1. Nephrogenic Systemic Fibrosis: An Update
Neil M. Rofsky, MD
BETH ISRAEL DEACONESS
MEDICAL CENTER
Harvard
Medical
School

2. MR Contrast Agents (Magnetopharmacuticals)
Signal Augmentation
Differential distribution
Safety

3. MR Contrast Agents: Principles
Unpaired electrons alter magnetic environment
A trait of certain metal ions
Indirectly affects the local H20
Naked metal ions are toxic!
Ligands for safety
(metal + ligand = chelate)
Gd3+
Gd-DTPA-BMA
(Omniscan)
Gd-DOTA
(Dotarem)

4. Nephrogenic Systemic Fibrosis (NSF): The Basics
Originally known as Nephrogenic Fibrosing Dermopathy (NFD)
Systemic proliferation of connective tissue (NSF)
“Over 215 cases reported worldwide..” from 1997-present
Strong epidemiologic association with Gd
Appears to be a class issue (Omniscan >>> Magnevist, OptiMARK)
Almost all renal insufficiency at exposure (most ESRD, on dialysis)
Proinflammatory events in many11 (e.g., vascular surgery, sepsis, thrombosis)
Some data suggests 3-5% incidence w/ Gd in setting of renal failure11
So far no co-factor identified (dialysate, ACEIs, EPO, etc.)
Theories of pathogenesis:
Liberation of Gd ion from carrier molecule10
Cutaneous deposition of free Gd ion10
Gd target attracts circulating fibrocytes (CFs)
CFs differentiate in the dermis to resemble dermal fibroblasts
Since it appears not to have existed prior to 1997, has been strong suspicion that a recently introduced agent or shift in the std of care might be the culprit
Investigators have examined: dialysate (and contaminants thereof), EPO, iron, coag abnormalities, ACE inhibitors, vascular surgery, induced anti-phospholipid antibodies
Investigation by dermatopathologists and the CDC has so far failed to identify a single causative medication
Male ≈ female
Middle-aged are most affected
Variety of ethnic backgrounds are represented

5. Patient Safety a Decade Later…
First recognized case of “NFD”
Gd “trigger” proposed for NSF (Grobner and Markmann)
FDA issues Public Health Advisory
FDA revises Public Health Advisory
Literature reports Gd in NSF skin biopsies7
1997
2000
Apr 2006
May 2006
Jun 2006
Dec 2006
Jan 2007
Detected in 1997
Described in 2000 by Dr. Shawn Cowper, a dermatopathologist at Yale
Popular press=MSNBC
Gd detected in 4 of 13 specimens from 7 NSF patients -> detected in 4 of 7 patients
First description of NSF in the literature
Danish Medicines Agency reports 25 cases of Gd-associated NSF
Press reports FDA warning to “kidney patients”
Editorial in Radiology

6. Gadolinium Agents in Review
Generic
Brand
Mfr
FDA Approval
Market Share (Doses)
Gadopentetate dimeglumine
Magnevist
Berlex
1988
(70 mil)
~50%
Gadodiamide
Omniscan GE
1993
35%
Gadoversetamide
OptiMARK
Tyco / Mallinckrodt
1999 5%
Gadoteridol
ProHance
Bracco
1992
10%
Gadobenate dimeglumine
MultiHance
2004
The relative distribution of Omniscan related cases is out of proportion to the market share. }
NSF: A Class Issue??

7. Uses of High Dose Gd (+/- renal insufficiency):
MRA
Peripheral
Renal
Neuro-onc (local practice patterns)
X-ray use (k-edge of Gd is inefficient) CT
Conventional Angio
In clinical practice, where is high dose Gd being utilized???

8. Nephrogenic Systemic Fibrosis (NSF): Diagnosis
Most prominent and visible effects in the skin
Discoloration & texture changes
Tightening, thickening, swelling → joint immobility
Burning, itching, sharp pain
Skin changes can be insidious -> confused w/ peripheral edema
Resembles scleroderma and eosinophilic fasciitis
Absent: monoclonal gammopathies9, Raynaud phenomenon and autoantibodies2
Yellowish scleral plaques
Fibrotic changes can be widespread (liver, lungs, heart)
Biopsy Findings
Skin biopsy: thickened collagen bundles with surrounding clefts, mucin deposition, ↑ fibroblasts, ↑ CD34+ dendrocytes2
Muscle biopsy: ↑ myofibroblasts2

9. Nephrogenic Systemic Fibrosis (NSF): Clinical Appearance
Reddened or darkened areas
Texture changes
“woody” or peau d’orange
Cowper SE. Nephrogenic Fibrosing Dermopathy [NFD/NSF Website] Available at Accessed 02/01/2007.

