Contrast induced nephropathy

Dear pearl of the day readers,

I suppose you could consider this is a part 2 on side effects/toxicity of Iohexol (omnipaque™). This pearl of the day comes at the personal request by one of my coresidents to cover this topic.

Epidemiology

Contrast induced nephropathy (CIN) is an increase in serum creatinine > 25% after administration of IV contrast.

2-10% of patients who received iodinated contrast media suffer acute kidney injury (AKI). The peak of AKI is seen 2-3 days later.

A caveat here is that many times patients will develop AKI from other etiologies after receiving contrast. This makes sense because they needed a CT scan for some clinical indication.


Patients who have pre-existing renal disease or elevated serum Cr are at higher risk for CIN. There are scoring models to see who is at higher risk, but this applies more to interventional procedures requiring higher contrast loads. If you are curious about the scoring systems they can be found here: http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO%20AKI%20Guideline.pdf

Side note I found interesting: in patients who had no protein in the urine, only 1% had a Cr>1.7 mg/dL. So no protein in the urine means they probably do not have kidney disease.

Mechanism

The putative mechanism of injury to the kidneys is renal vasoconstriction and direct toxicity to the renal tubular cells, possibly through increased reactive oxygen species.

Chance of recovery

Patients who develop CIN have higher odds of mortality, 1.9. If the CIN requires dialysis, in hospital mortality at one institution increased from 7.1% to 35%.

One British study found that 0.9% of patients developed CKD within 6 months of receiving a contrast loads, compared to 0.17% of patients who developed CKD during the same time period.

So the chances are good the patient will recover.

Treatment

There is no proven treatment; however, pre-treatment with IV or PO fluids is the mainstay practice. In the sense that dehydration is bad for the kidneys, it is reasonable to try to avoid a second hit. However, conflicting data show that there was no difference between fluid pretreatment or not.

Several controversial studies may show that pretreatment with sodium bicarbonate was superior when compared to normal saline (NNT=10); theoretically, this effect is due to decreased free radical formation.

Also theoretically, N-acetyl cysteine (NAC) can help reduce oxidative stress on renal tubular cells. The official journal of the international society of nephrology actually recommends pretreatment in patients at increased risk for CIN with ORAL NAC. High dose oral NAC was shown to decrease the incidence of CIN by 76% in one study. Data is also conflicting here, but trends toward favoring the use of oral NAC in patients at risk for CIN.

Lastly, preliminary data also shows that statins may some how be protective through an unknown mechanism.

Final take home points

Be cautious:

-if the patient is on other nephrotoxic agents

-if the patient has a slightly elevated creatinine compared to baseline (even if it still normal)

-if there is protein in the urine

-if they have a history renal disease

-if eGFR<60

Balance the risk of contrast against the risk of not-performing the correct radiology study. This will be different for every patient.

TR,

W

References

http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO%20AKI%20Guideline.pdf

Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004;291(19):2328-34.

Patschan D, Buschmann I, Ritter O. Contrast-Induced Nephropathy: Update on the Use of Crystalloids and Pharmacological Measures. Int J Nephrol. 2018;2018:5727309.

Reuben Strayer's response to my post is quite poignant and definitely worth a read:

Despite how penetrated the notion of CIN is in our teaching and practice, and how much time and energy we spend on its supposed prevention, there is considerable controversy as to whether CIN actually exists/occurs.

paper

audiocast

Farkas’ blog post

Morgenstern's blog post

I’ve pasted conclusions from the latter below. The most important point is if you have a high concern about a dangerous condition and require an IV contrast-enhanced CT scan to rule it in/out, the patient’s creatinine should factor minimally if at all in your decision around whether or not to do the scan. Do the scan.

It is not clear whether contrast is a significant cause of acute kidney injury. According the the American College of Radiologist, “at the current time, there is very little evidence that IV iodinated contrast material is an independent risk factor for AKI in patients with eGFR ≥30 mL / min/1.73m2”. (ACR manual 2017)

We need some large RCTs to settle this issue. There is clearly equipoise on this issue and there should be no barriers to running a RCT.

