# Renal Function Iin ICU

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Information about Renal Function Iin ICU

Published on August 1, 2007

Author: shivabirdi

Source: slideshare.net

RENAL FUNCTION IN THE ICU S. ESFANDIARI MD, SURGICAL INTENSIVE CARE UNIT

RENAL FUNCTION IN ICU Renal Clearance/GFR/ FENa Hepato -Renal Syndrome SIADH Rhabdomyiolosis, contrast induced ARF

Renal Clearance/GFR/ FENa

Rhabdomyiolosis, contrast induced ARF

Case Study 86 year Male 40 Kg had been admitted to ICU for G.I. Bleeding last 12 hr. BUN = 65 Creat 1.6 Urine Output = 30 cc/h BP = 140/90 C.I. 3.4L/min PCWP = 28 Medication Lasix 40 mg. Q/ d + Renal dose Dopa Urine Creat ( 2H)= 105 mg/L Urine Na = 60 Urine OS= 400 GFR=? < 15 > =35 = 19 =125 =60 DIAG A= ATN B=PUMP FAILURE C= NORMAL RENAL FUNC D= INSU DATA FOR DIAG

RENAL CLEARANCE/GFR Practical issues regarding creatinine, clearance in SICU A. Estimate Creatinine Clearance CL Cr = (140 - age) x lean BW in Kg 72 x S Cr Female = Estimate Value x .85

Case Study Calculate G.F.R V.S Measured Creatinine Clearance Estimate GFR 140 - 86 x 40 = 19 72 x 1.6

Case Study GFR = Cr C 2h = 105 x .5 = 32 1.6 GFR = 32 is normal for this patient age, Diagnosis = normal kidney function; High BUN is due to GI bleeding

CLEARANCE and GFR Plasma clearance is used to express the ability of the kidney to clean or “clear” the plasma of a substance. If a substance does not reabsorb and not exerted by the kidney then clearance = GFR C = Uc x UV (per min) Pc Ideal Agent = Non Toxin Non Reabsorbent Non Actively Excreted

CLEARANCE and GFR

Plasma clearance is used to express the ability of the kidney to clean or “clear” the plasma of a substance. If a substance does not reabsorb and not exerted by the kidney then clearance = GFR

C = Uc x UV (per min)

Pc

Ideal Agent =

Non Toxin

Non Reabsorbent

Non Actively Excreted

GFR/CLEARANCE ESTIMATE INULIN CREATININE 2H/ 24 H IOTHALAMATE (radio active tracer) gold standard

ESTIMATE

INULIN

CREATININE 2H/ 24 H

IOTHALAMATE (radio active tracer) gold standard

RENAL CLEARANCE/GFR ADVANTAGE : easy to calculate good for starting medication, antibiotics, etc in the patient in acute phase of ATN cost is cheap DISADVANTAGE: extremely inaccurate in obese and overloaded patients, septic patients, tendency to overestimate. Underestimate in small size old patient

easy to calculate

good for starting medication, antibiotics, etc in the patient in acute phase of ATN

cost is cheap

extremely inaccurate in obese and overloaded patients, septic patients, tendency to overestimate.

Underestimate in small size old patient

RENAL CLEARANCE/GFR (cont) 24 Creatinine Clearance or 2 Hours = CL Cr = Ucr x UV(cc/min) S cr needs volume of urine (cc/min) urine concentration of creatinine ( lab reports total amount of creatinine per vol of urine) serum concentration of creatinine

GFR example 150 cc urine collected over two hours U Cr is 40mg per dc/l Scr is 2mg /dl U volume 1.2 cc/min 40 X 1.2 =24 GFR= 24 2

example

150 cc urine collected over two hours

U Cr is 40mg per dc/l

Scr is 2mg /dl

U volume 1.2 cc/min 40 X 1.2 =24

GFR= 24 2

Iothalamate Sodium I 125 Clearance CL I TH = U ITH x UV/min S ITH (1) + S ITH (2) Extremely accurate Eliminate weight problems Fast, could be done within 3-4 hours Expensive Not available in smaller institution. Gold standard

Iothalamate Sodium I 125 Clearance

CL I TH = U ITH x UV/min

S ITH (1) + S ITH (2)

Extremely accurate

Eliminate weight problems

Fast, could be done within 3-4 hours

Expensive

Not available in smaller institution.

