2. Serum creatinine is not an accurate measure of the kidney function in potential kidney donor.
- How would you assess the renal function in a potential kidney donor?
- What are the different methods available and how accurate they are?
- Do you always measure the split function? What is the evidence?
It´s necessary to use the estimated glomerular filtration rate (eGFR), expressed in mL/min/1.73m2 which is initially calculated using the Epidemiology of Chronic Kidney Disease without confirmation (1). (Unclassified) Collaboration Equation (CKD-EPI).
When indicated, more accurate ways of assessing renal function can be used:
1 – Inulin clearance: a molecular weight polysaccharide, since it is filtered by the glomeruli, it is not synthesized or metabolized by the tubules, it is physiologically inert and is not reabsorbed or secreted by the renal tubules. Except for being an exogenous marker, it fulfills the other criteria that an ideal marker of glomerular filtration should have. However, despite its precision, this method is invasive and time-consuming, requires constant infusion due to the requirement of a plasmatic concentration of inulin in dynamic balance, also requires bladder catheterization, significant volume of blood sample and complex laboratory dosage, which makes the complicated test implementation
2 – Serum Cystatin C: a cysteine proteinase inhibitor protein synthesized by all nucleated cells at a constant production rate, and can be found in various biological fluids, such as serum, seminal fluid and cerebrospinal fluid. Serum levels of cystatin C are not affected by muscle mass and change very little with age, clear advantages when compared to creatinine. The main attributes of cystatin C as a biochemical marker to assess renal glomerular filtration function are its small size and high isoelectric point, which allow this protein to be easily filtered through the glomerular membrane, being reabsorbed in the proximal tubule in a significant proportion and , then, almost completely catabolized in this site, not being excreted in the urine.
3- GFR measurement using radioisotopes:
– 51Cr-EDTA: considered the radiopharmaceutical of choice for the determination of GFR by plasma clearance in clinical routine, since it has plasma clearance very similar to that of inulin and is quantified in the scintillator
– 125I-iothalamate: it is a simple and accurate test, performed with a single subcutaneous injection. This technique is efficient, reproducible, simple and practical, even in healthy children and in patients with mild or advanced kidney disease.
There are indications for measure the split function: disparity in size between the two kidneys (>10%) in a potential donor, if the renal function is close to the acceptable limit for donation, or when there is abnormality or anatomical complexity.
In these situations, the measurement is used by combining 51Cr-EDTA and 99mTc-DMSA.
1_ to assess the kidney function of potential living kidney donor simply we start with estimated GFR depending on serum creatinine.
However, it is not accurate as creatinine is affected by many factors as muscle mass, BMI and protein intake.
2_ other methods to evaluate kidney function:
_ we can proceed to measured GFR depending on urine craetinine and Na and serum creatinine and Na.
_many equations for estimated GFR as CKD_EPI that needs serum creatinine and cystatin C.
3_ measuring split kidney function by radioactive substance:
_ is done routinely in some centers.
_ other guidelines perform it only in case of presence discrepancy in kidney size more than 10 % or in case of presence of anatomical , urological or vascular abnormalities in initial kidney imaging.
1- Estimated of glomerular filtration rate (eGFRcr) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and employing a creatinine assay with calibration traceable to standardized reference material. A correction factor must be applied to eGFRcr values estimated for people of African-Caribbean or African family origin (multiply eGFRcr by 1.159).
2- Measurement of GFR using a reference standard measure such as clearance of
inulin, 51Cr-EDTA, 125I-iothalamate or iohexol.
3- Divided renal function, measured by combining 51Cr-EDTA and 99mTc-DMSA, done where there is a size difference between the two kidneys (>10%) in a potential donor, if renal function is close to the acceptable threshold for donation, or when there is anatomical abnormality or complexity. The kidney with lower function is usually donated.
4- Normal Kidney Function & Change in Kidney Function with Aging:
Recent data accurately define gender and age-specific mean and normal ranges for
measured GFR in over 3000 healthy potential UK living kidney donors. Data on
glomerular filtration rate measured by 51Cr-EDTA clearance in donors at two large
UK centres were amalgamated with patient level data from a recent study of GFR in
over 1800 potential donors from 15 UK centres (6,7). This study conclusively
indicates that renal function corrected for BSA is significantly higher for men than
women after age 40 years. GFR in this normal population remains stable in both
sexes until aged around 40 years and then declines each decade at a rate of 6.6 mL/min/1.73m2 for men and 7.7 mL/min/1.73m2 in women.
for example if the age between 20 to 29 years, the measured GFR is (74 to 126 )
(mL/min/1.73m2) for males and (72 to 125) mL/min/1.73m2 for females.If the age is 55, the measured GFR is (60 to 112) mL/min/1.73m2 for males and (56 to 109) mL/min/1.73m2 for females.
The initial assessment of renal function in potential living kidney donors is by measurement of serum creatinine
This is most frequently done (CKD-EPI) equation to estimate glomerular filtration rate (eGFRcr).
The estimated glomerular filtration rate (eGFR), should be used as the basis for the first screening of donor candidates
calculated using a creatinine test that has been standardised to the International Reference Standard. (B1)
GFR must then be measured using a reference technique (mGFR), such as the clearance of 51Cr-EDTA, 125iothalamate, or Iohexol, in accordance with the British Society of Nuclear Medicine’s recommendations. (B1)
Split Renal Functions :
Measured by Technetium-99m isotope renal scan :
Indicated if:
If there is a volume difference between the two kidneys (more than 10%)
Renal function is almost at the appropriate threshold for donations
There is anatomical abnormality or complexity
How would you assess the renal function in a potential kidney donor?
Measuring eDFR , GFR and Differential kidney function assessment
eGFR through many formulas where the most used is CKD – EPI Equation
GFR using insulin or cr EDTA or serum cystatin
Differential kidney function assessment using DMSA scan
Transplantation can proceed if GFR is more than 90 ml/min/1.73 m2 and rejected if below 60
Also assessment of kidneys needs check of proteinuria as well as ultrasound abdomen and pelvis.
Do you always measure the split function? What is the evidence?
Differential kidney assessment of a donor is requested in the presence of kidney anatomical abnormalities with more than 10 % discrepancy in size or vascular or parenchyma abnormalities.and the kidney with the lower split function is used for donation .
It should be expressed by
· Calculated GFR (not serum creatinine) in mL/min per 1.73 m2, as recommended by KDIGO 2017, and should be repeated twice for confirmation.
· Urinary or plasma clearance of inulin.
· Urinary or plasma clearance of iothalamate.
· Urinary or plasma clearance of 51Cr-EDTA.
· Urinary or plasma clearance of iohexol.
· Urinary clearance of 99mTc-DTPA.
· Other options are measured Creatinine clearance was (mCrCl) and GFR estimated from serum creatinine and cystatin C levels (eGFRcr-cys)
Assessment of GFR in the donor is the main tool to identify best donor selection. Unilateral nephrectomy resulting in reduced renal mass by 50 % hence GFR drops by 50% however the compensatory mechanism in the other kidney limit the reduction to 30%. Ibrahim HN et al 2009, Lenihan CR et al 2015.
The KDIGO guidelines forbid donation when the GFR is less than 60 mL/min/1.73 m2, regardless of age.
A GFR of 60 mL/min/1.73 m2 appears to be a universal contraindication to donation. Similarly, even for the youngest candidates, a GFR greater than 90 mL/min/1.73 m2 is never considered incompatible with donation. (KL Lentine et al., 2017).
Yes the spit function is requested for the donor to decide which kidney will be donated by the living donor as suggested by KDIGO guidelines. Though, the evidence that justifies doing so is limited (1,2,3) however recently, Won Ik Seo (2020) reported that the donors who donated the better-functioning kidney had poorer renal function after donation(4).
1. Won Ik Seo, Chan Ho Lee, Tae Yong Park, Wansuk Kim, Kweonsik Min, Jae Il Chung, Yun Hee Park, Sun Woo Kang, Yeong Hoon Kim, Min Ji Kim, Yunmi Kim and Taehee Kim. Role of Prior Split Renal Function for Living Kidney Transplantation in Recipients and Donors. Transplantation Proceedings, 2020-12-01, Volume 52, Issue 10, Pages 3002-3008.