We should stop using the term “CIN or contrast induced nephropathy” as it implies a degree of causation that simply is not supported by the literature. Post contrast acute kidney injury more appropriately describes what is occurring.

If a patient needs contrast to make an important diagnosis and there isn’t an easily available alternative test, just do the scan. Even if contrast causes acute kidney injury, true patient oriented harms are only seen in a very small number of patients. There is a balance, but as long as the pretest probability of important pathology is higher than the chance of harm (probably less than 1%), the patient will still benefit from the contrast CT.

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Nephrotic Syndrome Pearl of the Day

Nephrotic Syndrome

Pathophysiology

Think about it like this: Glomerular basement membrane problem, you spill all your protein (albumin) from your plasma into your urine, leading to high urine protein, low serum protein, and edema. It may help to simply think of it as decreased oncotic pressure causing movement of fluid from the intravascular space to the interstitial space; in reality the pathophysiology of edema in nephrotic syndrome is a little more complicated - has to do with a combination of primary (due to renal disease) and secondary (via RAS pathway) sodium retention.

Thus,

nephrotic syndrome is defined by:

1. Heavy proteinuria

(protein excretion > 3.5 g/24 hours; UPEE>3.5; >2 in children)

2. Hypoalbuminemia

(< 3 g/dL; <2.5 in children)

3. Peripheral edema

(Hyperlipidemia and thrombotic disease are frequently observed with nephrotic syndrome but not required for the diagnosis, may also be immunosuppressed)

(UA should have no significant hematuria, casts, or RBCs which would suggest a nephritic picture)

Measuring Proteinuria 

The most convenient way is to calculate a 

Urinary Protein Excretion Estimation (UPEE)

(insert infantile bathroom humor here)

UPEE (g/day) = (urine protein (mg/dL)) / (urine creatinine (mg/dL))

This works because a random urine protein to urine creatinine ratio very closely approximates the true 24 hour urine protein excretion, as shown below.

Image result for urine protein to creatinine ratio

Interpretation:

UPEE <2.0 g/day —> Within normal limits

UPEE 2.0–3.5 g/day —> Above normal limit - investigate further

UPEE >3.5 g/day —>Nephrotic range

Nephrotic vs Nephritic

Remember to always think of nephrotic syndrome in contrast to nephritic syndrome! I love this image:

Image result for nephrotic nephritic

Workup

1.

Make the diagnosis: urinalysis, urine protein, urine creatinine, serum albumin, a lipid panel, basic metabolic panel

2. Consider further testing to differentiate primary vs secondary on a case-by-case basis: HIV, ANA, complement (C3/C4 and total hemolytic complement), serum free light chains and urine protein electrophoresis and immunofixation, syphilis serology, hepatitis B and hepatitis C serologies, and the measurement of cryoglobulins; when in doubt, run it by nephrology

3. Consider testing for complications: POCUS for pleural effusion/ascites; CXR for pleural effusion, dopplers or CTA for venous thromboembolism; antithrombin III, plasminogen, protein S (hyper coagulability); immunoglobulins; 

3. Usually renal biopsy is required for definitive diagnosis

Etiology/Treatment/Dispo

In children 10 years or younger, it is minimal change disease (MCD) 90% of the time. Most MCD responds to corticosteroids.

In children >10 years, it is MCD >50% of the time.

In adults focal segmental glomerulosclerosis (FSGS) is the most common etiology (35%). It can be primary/idiopathic, or associated with other disease processes, most commonly HIV or massive obesity.

Untitled.jpg

In most cases, a biopsy will be needed in order to confirm diagnosis.

Admit patients with severe edema, pulmonary effusions or respiratory symptoms, or signs and symptoms suggestive of systemic infection or thrombotic complications to the hospital.

Discharge with nephrology follow up ASAP and low salt diet if only mild-moderate edema.

In kids age 1-10, may consider starting a course of steroids (

Prednisone 2 mg/kg/day x 6 wks then 1.5 mg/kg every other day x 6 wks) only if:

  • Age 1-10

  • No renal insuficiency

  • No macroscopic hematuria

  • No sx systemic disease

  • No HTN

  • Normal C3 levels

Special scenarios

Nephrotic syndrome + chest pain?