Gold standard

Case Study 4 (cont) Ccr = 140 - Age x B.W. = 140 - 43 x 105 = 110 72 x Pcr 72 x 1.4 Female correction = Ccr x .85 = 110 x .85 = 94

Case Study 4 ESTIMATED VS MEASURED CREATININE CLEARANCE 43 year old female; weight 105 kg; evaluated for possible renal disease. Plasma creatinine 1.4/DL Urine creatinine 62/DL Urine volume 24 hours 1080 cc Consider zosyn dose

case 4 C cr measured 24 hour urinary creatinine clearance Ccr = Ucr x Uv min = 62x .75 = 33 Pcr 1.4

Interpretation= GFR Dialysis <10 >6 End stage Aggressive hydration 40-60 2-6 Severe hypovolemia Diuretics/dialysis 10-20 2-4 ATN None,protection strategy 20-30 2-4 C.Renal insufficiency None 30-80 1-2 Age >60 None 80-120 1-2 Normal TX GFR Serum Cr condition

Case Study 2 55 year old male admitted to I.C.U. after AAA operation: Aorta clamp time 45 minutes otherwise uneventful course. Urine output 250 cc/h PCWP = 19 C.I. 3.1 Patient I/O last 24 hour 11500/8500 Pcr 1.8 (Preop Cr 1.1) BUN = 30 Urine Na 65 Urine osm 200 Ur cr = 15 PNa = 130 Possible Diagnosis: High Output A.T.N. Diabetes Insipidus S.I.A.D.H. Over hydration Fluid Mobilization

55 year old male admitted to I.C.U. after AAA operation: Aorta clamp time 45 minutes otherwise uneventful course. Urine output 250 cc/h PCWP = 19 C.I. 3.1 Patient I/O last 24 hour 11500/8500 Pcr 1.8 (Preop Cr 1.1) BUN = 30 Urine Na 65 Urine osm 200 Ur cr = 15 PNa = 130

Possible Diagnosis:

High Output A.T.N. Diabetes Insipidus

S.I.A.D.H. Over hydration

Fluid Mobilization

Case Study 2 (cont) FENa = UNa x Pcr x 100 = 65 x 1. 8 x 100 = 6% PNa x Ucr 130 x 15 2h urinary creatinine clearance Ccr = Ucr x UV (min) = 15 x 4 = 33 Pcr 1.8

CASE 2 ATN FENA 65 LOW GFR=33

Fractional excretion of Na Ratio of the Na excreted < 1% to Na reabsorbed 99%

FeNa Inexpensive,easy in ICU To identify pre renal from renal or hepato-renal Could be used as follow-up during recovery phase Little influenced by low salt diet or excess of salt intake Diuretics should not be used at least 8 hours prior to test Renal dose of dopamine although theoretically influence Na + excretion, but in practice it is usually ignored .

Inexpensive,easy in ICU

To identify pre renal from renal or hepato-renal

Could be used as follow-up during recovery phase

Little influenced by low salt diet or excess of salt intake

Diuretics should not be used at least 8 hours prior to test

Renal dose of dopamine although theoretically influence Na + excretion, but in practice it is usually ignored .

FRACTIONAL - EXCRETION NA + EVALUATION OF TUBUL INTETEGRITY FE Na = U/P Na + x P/U cr OR FENA= Una + x P cr x 100 PNa + x U cr

EVALUATION OF TUBUL INTETEGRITY

FE Na = U/P Na + x P/U cr OR

FENA= Una + x P cr x 100

PNa + x U cr

FENA FENA= Una + x S cr x 100 S na X Ucr

FENA/NORMAL VALUE U/sodium= 30 U cr =60 Scr =1.2 Sna =140 30 X 1.2 X100 = 1.14 140 x60

U/sodium= 30

U cr =60

Scr =1.2

Sna =140

30 X 1.2 X100 = 1.14

140 x60

FRACTIONAL - EXCRETION NA + FE Na >3% = Renal tubular dysfunction, A.T.N.P0S DIURETIC USE FE Na <1% = Hypovolemia - low cardiac output FE Na 1% - 2% = Not significant diagnostic value FE Na are low in these conditions: 10% - 15% A.T.N. H.R.S. FENA LOW <1% NO RESPONSE TO VOLUME OR INOTROPIC AGENTS

FE Na >3% = Renal tubular dysfunction, A.T.N.P0S DIURETIC USE

FE Na <1% = Hypovolemia - low cardiac output

FE Na 1% - 2% = Not significant diagnostic value

FE Na are low in these conditions:

10% - 15% A.T.N.