2. 8. Andrews P.A., Burnapp L.: British Transplantation Society/Renal Association UK guidelines for living donor kidney transplantation 2018: summary of updated guidance. Transplantation 2018; 102: pp. e307.
3. 9. Lentine K.L., Kasiske B.L., Levey A.S., et. al.: KDIGO clinical practice guideline on the evaluation and care of living kidney donors. Transplantation 2017; 101: pp. S1-S109.
4. 10. Ibrahim H.N., Foley R., Tan L., et. al.: Long-term consequences of kidney donation. N Engl J Med 2009; 360: pp. 459-469.
We assess renal function in a potential donor by:
Different methods available include:
eGFR methods:
CKD-EPI equation provides the least biased estimate at normal or mildly reduced GFR values, and recommended as the formula to calculate eGFR in living kidney donor candidates
mGFR methods: using exogenous filtration markers labelled with nuclear tracer (chromium 51/technetium 99m)
Creatinine clearance(CrCl): overestimates GFR by 10–20%, creating a
positive bias. It is susceptible to error due to inaccurate urine collections.
At our centre, we always use eGFR using CKD-EPI equation and mGFR using Tc99 labelled DTPA scan before considering living kidney donor for donation. Not all guidelines recommend using mGFR methods for estimating GFR for living donation.(1)
Reference:
How would you assess the renal function in a potential kidney donor?
· KDIGO recommends use of eGFR from serum creatinine for initial assessment, followed by confirmation with one or more additional measurements, depending on availability: measured GFR, 24-hour creatinine clearance, eGFR from the combination of serum creatinine and cystatin C (eGFRcr-cys), or repeat eGFR. The last option (ie, repeat eGFR) is the least preferred.
· If kidney function is evaluated via a creatinine clearance, the adequacy of the 24-hour urine collection should be carefully assessed . Furthermore, the dietary intake of protein should be at least 1 g of protein per kg of body weight since a low-protein diet may decrease creatinine clearance by as much as 10 mL/min .
· Creatinine is derived from the metabolism of creatine in skeletal muscle and from dietary intake of cooked meat. It is released into the circulation at a relatively constant rate. Mean serum creatinine values differ between males and females (due to differences in muscle mass and, therefore, creatinine generation) as well as other factors]. Such factors are non-GFR determinants of the serum creatinine. Estimated GFR calculated with any creatinine-based equation will therefore be less accurate in people with more prominent non-GFR determinants of the serum creatinine (eg, high or low muscle mass or creatine/creatinine intake, children, patients with cirrhosis, serious chronic illness such as chronic heart failure, amputations or neuromuscular disease, or those with a high-protein or vegetarian diet)
· There are several key limitations of using creatinine to estimate GFR (eGFR). These include variations in creatinine production, variations in creatinine secretion, extrarenal creatinine excretion, and issues associated with creatinine measurement. (1)
· Initial evaluation of donor candidates should be using estimated glomerular filtration rate (eGFR), expressed as mL/min/1.73m2 computed from a creatinine assay standardised to the International Reference Standard. GFR must subsequently be assessed by a reference measured method (mGFR) such as clearance of 51Cr-EDTA, 125iothalamate or Iohexol performed according to guidelines published by the British Society of Nuclear Medicine. (3)
What are the different methods available and how accurate they are?
Do you always measure the split function? What is the evidence
It is not used all the time Differential kidney function, determined by 99mTcDMSA scanning is recommended where there is >10% variation in kidney size or significant renal anatomical abnormality. (C1 recommendation)(3).Split renal function (SRF), or differential renal function, is a determination of the relative contribution of each of the two kidneys to total renal function. SRF is helpful for evaluating and guiding the management of a wide range of renal disorders. SRF can be estimated with renal scintigraphy performed with various radionuclides, including 99mTc-labeled dimercaptosuccinic acid (99mTc-DMSA), 99mTc-labeled mercaptoacetyltriglycine (99mTc-MAG3), and 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) . Other noninvasive modalities and procedures for calculating SRF include CT angiography , dynamic contrast-enhanced MR urography , and DWI . Among these, 99mTc-DMSA renal scintigraphy has been considered the most sensitive method for proving the existence of parenchymal damage due to acute or chronic pyelonephritis and acquiring data on differential kidney function.(2)
1- Up to date
2- Cao X, Xu X, Grant FD, Treves ST. Estimation of Split Renal Function With 99mTc-DMSA SPECT: Comparison Between 3D Volumetric Assessment and 2D Coronal Projection Imaging. AJR Am J Roentgenol. 2016 Dec;207(6):1324-1328. doi: 10.2214/AJR.16.16307. Epub 2016 Sep 13. PMID: 27623376; PMCID: PMC5559895.
3- BTS/RA Living Donor Kidney Transplantation Guidelines 2018
Question 1
British transplantation guidelines : recommend mGFR in everyone after initial screening using eGFR.
KDIGO guidelines : recommend eGFR,followed by confirmation with mGFR or CrCl.
OPTN recommend mGFR or 24-hour CrCL.
Question 2
1.eGFR : creatinine based equations (Cockcroft-Gault,MDRD,CKD-EPI)
The 2009 CKD-EPI equation gives the least biased estimate at normal or mildly reduced GFR values, and it is recommended as the equation to calculate eGFR in living kidney donor.But it lacks accuracy as it different from mGFR by 30%.
2.mGFR : using an exogenous filtration marker is considered the gold standard for GFR assessment , historically inulin but currently used methods for mGFR include chromium 51-labeled EDTA ,iohexol and iothalamate.Renal clearance is better than plasma clearance.
3.CrCL : due to cost effectiveness and availability , many centers rely on CrCl for assessment of GFR.
Question 3
No, split kidney function is recommended where there is more than 10% variation in kidney size or significant renal anatomical abnormality.
Evaluation of GFR can be done by estimation which is a mathematical equation based on multiple variants like age, sex, race, and serum creatinine which give you estimated values of the GFR but still measured GFR is more accurate, and not all equations valid for all population and can be affected by multiple factors like muscle mass, pregnancy, and liver failure. On the other hand, measured GFR is more complicated and can be done using an endogenous substance like creatinine, or cystatin c, an exogenous substance like inulin, and an isotopic substance like tech-99. Still, inulin clearance is the gold standard as its substance is not reabsorbed or secreted by kidney tubules and is freely filtered from the glomeruli.in clinical practice, screening is done by estimated eGFR followed by confirmation by measured GFR the exact equation, and the exact substance for estimation and measurement based on each center experience. Most centers use CKD-EPI for eGFR and 24h urinary creatinine clearance for measured GFR. guidelines are shown in the attached picture.
Based on BTS guidelines, a renal isotope scan affords the exact split function of each kidney and if there is a difference of more than 10% in GFR the higher kidney should be kept for the donor. But still, not mandatory and some centers use kidney size as an alternative method and if there is more than a 2cm difference considered significant. In our center experience, we use split function as routine practice because ultrasound size evaluation is operator dependent and may be mis-leaded by misevaluation
References :
British Transplantation Society http://www.bts.org.uk March 2018 The Evaluation of Kidney Function in Living Kidney Donor Candidates 2021 Sep 30; 2(9): 1523–1530.
Serum cr and urea
Urine R/E and urine for hematuria and proteinuria
Urine for protein: creatinine ratio
24 hrs urine protein
e GFR using CKD-EPI
confirmed by m GFR if available or repeat CKD-EPI +cr + Cystatin
U/S abdominal looking for kidney size and any abnormality
If there is a difference in size by > 10% then
DMAS or EDTA scan
CT angio for renal arteries
Methods to GFR calculation are:
A- eGFR, determined by a marker (either endogenous or exogenous) that should be freely filtered, and not reabsorbed, metabolized or secreted.
1- S. Cr has not had all the above characteristics as it is secreted by renal tubules (up to 40%) also
S. Cr depends on muscle mass, dietary protein, age, and race, some drugs like cimetidine and it is not suitable for AKI. (needs stable kidney function)
2- Cystatin-C is better than Cr because it is not affected by body mass and gender.
