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Contents

  1. 16.1 Renal Scintigraphy (Tc-99m MAG3, Tc-99m DTPA)
  2. 16.2 Diuretic Renography (F+20, F-15, F0 Protocols)
  3. 16.3 Captopril Renography (Renovascular Hypertension)
  4. 16.4 GFR and ERPF Calculations
  5. 16.5 Renal Cortical Scintigraphy (Tc-99m DMSA)
  6. 16.6 Vesicoureteral Reflux (Direct/Indirect Cystography)
  7. 16.7 Evaluation of the Renal Transplant
  8. Key Points for the Board
  9. Current guidelines on this chapter's topics
← Back‹ Chapter 15Chapter 17 ›

Chapter 16Clinical applicationsLast reviewed: 14 Nov 2026 · What's new

Urinary System

Report template: Diuretic renography (Tc-99m MAG3 / DTPA)

This chapter's English text is a draft translation (prepared with Claude and checked against a terminology glossary and automatic checks); specialist review is in progress. Please report errors with the feedback button.

Solve questions (26) →
Contents
  1. 16.1 Renal Scintigraphy (Tc-99m MAG3, Tc-99m DTPA)
  2. 16.2 Diuretic Renography (F+20, F-15, F0 Protocols)
  3. 16.3 Captopril Renography (Renovascular Hypertension)
  4. 16.4 GFR and ERPF Calculations
  5. 16.5 Renal Cortical Scintigraphy (Tc-99m DMSA)
  6. 16.6 Vesicoureteral Reflux (Direct/Indirect Cystography)
  7. 16.7 Evaluation of the Renal Transplant
  8. Key Points for the Board
  9. Current guidelines on this chapter's topics
Learning objectives and modules4 modules · about 2 h 50 min

Learning objectives

After this chapter you will be able to:

  • Compare renal agents (MAG3, DTPA, DMSA) by excretion mechanism and purpose.
  • Interpret the phases and quantitative parameters of the renogram.
  • Select diuretic renography protocols and distinguish obstruction from dilatation.
  • Explain the physiological basis and interpretation criteria of captopril renography.
  • Explain the methods for measuring GFR and ERPF.
  • Interpret DMSA scintigraphy, studies for vesicoureteric reflux and complications of the transplanted kidney.

Modules

The chapter is divided into study modules without changing the order of the text: read, watch the animations, then answer the questions linked to those headings.

  1. Module 116.1 Renal Scintigraphy (Tc-99m MAG3, Tc-99m DTPA)40 min · 2 animations · 15 questionsAnswer the questions →
  2. Module 216.2–16.3 Diuretic Renography (F+20, F-15, F0 Protocols) · Captopril Renography (Renovascular Hypertension)45 min · 1 animation · 20 questionsAnswer the questions →
  3. Module 316.4–16.5 GFR and ERPF Calculations · Renal Cortical Scintigraphy (Tc-99m DMSA)45 min · 1 animation · 19 questionsAnswer the questions →
  4. Module 416.6–16.7 Vesicoureteral Reflux (Direct/Indirect Cystography) · Renal Transplant Assessment · Key Points for the Board40 min · 14 questionsAnswer the questions →

Times are estimates: 130 words per minute, 3 min per animation, 1.5 min per question.

Tip cards (43) →

MOST FREQUENTLY ASKED IN THIS CHAPTER

✓
Tc-99m MAG3: Tubular secretion (~95-98%; protein binding ~90%), extraction fraction ~ 40-50%, measures ERPF, the preferred agent
✓
Tc-99m DTPA: Glomerular filtration, extraction fraction ~20%, measures GFR
✓
Tc-99m DMSA: Cortical retention, static imaging, pyelonephritis/scar, differential function (most accurate)
✓
MAG3 → good images even with low function → general preference
✓
DTPA → when GFR measurement is required
✓
Phase 1: Vascular (0-30 s) → perfusion
✓
Phase 2: Parenchymal (1-5 min) → uptake → Tmax occurs here → differential function is calculated here

16.1 Renal Scintigraphy (Tc-99m MAG3, Tc-99m DTPA)15 questions

Basic Principles

Renal scintigraphy (renography) is a nuclear medicine method that dynamically assesses renal perfusion, function and drainage. After IV injection, the passage of the radiopharmaceutical through the kidneys is recorded on serial images and time-activity curves (renograms) are generated.

•
Main indications (SNMMI/EANM adult guideline, 2018): acute and chronic renal failure; unilateral or bilateral renal disease (including space-occupying lesions); obstructive uropathy (diuretic renography, 16.2); renovascular hypertension (captopril renography, 16.3); after renal transplantation (16.7); pyelonephritis and parenchymal scarring (DMSA, 16.5). No specific preparation is needed: the patient does not fast, is well hydrated and voids before the scan
–
Choice of agent: MAG3 is preferred for functional imaging because it accumulates rapidly in the tubules (obstruction, increased parenchymal transit, transplant dysfunction, trauma and urinary leak); DTPA given at higher activity shows perfusion better and gives a lower radiation dose

Radiopharmaceuticals

A) Tc-99m MAG3 (Mercaptoacetyltriglycine / Mertiatide)

•
Excreted by tubular secretion (~95-98% tubular secretion, glomerular filtration negligible)
•
Plasma protein binding: 90% → glomerular filtration limited
•
Renal extraction fraction: ~40-50% (much higher than DTPA)
•
Gives good image quality even in patients with reduced renal function
•
Preferred agent → especially in paediatric patients and those with reduced renal function
•
Used to measure ERPF (Effective Renal Plasma Flow)
•
Activity: 185-370 MBq (5-10 mCi) in US (SNMMI) practice; EANM recommends 75 MBq in adults (sufficient with modern cameras)
•
EANM: Labelling of the betiatide kit requires heating (no heating is needed for the ready-made mertiatide preparation); protein binding is 80-90% (strong but reversible)
•
Kinetics according to EANM: in a single pass ~5% is removed from plasma by glomerular filtration and ~50% by proximal tubular secretion; total first-pass extraction is ~55%, and hepatobiliary elimination ~10% (beware of liver activity when assessing the right kidney in patients with poor function)
•
EANM activity: 75 MBq in adults (at least 15 MBq in children); 7.0 µSv/MBq, i.e. ~0.53 mSv; the bladder receives the highest organ dose (110 µGy/MBq)
•
MAG3 clearance is not an absolute GFR marker; because its value is lower than that of OIH it should not be reported as ERPF, but used only as an index of tubular function
•
Probenecid competes with MAG3 for binding to organic anion transporters; stopping it should be considered

B) Tc-99m DTPA (Diethylenetriaminepentaacetic Acid)

•
Excreted by glomerular filtration (no tubular secretion or reabsorption)
•
Plasma protein binding: <10% → freely filtered
•
Renal extraction fraction: ~20% (lower than MAG3)
•
Used to measure GFR (Glomerular Filtration Rate)
•
Image quality in patients with reduced renal function is lower than with MAG3
•
Activity: 185-370 MBq (5-10 mCi) in US (SNMMI) practice; EANM recommends 37-185 MBq in adults
•
EANM: A small molecule (393 g/mol) that distributes freely in the extracellular space. It does not cross the blood-brain barrier but crosses the alveolocapillary membrane (aerosol ventilation → see Chapter 17); it is not absorbed when taken orally
•
EANM activity: 37-185 MBq in adults (at least 20 MBq in children); 4.9 µSv/MBq. ~90% is excreted in the urine within 24 hours
•
Because extraction is low in renal failure, MAG3, Tc-99m EC, I-123 OIH or DMSA are recommended instead of DTPA

Other tubular agents (EANM):

•
Tc-99m EC (ethylenedicysteine, bicisate): A metabolite of the brain agent Tc-99m ECD; protein binding is 20-45%. In a single pass ~17% is removed from plasma by glomerular filtration and ~50% by secretion; first-pass extraction is ~65% (slightly higher than MAG3). There is no hepatobiliary metabolism
•
I-123 OIH (ortho-iodohippurate): Used in place of PAH, the reference substance for ERPF measurement. Protein binding is 60-70% and first-pass extraction ~80% (the highest among tubular agents); hepatobiliary excretion <0.4%. 75 MBq in adults, 12 µSv/MBq
•
Tubular and glomerular function usually change together. The exceptions are acute obstruction and renovascular hypertension: GFR may fall severely while tubular secretion is preserved
•
Breastfeeding: No interruption is needed after DTPA, MAG3, EC and DMSA (for safety, 4 hours or one feed may be skipped); after I-123 OIH it is interrupted for 12 hours (DTPA is preferred in breastfeeding women)

In a cortical nephron the afferent arteriole from the interlobular artery enters the glomerulus; the efferent arteriole leaves at the same vascular pole and forms the peritubular capillaries around the tubules. Filtrate flows from the opposite urinary pole into the proximal tubule, the loop of Henle, the distal tubule that returns to the vascular pole at the macula densa, and the collecting duct. With DTPA some molecules are filtered in the glomerulus, with MAG3 most are protein bound and are secreted from the peritubular capillaries into the proximal tubular lumen, with DMSA molecules accumulate in proximal tubular cells; a counter shows the fraction taken up on first pass.

