Interpretation of Renal Diagnostic Tests

Christos Argyropoulos MD, PhD, FASNUniversity of New Mexico School of Medicine

Overview – Learning Objectives

• Assessment of Renal Function and Renal Damage in CKD

• Assessment of tubular function• Diagnostic Renal Imaging

*information on the slides intended as a handout/reference

NUMEROLOGY OF RENAL FUNCTION AND DAMAGE

eGFR and Albuminuria

The functions include: Filtration

− Glomeruli generate ultrafiltrate of the plasma.

Reabsorption − Tubules selectively

reabsorb substances from the ultrafiltrate.

Secretion− Tubules secrete

substances into the urine.

The nephron functions to maintain balance

GFR is equal to the sum of the filtration rates in all of the functioning nephrons (assessment of function).

GFR is not routinely measured in clinical settings:

Requires administration of exogenous tracers followed by measurements in plasma/urine or both

Estimation of the GFR (eGFR) gives a rough measure of the number of functioning nephrons:

May be done by measuring levels of endogenous filtration

markers or through clearance calculations

What is the glomerular filtration rate (GFR)?

Compounds that are not normally present in the body Principles of measurement:

− Tagged with radionucleotides – measurement through in vivo imaging (nuclear medicine) or by in vitro RIA

− HPLC assays (non tagged markers)− Multiple time points at blood (“disappearance curves”) or urine

125I-iothalamate (clinical research use mainly) 99mTc-DTPA (available clinically – used mainly in donor

transplant workup and pediatrics) Non-radioactive iohexol/iothalamate Disadvantages: exogenous admin/ $$-$$$ to

measure/time consuming procedures for patients Gold standard techniques when an objective,

accurate estimate of renal function is warranted (and when endogenous markers give conflicting results)

Exogenous Filtration Markers

Distributed freely and instantaneously throughout the extracellular space

Produced at relatively constant rates Not bound to plasma protein or cellular components Freely filtered at the glomerulus Not secreted or reabsorbed at the tubules Minimal pathways of non-renal clearance (e.g. liver) Resistant to degradation and stable in biofluid

samples Easy and inexpensive to measure

The Ideal Endogenous Filtration Marker

Byproduct of protein metabolism Produced by the liver (“urea cycle”) Significant non-renal influences:

− Increased production (high protein intake, GI bleeding, hypercatabolic states e.g. steroid therapy)

− Decreased production (malnutrition, chronic liver dz)− Volume status/effective renal blood flow (increased

tubular reabsorption) Not an ideal GFR marker:

− Significant non-renal influences− Significant reabsorption− But ratio of BUN/Creatinine assists interpretation of

potential causes and pathophysiology of Acute Kidney Injury

Endogenous filtration markers - Urea

Byproduct of muscle metabolism (derived from nonenzymatic conversion of creatine and phosphocreatine in muscles

Constant production (production is ~2% of total creatine pool per day)− Production rate is thus tied to the total creatine pool which

depends on muscle mass Not bound to human serum proteins Freely filtered at the glomerulus Significant component of tubular reabsorption (quoted as

5-15% but dependent on prevailing GFR) Less than ideal marker but better than BUN

Endogenous filtration markers - Creatinine

Serum Creatinine Levels Are Inversely Related to GFR

Clin J Am Soc Nephrol. 2009 May; 4(5): 899–906

• Inverse relationship means that

significant renal impairment may exist

even if serum creatinine is not greatly

elevated

• The same difference in serum

creatinine, has a different interpretation

depending on the prevailing renal

function

• Going from 1 to 1.3 => loss of 30%

of renal function

• Going from 2 to 4 => loss of 50% of

renal function

Non-renal factors affecting serum creatinineFactor Effect on Serum Creatinine Level CommentDemographics Aging Decreased Caused by decline in muscle massFemale sex Decreased Reduced muscle massEthnicity

African American Increased Higher average muscle mass in African Americans

Hispanic DecreasedAsian DecreasedBody Habitus Muscular Increased Increased muscle massMuscle wasting, amputation, malnutrition Decreased Reduced muscle mass ± decreased

protein intakeObesity No change No change in muscle massDiet Vegetarian Decreased Decrease in creatinine generation