10. Nephrogenic Systemic Fibrosis (NSF): Prognosis and Treatment
Course is chronic, progressive, variable
May be severely debilitating
Contractures - musculoskeletal
Wheelchair requirement in some
Complications may be fatal
Falls, fractures
Immobility, pneumonia
No consistently successful treatment
Symptoms may improve if renal function improves
Limited evidence for kidney transplantation, extracorporeal photopheresis (ECP)
Also in the literature: oral steroids, plasmapheresis
Sometimes stabilizes, but rarely spontaneously remits
No consistently effective therapy, but rapid correction in renal function may halt progression or reverse symptoms

11. What we know about Gd and NSF
Causation not established; data are suspicious, but have limitations
Retrospective studies
Info is limited (e.g., Creatinine at time of Gd exposure, contemporaneous administration)
Markedly prolonged half-life in renal failure
All cases had renal dysfunction at time of Gd exposure
Relationship between risk and level of dysfunction
Relationship between risk and cumulative dose?
Theoretical risk with any Gd contrast agent
Risk different across agents (e.g., due to excess chelate)?
Cases typically develop in days to few months after Gd exposure
Appears that cases in NSF registry were acidotic at the time of Gd exposure; Cumulative dose is a frequent admins in short time interval.
Roughly 90% of NSF cases associated w/ Omniscan, rate out of proportion to 35-40% market share
Documented cases developed within 2 days to 18 months after Gd exposure; most within a few months
Half-life of gadodiamide (hours)4
Normal renal function
1.3 h
End-stage renal failure
34.3 h
Hemodialysis (HD)
2.6 h
Peritoneal dialysis (PD)
52.7 h

12. Amine backbone structure
Brand Name, Chemical Name
Amine backbone structure
log Kst
(Stability constant)
OptiMark,
GdDTPA-BMEA
Linear
16.8
Omniscan,
GdDTPA-BMA
Magnevist,
GdDTPA
22.2
MultiHance
GdBOPTA
22.6
Gadovist
GdDO3A-butrol
Macrocyclic
21.0
ProHance,
GdHPDO3A
23.8
Dotarem
GdDOTA
25.6
Thermodynamic
stability

13. Gd-DTPA
(Magnevist)
Gd-DTPA-BMA
(Omniscan)
Gd-BOPTA
(MultiHANCE)
(Optimark)
Gd-DOTA
(Dotarem)
Gd-EOB-DTPA (Primovist)
Gd-BT-DO3A (Gadovist)
Gd-HP-DO3A (ProHANCE)

14. ML  M + L KD = [ M ] [ L ] [ ML ] 10 -23 = x  x 500 (mM)
OR, 5 x 10 –21 = x2
OR, 7 x 10 –10 = x = [Gd 3+ ]

15. Brand Name, Chemical Name Amine backbone structure log Kst
(Stability constant)
Dissociation rate in 0.1M HCl ( sec-1)
OptiMark,
GdDTPA-BMEA
Linear
16.8
>2.2x10-2
Omniscan,
GdDTPA-BMA
>2x10-2
Magnevist,
GdDTPA
22.2
1.2x10-3
MultiHance
GdBOPTA
22.6
-not reported-
Gadovist
GdDO3A-butrol
Macrocyclic
21.0
2.8x10-6
(estimated from data)
ProHance,
GdHPDO3A
23.8
6.4x10-5
Dotarem
GdDOTA
25.6
8.4x10-7

16. The themodynamic stability constant determines the concentrations
the themodynamic stability constant determines the concentrations of the Gd-chelate, free chelate, and free gadolinium at equilibrium, while rates of formation and dissociation, dictated by Ea , determine how rapidly these compounds reach equilibrium. In principle it is possible to have a chelate with a relatively low stability constant and high value of Ea, resulting in a ”kinetically trapped” chelate that does not dissociate on any relevant time scale.
The themodynamic stability constant determines the concentrations
of the Gd-chelate, free chelate, and free gadolinium at equilibrium;
The rates of formation and dissociation, dictated by Ea ,
determine how rapidly these compounds reach equilibrium.