Continuous stream · no seeking

Key idea: DTPA is filtered (GFR, ~20%), MAG3 is secreted (ERPF, ~55%), DMSA stays in the tubular cell (cortex); the route of the agent decides what it measures.

Source: book (16.1: DTPA protein binding <10%, extraction ~20%; MAG3 secretion ~95-98%, protein binding ~90%, EANM 5% + 50% = ~55%, summary 40-50%; 16.5: DMSA proximal tubule, 40-50% in cortex at 2-4 h). Nephron anatomy: OpenStax Anatomy & Physiology 2e §25.3-25.4 (vascular and urinary pole, macula densa, peritubular capillaries). The per-pass cellular uptake of DMSA is representative. Transporters: MAG3 OAT1/OAT3 and MRP2/MRP4 (Kobayashi et al., Nucl Med Biol 2020); DMSA megalin/cubilin (Weyer et al., J Nucl Med 2013); filtration barrier OpenStax §25.5.

How to use: a single click on the drawing pauses and resumes; ← → change steps (DTPA, MAG3, DMSA).

Speed
Test yourself:Chapter 16 · question 15Chapter 16 · question 17
Did this animation help you understand the topic?

Figure 16.1: Excretion/retention mechanisms of renal radiopharmaceuticals in the nephron: DTPA glomerular filtration, MAG3 tubular secretion, DMSA binding to proximal tubular cells (schematic).

BOARD TIP
▸
"Which agent for measuring GFR?"

→ Tc-99m DTPA (excreted by glomerular filtration).

▸
"DTPA vs MAG3 → which has the higher extraction fraction?"

→ MAG3 (~40-50% vs ~20%).

▸
"Which agent is preferred with low renal function?"

→ MAG3 (better image quality).

BOARD TIP

▸
"Preferred agent for renal scintigraphy?"

→ Tc-99m MAG3 → high extraction fraction, good images even with low renal function.

▸
"Route of MAG3 excretion?"

→ Tubular secretion (~95-98%).

▸
"What does MAG3 measure?"

→ ERPF (Effective Renal Plasma Flow).

MAG3 vs DTPA:

FeatureTc-99m MAG3Tc-99m DTPA
Route of excretionTubular secretion (~95-98%)Glomerular filtration
Protein binding90%<10%
Extraction fraction~40-50%~20%
Parameter measuredERPFGFR
Image with low functionGoodPoor
When preferredGeneral preferenceWhen GFR measurement is required

The Renogram Curve

The time-activity curve obtained on dynamic renal scintigraphy has three phases:

Phase 1 – Vascular (Perfusion) Phase (0-30 seconds):

•
First arrival of the agent at the kidney → rapid rise in activity
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Reflects renal perfusion
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The transit time between aorta and kidney is assessed
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A transient focal increase in activity in the hilar/medial region during the perfusion phase, with no uptake in this area in later phases, suggests a renal artery aneurysm or AVM
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Normally the kidneys appear within 2-3 seconds of the abdominal aorta (a delay suggests vascular pathology); the liver, supplied mainly by the portal vein, appears after the kidneys
•
Early visualisation of the IVC in the perfusion phase suggests an intrarenal or extrarenal AV fistula (e.g. after transplant biopsy) or injection into a lower limb vein

Phase 2 – Parenchymal (Concentration / Uptake) Phase (1-5 minutes):

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Uptake of the agent by tubular cells or glomeruli
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Activity continues to rise → reaches its peak (Tmax)
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Normal Tmax: 3-5 minutes (with MAG3)
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Reflects parenchymal function

Phase 3 – Excretion (Drainage) Phase (5+ minutes):

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Passage of the agent into the collecting system and bladder
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Activity begins to fall → the curve descends
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Normal: Steady decline after the peak
•
T½ (half-time): Time for peak activity to fall by half → normal: <10 minutes (MAG3)

Tc-99m MAG3 moves through the kidney from the vessels to the parenchyma, calyces, pelvis and ureter; the renogram curve, Tmax and T½ and the post-diuretic curve types (I, II, IIIa, IIIb, IV) are shown.

Continuous stream · no seeking

Key point: the renogram's shape reflects the transit of the tracer through the kidney; after furosemide a T½ under 10 minutes excludes obstruction, over 20 minutes suggests obstruction.

Source: book (normal Tmax 3–5 min, T½ < 10 min; post-diuretic < 10 / 10–20 / > 20 min); curves from a schematic compartment model, kidney anatomy schematic (seven pyramids, minor and major calyces: OpenStax Anatomy & Physiology 2e §25.3).

Test yourself:Chapter 16 · question 2Chapter 16 · question 19
Did this animation help you understand the topic?

Figure 16.2: The three phases of the normal renogram curve, Tmax and T½ measurement; inset: the first 60-second perfusion phase (schematic).

Abnormal Renogram Patterns:

•
Obstructive pattern: Activity rises continuously and does not fall → "rising curve" → dilated collecting system + no drainage
•
In acute complete obstruction a calyceal fornix may rupture; perirenal extravasation or urinoma may develop
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Reduced function: Low peak, low uptake → parenchymal damage
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Vascular disorder: Delayed or reduced perfusion in phase 1
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Dilated non-obstructive: Delayed peak but drainage present (improves after diuretic)
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Sawtooth fluctuations in the drainage phase suggest VUR occurring during renography; they are not a sign of obstruction
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Dehydration mainly prolongs parenchymal transit time, whereas acute obstruction impairs the excretion phase. Differential function is calculated from the uptake phase
•
The commonest cause of a progressively rising background curve is an infiltrated injection; renogram and clearance/function calculations then become unreliable
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Tubular toxicity (aminoglycosides, cisplatin, ciclosporin, heavy metals) affects tubular agents more than DTPA: parenchymal retention with MAG3 and OIH, and reduced uptake with DMSA

Differential Renal Function (Split Function)

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The contribution of each kidney to total function → expressed as a percentage (%)
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Normal: Each kidney 45-55% (symmetric)
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Below 40% → significant functional asymmetry
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Calculation: Relative uptake between 1 and 2 minutes (MAG3) or 2 and 3 minutes (DTPA)
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Clinical significance: In assessing obstruction, reflux, renal artery stenosis
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EANM: The best quantification method is the Rutland-Patlak plot (the heart must be in the field of view); in the area/integral method minutes 1-2 are used for MAG3 and minutes 2-3 for DTPA
•
Symmetry criterion: 50 ± 7.5%. Area-normalised background subtraction is mandatory; the most accurate background ROI is a C-shaped (perirenal) ROI surrounding the kidney inferiorly, laterally and superiorly
•
Attenuation correction: µ = 0.14/cm for Tc-99m; kidney depth is calculated by the Tonnesen formula or from a lateral image
•
Separating parenchyma from pelvis: Parenchymal ROI, parametric imaging, mean transit time (MTT; by deconvolution) or factor analysis
BOARD TIP
▸
"In which phase is differential renal function calculated?"

→ Phase 2 (parenchymal/uptake phase) → minutes 1-2 (MAG3).

▸
"Normal differential function?"

→ Each kidney 45-55%.

▸
"Threshold for significant asymmetry?"

→ 40%.

