Nephrology CBP Prese..

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Transcript of Nephrology CBP Prese..

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Case Presentation43 year old gentleman with Crytogenic Cirrhosis

is admitted to the ICU after massive GI bleed secondary to bleeding esophageal varices. His varices have been successfully banded and he is admitted post-procedure. He received multiple units of blood, as well as platelets to correct his thrombocytopenia and FFP to correct his coaglulopathy (INR 4.3). He also received 6 L of crystalloid. He is now hemodynamically stable, however, his respiratory requirements have increased, in keeping with his CXR findings of acute pulmonary edema.

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PSV, 12/5, FiO2 .45

He is kept intubated over night and given multiple boluses of Lasix (total of 200mg) to help encourage diuresis.

When assessed in the morning, it is noted that he has been anuric over night. His admission BUN/Cr were 11/87, and are now 23/192. He is now on PSV 16/8 and FiO2 is .65.

His electrolytes reveal: Na – 128, K – 5.3, Cl- 97, tCO2 – 18.

ABG: 7.31/39/84/19/-2

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Question 1Briefly describe Hepatorenal syndrome and it’s

pathophysiology. What are some predisposing factors? (Federico)

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DEFINITION

Hepatorenal syndrome is a clinical condition that usually occurs in patients

with advanced liver disease and portal hypertension that is characterized

by :

-Renal failure, with creatinine level more than 1.5mg/dl

-Marked decrease in GFR and renal plasma flow (RPF) in the absence of

other identifiable cause of renal failure.

-Marked abnormality in systemic hemodynamics

-Activation of endogenous vasoactive systems.

HRS occurs predominantly in the setting of cirrhosis, but it may also

develop in other types of severe chronic liver diseases, such as alcoholic

hepatitis, or in acute liver failure.

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The theory that best fits with the observed alterations in the renal and

circulatory function in HRS is the vasodilation theory, which proposes that HRS

is the result of the effect of vasoconstrictor systems acting on the renal

circulation and activated as a homeostatic mechanisms to improve the

extreme underfilling of the arterial circulation. That leads to decreased renal

perfusion and glomerular filtration rate (GFR) but tubular function is

preserved.

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There are two well-differentiated clinical patterns of HRS

Type 1 HRS

•Characterized by rapid and progressive impairment of renal function

defined as a doubling of the initial serum creatinine to a level greater

than 2.5 mg/dl or a 50% reduction of the initial 24-hour creatinine

clearance to a level lower than 20 ml/min in less than 2 weeks.

•Usually occur in severe liver failure (Jaundice, encephalopathy, and

coagulopathy)

•Occur frequently after precipitating factor (e.g. GI bleeding)

•Median survival time is only 2 weeks

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Type 2 HRS

•Characterized by a less severe and non-progressive reduction of GFR.

•Associated with relatively preserved liver function.

•The main clinical consequence of this type of HRS is refractory ascites,

due to a lack of response to diuretics.

•Median survival time is about 6 months.

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The International Ascites Club has defined criteria for the

diagnosis of HRS. Major criteria, necessary only for the

diagnosis, are as follows:

1. Low GFR, defined by a serum creatinine greater than 1.5

mg/dL or 24-hour clearance lower than 40 mL/min

2. Absence of shock, ongoing bacterial infection, fluid losses

and current treatment with nephrotoxic drugs

3. No sustained improvement in renal function (decrease in

serum creatinine to <1.5 mg/dL or increase in clearance to

>40 mL/min) following diuretic withdrawal and plasma

volume expansion with albumin (or 1.5 L of isotonic saline).

4. Proteinuria less than 500 mg/d

5. Absence of any evidence of obstructive uropathy or

parenchymal disease as shown by ultrasonography

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Precipitating factors

1. Bacterial infections

2. Bleeding

3. Large volume paracentesis without plasma expansion

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Patient remains anuric and is given a further bolus of 100mg of Lasix.

Patient remains anuric despite most recent dose of Lasix.

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Question 2Any role for increasing doses of Lasix in an

anuric patient? Any harm? Any benefit? (Federico)

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Diuretics in AKIRegarding

an increased appreciation for the potential

detrimental downstream effects of

volume overload, it may be reasonable to

try diuretics for control of volume overload.

