Presented by:

Haya M. Al-Malaq

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Outlines

• Part I – Lab Evaluation of RF.

• Part II – AG induced ATN.

• Part III – Amphoteracin B induced nephrotoxicity.

• Part IV – Post-renal ARF.

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Definition

• It is an abrupt decline in glomerular and tubular function, resulting in the failure of the kidneys to excrete nitrogenous waste products & to maintain fluid & electrolyte homeostasis.

• Increase in > 50% over baseline Cr & GFR <10mL/min, or <25% of normal

• Azotemia is a consistent feature of acute renal failure (ARF), oliguria (UOP <400-500 mL/d) is not.

• Anuria i.e. UOP < 0.5 ml/kg/h

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History & Physical Examination

• Shows the cause of ARF. • Is the patient on any medications.• A thorough physical examination in used conjunction with the

history can be invaluable in confirming the cause of ARF.

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GFR

GFR:

Normal GFR: 100 ml/min/1.72m2

Glomerular Filtration Rate (GFR)

• The total kidney GFR is equal to the sum of the filtration rate of all the functioning nephrones and represent the total functional mass of the kidney.

• It is a reliable index that can be used to evaluate the progression of renal disease.

• Markers that are freely filtered at the glomerulus are best indicator for accurate measurement of GFR (ideally should be inert, freely filtered without secretion, reabsorption metabolism or production by tubules)

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BUN

• BUN is produced by the liver, transported in the blood, excreted by the kidneys.

• The conc. of BUN reflects KF b/c it is completely filtered, reabsorbed & secreted.

• ARF, CRF r the common cause of elevated BUN.

• Normal BUN level (8-18 mg/dl or 3.0-6.5 mmol/l).

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BUN

• Do NOT quantify the extent of kidney dysfunction.

• Hi prot intake or catabolism, GI bleeding, hydration status, terminal stage of liver disease all affect BUN level.

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Creatinine & Creatinine Clearance • Most widely used clinical measurement of CLcr.

• Produced at a constant rate of non-enzymatic hydrolysis of muscle stores.

• So individual muscle mass, age, sex are predictors of Cr production.

• It is freely filtered & about 10-20 % secreted.

• Cimetidine & trimethoprim inhibit Cr secretion & so increase SrCr with out affecting GFR.

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Determination of CLcr by Cockcroft-Gult Equation

CLcr = (140 – Age) (IBW)

(72) (SrCr in mg/dl)

Male IBW= 50 + ( 2.3 * height > 60 inches )

Female IBW= 45 (2.3 * height > 60 inches )

* 0.85 in females

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Limitation of this method is that it produce falsely high CLcr in the early stages of ARF & falsely low CLcr when ARF is

resolving.

CG is also in accurate in patients that have low muscle mass as elderly, obese, or cachectic.

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Determination of CLcr by 24 Hour Urine Collection

CLcr (ml/min) = Uv (ml) * Ucr (mg/dl)

0.5 (SrCr1 + SrCr2)

SrCr1(mg/dl)= at the beginning of urine collection

SrCr2 (mg/dl)= at the end of urine collection

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Limitation of this method is that the accuracy of the calculation depends on the accuracy of the urine collection process.

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Case

• H.H is a 43 yo 80 kg man being treated for G-ve septic shock.

• HPI: • He was admitted to the hospital 6 days ago but he has spent

the last 3 days intubated in the medical respiratory ICU b/c of hypotension, respiratory failure and altered mental status.

• Hospital course:• Since admission he has received ceftriaxone 2g/d, gentamycin

140 mg IV q8hrs.

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Case

• Admission labs:• BUN 13 mg/dl (8-18)• SrCr 0.9 mg/dl (0.5-1.2)• WBC 23,500 cells/mm3 (4000-9000) with left shift (90%

PMN & 12% Bands)• Serial bl & urine & sputum culture were +ve for Acinetobacter

Baumanii sensitive to ceftriaxone & gentamycin.

• In addition to the previous antibiotics current medications include norepinephrine IV 18 g/min, pancuronium 0.02 mg/kg IV q3hrs, famotidine 20 mg IV q12hrs, lorazepam IV 2mg/hr.

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Case

• H.H VS include T 38.6 oC; BP 90/40 mmHg; P 135 beats/min; RR 20 breaths/min

• New Labs:• BUN 65• SrCr 5.4• WBC 16,500 with left shift.• Over the last 2 days the urine output started to decline & today

is 700 ml/24 hrs (1,500-2,500).

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Case

• Urine analysis & electrolytes:• Na 55 mEq/L (20-40)• Cr 26 mg/dl (50-100)• Many WBC (0-5)• 3% RBCs casts (0-1%)• Granular casts (-ve)• Osmolality 250 mOsm/kg (400-600)• Sr genta Cp 15 mg/dl (6-10), Ct 9.1 mg/dl (<2)

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Case

• Given the history and lab data what is the source of HH ARF?

• How does AG induced ATN presents & what is the MOA?

• Is extended interval AG dosing less nephrotoxic than multiple daily dosing?

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Case

• H.H remained febrile for the next several days despite being covered by broad spectrum AB.

• His gentamycin & ceftriaxone were stoped 3 days ago & imipenem 500mg IV q12hrs was started.

• Today he is febrile 39 oC, blood fungal culture optained 5 days ago was positive for candida tropicalis sensitive only to Ampho B.

• Labs : BUN 75; SrCr 6.1; WBC 17,500 , UOP 600 ml/day * 3d

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Case

• Are there any concerns with administration of Ampho B to H.H if he still remains in ATN?

• How do lipid based Ampho B products reduces nephrotoxicity?

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Classification

Causes & Symptoms

• Obstruction of urine flow by stone, malignancy (prostate, cervix), prostatic hypertrophy, bilateral ureter stricture and bladder outlet obstruction (as in prostatic hypertrophy).

• Onset of S & S are gradual; presents as decreased force of urine stream, dribbling, or polyurea.

• Drugs my ply a role in crystal formation so should be included in the differential diagnosis.

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Nephrolithiasis

• Common with genetic predisposition.

• Risk factors: • Low urine volume.• Hypercalciuria.• Hyperoxaluria.• Hyperuricosuria.• Chronic hi or lo urine PH.

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• Types: • Calcium stones (70-80%).• Struvite (Mg Al ph, 2-20%,

can result in irreversible kidney damage).

• Uric acid (chemotherapy pts).

• Crystal (rare herditory disorder).

Presentation & Treatment

• TA is a 48yo man, ER

• Cc: sharp pain radiating to the groin, dysuria, hematouria,*4hr similar to a previous episode of Ca nephrolithiasis.

• HPI:• On questioning he admits that he had not been drinking much

fluids over the past wk owing to a busy work schedule and his urine volume has been markedly lower than usual.

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Presentation & Treatment

• Labs:• BUN 34 mg/dl (5-20)• SrCr 1.5 mg/dl (0.5-1.2)• Urine sampled showed large amount of Ca oxalate crystals

which indicates that the pt passed a kidney stone.

• What Sub & obj data suggest nephrolithiasis and how to prevent this from occurring in the future?

• Can drugs crystallize the urine & cause ARF?

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