Patient Preparation

•
Good hydration → the most important preparation → dehydration may create a false obstructive pattern
•
500 mL oral fluid or IV hydration before injection
•
Imaging position: Posterior (the kidneys are posterior)
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The bladder should be empty (before injection)
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ACE inhibitors → should be stopped if captopril renography is to be performed (→ see 16.3)
•
EANM: Oral hydration of ~7 mL/kg if possible; for IV hydration a low-sodium solution is used, and in infants a saline-glucose mixture is preferred to pure glucose
•
Drinking plenty of fluids and voiding frequently after the study is the simplest way to reduce the dose to the bladder, the critical organ

16.2 Diuretic Renography (F+20, F-15, F0 Protocols)9 questions

Indication

•
In patients with hydronephrosis → distinguishing true obstruction from a dilated non-obstructed system
•
Especially: Ureteropelvic junction (UPJ) obstruction, ureterovesical junction (UVJ) obstruction
–
Commonest level of obstruction: UPJ in children, ureterovesical junction (UVJ; often due to stones) in adults
•
Evaluation of prenatal hydronephrosis in paediatric patients

Principle

•
Furosemide (Lasix) → diuretic → increases urine flow
•
Furosemide inhibits the Na-K-2Cl cotransporter in the thick ascending limb of the loop of Henle; given IV, diuresis peaks at ~15 minutes (which is why the F-15 protocol was designed)
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If there is no obstruction → after diuretic the dilated collecting system empties rapidly → the curve falls
•
If there is true obstruction → the diuretic is ineffective → the curve does not fall or falls very slowly

Furosemide Protocols

F+20 (Standard Protocol):

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Furosemide is given 20 minutes after the radiopharmaceutical injection
•
Furosemide dose: Adult 40 mg IV (0.5-1 mg/kg)
•
Paediatric: 1 mg/kg IV (maximum 40 mg)
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The most widely used protocol
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Advantage: A baseline renogram is obtained first, then the diuretic response is assessed
•
Disadvantage: "Reservoir effect" in very dilated systems → false-positive obstruction

F-15 (Early Diuretic Protocol):

•
Furosemide is given 15 minutes BEFORE the radiopharmaceutical
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The agent is injected after the diuretic effect has begun
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Advantage: Reduces the reservoir effect → prevents false positives in dilated non-obstructed systems
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Preferred especially in very dilated collecting systems
•
F-15 (the 'well-tempered' renogram) also reduces the proportion of equivocal results

F0 (Simultaneous Protocol):

•
Furosemide and the radiopharmaceutical are given at the same time
•
Less widely used
BOARD TIP
▸
"Which diuretic protocol is preferred in a very dilated collecting system?"

→ F-15 → reduces the reservoir effect.

▸
"Standard diuretic renography protocol?"

→ F+20.

▸
"Furosemide dose?"

→ Adult: 40 mg IV, paediatric: 1 mg/kg.

Radiopharmaceutical (MAG3) IV Furosemide IV (adult 40 mg; child 1 mg/kg, max 40 mg) Imaging F+20 (standard) Baseline renogram first, then diuretic response; very dilated system: reservoir effect F0 (simultaneous) Furosemide and radiopharmaceutical at the same time F-15 (early diuretic) Diuresis peaks at ~15 min; reduces the reservoir effect −15 0 10 20 30 40 Time relative to radiopharmaceutical injection (min)

Figure 16.3: Timing of furosemide and radiopharmaceutical administration in diuretic renography protocols (schematic).

Did this figure help you understand the topic?

Interpretation of Diuretic Renography

T½ (half-time after diuretic):

•
T½ <10 minutes: Non-obstructive (normal drainage)
•
T½ 10-20 minutes: Equivocal → clinical correlation needed
•
T½ > 20 minutes: Obstructive pattern

Curve Patterns:

•
Type I (Normal): Rapid rise, a sharp peak at 3-5 minutes and then a steady, rapid decline. T½ is usually <10 minutes; normal drainage is shown without the need for a diuretic and obstruction is excluded.
•
Type II (Obstructive): The curve rises continuously or plateaus; there is no significant fall after furosemide. T½ is >20 minutes or cannot be calculated. Suggests true mechanical obstruction, especially UPJ obstruction, and strongly supports surgical evaluation.
•
Type IIIa (Dilated, non-obstructed): Drainage is initially slow; after furosemide the curve falls markedly and continuously, with T½ usually falling to <10 minutes. The large pelvis acts as a reservoir; the system is dilated but functionally patent, and conservative follow-up is appropriate.
•
Type IIIb (Equivocal): The fall after diuretic is slow and inadequate; T½ is mostly between 10-20 minutes. Partial or intermittent obstruction, a bathtub effect in a dilated system, or a weak diuretic response due to dehydration, reduced renal function or an inadequate furosemide dose may be considered.
•
Additional evaluation for type IIIb: Post-void images, PTT, NORA and serial differential renal function (DRF) should be assessed together.
•
T½ varies with renal function, hydration and pelvic volume. More reliable measures of drainage are output efficiency, NORA and an upright post-micturition image; in nephroptosis images are acquired upright or sitting
•
Parenchymal transit time (PTT) is not affected by pelvic dilatation. A prolonged PTT supports obstruction; if whole-kidney transit is long but PTT is normal, stasis without obstruction is considered
•
Type IV (Homsy sign): A brief fall after furosemide is followed by an active re-rise. This pattern indicates masked obstruction; it differs from the slow fall or plateau of type IIIb, may at first be mistaken for normal drainage, and strongly supports an indication for surgical intervention.

Tc-99m MAG3 moves through the kidney from the vessels to the parenchyma, calyces, pelvis and ureter; the renogram curve, Tmax and T½ and the post-diuretic curve types (I, II, IIIa, IIIb, IV) are shown.

Continuous stream · no seeking

Key point: the renogram's shape reflects the transit of the tracer through the kidney; after furosemide a T½ under 10 minutes excludes obstruction, over 20 minutes suggests obstruction.

Source: book (normal Tmax 3–5 min, T½ < 10 min; post-diuretic < 10 / 10–20 / > 20 min); curves from a schematic compartment model, kidney anatomy schematic (seven pyramids, minor and major calyces: OpenStax Anatomy & Physiology 2e §25.3).

Test yourself:Chapter 16 · question 3
Did this animation help you understand the topic?

Figure 16.4: Diuretic renography curve types (F+20) and interpretation ranges for post-diuretic T½ (schematic).

BOARD TIP
▸
"Type IIIb?"

→ The equivocal/grey zone with T½ 10-20 min; assessed with post-void images, PTT, NORA and serial DRF.

▸
"Type IV (Homsy sign)?"

→ Active re-rise after a brief fall; occult obstruction.

Causes of False-Positive Obstruction

•
Dehydration (the commonest cause) → inadequate urine flow
•
Very dilated collecting system → "reservoir effect" (reduced with F-15)
•
Full bladder → raised bladder pressure → drainage impeded
•
Severe loss of renal function → inadequate diuretic response
•
Inadequate furosemide dose

Causes of False-Negative Obstruction

•
Partial obstruction → may be overcome by the diuretic
•
Overhydration → very high baseline urine flow
•
Report content (SNMMI/EANM 2018): in addition to the common items (see 27), most recent serum creatinine and its date, drugs affecting renal haemodynamics (diuretic, ACE inhibitor, ARB, calcium channel blocker, NSAID), relevant urological procedures (pyeloplasty, stent, nephrostomy) and prior imaging; type and volume of hydration, whether the patient voided before acquisition, patient and camera position, furosemide dose and timing (F-15, F0, F+20). Findings: relative function of each kidney (percentage and normal range), one or two transit parameters (e.g. Tmax, post-furosemide T½) with normal ranges, drainage after voiding and standing, and combined interpretation of curves and images

16.3 Captopril Renography (Renovascular Hypertension)11 questions

Pathophysiology

Renovascular hypertension (RVH):

•
Renal artery stenosis → reduced renal blood flow → RAAS (Renin-Angiotensin-Aldosterone System) is activated
•
Angiotensin II → efferent arteriolar vasoconstriction → GFR is maintained (compensatory mechanism)
•
Result: GFR appears preserved on the stenotic side (thanks to angiotensin II)
•
Causes of RAS: The commonest is atherosclerosis (older age, ostial/proximal location); the other is fibromuscular dysplasia (young women, mid-distal segment)
•
Clinical features prompting captopril renography: abdominal bruit, resistant or accelerated HT, HT starting before 30 or after 55 years of age, rise in creatinine with ACEI, unexplained renal asymmetry, flash pulmonary oedema

Effect of the ACE inhibitor (captopril):

•
Captopril → blocks angiotensin II production → efferent arteriolar dilatation
•
Efferent arteriolar dilatation → GFR falls (on the stenotic side)
•
This fall in GFR appears as asymmetry on the renogram → diagnostic
stenosis (plaque) afferent efferent to peritubular capillaries proximal tubule GFR maintained Baseline (no captopril) angiotensin II → efferent vasoconstriction stenosis (plaque) afferent efferent to peritubular capillaries proximal tubule GFR falls ↓ After captopril ACE inhibition → efferent dilatation captopril 25-50 mg oral (60 min before) Stenotic-side renogram (MAG3) 0 5 10 15 20 25 Time (min) Counts Tmax ↑ Baseline After captopril Positive captopril renogram (on the stenotic side) • Prolonged Tmax (most sensitive criterion) • Uptake / differential function ↓ • Cortical retention ↑ (20-min / peak ↑) • Prolonged T½ • Marked worsening vs baseline

Figure 16.5: Physiological basis of captopril renography: efferent dilatation by angiotensin II blockade, fall in GFR and renogram changes on the stenotic side (schematic).

Did this figure help you understand the topic?
BOARD TIP
▸
"Principle of captopril renography?"

→ ACE inhibitor → angiotensin II blockade → efferent arteriolar dilatation → GFR falls on the stenotic side → asymmetry on the renogram.

▸
"Role of angiotensin II?"