Ingestion of cooked meats Increased Transient increase in creatinine generation

Medications, Endogenous Substances

Cimetidine, trimethoprim, probenecid, potassium-sparing diuretics Increased Reduced creatinine tubular secretion

Ketoacids, ascorbic acid, glucose, some cephalosporins Increased Interference with alkaline picrate assay

(Jaffé reaction) for creatinine

Bilirubin, hemoglobin Decreased Interference with alkaline picrate assay (Jaffé reaction) for creatinine

Flucytosine, praline, hemoglobin Increased Interference with enzymatic assays for creatinine

Metamizole, methyldopa, ethamsylate Decreased Interference with enzymatic assays for creatinine

Fibrates/agents causing rhabdomyolysis Increased Increased muscle breakdown

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/nephrology/kidney-function/

A typical “normal” reference range of 0.6–1.2 mg/dL listed on many lab reports does not account for muscle mass, age, gender, and race.

A 28-year-old African American man with serum creatinine of 1.2 may have a normal renal function.

A 78-year-old white woman with serum creatinine of 1.2 likely has moderate renal impairment

“Normal” serum creatinine may not be normal

Do not use with:− Rapidly changing creatinine levels

Example: acute kidney injury

− Extremes in muscle mass, body size, or altered diet patterns− Medications that interfere with the measurement of serum

creatinine (but these make 24hr collections more accurate!)− Pregnant women

These limitations apply to serum creatinine AND formulas that use the serum creatinine to estimate GFR

Serum Creatinine-based estimates of kidney function have limitations

Collect urine over a defined period of time and simultaneous plasma levels to calculate a clearance:

For a 24hr clearance the calculation (that will be tested on the boards) may take one of the forms

Creatinine Clearance And GFR

Normal Creatinine Clearance: 80-120 ml/min

Requires a timed collection (inconvenient) Errors of collection (usually under-collection) May assess the adequacy of collection by looking at the total

creatinine in the urine− 15-20 mg/kg/day in women− 20-25 mg/kgr/day in menExample: A 85 kgr man performs a 24hr collection. Urine Creatinine concentration: 90mg/dL, urine volume is 1.6L. Was this a proper collection?

In the modern era: ClCr overestimates true eGFR by 15-20% because of tubular secretion - compensated up to the early 2000s by errors in laboratory assays (?Is there a way to compensate in the modern era)

Niches: immunologic mediated proteinuric diseases (e.g. lupus), Acute Kidney Injury (timed 4-6hr collections), kidney transplant living donor evaluation

Disadvantages and Caveats of ClCr

eGFR is not the measured GFR.

Use formulats to estimate GFR – these are derived from population-based study relating eGFR to measured GFR (with an exogenous tracer)

eGFR is based on serum creatinine levels.

Previous methods to estimate kidney function also are based on serum creatinine.

Creatinine assays are now standardized.− Isotope Dilution Mass Spectrometry (IDMS)

eGFR estimates the measured GFR

Equation Name Equation Derivation Population

Cockcroft-Gault (1976) [140 − age] × wt (kg)/creatinine (µmol/L) × 0.81 Female: × 0.85 (140 − age) × lean body weight (kg)/Cr [mg/dL] × 72

•249 male veterans •Median GFR 34

MDRD equation (1999) 175 × SCr −1.154 × age −0.203 × 0.742 (if female) × 1.212 (if black) •1628 patients enrolled in the MDRD Study (mean age, 50.6 yr) •Mean GFR 39.8 mL/min/1.73 m 2

MDRD equation without ethnicity factor * 175 × SCr 1.154 × age −0.203 × 0.742 (if female)

CKD-EPI equation (2009)

141 × min(SCr/κ, 1) α × max(SCr/κ, 1) −1.209 × 0.993 age × 1.018 (if female) × 1.159 (if black) where: κ is 0.7 for females and 0.9 for males α is −0.329 for females and −0.411 for males min indicates the minimum of SCr/κ or 1 max indicates the maximum of SCr/κ or 1