H.R.S. FENA LOW <1% NO RESPONSE TO VOLUME OR INOTROPIC AGENTS

Case Study 5 70 year old woman 80 kg in very good health admitted in ICU after surgical removal of her spleen. She has been hypotensive and on pressors in PACU for a period of 6 hours prior to ICU admission: BP 110/70 BUN = 20 Creat 1.6/L urine output 30cc/h CVP = 12 Lasix drip, 2 mg/h + Dopa renal dose Urine Na = 65 Urine osm = 320 Urine Creatinine 48 mg/L SN a=135 DIAGNOSIS A= ATN B= SIADH C= HYPOVOLEMIA D=INSU DATA FOR DIAGNOSIS

Case Study 5 (cont) Estimated Creatinine Clearance from Cock Croft - Gault Ccr = (140-age) x BW = 140 - 30 x 80 = 76 72 x PCr 72 x 1.6 Correction for Female .85 = 65

Case 5 Urinary Cr clearance 2 h Ccr= Ucr x UV (min) = 48 x .5 = 15 Pcr 1.6

Dx=ATN

ATN/VASOCONSTRICTION HYPOVOLEMIA PRESSORS CONTRAST LOW CARDIAC INDEX HEPATO-RENAL

HYPOVOLEMIA

PRESSORS

CONTRAST

LOW CARDIAC INDEX

HEPATO-RENAL

ATN/VASODILATATION SEPSIS 50% IN SEPTIC SHOCK VASODILATION AND ^RBF REDIST BLOOD FLOW FROM CORTEX TO MEDULLA INCREASE NO PRODUTION NOREPINEPHRINE MAY BE HELPFUL (renal dose Nor-epinephrine)

SEPSIS

50% IN SEPTIC SHOCK

VASODILATION AND ^RBF

REDIST BLOOD FLOW FROM CORTEX TO MEDULLA

INCREASE NO PRODUTION

NOREPINEPHRINE MAY BE HELPFUL (renal dose Nor-epinephrine)

Intrarenal blood flow distribution in hyperdynamic septic shock: Effect of norepinephrine. Di Giantomasso, David MBBS; Morimatsu, Hiroshi MD; May, Clive N. PhD; Bellomo, Rinaldo MD [LABORATORY INVESTIGATIONS]

Intrarenal blood flow distribution in hyperdynamic septic shock: Effect of norepinephrine.

Di Giantomasso, David MBBS; Morimatsu, Hiroshi MD; May, Clive N. PhD; Bellomo, Rinaldo MD

[LABORATORY INVESTIGATIONS]

Dopamine Action INCREASE CO/INC RENAL BLOOD FLOW  NA EXEC LIKE DIURETICS DOES NOT  GFR  PULSE, PB  T-CELL, MORE INFECTIOUS A-FIB  GROWTH HORMONE

INCREASE CO/INC RENAL BLOOD FLOW

 NA EXEC LIKE DIURETICS

DOES NOT  GFR

 PULSE, PB

 T-CELL, MORE INFECTIOUS

A-FIB

 GROWTH HORMONE

Low Dose Dopamine Patients with Early Renal Dysfunction THE LANCET VOL 356 DEC 2000 AUSTRALIAN-NEW ZEALAND STUDY GROUP PACEBO-CONTROL RANDOMIZED STUDY MULTI-INSTUT 3 YEARS IN 23 ICU's 328 PATIENTS 2ug/K DOPAMINE NO SIGNIFICATN RENAL PROTECTION IN TWO GROUPS Lancet 2000;356

PACEBO-CONTROL RANDOMIZED STUDY

MULTI-INSTUT

3 YEARS IN 23 ICU's

328 PATIENTS 2ug/K DOPAMINE

NO SIGNIFICATN RENAL PROTECTION IN TWO GROUPS

Lancet 2000;356

Rhabdomyolysis Major crush injury/compartment synd Muscle edema, ischemia, necrosis Status epilepticus Prolong positional pressure under anesthesia Protracted fever Prolong use of vasopressor/cross clamp Cocaine, cracks/STATIN Malignant hyperthemria