17. Zn Gd L ↕ Gd + L Relaxivity ’s in solution pH 7.0 PO4
Compound  R1 at 3 days
Gd-DTPA ↓50%
Gd-DTPA-BMA ↓90%
Gd –BOPTA ↓60%
Gd-HP-DO NO SIG 
PO4
PO4
PO4
PbO4
Laurent S, et al.. Contrast Media Mol Imaging 2006;1:

18. Wedeking, Kumar and Tweedle
a very strong correlation between the dissociation rates of chelates in acid and the long-term deposition of Gd3+ in rat tissues such as liver and bone (femur).
a very strong correlation between the dissociation rates of chelates in acid and the long-term deposition of Gd3+ in rat tissues such as liver and bone (femur).
Wedeking, Kumar and Tweedle

19. “Acid dissociation rate constants were the most accurate parameters linking in vitro and in vivo dissociation. “ “Gd(HP-D03A) and Gd(DOTA)-, had the lowest residual Gd3+ in whole animals.” “No evidence of free Gd3+ could be detected for Gd(HP-D03A) using the free Gd3+ target tissues (liver and femur) at long residence times.”
Wedeking, Kumar and Tweedle, Mag Res Imag 1992

20. Algorithm for Gd-Enhanced MRI
Gd-MRI in last 7 days?
Consider delay to allow 7 days between Gd doses
START
YES NO
Proceeding
Inpatient
Outpatient / EU
“NO” to all
Response to Choyke questions
eGFR w/in 3 days
If worsening trend, day of exam
“YES” to any
eGFR within 4 weeks
DIALYSIS
eGFR < 30
On PD
eGFR < 30
On HD
eGFR < 30
No dialysis
eGFR 30-60
eGFR > 60
We have recently come across a questionarre that will obviate the need to obtain a serum creatinine in all patients.
Discussion w/ referrer
Discussion w/ referrer
Discussion w/ referrer
Limit Gd to mmol/kg*;
Consider hydration
Proceeding
Proceeding
Proceeding
Obtain central venous access
HD x 2 w/in 2 hrs and 24 hrs
Informed consent
ProHance™ or MultiHance™:
No > 0.1 mmol/kg
OK to proceed
*Except for run-offs, which are permitted up to 0.2 mmol/kg after risk:benefit discussion w/ referrer.

21. Algorithm for Gd-Enhanced MRI
Gd-MRI in last 7 days?
Consider delay to allow 7 days between Gd doses
START
YES NO
Proceeding
Outpatient / EU
“NO” to all
Response to Choyke questions
Point of service
query
We have recently come across a questionarre that will obviate the need to obtain a serum creatinine in all patients.
OK to proceed

22. Minimizing the Risk of NSF
Risk : benefit analysis
Reduce use of Gd in renal disease
FDA recommends avoiding for eGFR < 30
Consider non-contrast protocols
Consider alternate modality (e.g., CT, conventional angiogram)
Minimize dose if Gd is deemed imperative
Consider alternative agents
Gd-BOPTA (MultiHANCE®)
No reports (yet…)
Can reduce dose (has higher R1)
HOWEVER…clearance kinetics less favorable (binds protein)
ProHANCE
Hemodialyze patients with ESRD asap ?? *
Gd excretory rates 78%, 96%, 99% from 1st to 3rd HD session5
When using Gd, maximize pt condition*:
Hold drugs that decrease renal function (e.g., diuretics, NSAIDs)
Hydrate (consider bicarb – ? role of metabolic acidosis in NSF)
Informed consent
eGFR formula less accurate at 60, so may disqualify many people who can safely take Gd
Since 96% of Gd is cleared by end of 2nd HD session, consider 2 sessions, w/in 3 hours and w/in 24 hours
There are chemistry theories that predict dissociation of the Gd from its chelate in acidic environments.
*(not evidence based!!)