Equations are:
1. Cockcroft-Gault equation
2. MDRD is not accurate in Asian.
Both are not good in extremes of age.
3. CKD-EPI (2021 is the best it includes the gender, age and s.cr). it is more accurate in obese, black, elderly, and DM.
B- m GFR
Using
· Inulin which is the gold standard
· 51 CR EDTA
· 99mTc DTPA
· Iohexol or Iothalamate
C- Creatinine Clearance (CrCl)
It is calculated by measuring urinary 24 hrs creatinine concentration multiple by total urine volume divided by serum plasma concentration. (U x V)/ P
It is overestimates GFR by 10 –20% because its secreted by the renal tubule)
No, slit kidney function is measured if there is a discrepancy in kidney size of more than 10% or an anatomical abnormality. Renal scintigraphy by 99mTc-DTPA is done and a kidney with less function is usually donated.
How would you assess the renal function in a potential kidney donor?
What are the different methods available and how accurate they are?
Do you always measure the split function? What is the evidence?
Over many years, a lot of studies were done about the best marker for kidney function.
Creatinine is not the most accurate one because it is affected by many factors like muscle bulk, sex, activity and drugs, However, it is the most practical and most available test.
Many creatinine-based formulae are available to estimate GFR to avoid radio-isotopic scanning and 24h urine collection for creatinine clearance which carry a lot of cost and time consumption.
To assess kidney function of a donor we need to assess the e-GFR, excretory function, presence of blood and protein in urine.
Inulin clearance is the most accurate method to assess GFR. However, it is not practically used.
KDIGO 2012 guideline recommend the following:
1- E-GFR using serum creatinine and cystatin-c.
2- Split renal function by using renal isotopic scan DTPA.
For all donors we do split renal function via renal isotopic scan so we do nephrectomy to the kidney with lower perfusion.
CTA of renal vessels of the donors and plan the future anastomosis of the transplant.
According to the guidelines, the initial assessment is done using serum creatinine and estimation of GFR using CKD-EPI equation. Confirmation of GFR with m GFR using Cr-EDTA, iothalamate or iohexol clearance as a reference.
Screen for albuminuria using spot urine albumin/creatinine ratio, if there is proteinuria, confirm with 24 hour urinary protein.
screen for hematuria with microscopic examination of urinary sediment, persistent microscopic requires further evaluation.
In the presence of current or previous kidney stones , check for the cause
Direct measurements of GFR provide the most accurate evaluation of kidney function, guidelines do not systematically use this measurement as a reference.
mGFR :
1- Inulin : the gold standard
2- 51CR EDTA is the most widely used
3- 99mTc DTPA
4- iohexol or iothalamate.
It is known that CrCl overestimates mGFR while eGFR underestimates it, therefore, a reliable GFR could be the combination of two measurement methods.
eGFR :
1- Cockcroft-Gault
2- MDRD
3- CKD-EPI ( using creatinine or cycstatin C or combined)
Do you always measure the split function? What is the evidence?
It is not routinely done. But if there discrepancy in kidney size (> 10% difference), vascular or urological abnormalities by renal imaging. Split GFR measurement by 99mTc-DTPA is done in order to keep the best kidney for the recipient.
· Q1: The best method is mGFR by EDTA, iothalamate or DTPA. But initially eGFR by CKD-EPI, MDRD, Cockraft-gault or 24-hour creatinine clearance or cystatin-based formula if available.
· Q2: This 24-hour creatinine clearance is the most available but less accurate one.
MDRD or cockraft-gault formula are better for lower GFRS. CKD-EPI formula is more accurate than them. the most accurate method is inulin clearance that is not available. Hence, mGFR based on EDTA and other radioisotopes are the most accurate.
· Q3: No, but when available the split function test should be done to evaluate the donor’s kidneys more accurate, especially if there are more than 1 cm difference between two kidneys or detected renal scar by US.
1-We asses the donor kidney function by calculating the eGFR
2-Measurement of GFR by inulin or cystatin c which is more accurate,the other method calculated by CKD-EPI equation
3-No we don’t measured the split function unless there is different in size between the two kidneys
Assessment of renal function in candidate donors mainly relies on estimated GFR, as sCr per se is not the best accurate tool, other equations as ckd EPI, cystatin c as a biomarker based on the British Transplantation Society Living Donor Kidney Transplantation Guidelines 2018 not to depend only on creatinine.
Different methods applicable recently, DMSA scan, to measure the total GFR as well as the split renal function.
Measurement of the split renal function pre donation is necessary as it reveals hidden pathology with even normal total GFR, as variations between both kidneys exceeding 10 % or renal anatomical abnormalities in some cases. Evidence c
•How would you assess the renal function in a potential kidney donor?
-Cardiovascular assessment
-Common issues and co-morbidities in the potential donors – Age – Obesity – Diabetes – Hypertension – Proteinuria, Haematuria and Nephrolithiasis
-Imaging
>Kidney USS
>Abdominal CT Angio
>Abdominal MRI Angio
to assess : Kidney size • Kidney vasculature • Kidney pelvis and ureter • Kidney tumors • Kidney stones
1) serum renal profile, Urinalysis, 24 hours urine protein quantification, Renal system ultrasound, Renal CT angiogram .
2)
Inulin – The gold standard of exogenous filtration markers is inulin.
Cystatin C- Cystatin C is filtered at the glomerulus and not reabsorbed. However, it is metabolized in the tubules, which prevents use of cystatin C to directly measure clearance.
3) Yes if anatomical abnormality detected in donor.
Q1- How would you assess the renal function in a potential kidney donor?
Initial donor kidney function assessment should include serum creatinine level . although it is non sensitive test for assessing the GFR as there may be substantial loss of GFR befeore s creatinie elevation.
Estimated GFR can be calculated depending on CKD EPI equation which is the n=best of others .( there is significant imprecision of e GFR around the normal range .
More accurate measurement of GFR is by using reference standard measures such as clearance of
inulin, 51Cr-EDTA, 125I-iothalamate or iohexol. 51Cr-EDTA is the most widely used test .
Q2- What are the different methods available and how accurate they are?
There is different methods for assessing donor kidney function each with variable sensitivity and accuracy
1- Estimated GFR assessment
Indirectly assesses the GFR depending on s creatinine or cystatine level .
Cockgroft gault .
MDRD
CKD-EPI (THE MOST ACURATE ONE )
E GFRcr – eGFRcyst – eGFRcr-cyst
2- Measured GFR .
mGFR: inulin , iothalamate, 51Cr-EDTA , iohexol , 99mTc-DTPA .
Q3- Do you always measure the split function? What is the evidence?
No, it is not needed routinely in every donor . it is measured by combining 51Cr-EDTA and 99mTc-DMSA,
It is indicated in
· When there is a size discrepancy between the two kidneys (>10%) ,
· if renal function is close to the acceptable threshold for donation,
· when there is anatomical abnormality or complexity.
Note : the kidney with lower function is usually donated.
References :
British Transplantation Society http://www.bts.org.uk March 2018 The Evaluation of Kidney Function in Living Kidney Donor Candidates 2021 Sep 30; 2(9): 1523–1530.
*The methods for assessing GFR are in continuous debate, and the kidney function thresholds for accepting a donor may vary according to the guidelines.
*While direct measurements of GFR provide the most accurate evaluation of kidney function, guidelines do not systematically use this measurement as a reference.
*Finally, it is known that CrCl overestimates mGFR while eGFR underestimates it, therefore, another way to have a reliable GFR could be the combination of two measurement methods.
Attached guidelines and evidence for current estimation of renal function for the potential donor .
References :
1-McLeay SC, Morrish GA, Kirkpatrick CM, Green B. Encouraging the move towards predictive population models for the obese using propofol as a motivating example.
2-Documento de consenso sobre la Enfermedad Renal Crónica .
