5. A 29-year-old athletic male with excellent kidney function offered a kidney to his father who 61 years old, 111 mismatch, no DSA. He has no significant past medical history. No evidence of haematuria, but there is mild proteinuria on 24 hours urine collection (300 mg/day).
- What is your management?
- Substantiate your answer
Dear All
If I ask you to do only one test to confirm his proteinuria, what would it be and under what condition?
What is the sport urine test and how accurate it is?
Short and sweet reply, dear colleague Dr Ben
Regards,
Ajay
overnight proteinuria . compared to exercise test for protein.
Short and sweet reply, dear colleague Dr Sobair.
Regards,
Ajay
Urine albumin is the preferred measure of urine protein for assessment of kidney damage. Proteinuria can be secondary to overflow proteinuria in cases of paraproteinemia. Screening of donor albuminuria should be done using urine albumin creatinine ratio (ACR) in a random urine sample, Then confirmation with albumin excretion rate (mg/day).Potential donor with albumin excretion rate more than 100 mg/day should not be accepted for transplantation.
As per KDIGO guidelines:
Donor proteinuria should be measured as albuminuria, not total urine protein. Initial evaluation of donor albuminuria (screening) should be performed using urine albumin-to-creatinine ratio (ACR) in a random (untimed) urine specimen. Donor albuminuria should be confirmed using: • Albumin excretion rate (AER, mg/day [mg/d]) in a timed urine specimen • Repeat ACR if AER cannot be obtained
The gold standard for measurement of protein excretion is a 24-hour urine collection,
but this is cumbersome for patients and often collected inaccurately. Hence the urine
albumin /creatinine ratio (ACR) or protein /creatinine ratio (PCR) in a spot urine
sample are now the preferred methods as both correlate well with 24-hour urinary
protein excretion and overcome inaccuracies related to incomplete urine collection.
Both are supported by Kidney Disease: Improving Global Outcomes (KDIGO) as
appropriate methods to aid in the diagnosis of chronic kidney disease, but ACR is
preferred by both KDIGO and the National Institute for Health and Care Excellence
(NICE) as it has greater sensitivity than PCR for low levels of proteinuria.
if I ask you to do only one test to confirm his proteinuria, what would it be and under what condition?
Using KDIGO guideline, the 24 hours’ urine collection is the gold standard to quantify protein. The downfall to this study is the possibility of inaccurate collection for the 24 hours, there may be other pathologies that can increase the total urine excretion but may not be a true reflection of albumin being secreted like in MM.
What is the sport urine test and how accurate it is?
The accuracy of spot urine protein is not a 24-hour urine collection and as such reduce inaccuracy in collection the urine. Both ACR and PCR are accepted by KDIGO. But of the two, preferably the ACR since it eliminates the possibility of adding to the protein produced by the kidneys. Albumin is more accurate as it filters from the glomerular, we do know that there are damages to the kidneys.
Repeat 24hours urine collection for protein while patient not performing exercise for 2-3days.
If I ask you to do only one test to confirm his proteinuria, what would it be and under what condition?
I’ll do ACR albumin creatinine ratio early out of bed time or PCR protein:creatinine ratio also early out of bed time.
because 24 hour collection mostly not done correctly and can be affected by increased muscle mass , high BMI, … etc.
What is the sport urine test and how accurate it is?
It is a test better performed in early morning out of bed sample, predicts the true 24-hour protein excretion. There are two major limitations of using it:
1.The PCR and ACR are heavily influenced by the urine creatinine concentration.
2.Urine protein excretion can vary throughout the day (especially resulting from exercise and posture) and from day to day.
to repeat spot proteinuria at rest
To confirm his proteinuria
First he had to stop exercise for 24 – 48 hours then repeat measure uACR
I think sport urin test is uACR and it’s accuracy is similar to 24-hour albumin
Dear All
If I ask you to do only one test to confirm his proteinuria, what would it be and under what condition?
R/O orthostatic proteinuria
need repeat the test the first 48 h later after stop exercise
What is the sport urine test and how accurate it is?
Spot urine :collect one sample, preferably early in the morning.
protein /creatinine ratio X 1000
Albumin /creatinine ratio X 1000(The best )
-For many years, assessment of proteinuria was based on an accurately timed 24-hour urine collection, with 300 mg/24 hours pathological.
– However, the urine albumin /creatinine ratio (ACR) or protein /creatinine ratio (PCR) in a spot urine sample are now the preferred methods as both correlate well with 24-hour urinary protein excretion and overcome inaccuracies related to incomplete urine collection.
-ACR performed on a spot urine sample voided after waking is the recommended screening test, although both urine PCR and 24-hour urine protein collection are acceptable alternatives.
– A normal ACR of <2.5 mg/mmol in men and <3.5 mg/mmol in women equates to 30 mg/mmol defines macroalbuminura.
-Dipstick analysis alone is inadequate to detect low level but clinically significant albuminuria.
-Spot urine :collect one sample, preferably early in the morning.
protein /creatinine ratio X 1000
Albumin /creatinine ratio X 1000(The best ).
If I ask you to do only one test to confirm his proteinuria, what would it be and under what condition?
24 hour urine albumin, after 72 hours of rest.
Tests for urinary total protein cannot be standardized due to varying composition of urinary proteins. Hence urinary albumin is preferred.
What is the spot urine test and how accurate it is?
A spot urine albumin creatinine ratio (ACR) test measures urinary albumin and creatinine in a urine sample taken at any time of the day. The urinary concentration varies widely during a 24 hour period, hence testing urinary albumin alone in a spot urine sample can give false values. To ride over such fallacy, a spot urine sample should be tested for both albumin and creatinine together.
The urine ACR has been shown to have a sensitivity of 46% and 60% with sensitivity of 95% and 97% in men and women respectively (1).
Reference:
1) Jafar TH, Chaturvedi N, Hatcher J, Levey AS. Use of albumin creatinine ratio and urine albumin concentration as a screening test for albuminuria in an Indo-Asian population. Nephrol Dial Transplant. 2007 Aug;22(8):2194-200. doi: 10.1093/ndt/gfm114. Epub 2007 Apr 3. PMID: 17405790.
What is your management?
First to confirm proteinuria to especially he is athletic and proteinuria may be exercise related
, so I ask to repeat the test with rest about 3 days before
Proteinuria may be transient / physiological due to exercise , acute illness , fever orthostatic
Or pathological / persistent which needs work up and even renal biopsy.