•8254 participants from 6 research studies and 4 clinical populations (mean age, 47 yr) •Mean GFR 68 mL/min/1.73 m 2

CKD-EPI cystatin C (2012)

133 × min(SCysC/0.8, 1) −0.499 × max(SCysC/0.8, 1) −1.328 × 0.996 Age × 0.932 [if female] where: min indicates the minimum of SCysC/0.8 or 1 max indicates the maximum of SCysC/0.8 or 1

•5352 participants from 13 studies (mean age, 47 yr) •Mean GFR 68 mL/min/1.73 m 2

CKD-EPI creatinine–cystatin C (2012)

135 × min(SCr/κ, 1) α × max(SCr/κ, 1) −0.601 × min(SCysC/0.8, 1) −0.375 × max(SCysC/0.8, 1) −0.711 × 0.995 Age × 0.969 [if female] × 1.08 [if black] where: α is −0.248 for females and −0.207 for males κ is 0.7 for females and 0.9 for males min(SCr/κ,1) indicates the minimum of SCr/k or 1 and max(SCr/κ,1) indicates the maximum of SCr/k or 1 min(SCysC/0.8,1) indicates the minimum of SCysC/0.8 or 1 and max(SCysC/0.8,1) indicates the maximum of SCysC/0.8 or 1

A Plethora of Estimating Equations

Brenner’s and Rector The Kidney, 2016

Performance of Estimating Equations Against Measured GFR

MDRD is “blind” above 60

ml/min/1.73m2

Cockroft Gault has lower

limits of agreement with

the measured eGFR than

the MDRD

+

Use the CKD-EPI (found in UpToDate or QxCalculate) until labs switch over from MDRD to CKD - EPI

Reference range of eGFR:>60 ml/min/1.73m2 (MDRD)90-120 ml/min/1.73m2 (CKD-Epi)

13kDA– seems to function as an inhibitor of lysosomal proteinases and extracellular cysteine proteases

Constant production by all nucleated cells Not bound to human serum proteins Freely filtered at the glomerulus 100% reabsorbed and catabolized by the proximal tubule

− Can’t do a clearance calculation as the urinary levels are nil Limitations of Serum Cystatin Levels

Endogenous filtration markers – Cystatin C (and other low molecular serum proteins)

http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf

Cystatin – C v.s. Creatinine• Estimating equations

have been developed to use Cys-C alone or with SCr

• These equations do not always agree !

• Reserved for patients in which clinical impression disagrees with laboratory assessment of renal function (eGFR 45-60)

• Costs ~$150 in our state

Cockroft Gault ≠ MDRD for drug dosing

Ann Pharmacother 2012;46:1174-87

For patients with advanced age, low weight, and modestly elevated serum creatinine, further work is needed before the MDRD equations can replace the CG equation for dose adjustment in the labeling.

Individualized MDRD = MDRD x BSA

The cautious

approach to drug dosing

in renal disease

Pharmacotherapy. 2011;31(11):1130-1144. 

Normal Physiology of Proteinuria• Numerology:

– Normal protein load presented to the kidney: 10 kgr / day– Only 1 gram filtered in the glomerulus– Less than 150 mg of total protein (and less than 30 mg of

albumin) appears in the urine• The glomerular filtration barrier (basement

membrane and podocytes) restrict anything of a size >60 kDa to plasma

• LMW proteins (<20kDa) are filtered freely but reabsorbed almost completely

• Tubules secrete Tamm Horsfall protein which makes most of the normal urinary protein complement

Classification of Proteinuria• Glomerular (altered glomerular filtration

barrier, usually > 1gm/day, e.g. GNs)• Tubular (damage to the proximal tubule,

inhibiting the reabsorption of LMW proteins e.g. Fanconi syndrome)

• Overflow (normal or abnormal proteins produced in increased amounts that overwhelm the proximal tubule, e.g. hemolysis, rhabdomyolysis, myeloma, LCD)

• Postrenal non-albumin IgG/IgA secreted in UTIs/stone disease

Electrophoretic patterns in proteinuria

• Selectivity index (SI) urine IgG/

serum IgG serum transferrin/urinetransferrin• SI 0.10 highly selective; • SI 0.11 to 0.20 moderately

selective; • SI 0.21 nonselectivePatient with selective proteinuria

have tubulointerstitial disease (usually), milder forms of glomerular pathology and better response to therapy

Proteinuria/Albuminuria

• Though not a measure of GFR, it is a marker of kidney damage that independently predicts cardiovascular disease.