23. How do we screen for risk?
Choyke Questionnaire
Serum Creatinine
Point of Service Devices??

24. The Choyke Questionnaire
Pre-existing renal disease (OR 13.6)
Proteinuria (OR 8.7)
Prior kidney surgery (OR 8.1)
Hypertension (OR 5.4)
Gout (OR 4.6)
Diabetes (OR 3.2)
Completely negative responses:
450 (67%) of 673
446/450 (99%) Cr values 1.7 mg/dL
424/450 (94%) - normal Cr values
Choyke, et al. Tech Urol 1998; 4: 65.

25. Algorithm for Gd-Enhanced MRI
Gd-MRI in last 7 days?
Consider delay to allow 7 days between Gd doses
START
YES NO
Proceeding
Inpatient
Outpatient / EU
“NO” to all
Response to Choyke questions
eGFR w/in 3 days
If worsening trend, day of exam
“YES” to any
eGFR within 4 weeks
DIALYSIS
eGFR < 30
On PD
eGFR < 30
On HD
eGFR < 30
No dialysis
eGFR 30-60
eGFR > 60
We have recently come across a questionarre that will obviate the need to obtain a serum creatinine in all patients.
Discussion w/ referrer
Discussion w/ referrer
Discussion w/ referrer
Limit Gd to mmol/kg*;
Consider hydration
Proceeding
Proceeding
Proceeding
Obtain central venous access
HD x 2 w/in 2 hrs and 24 hrs
Informed consent
ProHance™ or MultiHance™:
No > 0.1 mmol/kg
OK to proceed
*Except for run-offs, which are permitted up to 0.2 mmol/kg after risk:benefit discussion w/ referrer.

26. Algorithm for Gd-Enhanced MRI
Gd-MRI in last 7 days?
Consider delay to allow 7 days between Gd doses
START
YES NO
Proceeding
Inpatient
Outpatient / EU
Response to Choyke questions
eGFR w/in 3 days
If worsening trend, day of exam
“YES” to any
Point of service
(stat creat)!
eGFR within 4 weeks
eGFR < 30
No dialysis
eGFR 30-60
eGFR > 60
We have recently come across a questionarre that will obviate the need to obtain a serum creatinine in all patients.
Discussion w/ referrer
Limit Gd to mmol/kg*;
Consider hydration
Proceeding
Informed consent
ProHance™ or MultiHance™:
No > 0.1 mmol/kg
OK to proceed
*Except for run-offs, which are permitted up to 0.2 mmol/kg after risk:benefit discussion w/ referrer.

27. Algorithm for Gd-Enhanced MRI
Gd-MRI in last 7 days?
Consider delay to allow 7 days between Gd doses
START
YES NO
Proceeding
Inpatient
eGFR w/in 3 days
If worsening trend, day of exam
DIALYSIS
eGFR < 30
On PD
eGFR < 30
On HD
We have recently come across a questionarre that will obviate the need to obtain a serum creatinine in all patients.
Discussion w/ referrer
Discussion w/ referrer
Proceeding
Proceeding
Obtain central venous access
HD x 2 w/in 2 hrs and 24 hrs
Informed consent
ProHance™ or MultiHance™:
No > 0.1 mmol/kg
*Except for run-offs, which are permitted up to 0.2 mmol/kg after risk:benefit discussion w/ referrer.

28. For Dialysis Patients

29. Hydration & HCO3 ???? Oral hydration Intravenous hydration Bicarb
1 Liter of H20 by mouth pre- and post- injection of contrast
Intravenous hydration
Contact the ordering physician or house staff for orders
Bicarb
150mEq of NaHCO3 (e.g. dilute in 1L D5W)
Pre: 1 hr prior to contrast administration
@ 3cc/kg/hr and for
Post: 6 hrs after contrast administration
@ 1cc/kg/hr
Modifications possible for pts with renal failure/CHF)
Encourage oral fluid intake if not on fluid restrictions

30. Perspective – Iodinated Contrast
Risk for severe adverse reactions
0.147% HI-ICM
0.031% NI-ICM (3/10,000)
Death
~ 1/100,000 either high or low osmolality.
Non Ionic Iodinated contast media
Caro AJR 1991 Apr; 156(4):