3-Thomassen SA, Johannesen IL, Erlandsen EJ, Abrahamsen J, Randers E. Serum cystatin C as a marker of the renal function in patients with spinal cord injury. Spinal Cord. (2002)
4-Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al.. CKD-EPI Investigators. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. (2012) 367:20–9. 10.1056/NEJMoa1114248
5-Filler G, Priem F, Lepage N, Sinha P, Vollmer I, Clark H, et al.. Beta-trace protein, cystatin C, beta(2)-microglobulin, and creatinine compared for detecting impaired glomerular filtration rates in children. Clin Chem. (2002) 48:729–36. 10.1093/clinchem/48.5.729
6-Shannon JA, Smith HW. The excretion of inulin, xylose and urea by normal and phlorizinized man. J Clin Invest. (1935)
According to British Transplantation Society Living Donor Kidney Transplantation Guidelines 2018:
regarding assessment of renal function Initial evaluation of donor candidates should be using estimated glomerular filtration rate (eGFR), expressed as mL/min/1.73m2 computed from a creatinine assay standardised to the International Reference Standard. (B1)
GFR must subsequently be assessed by a reference measured method (mGFR) such as clearance of 51Cr-EDTA, 125iothalamate or Iohexol performed according to guidelines published by the British Society of Nuclear Medicine. (B1
Differential kidney function, determined by 99mTcDMSA scanning is recommended where there is >10% variation in kidney size or significant renal anatomical abnormality. (C1)
Glomerular filtration rate is gold standard diagnostic measurement for estimation of kidney function can’t measure directly in humans .but determined from clearance measurements or serum levels of filtration markers, which are exogenous or endogenous solutes that are mainly eliminated by glomerular filtration.
Urinary clearance equals the rate of urinary excretion of the marker divided by its plasma concentration. Plasma clearance is the amount of marker eliminated from plasma per unit time factored by its plasma concentration. The gold standard method, which is recommended in selected circumstances, is urinary or plasma clearance of an exogenous filtration marker. it is noticed that blood levels of endogenous filtration markers are used to estimate GFR . Creatinine, which is widely available and frequently measured, is the most commonly used endogenous marker .
Cystatin C is another endogenous filtration marker. It is less commonly available compared with creatinine and is recommended as a confirmatory test.
split function for diagnosis of congenital abnormalities or anatomical abnormalities
References
uptodate
*In a potential kidney donor , we assess renal function with serum creatinine , eGFR by (CKD-EPI) or creatinine clearance , urine analysis , urinary protein /creatinine ratio , pelvi-abdominal ultrasound.
*The best method in calculation is CKD-EPI , others are MDRD, cr-EDTA ,the other direct measurement of renal function mGFR: urinary or plasma clearance of inulin , iothalamate, 51Cr-EDTA , iohexol and the radio-isotope scan TC-99m DTPA .
*Split renal function is routine done in centers to assess pre-operative both kidneys and identify the dominant kidney, kidney which has lower renal function is donated.
Currently in our center we usually calculate eGFR, for structural changes a ultrasound KUB, and a urinalysis for any proteinuria and hematuria.
According to KDIGO and KDOQI guidelines EPI-CKD method is a better choice, others are MDRD, SHWATZ, MODIFIED SHWATZ, CCG, cr-EDTA , etc, but non is 100% accurate, every equation has its limitations like wait, extreme of age, muscle mass, pregnancy etc.
No, we usually do not do split function, otherwise any anatomical finding in scan, then we will proceed for ( DTPA, MAG3 etc).
Creatinine depending on age and muscle mass, may not be accurate for evaluation but is practical and widely used in the form of estimated GFR (eGFR) calculated by formulas like CKD-EPI 2021 and MDRD. The Cocroft formula is not widely used anymore. In special situations, although it may vary depending on overhydration and usage of diuretics, creatinine clearance may be utilized. Instead, renal scintigraphy is used, but we mostly use it in cases of renal parenchymal problems and inconsistency of size and thickness between kidneys.
I apologize but I can not find my previous answer on that scenario!
Assessment of renal function is very important for kidney donors for Assessment of adequacy of the renal function for the donor and also for the quality of kidney being transplanted with.
This include the structural and functional test of the kidney. Functional test include GFR assessment using the traditional biomarkers like creatinine and cystatin and estimation formulae. The estimation formulae of most often in use is CKD Epi but there others like creatinine clearance, MDRD, CKD creatine and cystatin c, full age spectrum ect. The other functional screening means is urine analysis for blood and protein and quantification of urine protein as in 24hrs urine albumin or protein. Structural assessment will require ultrasound to see the size, rule our obstruction, ghe position and the presence of stones or cyst
Creatinine as a marker of kidney function is smear my so many non GFR determinant and even cystatin as great it is , it has been found to be affected by inflammation, steroid, thyroid function
The estimated equations are estimated as their names implies, they have their own precision, the ones with more markers of kidney function seem to do better.
The other direct measurement of renal function like inulin clearance, TC DTPA and EDTA Chromium, etc are radio isotopic studies done in specialised centres. They are meant for reference after the initial screening . Split renal function is routine done in most centres to determine pre- surgery the kidney the dominant kidney
In general LKD evaluation include:
What are the different methods available and how accurate they are?
More detailed assessment of potential donor function requires an accurate
measurement of GFR using a reference standard measure such as clearance of
inulin, 51Cr-EDTA, 125I-iothalamate or iohexol (1). This is used to inform potential
donors of the long-term risks of donation and potential recipients of the anticipated
level of kidney function being transplanted. 51Cr-EDTA is the most widely available
reference test. Recent data show a significant coefficient of variation of 51Cr-EDTA
measured GFR in potential living kidney donors across UK centres (2).
Direct measurement of glomerular filtration rate (GFR) using EDTA-Cr51 and the estimations based on creatinine (eGFR): Cr clearance (CCr) with 24-hour urine and estimated using Cockroft-Gault (adjusted by using body surface area-Mosteller formula-SC), MDRD-4, MDRD-6, and CKD-EPI
Formulas
– It Depend on the centre , some centres are doing as a routine , others do it only when indicated as below :
To help in decision-making where there is
1- a size disparity between the two kidneys (>10%) in a potential donor
2- if renal function is close to the acceptable threshold for donation
3- if there is anatomical abnormality or complexity.
(BTS/RA Living Donor Kidney Transplantation Guidelines 2018)
Initial assessment of renal function in living kidney donors is by measurement of serum creatinine which is usually performed by an estimate GFR using the CKD- Epidemiology Collaboration. Measurement of GFR using a clearance of inulin, 51Cr-EDTA, 125I-iothalamate or iohexol offer a more detailed assessment of potential donor function.
Initial assessment of renal function in living kidney donors is by measurement of serum creatinine which is usually performed by an estimate GFR using the CKD- Epidemiology Collaboration. Measurement of GFR using a clearance of inulin, 51Cr-EDTA, 125I-iothalamate or iohexol offer a more detailed assessment of potential donor function. These measurement are used to inform potential donors of the long-term risks of donation and potential recipients of the anticipated level of kidney function being transplanted. The mean age at donation of the cohorts has been around 45 years and the lower threshold for donation a GFR >80 mL/min/1.73m2. If the patient age is equal or more than 35 year old eGFR should be greater than 80 ml/min. If patient age is less than 30 year old eGFR should be greater than 90 ml/min.Donor kidney function should be expressed as glomerular filtration rate in mL/min per 1.73m2 ratger than mL/min. During the initial assesment the donor GFR should be estimated from seru creatinine (KDIGO Guidelines). Donor GFR should be confirmed by using a measured GFR (mGFR) (with an exogenous filtration marker) or a measured creatinine clearance (mCrCl) or an estimated GFR (using the combination of serum creatinine and Cystatin C) or a repeat estimated GFR from serum creatinine. Radionuclides or contrast agents is used to evaluate single kidney GFR in case of parenchymal, vascular or urological abnormalities or asymmetry of kidney size
I use the split function (combination of combination of 51Cr-EDTA and 99mTc-DMSA) in the presence of >10% variation in kidney size or anatomical abnormality of the kidneys.