Major crush injury/compartment synd

Muscle edema, ischemia, necrosis

Status epilepticus

Prolong positional pressure under anesthesia

Protracted fever

Prolong use of vasopressor/cross clamp

Cocaine, cracks/STATIN

Malignant hyperthemria

Mechanism of Rhabdomyolosis Release of myoglobin, which is 25% of HG size rapidly filtering by glomerlus, precipitate as an acid ferrihematin in proximal tubes, hypovolemia, urine pH<6 low urine output enhancing the process

Rhabdomyolysis Diagnosis Clinical High Index of Suspicion Serum Myoglobin >400 ug/l Urine Myoglobin >1000 mg/c Negative Test are Frequent CPK >1000

Clinical High Index of Suspicion

Serum Myoglobin >400 ug/l

Urine Myoglobin >1000 mg/c

Negative Test are Frequent

CPK >1000

Rhabdomyolisis CPK over 10000 associated higher incidence ARF

CPK over 10000 associated higher incidence ARF

Strategy for Renal Protection, Recovery Enhance DO 2  CI Hg preload, maintain perfusion pressure Renal vasodilatation Dopamine Fenoldapam Maintenance Tubular Flow u/o 100-200 cc/h Mannitol Loop Diuretics

Enhance DO 2  CI Hg preload, maintain perfusion pressure

Renal vasodilatation

Dopamine

Fenoldapam

Maintenance Tubular Flow u/o 100-200 cc/h

Mannitol

Loop Diuretics

Rhabdomyolysis Treatment High Urine Volume >200/h Mannitol Sodium Bicarb 25 meq/h Urine pH>6 Diuretics Hydration

High Urine Volume >200/h

Mannitol

Sodium Bicarb 25 meq/h

Urine pH>6

Diuretics

Hydration

Mechanism CIARF Renal vasoconstriction  leading to medullary ischemia  GFR Direct cytotoxic injury mediated by O2 free radical Intratubular obstruction

Renal vasoconstriction  leading to medullary ischemia  GFR

Direct cytotoxic injury mediated by O2 free radical

Intratubular obstruction

Risk factor contrast CIARF Odd ratio=5.5 Prior renal insufficiency Diabetes Large dose,multi-dose , Dehydration Bp<100i CHF NSAID ,ACE I Multiple myeloma

Odd ratio=5.5

Prior renal insufficiency

Diabetes

Large dose,multi-dose ,

Dehydration

Bp<100i

CHF

NSAID ,ACE I

Multiple myeloma

Prevention CIARF Hydration 1-3cc/kg saline 12 hours prior and post contrast Manitol 25 Gr 1 or lasix 80 mg hour prior to contrast Acetylcystrine 600mg bid day before and after of contrast ( Tepel NEJM 2000) reduce CIARF 2% vs. 21% control (Diaz- Sandoval 2002 AJC) 8%vs45 % Fenoldopam 1ug/kg/min 4 hours prior and after contrast (Tumlin 2002 AHJ) 21%vs45%

Hydration 1-3cc/kg saline 12 hours prior and post contrast

Manitol 25 Gr 1 or lasix 80 mg hour prior to contrast

Acetylcystrine 600mg bid day before and after of contrast ( Tepel NEJM 2000) reduce CIARF 2% vs. 21% control (Diaz- Sandoval 2002 AJC) 8%vs45 %

Fenoldopam 1ug/kg/min 4 hours prior and after contrast (Tumlin 2002 AHJ) 21%vs45%

Case Study 7 48 WF acute brain hemorrhage Intra abdominal bleed, massive fluid intake, transfusion of 40 units blood product urine output 180 cc/h, SCr = 2, Urine OSM = 325, Serum OSM = 340, SRNa = 160, Urine Cr = 10 Diagnosis A=DI B=ATN C=EXCESS Na INTAKE

48 WF acute brain hemorrhage

Intra abdominal bleed, massive fluid intake, transfusion of 40 units blood product urine output 180 cc/h, SCr = 2, Urine OSM = 325, Serum OSM = 340, SRNa = 160, Urine Cr = 10