• It is in the definition of stage 1 and stage 2 CKD.• Controversial whether microalbuminuria always represents

kidney disease (CKD stage 1) or whether it could reflect endothelial dysfunction without kidney damage.

• Generally use spot urine for albumin/creatinine ratio- but can use total protein/creatinine for significant proteinuria (>500-1000 mg/g)

• Albuminuria highly predictive for proteinuria, but 8% of pts with elevated PCR will have normal ACR

Definition of Proteinuria

KDIGO Classification Normal to mildly increased

Moderately Increased

Severely Increased

Method

24 hour excretion <150 mg/day 150-500 mg/day >500 mg/day

Protein reagent dipstick (screening) Negative to trace Trace to + + or greater

Spot urine protein/ creatinine ratio < 150 mg/g 150-500 mg/g >500 mg/g

Definition of AlbuminuriaKDIGO Classification Normal to mildly

increasedModerately Increased

Severely Increased

Clinical Term

Method Normal Micro-albuminuria

Overt/Macro-albuminuria

24 hour excretion <30 mg/day 30-300 mg/day >300 mg/day

Timed urine specimen <20 g/min 20-200 g/min >200 g/min

Spot-urine albumin specific dipstick

(screening)<3 mg/dl >3 mg/dl N/A

Spot urine albumin/ creatinine ratio (ADA) < 30 mg/g 30-300 mg/g >300 mg/g

Spot urine albumin/ creatinine ratio (gender

specific) (K/DOQI)

<17 mg/g (men)<25 mg/g (women)

17-250 (men)25-355 (women)

>250 (men)>355 (women)

Dipstick − Semi-quantitative, screening only

Affected by urine concentration, highly variable

− Detection of urine albumin > 300 mg/day (1+ approximates albumin excretion of 30 mg/day)

Urine protein/creatinine ratio‒ All proteins, not just albumin (myeloma/CIN)

Urine albumin-to-creatinine ratio (UACR)‒ Quantifies urine albumin− Steps toward standardization currently in progress− Standard for public health, clinical care, and research

Which urine test to use?

ACR > PCR > Auto strip > Manual strip (KDIGO 2012)

Standard of diabetes care (annual screen) Diagnosis

− Forty percent of people are identified with CKD on the basis of urine albumin alone.

− 50% of diabetics with CKD will NOT have abnormal albuminuria Prognosis

− Important prognostic marker, especially in diabetes mellitus (DM)− Used to monitor and guide therapy (but note ACP guidelines)

Tool for patient education and self-management (such as A1C or eGFR)

Urine albumin results are used for screening, diagnosing, and treating CKD

Urinary Measures of Albuminuria/Proteinuria are NOT perfect

These may affect either protein or albumin in the urine. For boards (and practice) purposes:• Repeat abnormal measurements obtained in acute illness (e.g. fever,

CHF exacerbations, UTI), or non steady state conditions (e.g. exercice)• Think of non-albumin proteins that may interfere (myoglobin,

hemoglobin, light chains) with total protein assays

Algorithm for the workup of albuminuria/proteinuria

http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf

Take-home points:• Confirm reagent strip devices

using quantitative test for ACR at least x 2

• Exclude orthostatic proteinuria by measuring Early Morning Urine

• Proteinuria + Hematuria = specialist evaluation

• Consider non-renal causes of proteinuria (e.g. CHF/UTI/exercise) especially in T1D with duration < 5 years

• PCR may substitute for ACR but note possibility of mistaking tubular for glomerular proteinuria