Early morning urine albumin/ creatinine ratio is recommended before kidney donation
ACR more than 30mg/mmol, PCR more than 50 mg/mmol, albumin excretion more than 300 mg/day or protein excretion more than 0.5 gm/day represent absolute contraindications to donation
ACR is preferred by both KDIGO and the National Institute for Health and Care Excellence (NICE) as it has greater sensitivity than PCR for low levels of proteinuria
The gold standard for measurement of protein excretion is a 24-hour urine collection and keep our patient free exercise, good hydrated and balanced protein diet.
The major limitations are correct collection and it’s a cumbersome for patients.
UPCR or UACR their limitation mainly that it is can vary throughout the day (especially resulting from exercise and posture) and from day to day.
a confident diagnosis requires an ACR on a spot urine sample voided immediately after waking
_ The most common explanation for protinuria in such healthy asthlete is orthostatic protinuria with heavy exercise , so single test is urine analysis and albumin creatinine ratio in 1st voided urine sample after awakening and ensuring he evacuated his baldder before sleep in the night before ( to exclude orthostatic effect).
_ spot urine Albumin/creatinine ratio. Is accepted as indicator for protinuria as quantitative method ( as accurate as and easier than ) 24 h urine collection for albumin excretion .
According to BTS/RA Living Donor Kidney Transplantation Guidelines 2018
ACR is preferred by both KDIGO and the National Institute for Health and Care Excellence (NICE) as it has greater sensitivity than PCR for low levels of proteinuria
Hence the urine albumin /creatinine ratio (ACR) or protein /creatinine ratio (PCR) in a spot urine sample are now the preferred methods as both correlate well with 24-hour urinary protein excretion and overcome inaccuracies related to incomplete urine collection. Both are supported by Kidney Disease: Improving Global Outcomes (KDIGO) as appropriate methods to aid in the diagnosis of chronic kidney disease.
Spot urine test correlates with 24-hour results, but from my experience for low values, the 24-hour (with optimal collection) is more accurate. Here, a first-morning sample will give us a clue as we need to rule out other non-glomerular causes. if the result of PCR is more than 0.3, I will perform another 24 sample collection.
to confirm his proteinuria: repeat the test after 48 hour rest of exercise.
the most accurate is urinary albumin excretion per day or repeat ACR (better morning sample)
spot urine analysis includes urinary albumin creatinine ratio and protein creatinine ratio (less sensitive and couldn’t substantiate for albumin excretion tests
for donation :
Urine AER < 30 mg/d is accepted
Albumin creat ratio is considered recommended screening test in spot urine sample more than 30 mg/mmol is absolute contraindication for donation where from 3-30 mg/mmol is carry risk of CKD and cardio-vascular mortality.
Alternative is protein creat ratio.
24 Hour urinary proteins levels is standard. Urine spot test for initial diagnosis and survelence. If urine spot is positive then better confirm with 24 hour urinary protein levels
if I ask you to do only one test to confirm his proteinuria, what would it be and under what condition?
Using KDIGO guideline, the 24 hours’ urine collection is the gold standard to quantify protein. The downfall to this study is the possibility of inaccurate collection for the 24 hours.overnight proteinuria . compared to exercise test for protein.Hence the urine
albumin /creatinine ratio (ACR) or protein /creatinine ratio (PCR) in a spot urine
sample are now the preferred methods as both correlate well with 24-hour urinary
protein excretion and overcome inaccuracies related to incomplete urine collection.
Both are supported by Kidney Disease: Improving Global Outcomes (KDIGO) as
appropriate methods to aid in the diagnosis of chronic kidney disease, but ACR is
preferred by both KDIGO and the National Institute for Health and Care Excellence
(NICE) as it has greater sensitivity than PCR for low levels of proteinuria.
This case:
I would prefer to repeat the test after 48 -72 hours of rest
Rule out fever and urinary infection
I would perform the spot urine albumin /creatinine ratio (ACR)
if ACR is <3 mg/mmol, then he can be accepted if all other parameters are normal
if ACR is > 30 mg/mmol, then he is absolutely rejected
if it is between, 3-30 mg/mmol, then decision has to be based on other paramters.
If I ask you to do only one test to confirm his proteinuria, what would it be and under what condition?
24-hour urine collection for albuminuria
it has to be done in afebrile, no urinary infection and rest for 48 to 72 hours
If albumin excretion is < 30 mg/24h, then the donor can be accepted
If it is > 300mg/24h, then the donor has to be rejected
What is the sport urine test and how accurate it is?
albumin /creatinine ratio (ACR) or protein /creatinine ratio (PCR) in a spot urine
sample
PCR sensitivity ranged from 63 to 99%; PCR specificity varied from 73 to 99%
For ACR, sensitivity ranged from 79 to 100% and specificity varied from 81 to 98%
Akbari A, Fergusson D, Kokolo MB, Ramsay T, Beck A, Ducharme R, Ruzicka M, Grant-Orser A, White CA, Knoll GA. Spot urine protein measurements in kidney transplantation: a systematic review of diagnostic accuracy. Nephrol Dial Transplant. 2014 Apr;29(4):919-26. doi: 10.1093/ndt/gft520. Epub 2014 Jan 26. PMID: 24470518.
Dear Dr Ahmed,
The proteinuria may be “benign” in Origen. This term describes proteinuria that is not due to renal disease, which may be transient (e.g. exercise, fever, extreme cold, seizures) or persistent (e.g. postural proteinuria) (1).
In our practice, we used to ask the person with mild, unexplained proteinuria to stop any vigorous exercise for several days and repeat 24 hours of urinary collection, usually after one week.
When postural proteinuria is suspected, we used to ask for a split urinary collection of 16 hours daytime and 8 hours overnight collection (or easier, we perform Alb/Cr ratio in the early morning and at night). If the early morning sample showed negative albuminuria while the night sample detected albuminuria, the diagnosis will be postural proteinuria.
References:
1) Steddon S, Ashman N, Chesser A, et al. Oxford Handbook of Nephrology and Hypertension. Second edition, Oxford University Press, ISBN 978–0–19–965161–0, 2014.
If I ask you to do only one test to confirm his proteinuria, what would it be and under what condition?
ACR on a spot urine sample voided immediately after waking
What is the spot urine test and how accurate it is?
A collection of one sample, preferably early in the morning.