The kidney with lower renal function is donated where the potential donor is considered suitable for donation
According to the guidelines, eGFR by CKD-EPI is the prefered calculator for measuring GFR; most guidelines recommend second-step evaluation using mGFR or cr-cl.
eGFR: Cockroft-gault
MDRD
CKD-EPI (the prefered method)
eGFRcr
eGFRcyst
eGFRcr-cyst
mGFR: urinary or plasma clearance of inulin.
urinary or plasma clearance of iothalamate,
urinary or plasma clearance of 51Cr-EDTA.
urinary or plasma clearance of iohexol.
urinary clearance of 99mTc-DTPA
No, only if there is size discrepancy, to evaluate the function of each kidney alone using DMSA scanning.
# How would you assess the renal function in a potential kidney donor?
*The initial assessment of renal function in potential living donors started initially by kidneys U/S, detecting the proteinurea and by measurement of serum creatinine.
*Estimating the GFR using the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI) as ml/min/1.73m2.
*Measurement of GFR using a reference standard measure such as clearance of inulin, 51Cr-EDTA, I-iothalamate or iohexol. 51 Cr- EDTA is the most widely viable reference test.
*Divided renal function, measured by combining 51C-EDTA and 99m Tc-DMSA, when there is a size disparity between the two kidneys (>10%), or when there is anatomical abnormality or complexity. Some centers choose to perform split function testing routinely on all donors.
#What are the different methods available and how accurate they are?
*eGFR: several creatinine- based equations(Cockcroft-Gault, MDRD,CKD-EPI…).The 2009 CKD-EPI equation provides the least biased estimate at normal or mildly reduced GFR values and has been recommended in calculate eGFR in living donor, however, there are lake of accuracy, especially in subject with close to normal GFR. In addition eGFRcr provides a slight underestimation with median difference between m GFR and e GFR of 3.5 ml/min per1.73m2.Less affected by muscle mass and diet, cystatin C by itself is not better at predicting GFR compared with creatinine. The 2012 eGFR cr +Cystatin C that includes both fares better at estimating GFR than either alone.
*m GFR, using an exogenous filtration marker is considered the gold standard for GFR assessment.
*CrCL, given the cost, resource, and time intensiveness, and lack of availability of mGFRmethods.
#Do you always measure the split function? What is the evidence?
Divided renal function, measured by combining 51Cr-EDTA and 99mTc-DMSA, can
be helpful in decision-making where there is a size disparity between the two
kidneys (>10%) in a potential donor, if renal function is close to the acceptable
threshold for donation, or when there is anatomical abnormality or complexity. If
suitable for transplantation, the kidney with lower function is usually donated. Some
centres choose to perform split function testing routinely on all donors, although the
evidence for doing so is limited.
#Guidelines for Living Donor KidneyTransplantation
United Kingdom Guidelines
© British Transplantation Society http://www.bts.org.uk
March 2018
The Evaluation of Kidney Function in Living Kidney Donor Candidates
2021 Sep 30; 2(9): 1523–1530.
_Renal function assessment of potential kidney donor:
-Urinalysis.
– eGFR based on serum creatinine is more accurate than using serum creatinine ..
– 2009 CKD-EPI creatinine equation ;having les bias with normal GFR is used unless other equations have been shown to be more accurate in certain limitations. GFR can be confirmed with one or more of the following :
• Measured GFR using exogenous substance eg urinary or plasma clearance of inulin, iothalamate, 51Cr-EDTA, iohexol , or urinary clearance of 99mTc-DTPA
• Measured creatinine clearance :
• eGFR using combination of serum creatinine and cystatin C
• Estimated GFR using serum creatinine .
. eGFR cys is not more accurate then eGFRcr, but using 2 markers has more precision; so eGFRcr-cys is preferred to eGFRcr & eGFRcys.
– Cystatin C is not affected by muscle mass and equations do not require specification of race. Hence, eGFRcys maybe more accurate than eGFRcr-cys in people with extremes of muscle mass, very high or very low meat intake, or race-ethnicity other than black or white.
_Split function measurement:
needed to leave the better kidney for the donor if there is clue to difference between the 2 kidneys : parenchymal, vascular or urological disorders or asymmetry of kidney size, split function should be done.
References:
Uptodate
– S.cr , eGFR using cr based formula ( CKD -EPI ) & measured GFR using 51cr EDTA , iohexol or 125 iothalamate .
– 99TC DMSA scan to assess split kidney function
– eGFR :
1- Cockcroft-Gault
2- MDRD
3- CKD-EPI ( using cr or cyctatin c or combined)
– Measured GFR :
1- Inulin : the gold standard
2- 51CR EDTA P the most widely used
3- 99mTc DTPA
4- iohexol or iothalamate.
– It Depend on the centre , some centres are doing as a routine , others do it only when indicated as below :
To help in decision-making where there is
1- a size disparity between the two kidneys (>10%) in a potential donor
2- if renal function is close to the acceptable threshold for donation
3- if there is anatomical abnormality or complexity.
(BTS/RA Living Donor Kidney Transplantation Guidelines 2018)
How would you assess the renal function in a potential kidney donor?
Combination of m GFR (measured GFR) and eGFR equations (estimated GFR),
in association with basic lab and radiological imaging, KFT (kidney function test), urine analysis and pelvi-abdominal US.
What are the different methods available and how accurate they are?
· mGFR (measured GFR) provide the most accurate way to assess GFR. This is done through cr clearance, nulin clearance, 51Cr-EDTA, 125I-iothalamate, or iohexol ,
1. CrCl, depends on creatinine which is secreted by renal tubules hence overestimates mGFR: creatinine is on the other hand affected by age, sex, muscle mass and diet.
2. The exogenous tracers are considered the gold standard , such as 51Cr-ethylenediaminetetraacetic acid (EDTA) , 125I-iothalamate
3. Inuline clearance: not metabolized nor absorbed or secreted by renal tubules, not 100% precise as it has a coefficient of variation of approximately 7% on repeated measurements in the same subjects .
4. 125I-iothalamate is secreted and reabsorbed by renal tubules and overestimates GFR
5. Ethylenediaminetetraacetic acid is reabsorbed through renal tubules and underestimates GFR.
6. DTPA and Iohexol are protein bound tend to prolonged stay in circulation and underestimate GFR.
7. Cystatin C (CysC), freely filtered, totally reabsorbed and not secreted by renal tubules. can be affected by hyperthyroidism, high-dose steroids, and cardiovascular disease .
· eGRF ( estimated GFR) : assessment of GFR is done through equations
eGFR equations underestimates GFR, incorporate endogenous markers, as well as demographic and anthropometric parameters .
1. the chronic kidney disease epidemiology (CKD-EPI)
2. Other equations include cystatin C (CysC), CysC +Cr , beta-trace protein , and beta2 microglobulin (B2M)..
Do you always measure the split function? What is the evidence?
No
According to British Transplantation Society-BTS 2018, mGFR with split function is done whenever there is more than 10% disparity between both kidneys choosing the less functioning for donation.
However Canadian Transplant Society-CTS 2015 recommends split function in asymmetric kidneys (>1 cm) .
References:
Pérez Loredo J, Lavorato CA, Negri AL. Tasa de filtración glomerular medida y estimada. Numerosos métodos de medición (Parte I). Rev Nefrol Dial Traspl. (2017) 35:153–64. Available online at: https://www.revistarenal.org.ar/index.php/rndt/article/view/34
Eurotransplant Statistical Report 2017. Available online at https://www.eurotransplant.org/cms/index.php?page=sr2017. (accessed February 9, 2019).
Davies DF, Shock NW. The variability of measurement of insulin and diodrast tests of kidney function. J Clin Invest. (1950) 29:491–5. doi: 10.1172/JCI102285
How would you assess the renal function in a potential kidney donor?
· Urinalysis with microscopy; urine culture (if clinically indicated).
· Measurement of urinary protein and albumin excretion.
· Measurement of glomerular filtration rate (GFR) by isotopic methods or a creatinine clearance calculated from a 24-hour urine collection.
· Genotyping for living-donor candidates with a family history of autosomal dominant polycystic kidney disease if age <40 years and there is one or more cysts present (by computed tomography [CT] scan or ultrasound) or if age ≥40 years and there is more than one cyst on imaging
· Donor candidates with a history of kidney stones or nephrolithiasis (>3 mm) identified on imaging must have a 24-hour urine stone panel including calcium, oxalate, uric acid, citric acid, creatinine, and sodium
What are the different methods available and how accurate they are?