→ Efferent arteriolar vasoconstriction → maintains GFR.

▸
"Captopril disrupts this"

→ GFR falls → diagnostic.

Protocol

Patient preparation:

•
ACE inhibitors → should be stopped 3-5 days before the study (long-acting → 5 days)
•
ARBs (angiotensin receptor blockers) → should be stopped
•
Diuretics → should be stopped 2-3 days before
•
Good hydration should be ensured

Captopril administration:

•
Oral captopril: 25-50 mg, 60 minutes before imaging
•
Blood pressure should be monitored (risk of hypotension)
•
Alternative: IV enalaprilat 0.04 mg/kg (at most 2.5 mg) is given, and the radiopharmaceutical is injected 15 min later. If marked hypotension develops, the patient is laid supine with legs raised and IV normal saline is given
•
Renography is performed after captopril

Two-day protocol (ideal):

•
Day 1: Baseline renography without captopril
•
Day 2: Captopril renography
•
The two studies are compared

One-day protocol (practical):

•
Captopril renography first → if normal, baseline is not needed
•
If abnormal → baseline renography is added
•
EANM: MAG3 is preferred in patients with raised creatinine. After captopril, BP and pulse are measured every 5-15 minutes; at discharge BP should have returned to at least 70% of its usual value

Criteria for a Positive Captopril Renogram

On the stenotic side after captopril:

•
Prolonged Tmax (delayed peak) → the most sensitive criterion
•
Reduced uptake (differential function falls)
•
Increased cortical retention (agent retained in the kidney, not excreted)
•
Prolonged T1/2 (delayed drainage)
•
Marked deterioration compared with the baseline study
•
EANM: After captopril uptake falls; Tmax, the 20-minute/peak ratio and cortical retention increase
•
Consensus thresholds (MAG3): Prolongation of Tmax by ≥2 min or a rise in the 20-min/peak ratio of ≥0.15; with DTPA the main finding is a fall in relative uptake
•
In patients with creatinine <1.7 mg/dL sensitivity and specificity are ~90%; dehydration and sodium depletion cause false positives
•
Probability: Worsening of findings after captopril indicates high, a normal captopril study or improvement with captopril low, and findings abnormal at baseline that do not change intermediate (indeterminate) probability of RVH

Assessment with DTPA vs MAG3:

•
DTPA: GFR-dependent → directly shows the fall in GFR after captopril → more specific
•
MAG3: Tubular secretion → increased cortical retention is more marked → more sensitive
•
Both can be used; MAG3 is generally preferred
BOARD TIP
▸
"Most sensitive criterion on captopril renography?"

→ Prolonged Tmax.

▸
"Captopril renography in bilateral renal artery stenosis?"

→ Symmetric deterioration on both sides → may be falsely negative (no asymmetry develops).

▸
"In which patients is captopril renography most reliable?"

→ Unilateral renal artery stenosis.

Limitations

•
Bilateral renal artery stenosis: Symmetric deterioration on both sides → no asymmetry → false negative
•
The commonest cause of symmetric bilateral cortical retention after captopril is hypotension or dehydration; failure to stop ACEI therapy reduces the sensitivity of the test
•
Reduced renal function (GFR <30 mL/min): Inadequate diuretic and captopril response
•
Single kidney: No comparison possible → careful interpretation
•
Use of captopril renography has declined → CT/MR angiography and Doppler US are more widely used
•
Anatomical RAS does not always mean RVH. The diagnosis of RVH is confirmed only by improvement of BP after revascularisation; a positive captopril renogram predicts this response. The gold standard for anatomical assessment is arteriography
•
Report content (SNMMI/EANM 2018): in addition to the common items (see 27), most recent creatinine, antihypertensive drugs (especially ACE inhibitors, ARBs and diuretics; when they were stopped), sodium restriction if indicated, hydration; dose and route of captopril (or enalaprilat) and how many minutes before the tracer it was given, voided volume and time (for urine flow rate); the order if baseline and captopril studies were done separately. Findings: relative function of each kidney and change in one or two transit parameters (e.g. Tmax, 20-minute/peak ratio) compared with baseline, and cortical retention on the images

16.4 GFR and ERPF Calculations12 questions

GFR (Glomerular Filtration Rate)

Definition: The volume of plasma filtered by the glomeruli per unit time

Normal values:

•
Adult: 120 ± 25 mL/min (corrected for body surface area: 125 mL/min/1.73 m2)
•
Renal blood flow: About 20-25% of cardiac output; renal blood flow ~1.2 L/min, renal plasma flow ~650-700 mL/min

Nuclear medicine methods:

A) GFR measurement with Tc-99m DTPA:

•
Camera-based (Gates method): Renal uptake is measured at 2-3 minutes → GFR is calculated
•
Advantage: Fast, practical, gives differential GFR (each kidney separately)
•
Disadvantage: Requires attenuation correction, limited accuracy
•
Plasma clearance method: Plasma clearance is calculated from blood samples
–
Single blood sample (simplified) or multiple blood samples
–
More accurate but more laborious

B) Gold-standard GFR measurement:

•
Inulin clearance → the physiological gold standard (not practical)
•
Cr-51 EDTA (widely used in Europe) → GFR by plasma clearance
•
I-125 iothalamate → the reference method in the USA
–
Iothalamate is an iodinated contrast agent labelled with I-125; because it undergoes a small amount of tubular secretion, it slightly overestimates GFR
•
Tc-99m DTPA plasma clearance → practical and reliable
•
With PET, GFR can be measured quantitatively with Ga-68 EDTA (dynamic PET, Patlak analysis) and renal blood flow with O-15 water or Rb-82; these applications are investigational

Cr-51 EDTA and plasma sampling (EANM):

•
Cr-51 EDTA: A GFR agent not used for imaging; the ratio of its clearance to inulin clearance is 0.85-1.01 and protein binding is <0.5%
•
Uses: Monitoring nephrotoxicity, dose calculation in chemotherapy (e.g. carboplatin), evaluation of living donors, dialysis and transplant decisions, clinical research
•
Situations in which plasma sampling should not be used: Hyperhydration therapy, ascites or oedema (expanded fluid compartment), expected GFR <30 mL/min. In these situations urine collection techniques are used
–
The 2018 BNMS guideline recommends adapted plasma methods for these situations: if expected GFR is <25 mL/min/1.73 m², a single sample taken at 24 hours (Gref-Karp); in ascites or oedema, where a single sample is not valid, a 4-sample technique with samples at 2, 4, 8 and 24 hours (Wickham)
•
Method: Slope-intercept method with 2-4 blood samples, or the single-sample method; blood is drawn from the arm opposite the injection arm
•
In the slope-intercept (single-compartment) method samples are taken between about 2-4 hours. Because the early rapid distribution phase is ignored, GFR is overestimated; the Brøchner-Mortensen correction is therefore applied
•
In studies performed together with Tc-99m, Cr-51 samples are left for 48 hours before counting so that Tc-99m decays; if a furosemide MAG3 study is also performed on the same day, EDTA is given first
•
Preparation: No caffeine after 22.00 the night before, a high-protein meal is avoided, physical activity is limited
•
Tc-99m DTPA clearance is higher than Cr-51 EDTA clearance; serial measurements should therefore always use the same agent (if possible the same manufacturer's product)
•
Sources of error (BNMS/EANM 2004): extravasation of the injection invalidates the result (checked by imaging the injection site); contamination of blood samples with the high specific activity injectate (the tracer is not injected through the line used for sampling); incorrect sampling technique and incorrectly recorded sample times; a large meal before or during the study and heavy exercise; overestimation of GFR in an expanded body fluid space (oedema, ascites); drugs affecting renal function that are not taken regularly. Substantial weight change (muscle wasting) makes interpretation difficult
–
The single-sample method offers no quality control for experimental errors such as extravasation; the slope-intercept method allows quality control checks
•
Items in the report: GFR, GFR corrected to 1.73 m² body surface area, and the reference range appropriate for the patient's age
•
According to EANM, camera-only GFR methods are less reliable than eGFR and should no longer be used

A GFR agent is injected into one arm and tubes are taken from the other arm at 120, 180 and 240 minutes; the area under the plasma concentration curve fills and clearance is computed as dose / area. In the second step the slope and intercept are drawn from the late samples on a log scale, the early area left out is shown, and the Brøchner-Mortensen correction is applied.

Continuous stream · no seeking

Key idea: clearance is dose / area under the curve; the slope-intercept method misses the early distribution component, overestimates GFR and is corrected with Brøchner-Mortensen.

Source: book (16.4: clearance = dose / area, slope-intercept with 2-4 samples, sampling from the other arm, Brøchner-Mortensen correction, Cr-51 EDTA, Tc-99m DTPA, when not to sample). Correction formula Brøchner-Mortensen 1972 (adults): Cl = 0.990778·Cl₁ − 0.001218·Cl₁². Dose and curve values are representative.