The urine (ACR) or (PCR) in a spot urine sample are now the preferred methods as both correlates well with 24-hour urinary protein excretion and overcome inaccuracies related to incomplete urine collection
the 24 hours urine protein is the gold standard to evaluate proteinuria
It should be done befor proceeding to biopsy
And must be properly collected
What is the sport urine test and how accurate it is?
Spot urine test: albumin creatinine ratio and protein creatinine ratio.
24h urine protein is more accurate if done correctly
ACR is better than PCR as it reflects amount of albumin filtered from the glomerular
If I ask you to do only one test to confirm his proteinuria, what would it be and under what condition?
according to BTS/RA Living Donor Kidney Transplantation Guidelines 2018 the gold standard test is early morning (ACR) and (PCR) can be an alternative option and to be done early morning ( after rest )
this patient has moderately increase protienurea could be exersise induced If repeated test after 24-48 hr showed the same result its relative contraindication .
if still more than 300 it is better to change the donor if he still want to donate he needs comprehensive work up and good discussion about the risk and out comes
*24 hours urinary proteins is the gold standard to evaluate for proteinuria.
It has to be done while patient not on exercise time , well hydrated.
*KDIGO accepted that ; The spot urine tests : are ACR and PCR but ACR is more accurate than PCR as it indicate mostly glomerular origin they filtered from.
24-hour urine protein collection is the gold standard test avoid exercise and also do ACR OR PCR to correlate the result.
Over-night 12 hours urine protein collection to exclude exercise-induced proteinuria. An alternative is performing a protein creatinine ratio on the first morning urine sample. Although a timed urine collection is a more reliable one.
Albumin creatinine ratio is the recommended screening.
sport urine test mean random urine sample test without preparation.
I would proceed with the investigation of proteinuria with the exception of performing a biopsy. I would replace its invasiveness with the urine test for athletes (95% specificity and 97% accuracy) to confirm probable dietary supplementation that led to proteinuria.
If the test is negative, proceed with a donor biopsy.
REFERENCE:
– Rapid Assessment of Exercise State through Athlete’s Urine Using Temperature-Dependent NIRS Technology. Lihe Ding, Lei-ming Yuan, Yiye Sun, Xia Zhang, Jianpeng Li, Zou Yan. J Anal Methods Chem. 2020; 2020: 8828213. Doi: 10.1155/2020/8828213
So better to do ACR ,albuminuria testing and not proteinuria
ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day
or protein excretion >500 mg/day represent absolute contraindication to donation. (C2)
But the donor is athletic, so repeat the test after 24 hr rest.
As the donor is athelets ( False positive proteinuria must be excluded )
So he needs to stop exercise for 48 hours
avoid high diet proteins
The gold standard for assessment of proteinuria is 24 hours urinary collection
if less than 150 mg can be accepted as potential donor
Orthostatic proteinuria should not be considered as a contraindication to donation. Orthostatic proteinuria appears benign), but a confident diagnosis requires an ACR on a spot urine sample voided immediately after waking
ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day represent absolute contraindications to donation
A 2007 study of US transplant centres found that proteinuria of 300 mg/day was the most prevalent exclusion criteria for kidney donors, although almost as many centres were using a protein excretion of 150 mg/day as a cut-of value
Proteinuria was linked to an increased risk of all-cause and cardiovascular mortality, kidney failure, acute kidney injury, and the progression of CKD in both the general population and populations at higher risk for CVD, according to a meta-analysis by the CKD Prognosis Consortium
Reference :
BTS
A 29-year-old athletic male with excellent kidney function offered a kidney to his father who 61 years old, 111 mismatch, no DSA. He has no significant past medical history. No evidence of haematuria, but there is mild proteinuria on 24 hours urine collection (300 mg/day).
What is your management? Substantiate your answer
However, all these factors only affecting in spot urine specimen than 24 hour urine protein.
The gold standard for measurement of protein excretion is a 24 hour urine collection.
The patient has proteinuria of 300mg/day which is between 150-500mg/day-. So, the patient need to evaluated for the proteinuria. The risk of cardiovascular morbidity and CKD has been associated with increasing proteinuria and albuminuria.
In the uncertainty of the proteinuria, I would like to repeat the spot urine ( morning sample) Albumin excretion ration, which is recommended by KDIGO. External factors such as protein supplement, post exercise and orthostatic proteinuria should be excluded.
An ACR threshold of ≥10 mg/g was associated with sensitivity and specificity of 88% each for detecting AER ≥30 mg/d. There was minor variation in area under the receiver operator curve based on age, sex, race, and body weight. One study reported excellent performance of ACR to detect AER of 30 mg/d. The area under the receiver operator curve was 0.93.
References:
KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors
BTS/RA 2018
The gold standard in the evaluation of proteinuria or albuminuria in living kidney donors is 24 hour urinary protein testing. (1,2)
He being an athlete advised to stop exercise for 48 hours and repeat 24 hours urine proteins after adequate rest.
Contraindications to donation as per guidelines (1,2):
Relative contraindication(1,2): Moderately increased
A moderate increase in proteinuria, albuminuria, and 24-hour urinary proteins has not been assessed over the long term for effects on kidney function and overall morbidity post-donation, but it may gradually increase over time and may precipitate kidney disease, which needs to be discussed.
Reference:
According to BTS guidelines
Urine albumin/creatinine ratio (ACR) performed on a spot urine sample is the recommended screening test for proteinuria, although urine protein/creatinine ratio is an acceptable alternative.
ACR > 30 mg/mmol,PCR>50 mg/mmol,albumin excretion >300 mg/day or protein excretion >500 mg/day are absolute contraindications to donation.
Moderately increased albuminuria (ACR 3-30 mg/mmol),and proteinuria (PCR 15-50 mg/mmol or 24-hour urine protein 150-500 mg/day) are relative contraindications to donation due to increased risk of CKD and CVD with increasing proteinuria.
Increased urinary protein excretion is a marker of kidney damage, reflecting either increased glomerular permeability or decreased tubular re absorption , also proteinuria may be due to lympho-proliferative disorder or lower urinary tract disease .
orthostatic proteinuria should not be considered as a contraindication to donation.
requires ACR on a spot urine sample voided immediately after waking.
The gold standard for measurement of protein excretion is a 24-hour urine collection, but often collected inaccurately, so ACR or PCR in a spot urine sample are now the preferred methods and both correlate well with 24 hour urinary protein excretion and to overcome inaccuracy due to incomplete urine collection.
