increase in risk of AKI.

Of note 18% of the patients who had AKI, their creatinine had not returned to baseline at 3 months post surgery and still qualified as AKI. This does not jive with the natural history of AKI, especialy relatively mild AKI. This makes me wonder if the baseline creatinine were abnormally low in some of the patients and the increase documented was not AKI but actually resolution of the creatine falling.

The primary concearn I have is that the study had 543 patients with AKI and only 9 had more than a doubling of creatinine. They used a very sensitive definition of AKI and like any test, when you increase the sensitivity you decrease the specificity. It is very possible that a large proportion of those patients defined as AKI didn’t actually have AKI, throwing the study into doubt.

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Some details on one of the deaths from the melamine milk contamination

This article talks about the family of the first infant to die from melamine milk contamination. The child, Yi Kaixuan was only 6 months old. He died back in May, months before any information about the contamination came out.

But on April 20, the baby wouldn’t stop crying and had problems urinating. Jiao took him to the village clinic, but they couldn’t pinpoint a problem.

Alarmed, Yi left his construction job and returned home. The family headed for the Gansu provincial capital, Lanzhou. On April 30, they took the baby to two city hospitals. Doctors were stunned, Yi said. They said they’d never seen a child with so many kidney stones, and the situation was critical.

A frenzy of testing followed, and the bills piled up past $145. The parents didn’t sleep all night, waiting.

Around noon the next day, a doctor came to tell them their baby had died.

Tragic.

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iPhone Medical Applications

I have four medical applications on my iPhone, of which I use two. Here is a quick review.

To show how the iPhone equipped physician approaches clinical problems I will use the DB’s Medical Rants most recent acid-base problem. He presents a case with the following information:

49-year-old man, previously in good health, presents after a few weeks of progressive weakness and dizziness. He admits to polyuria. Your job is to extensively discuss his lab tests.

The first step in my mind is to fully interpret the ABG. To do this we will use the application ABG.

ABG

This simply named program is an ABG calculator that runs through the standard algorithms for detecting multiple primary acid-base abnormalities. Can’t remember Winter’s Formula. As long as you don’t have boards coming up you can just plug’n chug and turn DB’s ABG into the following:

This does two of the calculations that DB describes at length:

  1. Winter’s formula (16 * 1.5 + 8 ±2) shows that the predicted pCO2 is 30-34. The patient’s CO2 is 33 so the patient has isolated and appropriately compensated pCO2 of 33. ABG displays this information in the second line when it describes the acid-base disorder as “Compensated metabolic acidosis.” It does not describe a second primary condition such as respiratory acidosis or alkalosis.
  2. Gap-Gap or delat-delta. The patient has a dramatically elevated anion gap at 27 (15 over the upper limit of normal of 12) but his bicarb of 16 is only 8 below normal. The difference between the delta gap and the delta anion gap is 7 (15-8) when this is added to the normal bicarbonate you get 31; so the patient had a pre-existing metabolic alkalosis with a bicarbonate of 31. ABG displays this information as the corrected bicarbonate.

The next step is adjusting his sodium for the hyperglycemia. To do this we will use Mediquations though Medical  Calc works just as well.

Mediquations
DB, in his discussion, states that he has unpublished data proving that no formula is effective at adjusting the serum sodium for the hyperglycemia. For those of us without his unpublished data should adjust the sodium using Katz’s traditional conversion (pdf of a letter to JAMA discussing adjusting sodium for hyperglycemia in DKA. Katz’s original conversion was discussed in a letter to the NEJM) of a drop in Na of 1.6 for every 100 the glucose is over 100 mg/dL. Nephrology fellows should additionally be aware of Hillier’s data showing the sodium falling 2.4 for every 100 of glucose. Both Mediquations and Medical calculator adjust the sodium using Katz’s conversion.

Of coarse you wouldn’t know it was Katz’s conversion because even if you tap on “More Info,” Mediquation does not provide the reference. Likewise you will not get the reference with Medical Calc.

Though DB did not explore free water defecits in his discussion of the case this is a clinically relevent point. You can use Mediquation to calculate the water deficit.


I feel that using ABG and Mediquations will make you a more effective physician without forcing you to memorize equations used only periodically.
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New Virus. Killing people. Scarrier than Lehman Brothers.

These emerging viral illnesses always scare the crap out of me. From the WHO:

13 October 2008 — The results of tests conducted at the Special Pathogens Unit, National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service in Johannesburg, and at the Special Pathogens and Infectious Disease Pathology branches of the Centers for Disease Control in Atlanta, USA, provide preliminary evidence that the causative agent of the disease which has resulted in the recent deaths of 3 people from Zambia and South Africa, is a virus from the Arenaviridae family.

Analysis continues at the NICD and CDC in order to characterize this virus more fully. CDC and NICD are technical partners in the Global Outbreak Alert and Response Network (GOARN).

Meanwhile, a new case has been confirmed by PCR in South Africa. A nurse who had close contact with an earlier case has become ill, and has been admitted to hospital. Contacts have been identified and are being followed-up

Love the name GOARN. Reminds me of the alien Kirk had to battle mano-a-mano.