• Elevated PCR with normal ACR may indicate interstitial kidney disease/Plasma Cell Disorder

• ACR/PCR > 2 may indicate glomerular process

Normal: ≥ 60 mL/min/1.73 m2

Kidney disease: 15–59 mL/min/1.73 m2

Kidney failure: < 15 mL/min/1.73 m2

How to explain eGFR results to patients

Explaining urine albumin

Staging of Chronic Kidney Disease by markers of renal filtration and damage

Patient with hypertensionand elevated creatinine

What is her kidney function?Lab parameter ValueSerum Creatinine 1.9 mg/dL

BUN 46 mg/dL

Pick your preferred equation to calculate her GFR…

• 100/Scr = 45.4• Cockroft-Gault = 25

ml/min• CKD-EPI = 25 ml/min• MDRD = 28 ml/min• 24-hour urine collection

= 27 ml/min

Patient with hypertensionand elevated creatinine

How can we characterize her kidney function?– Cause: Type 2 Diabetes

Albumin• 135 mg/gGFR• 100/Scr = 45.4 • C-G = 25 ml/min• CKD-EPI = 28 ml/min• MDRD = 28 ml/min• 24-hour urine = 27 ml/min

High Risk of Progression

ASSESSMENT OF TUBULAR FUNCTION

The functions include: Filtration

− Glomeruli generate ultrafiltrate of the plasma.

Reabsorption − Tubules selectively

reabsorb substances from the ultrafiltrate.

Secretion− Tubules secrete

substances into the urine.

The nephron functions to maintain balance

Two major categories:− Anatomical biomarkers

Proteins expressed at different locations in the nephron: lesions modify their levels in biofluids (blood/urine)

− Functional Biomarkers: different parts of the nephron do different

things, so one reasons from impaired function to lesion site (similar to neurology)

Biomarkers for Tubular Disorders

American Journal of Kidney Diseases 2013 62, 165-178DOI: (10.1053/j.ajkd.2012.12.022) Copyright © 2013 National Kidney Foundation, Inc. Terms and Conditions

Anatomical Biomarkers

Measures of Relative Density: Urine Osmolality

• Biomarker of ADH action on the distal tubule• Measured directly with an osmometer• Under regular conditions, one would expect

each 35-40 mOsm/kg to increase SG by 0.001• Proteinuria, mannitol, dextrans and

radiographic contrast may affect osmolality• Used to investigate disorders of concentration

and dilution (more to follow)

All proximal tubule (PT) physiology in one slide

http://dx.doi.org/10.1053/j.ajkd.2010.09.011

• Na+: PT reabsorb 60-70% by co/counterTx• CO3-: 90% of filtered load reabsorbed through

secretion of H and carbonic anhydrase• Cl-: 90% reabsorbed by active & passive routes• Oxalate: entire load reabsorbed in the urine• H2O: 70% through AQP1 under the control of

Angiotensin II• Glucose: ~100% through SGLT2 (low

affinity/high capacity) and SGLT1 (high affinity/low capacity) operating in series

• Phosphorus: tightly controlled by PTH/FGF23• Potassium: 60-70% paracellularly• Amino acids: entire load through multiple

transporters• Peptides: peptidase breakdown followed by

reabsorption through peptide and amino acid transporters

• Proteins (including trace albumin): megalin/cubilin complex

• Uric acid/organic anions: OAT/OATP• Organic cations: OCTs (creatinine/drugs)

Paracellular and Transcellular transport

Sodium Chloride: 25-35% of filtered load without H2O

Calcium and magnesium: 20% passive paracellular transfer. Calcium sensor controls the process by inhibiting potassium transfer which generates gradient for Ca/Mg transfer

Ammonium: generated by the PT, reabsorbed by the HL and then secreted again in the DT

Magnesium: 70% reabsorbed in the HL (Thick Ascending Limb)

All of Loop of Henle Physiology in one slide

http://dx.doi.org/10.1053/j.ajkd.2010.09.011

Sodium: 5-10% (DT – NCC the thiazide target) and via regulated transport (ENaC – amiloride target in the CD)