31. Conclusions
Gd is associated with NSF in pts with substantial renal insufficiency
Role of acidity seems likely
Risk:Benefit assessment is vital
What is the risk of not giving CE-MRI?
Guidelines should be submitted for institutional approval
Education is essential
Keep reading, keeping conversing!
Consider using Gadoteridol in high risk situations

32. References
Cowper SE. Nephrogenic Fibrosing Dermopathy [NFD/NSF Website] Available at Accessed 01/17/2007.
Cowper SE. Nephrogenic fibrosing dermopathy: the first 6 years. Curr Opin Rheumatol 2003; 15:785.
Grobner T: Gadolinium – a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrology Dialysis Transplantation 21(4): , April 2006.
Joffe P, Thomsen HS, Meusel M: Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Acad Radiol 5: , 1998.
Okada S et al. Safety of gadolinium contrast agent in hemodialysis patient. Acta Radiologica, 2001, 42(3):
Rofsky N et al. Renal lesion characterization with gadolinium-enhanced MR imaging: Efficacy and safety in patients with renal insufficiency. Radiology, July 1991, 180:
High WA, Ayers RA, Chandler J, Zito G, and Cowper SE. Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol 2007;56(1):21-26.
Stenver DI. Investigation of the safety of MRI contrast medium Omniscan. Danish Medicines Agency. Published May 29, Accessed February 6, 2007.
Boyd AS, Zic JA, and Abraham JL. Gadolinium deposition in nephrogenic fibrosing dermopathy. J Am Acad Dermatol. January
Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 2006;17:
Sadowski EA, Bennett LK, Chan MR, Wentland AL, Garrett AL, Garrett RW, et al. Nephrogenic systemic fibrosis: Risk factors and incidence estimation. Radiology Published January 31, Accessed February 1, 2007.
Gadolinium-based MR Contrast Agents and Nephrogenic Systemic Fibrosis1
Phillip H. Kuo, MD, PhD, Emanuel Kanal, MD, Ali K. Abu-Alfa, MD and Shawn E. Cowper, MD Published online before print January 9, 2007 (Radiology 2007, /radiol ) This Article
Submit a response
Alert me when this article is cited
Alert me when eLetters are posted
Alert me if a correction is posted
Services
this article to a friend
Similar articles in this journal Similar articles in PubMed
Alert me to new issues of the journal
Download to citation manager
Google Scholar
Articles by Kuo, P. H.
Articles by Cowper, S. E.
PubMed
PubMed Citation
© RSNA, 2007

34. For Non-Dialysis Patients (Conservative)
Creatinine / eGFR value OR
Choyke Questionnaire
We have recently come across a questionarre that will obviate the need to obtain a serum creatinine in all patients.
*diuretics, NSAIDs, and ACE inhibitors (the latter when used with a diuretic)
**Intravenous hydration with sodium bicarbonate for 1hr prior and 6hrs post Gd.

35. “Acid dissociation rate constants were the most accurate parameters linking in vitro and in vivo dissociation. “ “The most stable and least dissociation labile macrocycles, Gd(HP-D03A) and Gd(DOTA)-, had the lowest residual Gd3+ in whole animals.” “No evidence of free Gd3+ could be detected for Gd(HP-D03A) using the free Gd3+ target tissues (liver and femur) at long residence times.”

36. Gadolinium Chelates MR contrast agents (metal + ligand = chelate)
Gd  Brightening on T1-WI’s
Gd is toxic!
Chelate ‘shields’ the free metal while preserving its relaxation effect. Gd
Agents differ by how they are enclosed by the agents

37. Gadolinium Chelates MR contrast agents
Brightening on T1-weighted images
Gd is toxic!
Chelate used to ‘shield’ the free metal while preserving its relaxation effect.
Gd3+
Gd-DTPA-BMA
(Omniscan)
Gd-DOTA
(Dotarem)
Agents differ by how they are enclosed by the agents