KDIGO guidelines recommend using of ACR in a random sample as an initial screening test, confirmed by albumin excretion ratio or repeating ACR, if AER cannot be obtained.
Back to our scenario
29 years old,athletic, proteinuria is 300 mg/24 hour
protein in 24 hour urine collection is often inaccurate due to incomplete urine collection, also he is athletic may have a transient proteinuria.
Exercise-induced proteinuria is generally benign , it occurs in athletes, it also transient- lasting 24 to 48 hours ( Poortmans JR.Exercise and renal function.Sports Med.1984:1:125-153.
so we need to do ACR on a spot urine sample voided immediately after waking and after stopping exercise for 24 to 48 hours once for diagnosis then repeat it for confirmation.
If ACR is normal proceed to donation.
ACR > 30 mg/mmol,PCR>50 mg/mmol,albumin excretion >300 mg/day or protein excretion >500 mg/day are absolute contraindications to donation.
If there are moderately increased albuminuria (ACR 3-30 mg/mmol),and proteinuria (PCR 15-50 mg/mmol or 24-hour urine protein 150-500 mg/day) also I will refuse donation in this young male due to increased risk of CKD and CVD with increasing proteinuria.
In acohort, 7.2% of donors had a proteinuria in range of 30 to 300 mg/dL, but on follow-up 49.2% developed proteinuria. A total of 71.8% of donors who developed proteinuria were hypertensive. The mean ACR increased significantly. Donors with proteinuria (urine ACR >10 mg/mo) maintained BP below 140/90 mm Hg, and the albumin excretion decreased over 1 year of follow-up. Post-donation GFR was similar between donors with and without proteinuria(1)
Forty-eight studies from 27 countries followed a total of 5048 donors. An average of 7 years after donation (range 1–25 years), the average 24 h urine protein was 154 mg/day and the average GFR was 86 ml/min. In eight studies which reported GFR in categories, 12% of donors developed a GFR between 30 and 59 ml/min (range 0–28%), and 0.2% a GFR less than 30 ml/min (range 0–2.2%). In controlled studies urinary protein was higher in donors and became more pronounced with time (three studies totaling 59 controls and 129 donors; controls 83 mg/day, donors 147 mg/day, weighted mean difference 66 mg/day, 95% confidence interval (CI) 24–108). An initial decrement in GFR after donation was not accompanied by accelerated losses over that anticipated with normal aging (six studies totaling 189 controls and 239 donors; controls 96 ml/min, donors 84 ml/min, weighted mean difference 10 ml/min, 95% CI 6–15; difference not associated with time after donation (P=0.2)). Kidney donation results in small increases in urinary protein. An initial decrement in GFR is not followed by accelerated losses over a subsequent 15 years. (2)
A retrospective study evaluated the outcome of 25 elderly living kidney donors (eLKDs) who were ≥60 years old at the time of donation in our center. Only 5.56% of the eLKDs developed proteinuria post nephrectomy (P =1.000). Serum creatinine increased from 62.33 ± 14.39 mmol/L to 104.63 ± 28.53 mmol/L post 1-month donation (t[23] = –9.720, P = .000) and decreased to 99.67 ± 22.39 mmol/L post 1-year donation (t[17] = –8.415, P = .006), and latest results were 94.28 ± 20.74mmol/L (t[17] = –6.630, P = .033 (3)
Ref:
1- S. Thukral, A. Mazumdar, D.S. Ray,Long-Term Consequences of Complex Living Renal Donation: Is It Safe?,Transplantation Proceedings,Volume 50, Issue 10,2018,Pages 3185-3191
2- A.X. Garg, N. Muirhead, G. Knoll, R.C. Yang, G.V.R. Prasad, H. Thiessen-Philbrook, M.P. Rosas-Arellano, A. Housawi, N. Boudville, for the Donor Nephrectomy Outcomes Research (DONOR) Network,Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression,Kidney International,Volume 70, Issue 10,2006,Pages 1801-1810
3- En Thong Goh, Maisarah Jalalonmuhali, Kok Peng Ng, Ahmad Hafiz Wan Md Adnan, Albert Hing (Wong), Shian Feng Cheng, Shok Hoon Ooi, Chye Chung Gan,The Outcome of the Elderly Living Kidney Donors in a Single Tertiary Center in Malaysia,Transplantation Proceedings,Volume 54, Issue 2,2022,Pages 272-277
according to BTS/RA Living Donor Kidney Transplantation Guidelines 2018:
The significance of moderately increased albuminuria (ACR 3-30 mg/mmol) and proteinuria (PCR 15-50 mg/mmol or 24-hour urine protein 150-500 mg/day) has not been fully evaluated in living kidney donors. However, since the risk of CKD and cardiovascular morbidity increase progressively with increasing albuminuria or proteinuria such levels are a relative contraindication to donation.
But the question now is really there proteinuria or not ?
Still, 24h urinary protein is the gold standard for diagnosis and confirmation of proteinuria and after confirmation of this significant proteinuria should be differentiated from 2 two benign conditions including exercise-induced proteinuria and orthostatic proteinuria which can be done by complete physical rest 72h before urine collection and doing early morning urine PCR.
Donor positive points: Young, excellent kidney function, good immunological match
Further assessment needed for mild proteinuria on 24 hours’ urine collection (300 mg/day)
Assessment:
Detailed hx, clinical examination and investigation is mandatory.
According to BTS guidelines of proteinuria: ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day represent absolute contraindications to donation. In 2005 the Amsterdam Forum concluded by consensus that a 24-hour urinary protein excretion of >300 mg is a contraindication to donation. According to a 2007 survey among US transplant centres, the most common exclusion criterion for kidney donors was 300 mg/day proteinuria, but almost as many centres were using a protein excretion of 150 mg/day as a cut-off
In this donor after all workup If all insignificant, being athletic raised the possibility of orthostatic proteinuria
The gold standard for measurement of protein excretion is a 24-hour urine collection after rest time to confirm diagnosis.
Reference:
1. BTS/RA Living Donor Kidney Transplantation Guidelines 2018
Proteinuria of 300mg per 24 hrs in athletic male is acceptable for donation so we can proceed with some advise about to minimize the exercise
According to BRITISH TRANSPLANT SOCIETY regarding donor assessment for proteinuria .