·
Assessment of GFR in clinical practice – In most clinical settings, blood levels of endogenous filtration markers are used to estimate GFR (eGFR).
1. Creatinine, most commonly used endogenous marker
2. Cystatin C, is less commonly available compared with creatinine and is recommended as a confirmatory test
·
Estimating GFR (primary approach)
1. using the 2021 chronic kidney disease epidemiology (CKD-EPI) creatinine equation is recommended
2. the 2009 CKD-EPI equation
3. the Modification of Diet in Renal Disease (MDRD) study equation
4. the Cockcroft-Gault equation
·
Confirmation of eGFR (when needed) used:
1. For those with prominent non-GFR determinants of serum creatinine (eg, high or low muscle mass, a high protein diet, creatine supplements, vegetarian diet, liver disease, extreme frailty)
2. when confirmation of a CKD diagnosis is required in someone with a creatinine-based eGFR is 45 to 60 mL/min per 1.73 m2 and no other features of CKD (such as albuminuria or radiologic abnormalities)
3. in potential kidney donors
– To confirm eGFR in most patients, cystatin C is measured and the 2021 CKD-EPI creatinine- cystatin C equation is used
· Measurement of GFR in selected settings
when necessary, GFR can be measured using urinary clearance of an ideal filtration marker (eg, inulin, iothalamate, iohexol) or using plasma clearance (of 51Cr-EDTA or iohexol).
· GFR assessment for drug dosing
– using the Cockcroft-Gault equation to estimate kidney function
– use of the Cockroft-Gault equation could lead to inaccuracies in drug dosing in patients with kidney disease
· Limitations of creatinine-based eGFR
1. variations in creatinine production, variations in dietary intake (vegetarian diet, creatine supplements) or reduction in muscle mass (amputation, malnutrition, muscle wasting) produce different amounts of creatinine
2. variations in creatinine secretion, apart from the increase in creatinine secretion with a decline in true GFR, creatinine secretion can vary over time and can also be affected by certain disorders (nephrotic syndrome, sickle cell disease) and drugs (trimethoprim, Famotidine, imatinib)
3. extrarenal creatinine excretion, intestinal bacterial overgrowth and increased bacterial creatininase activity
4. issues associated with creatinine measurement. diabetic ketoacidosis, or bilirubin may affect the assay that measure creatinine.
Do you always measure the split function? What is the evidence?
We do not measure it routinely, but if there is any doubt about the kidney function or difference between both kidneys size, we measure it.
-s creatinine measurement,
-eGFR by Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration, ,(CKD-EPI),
-Urine analysis ,protein /creatinine ratio in urine.
-ultrasound for size and echogenicity.
What are the different methods available and how accurate they are
*eGFR:
commonly used creatinine-based equations (Cockcroft-Gault, Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI), the 2009 CKD-EPI equation provides the least biased estimate at normal or mildly reduced GFR values, and has been recommended as the equation to calculate eGFR in living kidney donor candidates .
*mGFR: mGFR using an exogenous filtration marker is considered the gold standard for GFR assessment but not available except in few centres.
*CrCl: CrCl overestimates GFR by 10–20%, creating a positive bias,Major limitations of creatinine clearance are dependency on accuracy of timed collection, and overestimation as a result of distal tubular creatinine secretion.
*In the United States, the Organ Procurement and Transplantation Network policy on living donation mandates either measured GFR or creatinine clearance as part of the evaluation.
GFR declines with healthy aging, and most international guidelines recommend use of age-adapted selection criteria.
The 2017 Kidney Disease: Improving Global Outcomes Guideline for the Evaluation and Care of Living Kidney Donors diverges from other guidelines and recommends using absolute cutoff of <60 ml/min per 1.73m2 for exclusion and ≥90 ml/min per 1.73m2 for acceptance, and determination of candidacy with intermediate GFR on the basis of long-term ESKD risk.
Do you always measure the split function? What is the evidence?
It is recommended when there is kidney size discrepancy in ultrasound or if there is anatomical abnormality.
, the kidney with lower function is usually donated.
The Evaluation of Kidney Function in Living Kidney Donor CandidatesNeetika Garg, Emilio D. Poggio and Didier Mandelbrot
Kidney360 September 2021, 2 (9) 1523-1530; DOI: https://doi.org/10.34067/KID.0003052021
How would you assess the renal function in a potential kidney donor?
Serum creatinine and estimation of GFR using CKD-EPI equation
What are the different methods available and how accurate they are?
Estimated GFR using Cockcroft-Gault, MDRD and CKD-EPI.
Creatinine-EDTA which is more accurate than serum creatinine
Do you always measure the split function? What is the evidence?
Yes, perform split function for all donors to decide the kidney with less function to be donated.
Reference: BTS /guidelines for living donor kidney transplantation
Baseline RFTs
urine analysis
GFR measurement by DTPA scan, we can use different formulas but none is perfect to tell us true GFR.
Different methods for GFR measurement are as mentioned above along with creating clearance which overestimates GFR
Cock craft
MDRD can also be used
We always do a split function test to keep the better kidney with the donor
Many thanks Dr Heba, Dr Manal MAlik and Dr Sehar, ,
Let us move to week 4.
Ajay
Initial assessment with serum creatinine and estimation of GFR using CKD-EPI equation
Confirmation of GFR with measured GFR using Cr-EDTA, iothalamate or iohexol clearance.
Evaluation of albuminuria: screening for albuminuria using spot urine albumin/creatinine ratio, if there is proteinuria, confirm with 24 hour urinary protein
Evaluation for hematuria with microscopic examination of urinary sediment, persistent microscopic hematuria requires further evaluation.
Donors with prior or current kidney stones should be assessed for the cause.
Differential kidney function using combination of Cr-EDTA and Tc-DMSA scan, to assess the kidney with better function and is beneficial when there is anatomical abnormality or size disparity.
Estimated GFR using creatinine based equations as Cockcroft-Gault, MDRD and CKD-EPI, CKD-EPI is the preferred equation in normal or mildly reduced GFR and is used in evaluation of potential donor.
Measured GFR: using exogenous filtration marker, accurate in GFR assessment, determine the long-term risk of donation.
Creatinine clearance: May overestimate GFR by 10-20% and is susceptible to error due to inaccurate urine collection
We perform split function for all donors to decide the kidney with lower function to be donated,
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
Lentine KL, Kasiske BL, Levey AS, Adams PL, Alberú J, Bakr MA, Gallon L, Garvey CA, Guleria S, Li PK, Segev DL. KDIGO clinical practice guideline on the evaluation and care of living kidney donors. Transplantation. 2017 Aug;101(8 Suppl 1):S7.
Garg N, Poggio ED, Mandelbrot D. The evaluation of kidney function in living kidney donor candidates. Kidney360. 2021 Jan 1.
GFR Measurement (mGFR)
Inulin is a fructose polysaccharide found in the roots of a variety of plants. It is not metabolized nor reabsorbed or secreted by the renal tubules, therefore, it can be quantitatively recovered in the urine after intravenous administration. Inulin clearance is constant and independent in plasma concentration. Inulin clearance continues to be the gold standard for the measurement of GFR.
GFR estimation depend on Creatinine (Cr). It’s amino acid generated in the muscle from ingested food. It spreads in total body water, it is filtered by the glomerulus, secreted by the tubules, and excreted in the urine.
2 method can be estimate GFR
modification of diet in renal disease (MDRD) and CKD-EPI.
MDRD Compared with Cockroft-Gault, MDRD is more accurate. The most important limitation of this formula is that it underestimates GFR.
CKD-EPI was validated in a cohort including not only patients with CKD but also individuals with normal renal function which provides a better correlation with normal subjects.
That’s why this equations better use in living kidney donor.
Another endogenous substance used to estimate GFR is Cystatin C (CysC), a protein that inhibits cysteine and is secreted by the majority of cells. CysC is freely filtered by the glomerulus, almost fully reabsorbed, and metabolized by tubular epithelial cells, it is not secreted and urinary excretion is negligible. Blood levels are less affected than creatinine by body mass, diet, age, and sex. Nevertheless, they can be affected by hyperthyroidism, high-dose steroids, and cardiovascular disease.