38. Nephrogenic Systemic Fibrosis (NSF): The Basics
Originally known as Nephrogenic Fibrosing Dermopathy (NFD)
Systemic proliferation of connective tissue (NSF)
~ 215 cases reported worldwide from
Strong epidemiologic association with Gd
All FDA-reviewed cases had prior Gd exposure
Appears to be a class issue (Omniscan >>> Magnevist, OptiMARK)
All had renal insufficiency at exposure (most ESRD, on dialysis)
Proinflammatory events in many11 (e.g., vascular surgery, sepsis, thrombosis)
Early data suggests 3-5% incidence w/ Gd in setting of renal failure11
So far no co-factor identified (dialysate, ACEIs, EPO, etc.)
Theories of pathogenesis:
Liberation of Gd ion from carrier molecule10
Cutaneous deposition of free Gd ion10
Gd target attracts circulating fibrocytes (CFs)
CFs differentiate in the dermis to resemble dermal fibroblasts
Since it appears not to have existed prior to 1997, has been strong suspicion that a recently introduced agent or shift in the std of care might be the culprit
Investigators have examined: dialysate (and contaminants thereof), EPO, iron, coag abnormalities, ACE inhibitors, vascular surgery, induced anti-phospholipid antibodies
Investigation by dermatopathologists and the CDC has so far failed to identify a single causative medication
Male ≈ female
Middle-aged are most affected
Variety of ethnic backgrounds are represented

40. G=S
G=-RT(LogKeq) k=Ae-Ea/RT

43. Staging of Chronic Kidney Dz
Death
Expected Outcomes ↑Risk of CIN, Dialysis, Death
↑Risk of NSF
Stage 1 Stage II Stage III Stage IV Stage V
CKD risk factors/ Mild ↓ Moderate ↓ Severe ↓ Kidney
damage w/ kidney kidney kidney failure
preserved GFR fxn fxn fxn ESRD
Kidney Fxn
(GFR [ml/min/1.73 m2])
Modified from: Am J Kidney Dis 2002;39(suppl):S1-266.

45. Algorithm for Choyke Screen; Outpt Efficacy Study
Outpatient / EU
Response to Choyke questions
Pre- service
Creat/ eGFR
“Yes” to any
“NO” to all
Point of service
query
“Yes”, “Yes”
“Yes”, “No”
“No”, “Yes”
“No”, “No”
Point of service
Creat/ eGFR
Point of service
Creat/ eGFR
Exam w/o
Creat
No F/U
Creat/ eGFR
F/U
Creat/ eGFR;
date
St 1 St 2 St 3 St 4 St 5

46. Algorithm for Gd-Enhanced MRI
Gd-MRI in last 7 days?
Consider delay to allow 7 days between Gd doses
START
YES NO
Proceeding
Inpatient
Outpatient / EU
Response to Choyke questions
eGFR w/in 3 days
If worsening trend, day of exam
“YES” to any
Point of service
(stat creat)!
eGFR within 4 weeks
eGFR < 30
No dialysis
eGFR 30-60
eGFR > 60
We have recently come across a questionarre that will obviate the need to obtain a serum creatinine in all patients.
Discussion w/ referrer
Limit Gd to mmol/kg*;
Consider hydration
Proceeding
Informed consent
ProHance™ or MultiHance™:
No > 0.1 mmol/kg
OK to proceed
*Except for run-offs, which are permitted up to 0.2 mmol/kg after risk:benefit discussion w/ referrer.

47. What we know about Gd and NSF
Causation not established; data are suspicious, but have limitations
Retrospective studies
Info is limited (e.g., Creatinine at time of Gd exposure, contemporaneous administration)
Markedly prolonged half-life in renal failure
All cases had renal dysfunction at time of Gd exposure
Relationship between risk and level of dysfunction
Relationship between risk and cumulative dose?
Theoretical risk with any Gd contrast agent
Documented cases with Omniscan >>Magnevist, OptiMARK
Risk different across agents (e.g., due to excess chelate)?
Cases typically develop in days to few months after Gd exposure
Appears that cases in NSF registry were acidotic at the time of Gd exposure; Cumulative dose is a frequent admins in short time interval.
Roughly 90% of NSF cases associated w/ Omniscan, rate out of proportion to 35-40% market share
Documented cases developed within 2 days to 18 months after Gd exposure; most within a few months
Half-life of gadodiamide (hours)4
Normal renal function
1.3 h
End-stage renal failure
34.3 h
Hemodialysis (HD)
2.6 h
Peritoneal dialysis (PD)
52.7 h