DDX: PE and myocardial ischemia because hyperthrombotic, pneumonia (immunosuppressed), pleural effusion

Consider POCUS, CXR, CTA, EKG, cardiac enzymes

Severe edema:

Requires lasix

May need albumin infusion prior to lasix if anasarca or signs of intravascular depletion

Hopefully you’ve already consulted ICU if you’re having to do this

Significant hypertension:

ACEi or ARB

SBP/Empyema:

Pleural effusions/ascites are common in severe fluid overload

Both are extra susceptible to infection in this state

Low threshold for diagnostic paracentesis/thoracentesis

References

Uptodate: Overview of heavy proteinuria and the nephrotic syndrome

Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e: Chapter 134: Renal Emergencies in Children

Michael Mojica, MD. “PEM Guides.” NYU Langone Medical Center, 2015. iBooks. 

https://itunes.apple.com/us/book/pem-guides/id1039923332?mt=11

Google Image Search

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Pearl of the Day: Complications of Vascular Access for Hemodialysis

Complications of Vascular Access for Hemodialysis- more frequent with autologous vein, polytetrafluorethylene, or bovine carotid artery graft (as opposed to native artery or vein) - account for more inpatient hospital days than any other complication of hemodialysis

Thrombosis and Stenosis - most common causes of inadequate dialysis flow (<300 mL/min) - grafts have higher rate of stenosis than fistulas - signs: loss of bruit or thrill over access - treatment: angiographic clot removal or angioplasty within 24 hours; direct injection of alteplase can be considered for thrombosis

Vascular Access Infections - 2 - 5% of AV fistulas, 10% of grafts - etiology: Staphylococcus aureus (most common), Gram-negative bacteria - signs/symptoms: hypotension, fever, leukocytosis - may not have pain, erythema, swelling, or discharge from access site - after 6 months, approximately 1/2 of patients with dialysis catheter develop bacteremia - diagnosis: peripheral and catheter blood cultures drawn simultaneously -> catheter is confirmed source if colony count is 4 times higher in catheter culture than peripheral culture - treatment: vancomycin IV (drug of choice) +/- gentamicin (if Gram-negative organisms suspected); consider access removal if fever for > 2 - 3 days

Hemorrhage - rare - causes: aneurysms, anastosmosis rupture, overanticoagulation

Management of Hemorrhage 1. manual pressure to puncture sites for 5 - 10 min and observe for 1 - 2 hours if ceased 2. apply pressure for 10 min using absorbable gelatin sponges soaked in reconstituted thrombin or chemical thrombotic (e.g., transexamic acid) 3. protamine 0.01 mg per unit of heparin dispensed during dialysis - if dose is unknown, protamine 10 - 20 mg is sufficient to reverse typical dose of heparin (usually 1000 to 2000 U) 4. desmopressin acetate 0.3 mcg/kg IV can be used as adjunct in consultation with nephrologist or vascular surgeon 5. consider placing figure-8 suture 6. tourniquet proximal to vascular access while awaiting urgent vascular surgery consultation

Vascular Access Aneurysms - caused by repeated punctures - usually asymptomatic, possibly occasional pain or impingement neuropathy - rarely rupture

Vascular Access Pseudoaneurysms - from subcutaneous extravasation of blood from puncture sites - signs: bleeding, infection at access site - diagnosis: arterial Dopper ultrasound studies - treatment: surgery

Vascular Insufficiency - usually occurs in extremity distal to vascular access - due to shunting of arterial blood to venous side of access - "steal syndrome" - signs/symptoms: exercise pain, nonhealing ulcers, cool/pulseless digits - diagnosis: Doppler ultrasound or angiography - treatment: surgery

High-output Heart Failure - occurs when >20% of cardiac output is diverted through access - signs/symptoms: Branham sign (drop in heart rate after temporary access occlusion) - diagnosis: Doppler ultrasound to measure flow rate - treatment: surgical banding of access

Resources Tintinalli's Emergency Medicine, 8th Edition

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