24hr Cr cl use to estimate GFR in donor person and all donor to accept donation should GFR > 80ml/ min. . It is well known that CrCl overestimates GFR and can lead to the approval of donors with a lower GFR than the optimal adjusted for age and sex.
KDIGO Clinical Practice Guideline for LKD evaluation recommends using eGFR as a test to identify candidates who may not need a subsequent GFR assessment.
combination of 2 methods, such as a CrCl and eGFR, may be more clinically useful.
Serum creatinine is the commonest bio marker available as a measure of renal function. But there are lot of demerits of creatinine in terms of accurate marker of renal function but in acute and chronic renal dysfunction.
Hence, instead of absolute serum creatinine, GFR was considered superior measure of renal function because apart from serum creatinine, it also takes into account weight, gender, age, ethnicity etc.
Now there are broadly 2 way of assessing GFR
At our center we do DTPA GFR for estimation because there is quite discrepancy in serum creatinine values and hence causes error in eGFR values to the tune of +/- 15ml/min/1.73sqm.
Split function estimation is by default included in DTPA reports in our labs but it’s ideally recommended when there is kidney size discrepancy in ultrasound. There could be other benefits like as a baseline value of function of remaining kidney after nephrectomy which can later be used to monitor remaining kidney function of donor. But further studies are needed to prove the same.
Harper KC, Salameh J-P, Akhlaq N, McInnes MDF, Ivankovic V, Beydoun MH, et al. (2021) The impact of measuring split kidney function on post-donation kidney function: A retrospective cohort study. PLoS ONE 16(7): e0253609. https://doi.org/10.1371/journal.pone.0253609
How would you assess the renal function in a potential kidney donor¿
measurement of glomerular filtration rate (GFR) using EDTA-Cr51 and the estimations based on creatinine (eGFR): Cr clearance (CCr) with 24-hour urine and estimated using Cockroft-Gault (adjusted by using body surface area-Mosteller formula-SC), MDRD-4, MDRD-6, and CKD-EPI
What are the different methods available and how accurate they are?
the different methods of GFR assessment, including eGFR, creatinine clearance, and measured GFR, and the current guidelines on GFR thresholds for donor acceptance. eGFR obtained using the 2009 CKD Epidemiology Collaboration equation that, although the best of estimating estimations, tends to underestimate levels and has limited accuracy, especially near-normal GFR values.
Measured GFR is considered the gold standard, although there is some variation in performance characteristics, depending on the marker and technique used. Major limitations of creatinine clearance are dependency on accuracy of timed collection, and overestimation as a result of distal tubular creatinine secretion.
The 2017 Kidney Disease: Improving Global Outcomes Guideline for the Evaluation and Care of Living Kidney Donors diverges from other guidelines and recommends using absolute cutoff of <60 ml/min per 1.73m2 for exclusion and ≥90 ml/min per 1.73m2 for acceptance, and determination of candidacy with intermediate GFR on the basis of long-term ESKD risk.
The role of cystatin C and other newer biomarkers, and data on the effect of predonation GFR on not just ESKD risk, but also advanced CKD risk and cardiovascular outcomes are needed.
eGFR Of the commonly used creatinine-based equations (Cockcroft-Gault, Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI)
mGFR: mGFR using an exogenous filtration marker is considered the gold standard for GFR assessment.
CrCl: given the cost, resource, and time intensiveness, and lack of availability of mGFR methods, many centers in the United States rely on timed CrCl for assessment of GFR
the accuracy of urine collection is assessed by comparing the measured creatinine excretion rate to the expected creatinine excretion rate of 20–25 mg/kg in men and 15–20 mg/kg in women
Do you always measure the split function? What is the evidence?
No
Split renal function (SPR) is a determination of the relative contribution of each of the two kidneys . It gives a useful information in several conditions such as evaluating unilateral renal disorders, assessing individual kidney function before and after intervention, and before live donor nephrectomy. Different radiopharmaceuticals such as technetium-99m dimercaptosuccinic acid (99mTc-DMSA), technetium-99m diethylenetriaminepentaaceticacid (99mTc-DTPA), technetium-99m mercaptoacetyltriglycine (99mTc-MAG3), Iodine 131 orthoiodohippurate and more recently technetium-99 m ethylenedicysteine (99mTc-EC) were used, However, 99mTc-DMSA as a static renal agent is considered the most reliable method to measure relative renal function and the most appropriate tracer for renal cortical imaging . I
The dSRF did not affect the post-KT renal function or graft survival in recipients.
How would you assess the renal function in a potential kidney donor?
Renal function in potential kidney donor is assessed by the followings1:
· Measurement of serum creatinine.
· An estimate of glomerular filtration rate (eGFRcr) using CKD-EPI equation and employing a creatinine assay with calibration traceable to standardized reference material.
· More detailed assessment requires an accurate measurement of GFR using a reference standard measure such as clearance of inulin, 51Cr-EDTA, 125I-iothalamate or iohexol.
· The Split or Divided renal function is measured by combining 51Cr-EDTA and 99mTc-DMSA, can be helpful in decision-making. where there is a size disparity between the two kidneys (>10%) in a potential donor.
What are the different methods available and how accurate they are?
GFR FORMULAE ;ESTIMATED AND MEASURED
Formulae that are commonly used in estimating GFR are Cockcroft-Gault, MDRD, CKD-EPI and the Nankivell formula which is an equation derived from kidney transplant recipients.
• The MDRD equation was derived from patients with CKD & it is well known that the formula underestimates GFR in patients with high GFR values.
• The CKD-EPI creatinine equation was derived from participants with higher GFR.CKD-EPI formula was derived from the MDRD introduces a “correction” for patients with lower creatinine values. It is as accurate as MDRD in estimating GFR in patients with GFR <60 mL/min/1.73 m2 and better than MDRD at estimating higher GFR.
• The MDRD 6-variable equation was considered the most accurate estimation of GFR; however, only at 1 and 5years post TX.
• CG was derived from normal kidney function population taking into consideration the patient’s serum creatinine, age, and weight. Hence, CG tends to overestimate GFR in obese or edematous patients.
• Nankivell equation was derived from an Australian-Caucasian kidney transplant recipients who treated with calcineurin inhibitors,Nankivell formula was reported to overestimates GFR significantly compared to measured GFR.
In terms of accuracy, studies showed that CG, MDRD, and Nankivell equation fared only 73%, 76%, and 68%, respectively.
Overall ,estimation of GFR in solid organ Tx is poorly validated and numerous sources of bias exist.
The reasons why GFR estimation formulas fail both in short- and long-term studies compared with measured formulas are addressed and are mainly due to:
• The differences in patient characteristics, change in weight, muscle mass and medication over time.
• The use of estimating methods for GFR determination are especially troublesome in clinical trials where correct assessment of GFR are crucial in determining correct dosing of medication and determination of a valid outcome.
MEASURED VS ESTIMATED GFR FORMULAE:
Measured glomerular filtration rate (mGFR) with an exogenous filtration marker is the most accurate, either with inulin, 51CrEDTA-clearance, 99mTc DTPA, iohexol or iothalamate. However, these methods are complex and more expensive to use in daily clinical routine.
Therefore, many centers prefer to use the estimating methods, (eGFR) being an easy measure of GFR . However, it should be clear that these methods are based on correlations or linear regression models between P-creatinine, P-cystatin C or both and variable patient variables and mGFR, in rather heterogeneous populations. Despite high correlation quotients between eGFR and mGFR seen in many of these studies, it is questionable whether such correlations reflect a clinically useful agreement between eGFR and mGFR in different patient populations, which most often they do not. In this context, it is important to look at predictive performance of different equations, that is, absolute bias, relative bias and accuracy, as suggested in the KDOQI guidelines.
Serum Creatinine as a measure of Kidney function :
Serum creatinine is an unreliable marker of renal function in transplanted patients due to many factors:
• The catabolic state seen in chronic illness, malnutrition, the weight change induced by muscle wasting and fluid overload that is often present in these patients.