1. Urine protein excretion should be assessed in all living donors.
2. A urine albumin/creatinine ratio (ACR) is the recommended screening test, urine protein/creatinine ratio (PCR) is an alternative method .
3. ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day represent absolute contraindications to donation .
4. The significance of moderately increased albuminuria (ACR 3-30 mg/mmol) and proteinuria (PCR 15-50 mg/mmol or 24-hour urine protein 150-500 mg/day) has not been fully evaluated in living kidney donors.
5. since the risk of CKD and cardiovascular morbidity increase progressively with increasing albuminuria or proteinuria such levels are a relative contraindication to donation.
This patient has mild proteinuria
First of all I have to exclude transient proteinuria which could occur in fever, exercise , infection.
Second postural proteinuria by using split urine protein assessment.
After exclusion of these factors persistence of mild proteinuria is considered relative contra indication , while moderate albumin excretion considered absolute contra indication.
references :
BTS living donor guideline 2018 .
As he is an athlete, his proteinuria may be related to it. So, it is better to repeat a 24- hour urine collection in rest and evaluate for albumin and creatinine as an alternative. In case of albumin excretion more than 300 mg/day or protein excretion more than 500 mg/day, he is excluded from donation. If albumin/creatinine is between 3-30 or 24-h urine protein is between 150-500 mg, there is a relative contraindication for donation especially in an athlete (according to BTS guideline). In our center we exclude proteinuria more than 150 mg/day if is not related to exercise.
Proteinuria in a young athletic gentleman should be repeated to exclude transient causes of proteinuria like orthostatic, exercise or fever induced.
I would repeat this test for proteinuria at least after 48 hours of complete rest without exercising.
The donor is a son of a patient known to have ESRD, this raises the concern for this young man to have a potential familial disease that should be excluded and confirmed via usual work up of patients with proteinuria. I will do C3, C4, ANA, ANCA, PLA2R, HCV AB, HBSAG, HIV AB and USS-KUB or CT-KUB.
He may need a kidney biopsy.
This potential donor has proteinuria of 300 mg/day which makes him a relative contra-indication as per BTS 2018 guidelines.
There is uncertainly proteinuria that precludes kidney donation.
most centers use 150 mg/24 hours as cut off
the gold standard for measurement of protein excretion is 24 hours of urine collection.
24 hours protein collection of 150 to 500 mg/dl has not been fully evaluated in living kidney donors. however, since the risk of CKD and CVS morbidities progressively with albuminuria or proteinuria such as level are relative contraindications to donation.
regarding this donor need to confirm proteinuria and if confirmed is a relative contraindication to donate.
references BTS guideline 2018
All potential live donors should be evaluated for proteinuria. It is associated with increase risk of CKD & its progression with increased cardiovascular morbidity and. mortality.
Mild proteinuria in live kidney donor without risk factors; black race, smoking, male gender & middle age, has insignificant risk of progression of CKD.
Proteinuria >500mg/day or albuminuria >300mg/day) is an absolute contraindication for donation, while proteinuria 150-500mg/day is as relative contraindication.
The index case is an athlete with no evidence of renal disease other than proteinuria; the following tests are needed for him as a donor:
Quantification of albuminuria excluding orthostatic proteinuria by split urine collection. and measurement of albuminuria after rest to exclude exercise induced proteinuria.
If the result of investigations revealed albuminuria <300mg/day or proteinuria <500mg/day or he had orthostatic proteinuria ; following counseling the donor regarding risk of donation, he can be accepted as a potential donor..
References:
BTS guideline, 2018.
The presence of proteinuria in a donor needs to be evaluated before accepting them..
The given donor is a male athlete and exercise is a known factor for exacerbation of the proteinuria…
The timing of the protein collection sample is also not mentioned as early morning urine sample could have orthostatic proteinuria….
according to BTS/KDIGO guidelines, urine protein measurement must be repeated twice with 24 hours gap to prove the presence of proteinuria…I would rule of fever, CCF and Exercise before giving the sample for proteinuria…
Urine spot protein creatinine ratio (uPCR), urine albumin to creatinine (uACR) are recommended as alternative to 24 hour timed urine collections…
Urine PCR >3 is a contraindication for organ donation….acceptable is urine PCR<0.3 is recommended for organ donation…While the microalbumiuria needs to be confirmed twice and persistant microalbuminuria in the absence of diabetes or other diseases warrants renal biopsy as the kidney disease could progress in the donor after transplant.. The presence of IgA or Alports are against organ donation…
I will repeat the urine PCR after 24 hours with no exercise and then decide on the organ donation
The approach for this young male candidate donor, with mild proteinuria:
History taking: time of testing was it related to strenuous exercise performed, history of consumption of over the counter gym supplements, history of smoking, history suggestive of edema, history of drug abuse. The history of original renal disease of the recipient is required.
Clinical examination for thorough assessment if edema exists, guided by further investigations (including immune profile and serum albumin).
At least two 24 urinary albumin quantification on two separate occasions is recommended, and it is to be away of exercise performance.
Positive tests for albuminuria is indicative for renal pathology, further evaluation by DMSA scan is needed as good renal functions might be misleading ,eGFR and split renal functions are of help to detect early eGFR changes despite proper renal functions .
Renal biopsy may be of value to rule out glomerular renal pathology.
The absence of intrinsic renal pathology allows donation, with close monitoring and follow up of the donor lifelong post donation.
According to KDIGO and British Transplantation Society guidelines, donors with proteinuria (ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day) are to be excluded from donation.
This patient could have postural proteinuria.
split 24 hour urinary quantification protein to creatinine ratio 8 hours and 16 hours.
Proteinuria may be related to the strenuous and continued physical exercise of the potential donor. There is a need to perform 24-hour proteinuria with at least 48 hours of rest and consider albuminuria.
A proteinuria >300mg/day rules out donation. The microalbuminuria value is not clearly defined for donation: a microalbuminuria >30mg/day is a relative contraindication. Donation is normally advised against when donors have extreme values of proteinuria (150-300mg/day) or microalbuminuria (30-300mg/day). However, each case can be evaluated individually, taking into account other factors such as age, obesity, HBP or glucose metabolism abnormalities.
Nefrologia 2010;30(Suppl 2):47-59
1) Enquire history of peripheral oedema, blood pressure control, BMI, smoking status. high risk behaviour.
2) Autoimmune workout : ANA / Antids DNA/C3/C4.