How to use: a single click on the drawing pauses and resumes; drag the time bar below to any moment; ← → change steps.

Speed
Test yourself:Chapter 16 · question 7Chapter 16 · question 23
Did this animation help you understand the topic?

Figure 16.6: Slope-intercept method in plasma-sampling GFR measurement and the logic of the clearance calculation (schematic).

BOARD TIP
▸
"Gold standard for GFR measurement?"

→ Inulin clearance (physiological).

▸
"Practical nuclear medicine method?"

→ Tc-99m DTPA (camera-based or plasma clearance).

▸
"Gates method?"

→ Camera-based GFR → fast, gives differential GFR.

ERPF (Effective Renal Plasma Flow)

Definition: The volume of plasma passing through and cleared by the kidneys per unit time

Normal values:

•
Adult: 600 ± 150 mL/min (corrected: 585 mL/min/1.73 m²)

Nuclear medicine method:

•
Measured with Tc-99m MAG3 (tubular secretion agent)
•
Camera-based or plasma clearance method
•
MAG3 clearance correlates well with ERPF but its value is lower than OIH/PAH clearance (~50-60%)

Gold standard:

•
PAH (para-aminohippuric acid) clearance → ERPF gold standard
•
I-131 OIH (orthoiodohippurate) → former reference agent (no longer used)
•
I-123 OIH: Renal extraction is 70-85% (~90% for PAH). It is faster than PAH and needs no catheter; in the single-sample method blood is taken at 44 minutes; activity 50-150 MBq
•
ERPF measurement is valid only if the patient is adequately hydrated; it should not be performed in renal artery stenosis or if drugs affecting the RAAS, ciclosporin or probenecid are being taken

Filtration Fraction (FF)

FF = GFR / RPF = 120 / 600 ≈ 20%

•
Normal: 18-22%
•
Increased FF → efferent arteriolar vasoconstriction (angiotensin II effect)
•
Reduced FF → efferent arteriolar dilatation (ACE inhibitor effect)
BOARD TIP
▸
"Gold standard for ERPF measurement?"

→ PAH clearance.

▸
"ERPF with nuclear medicine?"

→ Tc-99m MAG3.

▸
"Filtration fraction?"

→ GFR/RPF ≈ 20%.

▸
"What does a rise in FF mean?"

→ Efferent arteriolar vasoconstriction (angiotensin II).

16.5 Renal Cortical Scintigraphy (Tc-99m DMSA)8 questions

Radiopharmaceutical

Tc-99m DMSA (Dimercaptosuccinic Acid):

•
Binds to proximal tubular cells and shows cortical retention
•
2-4 hours after injection, 40-50% of the dose is retained in the renal cortex
•
Static imaging → shows cortical morphology (not dynamic)
•
Excretion: Minimal urinary excretion → the collecting system is not seen
•
Activity: In US (SNMMI) practice 111-185 MBq (3-5 mCi); EANM recommends 70 MBq in adults
•
EANM: ~50% of the injected activity is retained in the parenchyma. Uptake mechanism: DMSA binds to α1-microglobulin in plasma; this complex is filtered at the glomerulus and taken up into the cell by endocytosis via the megalin/cubilin receptors of the brush border in the proximal tubule. Most renal uptake occurs by this route; in megalin/cubilin-deficient mice renal uptake falls to ~11% of normal. The contribution of peritubular (blood-side) uptake is small
•
Tc-99m glucoheptonate (GHA): Mostly excreted by glomerular filtration, ~10-15% binds to the cortex; both early dynamic and late cortical images can therefore be acquired. Cortical image quality is lower than with DMSA
•
EANM activity: Adult 70 MBq (child at least 18.5 MBq); 8.8 µSv/MBq, i.e. ~0.62 mSv; the kidneys receive the highest organ dose (180 µGy/MBq)
•
Conditions reducing uptake: Fanconi syndrome (tubular metabolic acidosis), ammonium chloride (increases liver uptake), sodium bicarbonate, mannitol; captopril in unilateral RAS (reversible effect)
•
The DMSA kit should be used within 4 hours of preparation and air must not enter the vial: oxidation increases liver uptake and reduces renal uptake. Liver uptake also increases in renal failure; if necessary a delayed image is acquired 6-24 hours later
•
Its accuracy is slightly higher than CT and MR and markedly higher than US; it is recommended by guidelines for assessing renal damage due to recurrent febrile UTI
•
Contraindications: Hypersensitivity (absolute); pregnancy (relative, depending on benefit-risk assessment); breastfeeding need not be interrupted

Indications

•
Diagnosis of acute pyelonephritis (especially in children) → the most important indication
•
Assessment of renal scarring (after chronic pyelonephritis)
•
Measurement of differential renal function (the most accurate method)
•
Localisation of an ectopic kidney
•
Confirmation of a single kidney
•
Assessment of a renal mass (functioning vs non-functioning)
–
Molecular imaging of renal masses (SNMMI/EANM/ACNM 2025): Tc-99m sestamibi SPECT/CT (925 MBq, at ~75 min) shows uptake in mitochondria-rich oncocytoma and hybrid oncocytic/chromophobe tumour (sensitivity and specificity 89% in a meta-analysis); absence of uptake favours RCC. Zr-89 girentuximab PET/CT (an antibody binding carbonic anhydrase IX; 37 MBq, at ~day 5) shows clear cell RCC; uptake above the adjacent renal parenchyma is read as ‘hot’. In ZIRCON (masses ≤7 cm) sensitivity was 86% and specificity 87%. A mass that is cold on sestamibi and hot on girentuximab is almost certainly RCC; biopsy is considered for a mass cold on both. As of November 2026, Zr-89 girentuximab has not received FDA approval (complete response letter on manufacturing in August 2025)

Imaging and Interpretation

Normal findings:

•
Homogeneous, symmetric cortical uptake in both kidneys
•
Collecting system not seen (photopenic centre → normal)
•
Posterior imaging (SPECT may be added)

Acute pyelonephritis:

•
Focal or multifocal reduced uptake in the affected area (cortical defect)
•
Defects are seen most often at the poles (compound papillae are prone to intrarenal reflux); diffusely reduced uptake in an enlarged kidney is a less common pattern
•
Reduced uptake without volume loss → acute inflammation
•
Mechanism of the defect: Focal ischaemia caused by inflammation (vasoconstriction, interstitial oedema) and tubular cell dysfunction reduce DMSA uptake by the proximal tubule
•
SPECT → more sensitive than planar imaging
•
However, SPECT increases false-positive results and interobserver variation; in children, planar posterior and posterior oblique images are usually sufficient as routine

Renal scar:

•
Focal cortical defect + volume loss (cortical thinning)
•
Usually at the renal poles (upper and lower pole)
•
After chronic pyelonephritis / VUR
•
Acute pyelonephritis and scarring can also develop without VUR; the indication for DMSA is therefore not limited to patients with reflux
•
Acute pyelonephritis → follow-up DMSA 6 months later → assessment of scar formation
•
EANM: Reversible (infection-related) defects look patchy and do not distort the renal contour; irreversible defects are mostly triangular and change the contour
•
Normal appearance: The pyramids retain less activity than the cortex and there is no activity in the hilar/pelvic region; the upper poles of the two kidneys are closer to each other than the lower poles
•
The upper pole of the left kidney may appear flattened or hypoactive on the posterior image because of splenic impression; if the contour is normal on the posterior oblique image this is a normal variant, not a defect
•
Activity in the collecting system: May be seen because of dilatation, obstruction, reflux, inadequate hydration or early imaging, and affects the analysis
•
Shape variants: Horseshoe, S- or L-shaped, crossed fused and pancake kidney
•
Pseudotumours (hypertrophied column of Bertin, dromedary hump on the lateral border of the left kidney) show normal cortical uptake and can therefore be distinguished from a true mass
•
Simple cyst: Seen as a well-defined, round photopenic area; a wedge-shaped defect extending to the periphery suggests infarction or pyelonephritis
•
A focal photopenic lesion on DMSA is non-specific: Cyst, tumour, abscess, haematoma and infarction cannot be distinguished from one another; US or CT is needed
•
Tc-99m sestamibi SPECT/CT: Oncocytomas and hybrid oncocytic tumours take up sestamibi, whereas clear cell RCC is mostly photopenic; this helps to distinguish a benign oncocytic tumour
Normal Homogeneous, symmetric cortex; photopenic centre (collecting system) Acute pyelonephritis Focal/multifocal defect, NO volume loss (reversible) Renal scar Defect + volume loss (cortical thinning), often at a pole (irreversible) Posterior Left Right reduced uptake, contour preserved cortical thinning + contour change Defects mostly at the poles; imaging at 2-4 h (40-50% of dose in cortex).