The clinician should, however, be

careful not to delay initiation of RRT for

volume overload in the critically ill patient

with AKI

(Crit.Care 2010, vol 38, n1)

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Question 3Define Acute Kidney Injury (Federico)

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RIFLE CriteriaThe Acute Dialysis Quality Initiative Group

proposed the RIFLE system classifying ARF into 3 severity groups and 2 clinical outcome categories

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Incidence of AKI in the ICU

AKI occurs in ~ 7% of all hospitalized patients, whereas it occurs in 36% – 67% of critically ill patients.

On average, 5 % of ICU patients with AKI require renal replacement therapy.

Dennen P, Douglas IS, Anderson R. Acute kidney injury in the intensive care unit: an update and primer for the intensivist. Crit Care Med. 2010 Jan;38(1):261-75

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AKI and mortality

In most studies, mortality rates rise proportionally with severity of AKI.

Even small increases in serum creatinine have been associated with increasing mortality in various ICU populations despite adjusting for severity of illness and comorbidities.

In patients with AKI requiring RRT, mortality rates reach 50% to 70%.

Dennen P, Douglas IS, Anderson R. Acute kidney injury in the intensive care unit: an update and primer for the intensivist. Crit Care Med. 2010 Jan;38(1):261-75

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AKI and other outcomes

AKI is also associated with:

Increased length of stay Increased incidence of CKD and end-stage kidney disease Increased cost

For example, an increase in SCr of 0.5 mg/dl (38 mmol/L)was associated with a:

6.5-fold increase in the odds of death 3.5 day increase in LOS nearly $7500 in excess hospital costs

Dennen P, Douglas IS, Anderson R. Acute kidney injury in the intensive care unit: an update and primer for the intensivist. Crit Care Med. 2010 Jan;38(1):261-75

Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005 Nov;16(11):3365-70

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Traditional methods for detecting AKI

Currently available measures do not detect actual kidney injury the way troponin detects myocardial injury:

Creatinine Urea Urine output

Rather they are markers of abnormal renal function, that can be used to presume kidney inury has occurred.

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007 Dec;13(6):638-44.

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Serum creatinineUsed to estimate GFR

Pros Produced at a relatively constant rate Freely filtered by glomerulus Not reabsorbed or metabolized by the kidney.

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007 Dec;13(6):638-44.

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Serum creatinine Used to estimate GFR

Cons 10-40% is secreted by the tubules Relatively insensitive (may need a 50% reduction in

function before a detectable rise in SCr is seen) Creatinine production varies based on age/sex/muscle

mass/diet Certain disease states can increase production (rhabdo) Certain drugs can decrease secretion (cimetidine,

trimethoprim) Certain factorsmay affect assay (ketoacidosis, cefoxitin,

flucytosine) Does not reflect real-time changes in GFR

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007 Dec;13(6):638-44.

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Delay in SCr rise

Waikar SS, Bonventre JV. Creatinine kinetics and the definition of acute kidney injury. J Am Soc Nephrol. 2009 Mar;20(3):672-9

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UreaRate of production is not constant

Increases with protein intake Increases in critical illness (burns/sepsis/trauma) GI Bleed Steroids

40% - 50 % of urea is reabsorbed by the kidney (even more when dry)

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007 Dec;13(6):638-44.

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Urine outputPros

A dynamic gauge of kidney function. May be a barometer for change in kidney

perfusion

Cons Poor sensitivity and specificity Can have severe AKI with normal or increased

urine output

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care. 2007 Dec;13(6):638-44.

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Novel methods for detecting AKI

Serum Cystatin C

Kidney injury molecule-1

Neutrophil gelatinase-associated lipocalin (NGAL)

Urinary IL-18

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Serum cystatin c

An endogenous cysteine proteinase inhibitor

Synthesized at a relatively constant rate

Released into plasma by all nucleated cells in the body

Knight EL, Verhave JC, Spiegelman D, et al. Factors influencing serum cystatin C levels other than renal function and the impact on renal function measure- ment. Kidney Int 2004; 65:1416–1421

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Serum cystatin c

Reportedly not affected by patient age, sex, muscle mass or diet

However, one large study showed that age, sex, height, weight, smoking status, and CRP levels were all associated with cystatin c levels.