Calcium: 10% (DT), 5% in the CD Magnesium: 10-15% Potassium: major sites of fine

tuning Hydrogen: major site of fine

tuning

All of Distal Tubule and Collective Duct Physiology in one slide

http://dx.doi.org/10.1053/j.ajkd.2010.09.011

While the Proximal Tubule does the bulk of reabsorbing stuff, the distal nephron is the master regulator and the site of action of hormonal systems (ADH, Angiotensin 2) responsible for fine tuning

Functional Biomarker: Glucosuria• Dipsticks include a highly sensitive test based on an

oxidative reaction• Glucose is not normally present in the urine• Presence indicates that the plasma glucose is above

the threshold of renal reabsorption (180-250 mg/dl) OR interference with this process at the proximal tubule:– Proximal tubulopathies (e.g. Fanconi s)– SGLT2 inhibitors

• A positive test on the dipstick should be confirmed with an actual measurement due to the possibility of false +ve from ketones (or medications)

Functional Biomarker: Specific Gravity• Determined by the number, size and sensity of

particles in the urine• Reagent strip contains a polymer which is

saturated with Hydrogen ions. These are displaced by urinary cations=>change in local pH– Glucose and Urea DO NOT affect reagent strip SG (but

will affect SG measured in the lab by refractometry)– Poor correlation between SG and Urine osmolality– SG is falsely high when UpH<6, falsely low when

UpH>7• Isosthenuria: fixed SG @ 1.010 – clue to CKD in

real life and the boards

Functional Biomarker: Urine pH• Detected by a double indicator strip to give a broad range

of colors• When measured with electrodes, normal pH is 4.5 – 7.8• Reagents strips should not be trusted outside the range of

5.5 – 7.5• High upH (>7)may indicate either infection or overgrowth

(prolonged storage) with urea-splitting organisms• Alkalic pH is seen with diuretics, vomiting, gastric suction

and bicarbonate therapy• Acidic upH(<5) is commonly seen in systemic acidosis• upH> 5-5.5 in the setting of systemic acidosis →RTA• This is more or less a screening test

Functional Biomarker: Urine Osmolality

• Biomarker of ADH action on the distal tubule• Measured directly with an osmometer

(measures number of particles)• Under regular conditions, one would expect

each 35-40 mOsm/kg to increase SG by 0.001• Proteinuria, mannitol, dextrans and

radiographic contrast may affect osmolality• Used to investigate disorders of concentration

and dilution (more to follow)

Functional Biomarker: Renal Concentrating Ability

• Used to investigate polyuria and hyperosmolality• Assessed with the H2O deprivation test:

– Water deprivation for 18-24hrs should lead to a Uosm of > 900 mOsm/kgr

• Failure to concentrate (suggestive of diabetes insipidus) is assessed by exogenous vasopressin

• Central DI: +ve response to exogenous vasopressin

• Nephrogenic DI: no response to exogenous vasopressing

Functional biomarker: Urinary Acidification and Urinary Gaps

• Urine Anion Gap : UNA+UK-Ucl estimates urinary ammonium (remember we do not pee battery fluid)

• Positive UAG: RTA, hippurate and penicillin derivative antibiotics (positively charged)

• Negative UAG: Increased ammonium from extrarenal sources of acidosis

• Urine Osmolar Gap: Uosm – (2x(UNA+UK)+Uurea/2.8+Uglucose/18)

– Positive UOG associates with increased ammonium production. Useful when is UAG is +ve but still suspect extrarenal sources of acidosis

Functional biomarker: Alkali loading test

• Useful for the investigation of suspected proximal RTA

• IV sodium bicarbonate @ 0.5-1 mEq/kgr/hr• In proximal RTA, bicarbonate reabsorption is

defective• Loading with alkali will lead to saturation of

the process and urinary alkalization with fractional excretion of Bicarb >15-20% at a normal serum bicarbonate