3)Metabolic workout : HBA1C/ OGTT/ Lipid profile
4) Consent for biohazard status workout.
5)Cardiac function assessment : ECG / ECHO
5)Performed diagnostic kidney biopsy to exclude possibility of glomerular diseases.
British Transplant Society 2018
Recommendations
1) Urine protein excretion needs to be quantified in all potential living donors.
2) A urine albumin/creatinine ratio (ACR) performed on a spot urine sample is the recommended screening test, although urine protein/creatinine ratio (PCR) is an acceptable alternative.
3) ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day represent absolute contraindications to donation.
4)The significance of moderately increased albuminuria (ACR 3-30 mg/mmol) and proteinuria (PCR 15-50 mg/mmol or 24-hour urine protein 150-500 mg/day) has not been fully evaluated in living kidney donors.
Most likely orthostatic proteinuria, which can be confirmed with early morning spot urine albumin: creatinine ratio. After patient stop exercise for at least 48 hrs
24 hrs urine collection is a golden test for proteinuria although carries error in the collection and interfere with patients’ activities.
*Management regarding candidate 29 years donor ,with no past medical history , 111 mismatch , no DSA , having proteinuria 300mg/d: as a start , I will repeat 24 hours urinary proteins after 48 hours if still persistent , the candidate donor will be refused.
*According to KDIGO LKD guidelines, screening for donor albuminuria should be evaluated with urinary ACR, confirmed by albumin excretion rate (AER, mg/d) which accepted to be less than 30 mg/d for candidate donor.
*urinary ACR >30 mg/mmol , PCR >50 mg/mmol, Albumin excretion more than 300 mg/day or urinary ptn excretion >500 mg/day considered absolute contraindications for kidney donation.
*Causes of benign proteinuria : proteinuria after exercise, orthostatic proteinuria should be excluded by 1. Full rest and repeat 24 hours proteinuria in another time 1 day after exercise.
2.Good oral hydration.
So; if urinary protein excretion more than 500 mg/d should be excluded as kidney donation, and consider renal biopsy accordingly.
References:
*BTS/RA Living kidney donor Transplant. Guidelines,2018.
Urine protein excretion is a prerequisite test for evaluation of living kidney donor candidates. According to Kidney Disease: Improving Global Outcomes (KDIGO) living kidney donor guidelines, initial evaluation of donor albuminuria (screening) should be performed using random urine albumin-to-creatinine ratio (ACR).
Donor albuminuria should be confirmed using albumin excretion rate (AER, mg/d) in a timed urine specimen.
Urine AER <30 mg/d is considered an acceptable level for donation.
Persistent proteinuria with repeating the test after 48 h is considered to be a contraindication to kidney donation.
So first we have to exclude other non pathological causes of proteinuria as postural proteinuria, proteinuria after exercise and repeat 24h urine protein after 48 hours of rest and good hydration as he is athletic also avoid high protein diet or supplements.
if still present mangment would be according to severity
If ACR >300 mg/day or protein excretion >500 mg/day so there is a high risk of progression Ckd and risk for CVD therefore contraindication to donation and biposy to be considered if persistent of rising.
If proteinuria disappeared after 48 or became less than <30 mg/d donor can be accepted.
Moderate proteinuria the donor must be investigated to find cause and biposy to be done if he still wishes to donate then he must be informed about possible risk of Ckd .
References:
BTS/RA Living Donor Kidney Transplantation Guidelines 2018.
· I will do urine albumin/creatinine ratio (ACR) performed on a spot urine sample, or urine protein/creatinine ratio (PCR)
· If ACR on a spot urine sample voided immediately after waking became normal, this indicates orthostatic proteinuria, and this donor should not be excluded from donation
· ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day represent absolute contraindications to donation
· Moderately increased albuminuria (ACR 3-30 mg/mmol) and proteinuria (PCR 15-50 mg/mmol or 24-hour urine protein 150-500 mg/day) are a relative contraindication to donation.
Management
The donor has mild proteinuria. Persistent proteinuria can be a contraindication to kidney donation. Some centers practice exclusion of donors who have proteinuria above 150 mg/day.
Split urine collection can reveal whether proteinuria is orthostatic in nature. Further evaluation includes ANA panel, SPEP to look for monoclonal protein spike or immunofixation. Recheck for evidence of hematuria.
Renal ultrasound should be done if not yet done to check for hydronephrosis, masses, stones.
However, mildly elevated protein excretion with normal albumin excretion is normal for below 300 mg/d for kidney donor candidates. I would accept this donor.
References :
Reply to Prof Ahmed Halawa:
If I ask you to do only one test to confirm his proteinuria, what would it be and under what condition?
I would request a 24 hour urine collection as this is the most accurate test to measure proteinuria (particularly for low level proteinuria). The main limitation of this test is the possibility of inaccurate collection during the 24 hours time of collection. Before repeating the test the patient should stop physical activity for 48 hours.
What is the sport urine test and how accurate it is?
The urine albumin /creatinine ratio (ACR) or protein /creatinine ratio (PCR) in a spot urine sample seems now the preferred methods of protein measure as they both correlate with 24-hour urinary protein excretion avoiding inaccuracies caused by incomplete urine collection.
This potential donor has a normal kidney function with no haematuria but mild proteinuria. As he is an athlete I would ensure that this proteinuria is not due to strenuous physical activity.
Usually proteinuria after strenuous physical activity will resolve within 48 hours. Of course we need to ensure that the patient has stopped his physical activity before we repeat the urine test. I would arrange a 24 hours urine collection as this is the most accurate test to check for proteinuria. If repeated urine test confirm proteinuria I would exclude this patient from donation as proteinuria is associated with increased risk of cardiovascular morbidity and mortality and progression in CKD (Absolute contraindications to donation are ACR >30 ,PCR >50 mg/mmol or 24 hr albumin excretion >300 mg/day or protein excretion >500 mg/day while an ACR between 3-30 mg/mmol or PCR between 15 to 50 mg/mmol and or 24-hour urine protein between 150-500 mg/day are considered relative contraindications to donation).
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
KDIGO Guidelines
Urine protein excretion needs to be quantified in all potential living donors. (B1)
· A urine albumin/creatinine ratio (ACR) performed on a spot urine sample is the recommended screening test, although urine protein/creatinine ratio (PCR) is an acceptable alternative. (A1)
· ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day represent absolute contraindications to donation. (C2)
· The significance of moderately increased albuminuria (ACR 3-30 mg/mmol) and proteinuria (PCR 15-50 mg/mmol or 24-hour urine protein 150-500 mg/day) has not been fully evaluated in living kidney donors. However, since the risk of CKD and cardiovascular morbidity
increase progressively with increasing albuminuria or proteinuria such levels are a relative contraindication to donation.