• Changes and fluctuations in the tubular secretion of creatinine is also an important factor .
• Creatinine clearance measured by 24-hour collection of urine has been widely used, but is also biased by unstable tubular secretion of creatinine and the inaccurate collections of urine.
Do you always measure the split function? What is the evidence?
The split function, not always being measured as evidence for doing so is limited1. It has to be measured in the followings:
· where there is a size disparity between the two kidneys (>10%) in a potential donor.
· if renal function is close to the acceptable threshold for donation.
· when there is anatomical abnormality or complexity.
If the potential donor is suitable for transplantation, the kidney with lower function is usually donated.
Reference
1. BTS/RA Living Donor Kidney Transplantation Guidelines 2018
Exellant Assafi.
Serum creatinine is not an accurate measure of the kidney function in potential kidney donor.
How would you assess the renal function in a potential kidney donor?
The initial assessment of renal function in potential living kidney donors is by
measurement of serum creatinine. This is most commonly performed by an estimate
of glomerular filtration rate (eGFRcr) using the Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) equation and employing a creatinine assay with calibration
traceable to standardised reference material. A correction factor must be applied to
eGFRcr values estimated for people of African-Caribbean or African family origin
(multiply eGFRcr by 1.159) (1).
Screening identifies potential living donors with evidence of existing CKD (eGFRcr
<45 mL/min) who may be saved further investigation as potential kidney donors and
who may require investigation in their own right. However, there is significant
imprecision of eGFRcr around the normal range, making it unsuitable as a marker of
renal function without confirmation (1).
What are the different methods available and how accurate they are
More detailed assessment of potential donor function requires an accurate
measurement of GFR using a reference standard measure such as clearance of
inulin, 51Cr-EDTA, 125I-iothalamate or iohexol (1). This is used to inform potential
donors of the long-term risks of donation and potential recipients of the anticipated
level of kidney function being transplanted. 51Cr-EDTA is the most widely available
reference test. Recent data show a significant coefficient of variation of 51Cr-EDTA
measured GFR in potential living kidney donors across UK centres (2).
Direct measurement of glomerular filtration rate (GFR) using EDTA-Cr51 and the estimations based on creatinine (eGFR): Cr clearance (CCr) with 24-hour urine and estimated using Cockroft-Gault (adjusted by using body surface area-Mosteller formula-SC), MDRD-4, MDRD-6, and CKD-EPI
Formulas
Do you always measure the split function? What is the evidence
Divided Renal Function
Divided renal function, measured by combining 51Cr-EDTA and 99mTc-DMSA, can
be helpful in decision-making where there is a size disparity between the two
kidneys (>10%) in a potential donor, if renal function is close to the acceptable
threshold for donation, or when there is anatomical abnormality or complexity. If
suitable for transplantation, the kidney with lower function is usually donated. Some
centres choose to perform split function testing routinely on all donors, although theevidence for doing so is limited (4).
References
1. National Institute for Health and Care Excellence (2014). Chronic kidney disease
in adults: assessment and management. NICE guideline (CG182).
2. Peters AM, Howard B, Neilly MD, et al. The reliability of glomerular filtration rate
measured from plasma clearance: a multi-centre study of 1,878 healthy potential
renal transplant donors. Eur J Nucl Med Mol Imaging 2012; 39: 715-22.
3. Fleming JS, Zivanovic MA, Blake GM, Burniston M, Cosgriff PS. British Nuclear
Medicine Society. Guidelines for the measurement of glomerular filtration rate
using plasma sampling. Nucl Med Commun 2004; 25: 759-69.
4. KDIGO Living Donor Guidelines, 2016.
Well done.
Initial evaluation by using estimated glomerular filtration rate, subsequently be assessed by a reference measured method .
Initial assessment of renal function of a potential donor is by measurement of serum creatinine. This is the commonly measured estimated GFR using CKD EPI equation. In case of African- Caribbean or African family origin it needs multiplication by 1.159. This can identify potential live kidney donor with existing CKD. More detailed assessment done by using standard measures such as clearence of inulin, 51 Cr EDTA, 125 I-iothalamate or iohexol. 51 Cr- EDTA is mostly available test.
Divided renal function, measured by combining 51Cr-EDTA and 99Tc-DMSA, is used where there is > 10% size disparity in two kidneys or when there is anatomical abnormality or complexity. Evidence is limited.
Thankyou.
In our renal transplant center we do the following
according to Kidney Disease: Improving Global Outcomes-KDIGO 2017The initial recommended test is CKD-EPI + Cr, and then confirmatory testing, as needed.
Depending on availability, mGFR, with exogenous or endogenous markers, eGFR combining CysC + Cr or repeating an eGFR Cr can be used
Another tool suggested by the guideline is a web-based calculator to estimate the probability of having an mGFR below 60, 70, 80, and 90 ml/min/1.73 m2 (http://ckdepi.org/equations/donor-candidate-GFR-calculator/).
It is divided into two steps.
To accept a candidate routinely, they suggest an eGFR > 90 ml/min/1.73 m2 and < 60 ml/min/1.73 m2 to exclude the participant. For values in the middle decisions should be individualized and other risk factors should be considered.
This recommendation was based on a meta-analysis with almost 5 million healthy subjects where they found that for an eGFR > 90 ml/min/1.73 m2, the life-long risk of developing CKD was approximately 1% of any age and race. For subjects aged 60 years or older with an eGFR between 60 and 89 ml/min/1.73 m2, the risk is less than 1%
NO
Measurement of the split renal function (SRF) by nuclear scintigraphy can be helpful in deciding which kidney should be donated by the donor when the kidneys show a size disparity or an anatomical abnormality or complexity
thanks
Exellant,practical plan which is logically used by most centers.
Is there an explanation in the last study why subjects older than 60 and a eGFR 60 to 89 would have a less chance of developing CKD than younger ones with eGFR >90?
because younger one live longer time with single kidney and they not reach the age of developing HTN , DM or other renal disease
How would you assess the renal function in a potential kidney donor?
-Urinalysis.
-The KDIGO 2012 CKD guidelines for GFR evaluation in the general population recommend expressing kidney function as GFR and not as serum creatinine concentration, and recommend expressing GFR in mL/min per 1.73 m2 rather than mL/min which is applicable to living kidney donor candidates. The eGFR based on serum creatinine (eGFRcr) is the recommended initial test.
– The 2009 CKD CKD-EPI creatinine equation should be used unless other equations have been shown to be more accurate. It has minimal bias at normal GFR .
– GFR estimates using serum creatinine concentration are more accurate in estimating mGFR than the serum creatinine concentration alone .
-Donor GFR should be confirmed using one or more of the following measurements, depending on availability:
• Measured GFR (mGFR) using an exogenous filtration
marker, preferably urinary or plasma clearance of inulin, urinary or plasma clearance of iothalamate, urinary or plasma clearance of 51Cr-EDTA, urinary or plasma clearance of iohexol, or urinary clearance of
99mTc-DTPA
• Measured creatinine clearance (mCrCl)
• Estimated GFR from the combination of serum creatinine and cystatin C (eGFRcr-cys) following recommendations from the KDIGO 2012 CKD guideline
• Repeat estimated GFR from serum creatinine (eGFRcr)
-In general eGFRcys is not more accurate then eGFRcr; however using 2 filtration markers improves precision of GFR estimates compared with using either marker alone; thus eGFRcr-cys is generally recommended over eGFRcr or eGFRcys.
-Advantages of cystatin C compared with creatinine are that cystatin C is not affected by muscle mass and current equations do not require specification of race. Therefore, eGFRcys maybe more accurate than eGFRcr-cys in people with very large or very small muscle mass, very high or very low meat intake, or race-ethnicity other than black (African American or African European) or white.
Do you always measure the split function? What is the evidence?
– If there are parenchymal, vascular or urological abnormalities or asymmetry of kidney size on renal imaging, single(“divided” or “split”) kidney GFR should be assessed using radionuclides or contrast agents that are excreted by glomerular filtration (eg, 99mTc-DTPA).
Referrence:
KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors August 2017 . Volume 101 . Number 8S-
Well done remember we do split function test to leave the better one for the donor.