Functional biomarker: Urine – Blood PCO2

• Useful for the investigation of suspected distal RTA

• In distal RTA, hydrogen secretion is defective• Normally, alkalization of the urine is

associated with Urinary to Plasma PCO2 of 30mmHg or larger

• In distal RTA, the PCO2 in the 2 biofluids is similar

Functional Biomarker: Fractional Excretion

• The general calculation relates urine and plasma concentrations of analytes (sodium, urea, calcium, phosphorus, magnesium etc) to that of creatinine

• Kidneys are responsible for maintaining stability of internal environment, so if changes in the same direction as the electrolyte abnormality, kidneys are more or less to blame

• Caveat: need to know the reference range of the fractional excretion of each analyte

• Tubular flow changes the values of many of these quantities (=> many AKI indices are derived as FE)

Example: Investigation of AKI

Obstructive uropathy: early looks prerenal, late looks renal

Role of biomarkers is unclear – however B2M is useful in the investigation of nephrotoxicity when a PT toxin is suspected or given for prolonged courses (e,g, aminoglycosides)

Example: Transtubular Potassium Gradient (TTKG)

• Approximates the ratio of K in the CD to that in the peritubular capillaries

• Biomarker of aldosterone action in the CD– Osmolarity plays the role of Creatinine in this modified FE

• Formula can only be used if Uosm>300 and Una > 25– Distal K secretion is dependent on Na delivery – Molecular renal physiology suggests that urea transport may influence

TTKG violating one of the TTKG assumptions– Recent data suggest utility as a predictor of clinical events in CHF

• In hyperK: TTKG should be >10 (<7 indicates mineralocorticoid deficiency)

• In hypoK: TTKG should be <3 (if > 7 then suggests hypermineralocorticoid state)

RENAL IMAGINGAlmost done

Imaging modalities for the GU system• Plain films of the abdomen• Renal ultrasonography • Intravenous pyelography• Computed tomography • Magnetic resonance imaging • Radionuclide scanning • Renal angiography • Retrograde pyelography • Diuretic renography

Renal Ultrasound

• Widely available, cheap, no-exposure to radiation

• Assesses kidney size (small kidneys CKD, large kidneys obstruction, PKD, myeloma, obstruction, diabetes, amyloidosis)

• Assesses for and grades hydronephrosis– Major indication for the use of US in AKI

• Workup of cystic disease• Assesses renal location and contour (CAKUT)

US in patients with CKD

• Assesses for abnormalities of kidney size• Echogenicity (bilateral in CKD)• Presence of cysts (polycystic kidney disease• Thin renal cortex• These findings may help differentiate acute

from chronic kidney disease (when no records are available)

CT of the GU tract• Test of choice for assessing flank pain, hematuria,

trauma and renal masses• IV contrast required for the characterization of

tumor/ masses (see Bosniak classification)• IV contrast not required for renal stones• CT urography: volumetric reconstruction of the

kidneys, ureters and bladder in which the extraneous tissues have been removed

Nuclear Imaging

• Provides information about renal structure and function– Tc99m-DTPA: GFR assessment– Tc99m-MAG: defines renal plasma flow

• Both glomerular and tubular mechanisms of excretion• Used with Lasix to define the functional significance

(obstruction or not) of hydronephrosis– Tc99m-DMSA: concentrates in renal cortex/useful to

characterize dead, infarcted areas from viable parenchyma (e.g. diffuse cortical necrosis, scar)

Non-obstructive causes of hydronephrosis

• Increased urine production and flow• Acute and chronic infection• Vesicoureteral reflux• Papillary necrosis• Congenital megacalyces• Post-obstructive dilation• “Extra-renal” pelvis (may give the impression

of hydro)

Magnetic Resonance Imaging• MRI is useful mainly for the characterization of

complex renal lesions• Magnetic Resonance Angiography has a role in

renovascular hypertension (institution dependent)• Nephrogenic Systemic Fibrosis: a multisystem,

fibrosing condition involving skin, joints, internal organ– Associated with the use of Gadolinium in AKI or CKD– Restrict use of Gd in patients with eGFR<30, ok to use

when >40, gray zone when 30-40– In ESRD requires 2 x 4 hr dialysis session in the first 24

hours after exposure

Renal Stones – Unilateral obstruction

• Usually as a follow up to a renal U/S that has detected obstruction

• CT may be used to detect stones (if suggestive history), contrast studies or CT urography may also be required (e.g. radiolucent stones)