Orthostatic proteinuria should not be considered as a contraindication to donation.
Orthostatic proteinuria appears benign , but a confident diagnosis requires an ACR on a spot urine sample voided immediately after waking
So my decision
I will accept him as a donor after full assessment and counseling
Reference
BTS/RA Living Donor Kidney Transplantation Guidelines 2018 pg. 110, 113
This prospective young athletic donor is willing to donate his kidney to his father(>60 years).He has excellent kidney functions, no hematuria with mild proteinuria(300mg/day, the gray zone).
It is important in this case to determine whether this is benign and transient or a pathological proteinuria.
Transient proteinuria: Being an athlete, strenuous exercise can cause non nephrotic range proteinuria that usually reverts to normal physiological range after 24-48 hrs. other causes of transient proteinuria includes fever, acute illness and emotional stress.
SO, for this donor, it is important to check for proteinuria 48hours after stopping exercise while maintaining adequate hydration.
If proteinuria persists on a repeated urine sample , he should be excluded from donation according to guidelines as proteinuria is an important risk factor for CKD and cardiovascular morbidity and mortality.
Proteinuria can be checked by
– Spot early morning urine sample for ACR (best modality) or alternatively PCR. They correlate well with 24-hour urinary protein excretion and overcome inaccuracies related to urine collection.
Limitations: protein excretion vary throughout the day (with change in posture or exercise) and from day to day.
– 24 urine collection for proteins while not on exercise is the gold standard
Limitations: problems related to urine collection
Absolute contraindications to donation are ACR >30 ,PCR >50 mg/mmol or 24 hr albumin excretion >300 mg/day or protein excretion >500 mg/day
Relative contraindications are moderately increased albuminuria ACR 3-30 and proteinuria 15-50 mg/mmol or 24-hour urine protein 150-500 mg/day
References:
BTS Guidelines on living Kidney Transplantation
KDIGO Guidelines
This 29 year old physically fit man has proteinuria of 300 mg /day. There is no Hematuria and there is no significant medical history.
Proteinuria is an important entity and may represent Glomerular damage leading to protein leak with less absorption. Those with proteinuria are at higher risk of cardiovascular disease. It also increases the risk of ESRD. This risk is higher in males and Blacks.
KDIGO recommends initial check proteinuria with Urine ACR. Also to measure Proteinuria as albuminuria and not total urine proteins.
The first step to establish type of proteinuria like transient , physiological , orthostatic or pathological.
Orthostatic proteinuria will not preclude kidney donation.
It is very important to take detailed history like history of –
Acute febrile illness, exercise, urinary tract infection, family history of CKD, smoking, steroid medical conditions etc.
This proteinuria level will require confirmation by simply repeating urine testing for proteinuria . This means he to rest at least 3 days before repeating test.
This will include- Spot test and 24 urine testing.
ACR
PCR
24 urinary protein levels
ACR>30 mg/mmol and PCR >50 mg/mmol and proteinuria more than 300 mg 24 hours are contraindications to transplantation.
If the repeat Proteinuria levels are below 300 mg/day then he can donate , however if it is more than 300 mg/day then donation will be contraindicated .
Substantiate your answer
BTS Guidelines on living Kidney Transplantation 18
Hand Book of Kidney Transplantation
KDIGO Guidelines
In this scenario of a 29-year-old athletic male with excellent kidney function who is planned to offer a kidney to his father who 61 years old with good match with mild proteinuria on 24 hours urine collection.The management in this case include:
▪︎Repeat the 24 urine test for proteinuria: to rule out transient rise in proteinuria associated with exercise. Because athletes who practice sports of different types, generally can develop proteinuria which is usually a transient benign condition, always following exercise , and called exercise induce proteinuria , and may last for 24-48 hours post excersice. The test can be done 48-72 hours after stopping exercise and maintaining adequate hydration
☆ Note: Exercise proteinuria is both glomerular and tubular in origin, and is reversible (1).
▪︎ When interpreting the proteinuria detected on routine urinalysis, we must keep in mind the temporal relevance between exercise and urine collection.
– If urine is found to have been collected within 24 hours of intense exercise, repeat testing in the absence of prior exercise on at least one other occasion to differentiate between transient and persistent proteinuria. In confirming transient proteinuria after ex- ercise, we can reassure the patient that it is a benign condition.
– If the re- sult of a repeat test is high, we must turn our attention to another possible cause of proteinuria (2)
▪︎ Another test is testing either 24-hour urine albumin excretion or a spot urine albumin creatinine ratio.
☆Substantiate your answer
Practice recommendations (2):
1. Rely on a spot urine microalbumin-to-creatinine or protein-to-creatinine ratio to accurately assess proteinuria. ›
2. Repeat testing if routine urinalysis detects protein- uria—especially if the patient reports having exercised in the previous 24 hours .
_________________________________
Ref:
A Clerico et al. Exercise-induced proteinuria in well-trained athletes. Clin Chem. 1990 Mar. (2) Fahad Saeed, et al. Exercise-induced proteinuria? Urinalysis reveals an excessive level of protein, but your patient is a runner. How concerned should you be?
Urine protein excretion needs to be quantified in all potential living
donors.
A urine albumin/creatinine ratio (ACR) performed on a spot urine
sample is the recommended screening test, although urine
protein/creatinine ratio (PCR) is an acceptable alternative.
ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day
or protein excretion >500 mg/day represent absolute contraindications
to donation.
The significance of moderately increased albuminuria (ACR 3-30
mg/mmol) and proteinuria (PCR 15-50 mg/mmol or 24-hour urine
protein 150-500 mg/day) has not been fully evaluated in living kidney
donors. However, since the risk of CKD and cardiovascular morbidity
increase progressively with increasing albuminuria or proteinuria such
levels are a relative contraindication to donation.
In this case we have to differentiated between persistent or exercise induced proteinurea, so we have to repeat the dipstick test after 48 hours later after a period of rest, if proteinurea still persist then the ACR or PCR should be measured if abnormal result, the 24 hours urinary protein should be done and classified according to the above guidline.
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
What is your management?