Also found to be affected by abnormal thyroid function, immunosuppression (steroids), and systemic inflammation

Knight EL, Verhave JC, Spiegelman D, et al. Factors influencing serum cystatin C levels other than renal function and the impact on renal function measure- ment. Kidney Int 2004; 65:1416–1421

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Serum cystatin cAlmost 99% is filtered by the glomerulus

Not secreted or reabsorbed by the tubules

Therefore a rise in cystatin c is a good indication of a decrease in GFR

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care 13:638–644.

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Serum cystatin c

Cystatin C-based estimates of GFR may perform better in those with lower SCr concentrations such as:

Elderly patients Children Renal transplant recipients Cirrhotics Those that are malnourished

May be more sensitive to early and mild changes of kidney function compared with creatinine

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care 13:638–644.

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Kidney injury molecule-1A transmembrane glycoprotein that is normally

minimally expressed in kidney tissue.

Shows marked upregulation in proximal renal tubular cells in response to ischemic or nephrotoxic AKI

Shed from proximal cells and detected in the urine by immunoassay

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care 13:638–644.

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Kidney injury molecule-1

Urinary levels of KIM-1 are significantly higher in established AKI compared with other causes of AKI (i.e. PRA, contrast-induced nephropathy) or CKD.

Thus, KIM-1 may represent an early, noninvasive biomarker for proximal tubular AKI.

More studies needed to define its role

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care 13:638–644.

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Neutrophil gelatinase-associated lipocalin (NGAL)

Belongs to the lipocalin superfamily

Markedly upregulated in response to kidney ischemic or nephrotoxic injury

May be an early and sensitive urinary biomarker of ischemic and nephrotoxic AKI.

Early elevations in urinary NGAL after kidney transplan- tation have been shown to be predictive of: delayed graft failure Need for RRT during the first week following transplantation

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care 13:638–644.

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Interleukin-18 IL-18 can be induced in the proximal tubule and

detected in the urine in ischemic AKI

Is increased in the urine of patients with established AKI when compared to those with prerenal failure, urinary tract infection, CKD or healthy controls.

Elevated urinary IL-18 values have been shown to preceded clinical evidence of overt AKI (50% increase in SCr) by 24 – 48 h in critically ill patients with ARDS.

Urinary IL-18 values of at least 100pg/ml were associated with an estimated 6.5 increased odds of developing AKI within 24 h.

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care 13:638–644.

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Summary of novel markers

Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care 13:638–644.

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Question 5What are some traditional and novel methods

for early detection of kidney injury? (Marios)

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Patient continues to have increasing ventilation support requirments and is now on .85 FiO2. His K+ is now 5.6. He is given routine hyperK+ therapy. He has been started on vasopressors because of declining MAP

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Question 6, 7What are the indications for CRRT vs IHD. Is

one better? What are their associated advantages and disadvantages? (Neil)

When should RRT be initiated?

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A,E,I,O,U

CRRT review Chest 2007

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Acute Renal Failure Lancet review.pdf

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Bouman et al.TimingofCRRT-CurrOpCritCare2007.pdf

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CRRT review Chest 2007

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Lameire et al. Lancet 2005

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CRRTvsIHDCochrane2007.pdf

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Question 8Define the different modes of CRRT. Use a

diagram to highlight the differences? (Noemie)

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It is decided to start the patient on CRRT therapy. What kind of anticoagulation should he receive?

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Question 9

Compare the different modes of anticoagulation.

Explain the use of citrate and how to dose it. Please explain the calcium gap. (Noemie)

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Anticoagulation

Heparin Can be given systemically or through circuit Aim for PTT 35-45 sec

Regional citrate

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Intensive Care Med 2004;30:260-265

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Kidney International 2005;67:2361-2367

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Kidney International 2005;67:2361-2367

Intensive Care Med 2004;30:260-265

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AnticoagulationCitrate

Citrate infusion pre-filter Leads to calcium chelation and clotting time Aiming for post filter iCa btw 0.25-0.35 Post-filter calcium infusion to restore systemic Ca

and clotting function

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CitrateConcerns:

Pricy Operator training + time consuming Repeat labs q6h: Post filter iCa, Systemic iCa and

total Ca Risk of hypocalcemia

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CalciumTotal plasma Calcium:

40% bound to albumin

45% circulates as ionized calcium

15% bound to organic/inorganic anions

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Citrate and Calcium Gap50% of citrate cleared through dialyser

Remaining citrate metabolized in the liver to Bicarbonate

If citrate systemic delivery >> pt’s ability to metabolize citrate

Systemic accumulation of Calcium Citrate hypocalcemia

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Calcium gapCalcium gap: Total calcium - ionized Ca

Citrate accumulation causes Total calcium and iCa

Pt with acute renal failure and liver failure are at increased risk of citrate accumulation

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Tidbits from DodekCitrate toxicity, only clinically relevant if:

Leads to hypernatremiaLeads to metabolic acidosis (when citrate is not

metabolized, b/c it is an acid)+/- Metabolic acidosis (because it is converted to

HCO3)Hypocalcemia (but just turn up your Ca infusion) In relation to above, calcium gap not all that

relevant

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Question 10What is an ideal dialysis dose? (Todd)

 

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What is the ideal dialysis dose?

I don’t know.

And I’m not the only one.

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Speaking of flashbacks…2 recent studies addressing the issue of “dose”

of renal replacement therapy

The first included multiple RRT modalities…

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IHD, SLED, CVVHDF

Patients enrolled had ATN requiring dialysis and either sepsis or one additional nonrenal organ failure

Excluded patients with chronic kidney disease

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CVVHDF dose was 20 cc/kg/hr in the less intensive group and 35 cc/kg/hr in the intensive group

In the IHD/SLED patients, dosing was 3 times per week or 6 times per week, respectively

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Essentially no differenceMortality, recovery of renal function, ICU-free

days, organ failure scores, or discharge home without dialysis.

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The second rule of (city wide) Journal Club…

Critically ill patients with AKI requiring dialysis Excluded if on dialysis pre-admission

CVVHDF, with post-filter replacement fluid

25 cc/kg/hr vs 40 cc/kg/hr

Dialysate: replacement fluid (Hmosol B0) 1:1

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What does this mean…?

That the dose is unimportant? That the dose beyond a (not quite determined) value is not important? Are we looking for the wrong outcomes?

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What box should I check?

At RCH: 35 cc/kg hr (as opposed to 45) Saves a few bucks on dialysis/replacement fluid.

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Question 11

It turns out the patient has been feeling very suicidal lately 

What are the indications for RRT in acute intoxications (Todd)

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What are the indications for RRT in acute intoxications?

If there is indication of severe toxicity

If elimination can be improved by an extracorporeal technique. HD, HF, hemoperfusion, MARS

Current Opinion in Critical Care 2007, 13:668–673

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Dialysis techniques: Discussed already.

Hemoperfusion: adsorption of toxins

MARS: hemoperfusion technique using albumin exchanger.

Or hemofiltration

And possibly: Carbamazapine, diltiazem, phenytoin and mushrooms

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Patient stabilized on CRRT therapy and slowly his renal function has shown some improvements with production of small amounts of urine. His hemoglobin has remained stable and HD he is off pressors. However, you are called to his bed side stat as his BP has suddenly dropped. His repeat HgB shows a drop of 35. You are entertaining a retroperitoneal bleed and want to do a CT contrast of his abdo/pelvis. 

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Question 12 

Does RRT decrease the incidence of Contrast induced nephropathy? (Todd)

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Does Renal Replacement Therapy decrease the incidence of contast-

induced nephropathy?

It should. But there’s no evidence that it does. One trial randomized patients to low-dose

hemofiltration in ICU vs ward care with NS at 1cc/kg/hr, prior to PCI and found no difference in CIN or mortality. Duration was approx. 6 hours pre- and 20 hours post- contrast load.58 pts per group, average Cr 270.Other strategies, i.e. iso-osmolar contrast, NAC,

were included

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PRISMA geeks rejoice…Femoral HD line

Pump speed 100 cc/min

Replacement fluid at 1000 cc/hr

No net fluid off

Heparin anticoagulation

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The fine printControl group needed more renal replacement

therapy (25% vs 3% in intervention group)

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The end!You now know all about the kidneys!!!