Learning Objectives Evaluation of Kidney Function

Jaffe assay

is a colorimetric reaction (alkaline picrate method) that is inexpensive and widely available but subject to interference by cephalosporins, aminoglycosides, piperacillin, flucytosine, bilirubin, and ketoacids

Isotope-dilution mass spectrometry (IDMS)

is the calibration standard used for creatinine measurement

inter-laboratory variability

What does the IDMS traceable assay reduce?

IDMS

critical for accuracy of eGFR equations such as MDRD and CKD-EPI

serum creatinine

-production depends on muscle mass and its affected by patient characteristics

-inexpensive

-age

-sex

-muscle mass

-diet (meat intake)

What are the limitations of serum creatinine?

drugs that inhibit tubular secretion which falsely elevates Scr

-Cimetidine

-Trimethoprim

-Cobicistat

Jaffe

-(alkaline picrate method)

-Measures color change in creatinine–picrate reaction

-Cheap, commonly used

-False ↑ creatinine from cephalosporins, piperacillin, flucytosine, bilirubin, ketoacids

enzymatic assay

-enzymes convert creatinine to chromophore

-more accurate for patients with abnormal bilirubin

-more expensive

IDMS (improves accuracy of MDRD and CKD-EPI)

What is the gold standard creatinine assay type?

Cystatin C

low molecular weight protein produced at a constant rate by all nucleated cells

glomerulus

Where is Cystatin C filtered?

pros of Cystatin C

-no affected by muscle mass, diet or body size

-ideal for elderly, malnourished, amputees

cons of Cystatin C

-increased by inflammation, thyroid disease, glucocorticoids

-more expensive

BUN

-not a realiable marker alone

-affected by high protein diet, GI bleeding, corticosteroids, volume depletion

pre-renal AKI

BUN:Scr >20:1

intrinsic AKI

BUN:SCr 10-15:1

elevations

Piperacillin and other β-lactam antibiotics can react in Jaffe assays, leading to false _________ of serum creatinine.

flucytosine, cephalosporins and ascorbic acid

can also interfere with Jaffe assay giving spurisouly high results

-Piperacillin/Tazobactam

-Cephalosporins

-Flucytosine

-Ascorbic Acid

-Ketoacids and Bilirubin

What drugs DO NOT cause imaired kidney function BUT will interfere with the Jaffe assay reaction causing false elevations of SCr?

Cystatin C

is produced by all nucleated cells at a constant rate and is freely filtered by the glomerulus without tubular secretion

elderly, malnourished or amputee patients

Because Cystatin C is independent of muscle mass who is it useful in?

limitations of Cystatin C

-influence by inflammation

-thyroid disease

-glucocorticoid therapy

-higher assay costs

Creatinine

is derived from creatine metabolism in muscle, filtered and secreted by renal tubules

-muscle mass

-age

-sex

-race

-diet (high meat intake)

-certain meds

What is creatinine influence by?

combined CKD-EPI creatinine-cystatin C equations

improve accuracy over either biomarker alone

increasing creatinine load

Dietary protein intake, particularly ingestion of cooked meat within 24 hours, can raise serum creatinine by:

Cimetidine, Cobisistat and trimethoprim

inhibit tubular secretion of creatinine, leading to higher serum values without actual reduction in GFR

-Cephalopsorins

-Piperacillin

-Flucytosine

-Ascorbic acid

What drugs interfere with Jaffe Assays leading to falsely elevated creatinine?

increases

Strenuous exercise or rhabdomyolysis __________ creatinine generation.

inhibition of tubular secretion

some drugs block creatinine secretion in the proximal tubule → creatinine stays in blood even though GFR is unchanged

assay interference in Jaffe Method

Drugs or metabolites chemically react with alkaline picrate reagent, making the lab machine think more creatinine is present (NO renal injury)

increased creatinine production

Diet (high meat intake) or muscle breakdown increases creatinine generation but kidney function is normal

tubular secretion blockers

Trimethoprim, Cimetidine, Cobicistat

jaffe assay interferers

-Pipericillin

-Cephalosporins

-Flucytosine

-Ascorbic acid

-Bilirubin

-Ketoacids

increased production of Scr

-high protein diet

-recent cooked meat

-rhabdomyolysis

sarcopenia

Elderly patients often have ________ (loss of muscle mass), which reduces creatinine generation despite impaired renal function.

sarcopenia

the loss of muscle mass, strength, and function that comes with aging

overestimate

Cockcroft-Gault may particularly _________ in low-muscle-mass patients because it incorporates weight directly.

Cystatin-C based equations

may provide a more accurate reflection of GFR in elderly individuals, though inflammatory comorbidities can confound results

2 places past the decimal point

What is the best practice to report eGFR in mL/min/1.73 m2 using IDMS-traceable creatinine values?

>60 mL/min/1.73 m2

eGFR should be reported as ______ rather than exact values above this threshold due to inaccuracy at higher GFR levels.

-children

-pregnant women

-very elderly

-extremes of body size

What populations should laboratories include disclaimers about limited accuracy in specific populations?

1.73 m2

Normalization to ________ allows standardization but may overestimate or underestimate true GFR in obese or underweight patients.

24 hr urine measured creatinine clearance

requires accurate 24 hour urine collection

1.73

average adult BSA used to allow comparison across pts

normalization

is done using GFR x 1.73/BSA

lower

Obese patients may have ________ "true" kidney clearance than normalized values suggest.

worse

Underweight patients may appear ________ than they are

Mostellar equation

used to estimate BSA

-age

-sex

-IBW

-Scr

What is required for the cockcroft-gault equation?

-age

-sex

-race

-serum creatinine

What is required for the MDRD equation?

-age

-sex

-Scr

-optionally: cystatin C

What is required for the CKD-EPI equation?

2021 CKD-EPI

removed race as a variable

all except cockcroft gault

What equations should you normalize to BSA?

k in schwartz equation

is an age and sex specific constant

Schwartz formula

validated in children 1-19 years of age with CKD

maternal levels

What does serum creatinine reflect in neonates ( < 1 week old)?

about 1 yr

When does GFR reach adult levels in children?

kidney biopsy indications

-unexplained AKI

-suspected glomerulonephritis

-nephrotic syndrome

-rapidly progressive glomerulonephritis

-unexplained persistent hematuria or proteinuria

histopathological

Biopsy allows ________ classification which guides therapy.

complications of kidney biopsy

-bleeding

-arteriovenous fistula

-infection

minimal change disease

is characterized by nephrotic syndrome with normal light microscopy and podocyte effacement on electron microscopy

corticosteroids (prednisone) induces remission in most children and adults

What is the 1st line therapy for minimal change disease?

-calcineurin inhibitors (cyclosporine, tacrolimus)

-cyclophosphamide

What is the alternative tx for steroid resistant minimal change disease?

monitoring with minimal change disease

-bp

-kidney function

-glucose

-infection risk with steroids

-nephrotoxicity and drug levels for calcineurin inhibitors