Figure 16.7: Normal cortex, acute pyelonephritis and renal scar patterns on Tc-99m DMSA scintigraphy, posterior image (schematic).

Did this figure help you understand the topic?
BOARD TIP
▸
"Acute pyelonephritis vs renal scar (DMSA)?"

→ Acute: Focal reduced uptake without volume loss. Scar: Focal defect + volume loss (cortical thinning).

▸
"Most sensitive method for diagnosing acute pyelonephritis in children?"

→ Tc-99m DMSA SPECT (more sensitive than US and CT).

▸
"Differential function with DMSA?"

→ The most accurate method (based on cortical uptake).

Special Situations with DMSA

Medullary sponge kidney:

•
DMSA uptake in medullary calcifications → "medullary uptake" pattern

Horseshoe kidney:

•
Fusion at the lower poles → DMSA shows the distribution of functioning tissue
•
In a horseshoe kidney (the isthmus lies in front of the spine) and a pelvic ectopic kidney the posterior image is not sufficient; an anterior image is also acquired and differential function is calculated with the geometric mean
•
The horseshoe kidney is the commonest fusion anomaly
•
Multicystic dysplastic kidney: Mostly unilateral and non-functioning (no uptake on DMSA or MAG3); VUR or UPJ obstruction may be present in the contralateral kidney. The two commonest causes of a flank mass in the newborn are UPJ obstruction and multicystic dysplastic kidney

Ectopic kidney:

•
Pelvic or thoracic ectopic kidney → localisation with DMSA
•
Duplex collecting system (Weigert-Meyer rule): The upper pole ureter opens ectopically and causes obstruction (mostly ureterocele); the lower pole ureter shows reflux

16.6 Vesicoureteral Reflux (Direct/Indirect Cystography)7 questions

Vesicoureteral Reflux (VUR)

Definition: Backflow of urine from the bladder into the ureters and/or kidney

Clinical importance:

•
An important cause of recurrent urinary infections in children
•
May lead to chronic pyelonephritis and renal scarring
•
Reflux nephropathy → chronic renal failure
•
The likelihood of spontaneous resolution of VUR is high in low grades (I-II), at a young age and in unilateral reflux, and low in grade IV-V reflux

Assessment Methods

A) Voiding Cystourethrography (VCUG) – Radiological:

•
Gold standard → determines VUR grade (Grade I-V)
•
Shows urethral anatomy (posterior urethral valves → in boys)
•
Disadvantage: High radiation dose, invasive (catheterisation)
•
Preferred for initial assessment (especially in boys → excludes urethral pathology)

B) Direct Radionuclide Cystography (DRNC):

•
Tc-99m pertechnetate or Tc-99m sulphur colloid is instilled into the bladder through a catheter
•
Dynamic imaging during bladder filling and voiding
•
Presence and duration of VUR are assessed
•
Advantages:
–
100-fold lower radiation dose than VCUG
–
Continuous dynamic imaging → higher chance of catching intermittent reflux
–
More sensitive for detecting VUR (continuous monitoring)
•
Disadvantages:
–
Anatomical detail is insufficient, so the international I-V grading cannot be applied; only a coarse three-step grading is used: I ureter, II pelvicalyceal system, III dilated system
–
Does not show urethral anatomy
•
Use: Follow-up of known VUR and screening in girls
•
Because of its low dose, DRNC is also preferred for screening siblings of children with VUR (VUR prevalence in siblings ~30%)
•
Agents recommended by EANM: Tc-99m sulphur colloid or Tc-99m DTPA (not absorbed even from an ileal augmented bladder) or Tc-99m pertechnetate (may be absorbed through the wall of an augmented bladder and excreted by the kidney, causing a false-positive result); given in sterile normal saline at body temperature
•
Activity is 20 MBq and is not adjusted for weight; effective dose ~0.048 mSv, ovarian dose 0.005-0.01 mGy
•
The bladder is not catheterised during active UTI; otherwise there is no contraindication and no special preparation is needed
•
Also used to assess the result of endoscopic or surgical treatment and to look for VUR in transplant recipients; assessment is difficult in ectopic pelvic and transplant kidneys
•
Phases of direct RNC: Filling, voiding and post-void. A small child lies supine with the camera posterior. Expected bladder capacity is (age + 2) × 30 mL. Bilateral reflux gives a "Mickey Mouse ears" appearance
•
Residual urine volume = voided volume × post-void counts / (pre-void counts − post-void counts); can be calculated after direct or indirect cystography or after renography
BOARD TIP
▸
"Preferred method for VUR follow-up?"

→ Direct radionuclide cystography (DRNC) → low radiation, high sensitivity.

▸
"For initial assessment?"

→ VCUG (anatomical detail, VUR grade, urethral pathology).

▸
"Advantage of DRNC over VCUG?"

→ Low radiation + continuous dynamic imaging → higher chance of catching intermittent reflux.

C) Indirect Radionuclide Cystography (IRNC):

•
After standard MAG3 or DTPA renography → when the bladder is full → imaging during voiding
•
MAG3 is preferred for IRNC: Because of its high extraction and rapid passage into urine, renal and background activity remain low; reflux is better detected when the bladder is full
•
No catheterisation required (non-invasive) → the greatest advantage
•
Requires patient cooperation → feasible in toilet-trained children (usually >3 years)
•
Can be performed in the same session as renography → no additional radiation dose
•
Disadvantage: Reflux is assessed only during voiding → filling-phase reflux cannot be captured
•
~20% of refluxes are seen only in the filling phase and therefore cannot be detected with IRNC
•
Lower sensitivity than DRNC
BOARD TIP
▸
"VUR assessment method that requires no catheterisation?"

→ Indirect radionuclide cystography (IRNC).

▸
"Disadvantage of IRNC?"

→ Reflux is assessed only in the voiding phase → filling-phase reflux may be missed.

▸
"In which age group can IRNC be performed?"

→ Toilet-trained children (>3 years).

Comparison of VUR Assessment Methods:

FeatureVCUGDRNCIRNC
MethodRadiological (fluoroscopy)Nuclear (with catheter)Nuclear (no catheter)
CatheterisationYESYESNO
Radiation doseHighVery lowVery low
VUR gradingYES (Grade I-V)Coarse (3 steps)Coarse (3 steps)
Urethral anatomyYESNONO
SensitivityHighHighestLow
Filling-phase refluxYESYESNO
UseInitial assessmentFollow-upFollow-up (cooperative patient)

16.7 Renal Transplant Assessment7 questions

General Information

•
The transplant kidney is usually placed in the iliac fossa (right or left)
•
Renal artery → iliac artery, renal vein → iliac vein, ureter → bladder anastomosis
•
Imaging position: Anterior (the transplant kidney lies in the pelvis)
•
Radiopharmaceutical: Tc-99m MAG3 (preferred) or Tc-99m DTPA
–
Activity and acquisition (SNMMI/EANM 2018): because the perfusion phase contributes to the evaluation only in transplants, about 370 MBq (10 mCi) may be needed to visualise the bolus; 37-185 MBq (1-5 mCi) is sufficient for other indications. The gamma camera is placed anteriorly over the graft. DTPA shows perfusion better; MAG3 is better for function, parenchymal transit, obstruction and urine leaks. Scintigraphy is now used mostly for surgical complications (leak, arterial stenosis, obstruction); a urinoma is localised with SPECT/CT at the end of the study

Indications

•
Postoperative baseline assessment (reference study)
•
Acute tubular necrosis (ATN) vs acute rejection
•
Vascular complications (renal artery thrombosis, renal vein thrombosis)
•
Urine leak (urinoma)
•
Assessment of obstruction
•
Chronic rejection / chronic allograft nephropathy

Transplant Renography Findings

A) Normal Transplant:

•
Good perfusion (Phase 1) → rapid uptake (Phase 2) → normal drainage (Phase 3)
•
Short aorta-to-kidney transit time (transplant kidney close to the iliac artery)
•
Normal renogram curve
–
In a normal graft the radiopharmaceutical is taken up promptly and homogeneously, excreted into the collecting system and ureter in time, and no retention remains at the end of the study; if no spontaneous excretion is seen, furosemide may be given about 10 minutes after injection to exclude outflow obstruction (Khor 2015)
–
In a transplant, ureteral peristalsis is reduced by denervation; persistent visualisation of the whole ureter without obstruction or rejection is common. In acute rejection the ureter, as part of the graft, may lose peristalsis and produce pseudo-obstruction (SNMMI/EANM 2018)

B) Acute Tubular Necrosis (ATN):

•
The commonest early postoperative complication
•
Usually in transplants from deceased donors (long cold ischaemia time)
•
Renography findings:
–
Perfusion: Preserved (normal or mildly reduced)
–
Uptake: Reduced (tubular damage → low agent uptake)
–
Drainage: Delayed or absent
–
Increased cortical retention → agent remains in the kidney
–
In ATN (and contrast nephropathy) with DTPA the kidney appears at blood-pool intensity and progressively fades; with tubular agents progressively increasing parenchymal retention is seen
–
The typical clue is a mismatch between perfusion and function: While perfusion is relatively good, MAG3 continues to accumulate in the parenchyma (rising curve) and urinary excretion is minimal or absent
•
Gradual improvement is expected on serial studies (days-weeks)

C) Acute Rejection:

•
Usually 1 week - 3 months after transplantation
•
Renography findings:
–
Perfusion: Reduced (vascular component → the most important difference from ATN)
–
Uptake: Reduced
–
Drainage: Delayed or absent
•
Difference from ATN: Perfusion markedly reduced (in ATN perfusion is preserved)
•
Deterioration on serial studies (improvement is expected in ATN)
BOARD TIP
▸
"ATN vs acute rejection?"