• IVP as an alternative if CT is not available• When functional significance of hydro unclear,

may do MAG3 renogram

NephrocalcinosisCortical• Acute cortical necrosis • Chronic glomerulonephritis • Alport syndrome • Prolonged hypercalcemia and/or

hypercalciuria • Poisoning and toxicity • Rejected renal transplant • Sickle cell disease (a rare cause) • Vitamin B6 (pyridoxine)

deficiency (also a rare cause)

Medullary• Hyperparathyroidism • Medullary sponge kidney • Tuberculosis of the kidneys • Renal tubular acidosis • Renal papillary necrosis • Immobilization • Milk-alkali syndrome • Sarcoidosis • Hyperoxaluria • Glucose-galactose malabsorption

Preferred imaging test: non enhanced CT

Medullary Nephrocalcinosis

Cortical Nephrocalcinosis

Renal Infections

• Imaging is rarely needed in uncomplicated pyelonephritis

• Use it when suspecting complicated pyelonephritis (e.g. stones) or to assess for complications– Renal and perinephric abscess, emphysematous

pyelo or xanthogranulomatous pyelo

Approach to cysts and renal masses• CT is the study of choice for detecting and

evaluating renal masses• US may be the only test that needed if the

mass is a Bosniak I or II (see next slide)• MRI has a role above and beyong CE-CT in

differentiating a complex cyst from a cystic Ca• Adult-acquired cystic disease is seen in

patients with ESRD– Screening with Ultrasound– Follow up with CT or MRI

Renal Cysts And The Bosniak System

http://pubs.rsna.org/doi/pdf/10.1148/rg.351130016

Autosomal Dominant Polycystic Kidney Disease

ADPKD1 genotype

• At least 2 cysts in 1 kidney or 1 cyst in each kidney in an at-risk patient younger than 30 years

• At least 2 cysts in each kidney in an at-risk patient aged 30-59 years

• At least 4 cysts in each kidney for an at-risk patient aged 60 years or older

Family History/Unknown Genotype

• Three or more (unilateral or bilateral) renal cysts in patients aged 15-39 years

• Two or more cysts in each kidney in patients aged 30-59 years

Fewer than 2 renal cysts in the findings provides a negative predictive value of 100% and can be considered sufficient for ruling out disease in at-risk individuals older than 40 years

Renovascular HTN: Image ONLY if results will make one consider revascularization

Kaplan’s Clinical Hypertension 2014

The American College of Radiology has released guidelines (last update 2012) to guide the workup for specific clinical scenarios

https://www.guideline.gov/content.aspx?id=37941

High index of suspicion of renovascular hypertension and normal renal function

https://www.guideline.gov/content.aspx?id=37941

High index of suspicion of renovascular hypertension and decreased renal function

https://www.guideline.gov/content.aspx?id=37941

A simple (and cheap) algorithm

Kaplan’s Clinical Hypertension 2014

Imaging Techniques & DiagnosesSymptom/Suspected Diagnosis Imaging Modality

Renal Failure of Unknown Cause U/S

Hematuria CT

Severe Hypertension (nl renal fx) CT angio with imaging of adrenals

Severe Hypertension (abn renal fx) MR Angiography (TOF)

Renal Artery Stenosis Renal Dopplers/MR Angiography

Renal Infection CT

W/U of Hydronephrosis CT/IVU/or DTPA if unknown significance

Retroperitoneal fibrosis Contrast Enhanced CT

Papillary Necrosis Contrast Enhanced CT

Cortical Necrosis Contrast Enhanced CT

Renal Vein Thrombosis Contrast Enhanced CT (MRV if ↑ SCr)

Renal Infarction Contrast Enhanced CT

Nephrocalcinosis CT

Comprehensive Clinical Nephrology Mosby , 2007

Institution dependent – may differ from the correct board answer