Diagnosis

A=DI B=ATN C=EXCESS Na INTAKE

CASE UV-3 cc/minXUCr-10 GFR= ----------------------- =15 S Cr-2

UV-3 cc/minXUCr-10

GFR= ----------------------- =15

S Cr-2

Case Study 7 (cont) FENA UNa - 111  Sr cr - 2 SNa - 160  Ucr - 15 x 100 = 9%

CASE DIAGNOSIS = ATN D .I . URINE OUT PUT MUCH HIGHER, UOSM IS <100 SG<1020 fena not high

DIAGNOSIS = ATN

D .I . URINE OUT PUT MUCH HIGHER, UOSM IS <100 SG<1020 fena not high

Case Study 45 year old male with Cirrhosis and large acites admitted in I.C.U.for hypotension and low urine out put Patient urinary output 20 cc/h C.I. 5L/min PCWP = 20 BP = 130/70 P Na= 130 U Na = 5 meq/l Urine osmo = 580 Pcr 2.6 BUN = 60 meq/l Urine Cr = 92

Case Study (cont) Possibilities: S.I.A.D.H. Syndrome Hypovolemia A.T.N. Hepato - Renal Syndrome None of above

Possibilities:

S.I.A.D.H. Syndrome

Hypovolemia

A.T.N.

Hepato - Renal Syndrome

None of above

Case continue Cl Cr =GFR= Ucr x UV/min = 92 x .3 = 11 S Cr 2.6

Cl Cr =GFR= Ucr x UV/min = 92 x .3 = 11

S Cr 2.6

Case study cont FENa = U Na x Pcr = 100 = 5 x 2.6 = 0.10 PNa x Ucr 130 x 92

FENa = U Na x Pcr = 100 = 5 x 2.6 = 0.10

PNa x Ucr 130 x 92

Case 3 DX= HRS LOW GFR =11 LOW FENA=.1 H/O LIVER DISEASE

Pathology in Hepato Renal Symptoms Cortical vasoconstriction due to decreased effective blood volume The role of angiotensin and mediators not well-defined Although the hemodynamic values are not compatible with hypovolemia or congestive heart failure the renal functions are very similar to pre-renal dysfunction Not responsive to volume and pressor therapy Liver transplant in a definitive treatment in the patients with primary liver pathology Support the patient with CVVHD or hemodialysis

Cortical vasoconstriction due to decreased effective blood volume

The role of angiotensin and mediators not well-defined

Although the hemodynamic values are not compatible with hypovolemia or congestive heart failure the renal functions are very similar to pre-renal dysfunction

Not responsive to volume and pressor therapy

Liver transplant in a definitive treatment in the patients with primary liver pathology

Support the patient with CVVHD or hemodialysis

Hepato Renal Syndrome Primary Pathology in liver, e.g. CIRRHOSIS No clinical evidence of low C.O. or hypovolemia No response to therapy, volume loading or Pressors Good response to liver transplant S Cr 3-5 GFR=20-10

Primary Pathology in liver, e.g. CIRRHOSIS

No clinical evidence of low C.O. or hypovolemia

Good response to liver transplant

S Cr 3-5 GFR=20-10

Hepato-Renal

URINARY INDICES IN HEPATO-RENAL SYNDROME

Case 71 /Y/MALE 50 Kg IN PACU POST PNUMONECTOMY FOR LUNG CA BLOOD LOSS 3 LITER TRANSFUSE 5 RBC 2 FFP 4 LITER LR URINE 15-20 CC/H LAST 4-6 HOURS NO RESPONSE TO LITER HEXTAN AND  IV FOLEY OK Bp=130/60 pulse=90 CVP=12 PCWP=16 CI=3.2 SNa=136 SCr=1.6 / BASELINE 1.6

71 /Y/MALE 50 Kg IN PACU POST PNUMONECTOMY FOR LUNG CA BLOOD LOSS 3 LITER

TRANSFUSE 5 RBC 2 FFP 4 LITER LR

URINE 15-20 CC/H LAST 4-6 HOURS NO RESPONSE TO LITER HEXTAN AND  IV FOLEY OK

Bp=130/60 pulse=90 CVP=12 PCWP=16 CI=3.2 SNa=136 SCr=1.6 / BASELINE 1.6

case U Cr=80 UOS=750 UNA=65

Case Study (cont) FENa = UNa x Pcr x 100 65 x 1.6 x 100 = 1.02 PNa x Ucr 136 x 80 DIAGNOSIS 1. A.T.N. 2. CHF 3. HYPOVOLEMIA 4. SIADH 5.NORMAL POST OP /ACCEPTABLE U/O FOR HER SIZE