→ Perfusion: preserved in ATN, reduced in rejection.

▸
"On serial studies?"

→ ATN: Gradual improvement, rejection: Deterioration.

▸
"When is ATN seen?"

→ Early postoperative, especially with deceased donors.

▸
"When does rejection occur?"

→ 1 week - 3 months after.

Comparison of ATN vs Acute Rejection:

FeatureATNAcute Rejection
TimingEarly postoperative1 week - 3 months
Donor typeDeceased (common)Both
PerfusionPreservedReduced
UptakeReducedReduced
DrainageDelayedDelayed
Serial follow-upGradual improvementDeterioration
TreatmentSupportive (dialysis)Increased immunosuppression

D) Hyperacute Rejection:

•
During surgery or within hours
•
Perfusion: Absent (complete vascular occlusion)
•
Uptake: Absent → "photopenic kidney"
•
Preformed antibodies → humoral rejection
•
Accelerated acute rejection develops in the first days (~day 1-5) in a presensitised recipient. Hyperacute and chronic rejection are irreversible, whereas acute rejection may respond to treatment

E) Renal Artery Thrombosis:

•
Perfusion: Absent → blood flow to the kidney is cut off
•
Uptake: Absent → "photopenic kidney"
•
Must be distinguished clinically from hyperacute rejection
•
Requires emergency surgical intervention

F) Renal Vein Thrombosis:

•
Perfusion: Reduced (venous congestion → arterial flow falls)
•
Uptake: Reduced
•
Kidney enlarged and oedematous
•
Confirmation with Doppler US

G) Urine Leak (Urinoma):

•
On renography → the agent leaves the kidney but accumulates outside the bladder
•
Extravasation at the anastomosis or along the ureter
•
On delayed images → an increasing collection of activity outside the bladder
•
May require surgical repair
•
A urinoma appears photopenic on early images and accumulates activity over time (bladder and diverticulum must first be excluded); the leak is most often at the ureterovesical anastomosis
•
Lymphocele: A collection formed by damage to lymphatic vessels, lying adjacent to the transplant and remaining photopenic on delayed images; the absence of activity accumulation distinguishes it from a urinoma
–
Pitfall: on delayed images, bowel activity from hepatobiliary excretion of MAG3 can mimic a urine leak; with delayed graft function a leak may only become visible once urine output increases (false negative). With a slow leak a urinoma may be indistinguishable from other collections
•
Timing: A haematoma appears in the early postoperative period, a urinoma mostly in the first 2-3 weeks, and a lymphocele within weeks or months (mostly after the 2nd week)
•
If perfusion is markedly reduced while function is relatively preserved, compression by a peritransplant collection or a subcapsular haematoma (Page kidney) should be considered
BOARD TIP
▸
"Photopenic kidney on transplant renography (no perfusion and no uptake)?"

→ Hyperacute rejection or renal artery thrombosis.

▸
"Activity accumulating outside the bladder?"

→ Urine leak (urinoma).

▸
"Imaging position for a transplant kidney?"

→ Anterior (pelvic location).

H) Obstruction:

•
Stricture of the ureterovesical anastomosis
•
On renography: Rising curve, no drainage
•
Assessment with diuretic renography (F+20)

I) Chronic Rejection / Chronic Allograft Nephropathy:

•
Develops months-years later
•
Perfusion and uptake gradually decline
•
In stable chronic rejection parenchymal transit is mostly normal, whereas in ATN, acute rejection and ciclosporin toxicity it is prolonged
•
Differential diagnosis: Ciclosporin/tacrolimus nephrotoxicity
–
Calcineurin inhibitor toxicity: Mostly appears after the first month; perfusion is preserved, parenchymal transit and excretion are delayed (similar to ATN but with a later onset)
•
Definitive diagnosis: Biopsy

Transplant Perfusion Index (Hilson Index)

•
Aortic and transplant kidney perfusion curves are compared
•
A perfusion index is calculated → helps to distinguish rejection from ATN
•
High perfusion index → reduced perfusion → favours rejection
–
The Hilson perfusion index is calculated from the first-pass curves of the graft and the adjacent iliac artery; values below 150 are considered normal (Hilson 1978)
•
Report content (SNMMI/EANM 2018): in addition to the common items (see 27), date of transplantation and postoperative day, most recent creatinine and urine output, urological procedures (stent, nephrostomy) and prior imaging, agent used; perfusion (graft and aortic curves, perfusion index if needed), parenchymal uptake and transit, excretion into the collecting system and bladder; assessment for urinary leak (collection of activity around the graft or in a pocket, localised with SPECT/CT), obstruction and vascular problems, and change from previous renography
Transplant renography (Tc-99m MAG3, anterior; phase 1 perfusion) Perfusion (phase 1)? Absent No uptake → "photopenic kidney" Hyperacute rejection (within hours, preformed Ab) or renal artery thrombosis → emergency surgery Reduced Uptake ↓, delayed drainage Acute rejection (1 wk-3 mo; worsens on serial studies) Renal vein thrombosis (large, oedematous kidney; Doppler) Preserved Uptake ↓, delayed drainage, cortical retention ↑ ATN (early postop, deceased donor; gradual improvement on serial studies) Calcineurin inhibitor toxicity (mostly after the first month) Other findings: • Increasing activity outside the bladder → urine leak (urinoma; photopenic early, fills over time) • Collection still photopenic on delayed images → lymphocele • Rising curve, no drainage → obstruction (diuretic renography, F+20) • Perfusion and uptake ↓ over months-years → chronic rejection / drug toxicity (definitive: biopsy)

Figure 16.8: Differential diagnosis flow on transplant renography according to perfusion and uptake findings (schematic).

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Key Points for the Board

Renal Scintigraphy Agents:

•
Tc-99m MAG3: Tubular secretion (~95-98%; protein binding ~90%), extraction fraction ~40-50%, measures ERPF, preferred agent
•
Tc-99m DTPA: Glomerular filtration, extraction fraction ~20%, measures GFR
•
Tc-99m DMSA: Cortical retention, static imaging, pyelonephritis/scar, differential function (most accurate)
•
MAG3 → good images even with low function → general preference
•
DTPA → when GFR measurement is needed

Renogram Curve:

•
Phase 1: Vascular (0-30 s) → perfusion
•
Phase 2: Parenchymal (1-5 min) → uptake → Tmax occurs here → differential function is calculated here
•
Phase 3: Excretion (5+ min) → drainage → T½ is calculated here
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Normal Tmax: 3-5 min (MAG3), Normal T½: <10 min

Diuretic Renography:

•
T½ <10 min → non-obstructive
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T½ 10-20 min → equivocal
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T½ > 20 min → obstructive
•
Commonest cause of false positives: Dehydration
•
In a very dilated system: F-15 protocol preferred (reduces the reservoir effect)
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Furosemide dose: Adult 40 mg IV, paediatric 1 mg/kg
•
Commonest level of obstruction: UPJ in children, UVJ in adults (mostly stones)
•
Sawtooth fluctuation in the drainage phase → VUR during renography (not a sign of obstruction)

Captopril Renography:

•
Principle: ACE inhibition → efferent arteriolar dilatation → fall in GFR → asymmetry
•
Most sensitive criterion: Prolonged Tmax
•
ACE inhibitors should be stopped 3-5 days before the study
•
False negative in bilateral stenosis (symmetric deterioration → no asymmetry)
•
Positivity thresholds (MAG3): Prolongation of Tmax by ≥2 min, rise in the 20-min/peak ratio of ≥0.15; with DTPA a fall in relative uptake
•
Use has declined today → CT/MR angiography more widely used

GFR and ERPF:

•
GFR gold standard: Inulin clearance (physiological), practical: Tc-99m DTPA
•
ERPF gold standard: PAH clearance, practical: Tc-99m MAG3
•
Normal GFR: 120 ± 25 mL/min
•
Normal ERPF: 600 ± 150 mL/min
•
Filtration fraction: GFR/RPF ≈ 20%
•
Gates method: Camera-based GFR → fast, gives differential GFR

DMSA Scintigraphy:

•
Imaging: 2-4 hours after injection
•
Acute pyelonephritis: Focal reduced uptake, NO volume loss
•
Renal scar: Focal defect + volume loss (cortical thinning)
•
Most sensitive method for diagnosing acute pyelonephritis in children (with SPECT)
•
Most accurate method for measuring differential function
•
Pseudotumour (column of Bertin, dromedary hump) shows normal cortical uptake → distinguished from a true mass

VUR Assessment:

•
Initial assessment: VCUG (anatomical detail, VUR grade, urethral pathology)
•
Follow-up: DRNC (low radiation, high sensitivity, continuous dynamic imaging)
•
Catheter-free method: IRNC (requires a cooperative patient, >3 years, voiding phase only)
•
DRNC radiation dose: ~1/100 of VCUG

Renal Transplant:

•
Imaging: Anterior (pelvic location)
•
Preferred agent: Tc-99m MAG3
•
ATN vs Acute Rejection → the most important difference: Perfusion
•
ATN: Perfusion preserved, improvement on serial follow-up
•
Rejection: Perfusion reduced, deterioration on serial follow-up
•
Photopenic kidney (no perfusion + no uptake): Hyperacute rejection or renal artery thrombosis
•
Activity collection outside the bladder: Urine leak (urinoma)
•
A urinoma is photopenic early and accumulates activity over time; a lymphocele remains photopenic on delayed images too
•
ATN → common with deceased donors (cold ischaemia)
•
Chronic rejection → definitive diagnosis: Biopsy

Frequently Asked Board Themes:

•
"Which agent with low renal function?" → MAG3
•
"Which agent for GFR measurement?" → DTPA
•
"Most sensitive for diagnosing pyelonephritis?" → DMSA SPECT
•
"Preferred for VUR follow-up?" → DRNC
•
"Difference between transplant ATN and rejection?" → Perfusion (preserved in ATN)
•
"Principle of captopril renography?" → Efferent arteriolar dilatation → fall in GFR
•
"Limitation of captopril renography in bilateral stenosis?" → False negative
•
"Filtration fraction?" → 20% (GFR/RPF)

Additional Notes from EANM Guidelines:

•
First-pass extraction: OIH ~80% > Tc-99m EC ~65% > MAG3 ~55% > DTPA ~20%
•
EANM activities: MAG3 75 MBq, DTPA 37-185 MBq, DMSA 70 MBq, DRNC 20 MBq
•
MAG3: 80-90% protein binding, ~10% hepatobiliary; its clearance is not reported as ERPF; probenecid is stopped
•
Differential function: Rutland-Patlak best; symmetry 50 ± 7.5%; C-shaped perirenal background ROI; µ = 0.14/cm
•
Cr-51 EDTA: Clearance ratio to inulin 0.85-1.01; ascites/oedema/GFR <30 → EANM: urine collection instead of plasma sampling (BNMS 2018: adapted plasma methods with late/24-hour samples)
•
DMSA: Acute defect is patchy and follows the contour; scar is triangular and distorts the contour; Fanconi, bicarbonate, mannitol reduce uptake
•
DRNC: Pertechnetate may be absorbed in an augmented bladder → false positive → use DTPA or colloid
•
Captopril: Dehydration/sodium depletion cause false positives; at creatinine <1.7 mg/dL sensitivity/specificity ~90%

Current guidelines on this chapter's topics

The latest guidelines and consensus documents on the procedures covered in this chapter (official EANM index and primary sources, November 2026). Comparison of the text with these versions is in progress; consult the guideline itself for details.

  1. 2025SNMMI/EANM/ACNM Procedure Standard/Procedure Guideline on the Use of Molecular Imaging for Renal Mass Characterization (opens in a new tab)
  2. 2018SNMMI and EANM Practice Guideline for Renal Scintigraphy in Adults (opens in a new tab)
  3. 2018SNMMI Procedure Standard/EANM Practice Guideline for Diuretic Renal Scintigraphy in Adults With Suspected Upper Urinary Tract Obstruction 1.0 (opens in a new tab)

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Step 1/3

DTPA: filtration

About 20% of the plasma arriving in the afferent arteriole is filtered in the glomerulus (filtration fraction). DTPA is barely protein bound (<10%), so it passes freely through the filtration barrier (fenestrated endothelium, basement membrane, podocyte slit diaphragm), while albumin does not; it is neither secreted nor reabsorbed: filtered molecules go to urine, the rest leave via the efferent arteriole and peritubular capillary to the renal vein. First-pass extraction ~20%; DTPA measures GFR.

DTPA: glomerular filtrationcortexmedullaafferent arterioleefferent arterioleBowman'scapsulemacula densaproximal tubuledistal tubuleloop of Henlecollectingductperitubular capillariesinterlobular arteryinterlobular veinurine ↓Cortical nephron; simplified, not to scale.
Filtration barrier (magnified)glomerular capillary (blood)fenestrated endotheliumglomerular basement membranepodocyte foot processes and slit diaphragmBowman's space (filtrate)albumin is not filteredschematic, not to scaleTc-99m DTPA → GFRGlomerular filtrationprotein binding <10%extraction ~20% (FF ≈ GFR / RPF)not secreted or reabsorbed→ measures GFR; image quality falls in renal failurearteryveinperitubular capillarytubule (urine)passed 0 · to urine 0 · taken up on first pass: 0%

Vascular phase (first ~30 s): the agent reaches the kidney through the renal artery. Parenchymal phase (1-5 min): the agent is taken up by tubular cells, the curve rises and peaks (Tmax); normal Tmax 3-5 min (MAG3). Excretion phase: the agent passes with urine into the calyces, pelvis and ureter and the curve falls; normal T½ < 10 min. All dots are the same agent (Tc-99m MAG3); where it is shows the phase.

KidneyUreterTc-99m MAG3 (tracer)
Normal · Tmax … min · T½ … minVascularParenchymalExcretion05101525 minKidney counts

Hover over the graph or drag with your finger: the kidney shows its state at that minute. Tap a kidney structure to see its name; Space or the ⏸ button below pauses and resumes; ← → change the step and curve type.

Curves are computed with a schematic compartment model (blood → parenchyma → pelvis → ureter); Tmax and T½ are measured from the curve and interpreted with the book's ranges: normal Tmax 3-5 min, T½ < 10 min (MAG3); post-diuretic T½ < 10 min non-obstructive, 10-20 min equivocal, > 20 min obstructive. The degree of dilatation is schematic. The vascular phase (first 30 s) appears narrow at this scale.

In the F+20 protocol furosemide is given at 20 min (adult 40 mg IV) and post-diuretic T½ is measured: < 10 min non-obstructive, 10-20 min equivocal, > 20 min or no fall obstructive. Change the type: in II the pelvicalyceal system is dilated, calyces blunted and the UPJ narrow; the curve does not fall. In IIIa the system is dilated but not obstructed: furosemide increases urine flow and the system empties quickly. In IIIb the fall is slow. In IV (Homsy) the pelvis distends again after a brief fall and the curve rises; T½ alone may look normal: this is masked obstruction.

Curve type:
KidneyUreterTc-99m MAG3 (tracer)
Type II · Obstructive05101520253040 minKidney countsFurosemide (F+20)

Hover over the graph or drag with your finger: the kidney shows its state at that minute. Tap a kidney structure to see its name; Space or the ⏸ button below pauses and resumes; ← → change the step and curve type.

Curves are computed with a schematic compartment model (blood → parenchyma → pelvis → ureter); Tmax and T½ are measured from the curve and interpreted with the book's ranges: normal Tmax 3-5 min, T½ < 10 min (MAG3); post-diuretic T½ < 10 min non-obstructive, 10-20 min equivocal, > 20 min obstructive. The degree of dilatation is schematic. The vascular phase (first 30 s) appears narrow at this scale.

Step 1/2

Clearance = dose / area

The GFR agent (Cr-51 EDTA or Tc-99m DTPA) is injected into one arm; blood samples are taken from the other arm. Plasma concentration falls fast at first with distribution, then slowly with renal clearance. Clearance is the dose divided by the area under the plasma curve: here 3000 kBq / 30 kBq·min/mL = 100 mL/min.

Clearance = dose / area under the curvet = 240 mininjection (3000 kBq)sampled from other arm120 dk180 dk240 dkClearance = dose / areaExample values are representative.
Plasma concentration0.00.20.4060120180240after injection (min)kBq/mLarea under the curve (0-240 min): 24.1 kBq·min/mL→ area extrapolated to ∞ 30 → 3000 / 30 = 100 mL/min