FENa = UNa x Pcr x 100 65 x 1.6 x 100 = 1.02

PNa x Ucr 136 x 80

DIAGNOSIS

1. A.T.N.

2. CHF

3. HYPOVOLEMIA

5.NORMAL POST OP /ACCEPTABLE U/O FOR HER SIZE

Case Study 1 DX= SIADH High U/OSM (750) LOW Sr /OSM Low Serum Na (136) High Urinary Na (65) Mild Oliguria 15-20 cc/h Clinical Presentation Lung CA Positive Pressure Vent

High U/OSM (750)

LOW Sr /OSM

Low Serum Na (136)

High Urinary Na (65)

Mild Oliguria 15-20 cc/h

Clinical Presentation Lung CA

Positive Pressure Vent

SIADH IN ICU PATIENTS ETIOLOGY Pre-existing medical condition ( i.g ., lung tumors, brain tumors, CVA, et.) Surgical procedure ( i.e., bone surgery, lung surgery, abdominal surgery) Positive pressure ventilation Pain and analgesic drugs

ETIOLOGY

Pre-existing medical condition ( i.g ., lung tumors, brain tumors, CVA, et.)

Surgical procedure ( i.e., bone surgery, lung surgery, abdominal surgery)

Positive pressure ventilation

Pain and analgesic drugs

SIADH IN ICU PATIENTS DIAGNOSIS Relative hyponatremia serum Na + usually 130 - 140 mEq/L, normal S Na does not rule it out Relative oliguria urine output <30 cc or significantly less than intake (75/80%)  urinary Na + > 30 mEq/L Range: 30 - 120 mEq/L  urine osmolality > 500

DIAGNOSIS

Relative hyponatremia serum Na + usually 130 - 140 mEq/L, normal S Na does not rule it out

Relative oliguria urine output <30 cc or significantly less than intake (75/80%)

 urinary Na + > 30 mEq/L Range: 30 - 120 mEq/L

 urine osmolality > 500

SIADH IN ICU PATIENTS TREATMENT DO NOT DO ANYTHING (most of cases) Very low dose of lasix if renal function OK (2-10 mg) Rule out other condition

TREATMENT

DO NOT DO ANYTHING (most of cases)

Very low dose of lasix if renal function OK

(2-10 mg)

Rule out other condition

RX 5 MG LASIX URINE OUTPUT TO 90 CC/H

5 MG LASIX

URINE OUTPUT TO 90 CC/H

Free Water Clearance In a patient with prerenal oliguria, the urine flow may be 0.5 ml/min, serum osmolarity 300 mOsm/liter, and urine osmolarity 600 mOsm/liter: Cl OSM = (600)(0.5) = 1.0 ml/min (300) Cl H2O = urine flow (ml/min) _ Cl OSM = 0.5 - 1.0 = -0.5 ml/min

Free Water Clearance Cl H2O = Urine Volume/min - Cl OSM Example: Serum OSM = 300 MSO Urine OSM = 600 MSO Urine Value 120 cc/h Cl OSM = Uosm x UV = 600 x 2 = 4 S OSM 300 Cl H2O = UV = Cl OSM = 2- 4 = - 2 

Tests to Evaluate Tubular Dysfunction Osmolar Clearance CL OSM = Uosm x Uv SERUM OSO Refers to total number of osmotically active solute particles instead of single substance: If CL OSM in equal with urine volume means no solute, would be cleared by kidney.

Free Water Clearance Cl OSM = (0.5)(200) = 0.36 ml/min (280) Cl H2O = 0.5 - 0.36 = 0.14 ml/min . IF FREE WATER Cr POSITIVE MEANS LACK OF CONCENTRATION CAPABILTY

FILTERATION, EXCRETION, REABSOBTION ELCTROLYTES

Free Water Clearance Free-water clearance (Cl H2O ) is defined as urine volume per minute minus osmolar clearance and is normally negative. Isosthenuria (urine osmolarity the same as plasma) is one of the earliest and most consistent functional characteristics of ATN As urine osmolality falls, osmolar clearance also falls and free-water clearance becomes less negative. If urine osmolality falls below that of serum, free-water clearance becomes positive, a fall in osmolar clearance may occur, even before a fall in Cl cr or serum Cr . in some patients as ATN is developing.

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