This 29 year old physically fit man has proteinuria of 300 mg /day. There is no Hematuria and there is no significant medical history.
Proteinuria is an important entity and may represent Glomerular damage leading to protein leak with less absorption. Those with proteinuria are at higher risk of cardiovascular disease. It also increases the risk of ESRD. This risk is higher in males and Blacks.
KDIGO recommends initial check proteinuria with Urine ACR. Also to measure Proteinuria as albuminuria and not total urine proteins.
The first step to establish type of proteinuria like transient , physiological , orthostatic or pathological.
Orthostatic proteinuria will not preclude kidney donation.
It is very important to take detailed history like history of –
Acute febrile illness, exercise, urinary tract infection, family history of CKD, smoking, steroid medical conditions etc.
This proteinuria level will require confirmation by simply repeating urine testing for proteinuria . This means he to rest at least 3 days before repeating test.
This will include- Spot test and 24 urine testing.
ACR
PCR
24 urinary protein levels
ACR>30 mg/mmol and PCR >50 mg/mmol and proteinuria more than 300 mg 24 hours are contraindications to transplantation.
If the repeat Proteinuria levels are below 300 mg/day then he can donate , however if it is more than 300 mg/day then donation will be contraindicated .
Substantiate your answer
BTS Guidelines on living Kidney Transplantation 18
Hand Book of Kidney Transplantation
KDIGO Guidelines
Initial assessment should include evaluation and confirmation of persistent or transient proteinuria as exercise induced proteinuria should be highly suspected. Exercise induced proteinuria is generally benign and a function of the intensity rather than the duration of exercise. It is transient and lasts 24 to 48 hours after sport.
As patient’s proteinuria was detected in 24 hour urine collection which is the gold standard, repeated collection should be performed 72 hours after last training, so that exercise induced proteinuria is ruled out.
the index donor is
29 years old male
No past medical history
No DSA
III mismatches
No hematuria
Only proteinuria 300mg.
What is your management. –
Really urine protein exertion need to be quantified mall potential living donor and the recommended screening test is albumin creat ratio on spot urine sample and alternative is urine protein creat ratio
First donor must be evaluated.by
Full history and general examination
Lab for urine examinations urine . Culture to exclude haematuria or infection
Then we will do albumin creat ration is more than 30 mg/mmol is absolute contraindications for donation and if moderate from 3-30 mg/mmo is relative contraindication but carry risk of progressive Kidney disease and cardie- vascular morbidity and mortality.
As per kdigo guidelines we have to repeat the ACR or APR , before confirming presence of proteinuria.
24 hr proteinuria though good might have some accuracy issues because of the collection.
irst we must to differentiate between transient and persistent proteinuria repeat testing after 48 hrs off exercises if the result was negative proteinuria so we consider him as potentially living donor and accept him.
A urine albumin/creatinine ratio (ACR) performed on a spot urine sample is the recommended screening test, although urine protein/creatinine ratio (PCR) is an acceptable alternative.
ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day represent absolute contraindications to donation.
The significance of moderately increased albuminuria (ACR 3-30 mg/mmol) and proteinuria (PCR 15-50 mg/mmol or 24-hour urine protein 150-500 mg/day) has not been fully evaluated in living kidney donors. However, since the risk of CKD and cardiovascular morbidity increase progressively with increasing albuminuria or proteinuria such levels are a relative contraindication to donation.
Isolated proteinuria — Isolated proteinuria is defined as proteinuria without abnormalities in the urinary sediment, including hematuria, or a reduction in glomerular filtration rate (GFR), as well as the absence of hypertension or diabetes. In most cases of isolated proteinuria, the patient is asymptomatic, and the presence of proteinuria is discovered incidentally by use of a dipstick during routine urinalysis. The urine sediment is unremarkable (fewer than three erythrocytes per high-power field and no casts), protein excretion is less than 3.5 g/day (non-nephrotic), serologic markers of systemic disease are absent, and there is no hypertension, diabetes, and also no edema or hypoalbuminemia.
This benign presentation of isolated non-nephrotic proteinuria is different from that in patients with more prominent kidney disease who have one or more of the following: nephrotic-range proteinuria (≥3.5 g/day), lipiduria, edema, hypoalbuminemia, and/or an active urine sediment containing red cells (which are often dysmorphic) and red cell casts.
Types of proteinuria — There are four basic types of proteinuria
●Glomerular proteinuria
●Tubular proteinuria
●Overflow proteinuria
●Postrenal proteinuria
Glomerular proteinuria (ie, albuminuria) can be identified on a urine dipstick.Some patients have more than one type of proteinuria.
Reference
Update
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
If I ask you to do only one test to confirm his proteinuria, what would it be and under what condition?
Being athletic we need to be sure is it protein or albumin as he is athletics may release muscle protein in the urine for that in this case batter to depends of 24 hr albuminuria after 72 hr of rest .
What is the spot urine test and how accurate it is?
a first-morning sample will give us a clue as we need to rule out other non-glomerular causes. if the result of PCR is more than 0.3, I will perform another 24 sample collection.
a 24-hour urine evaluation for proteinuria is the gold standard, but some issues that lead to proteinuria either transient or orthostatic can be detected. an athletic man with high body mass may have that much low proteinuria, especially after exercise or a diet very rich in protein. To ensure that we can test for a SPOT urine check from the first or maximally second sample (preferably first in this case)
_ according to Guidelines, presence of persistent significant protinuria is contraindication to donation as it is associted with risk of CKD progression and cardiovascular morbidity and mortality.
_ this young age donor with his father (ESKD) without mentioned identified etiology which can be the same etiology of protinuria in his son.
_ so 1st step is to confirm presence of significant protinuria by repeated assessment of ACR in the morning sample (after stopage of exercise for 48 h ) and ensure good hydration.
_ if protinuria disappeared , it is related to orthostatic protinuria and prolonged exercise ( so he can donate ) after evaluation and exclusion of other risk factors and sure, need for identification of original kidney disease ( to avoid having the same pathology in such related living donation) as genetic FSGS (in spite of absence of clinical clues to such secnario ).
_ while if protinuria persist, he should be precluded as per guidelines:
_ ACR more than 30 mg/mmol is CI to donation and albuminuria more than 300 mg/24 h.
uncertainty is present regarding the threshold of proteinuria that precludes kidney donation. the Amsterdam Forum in 2005 conclude by consensus that a 24-hour urinary protein excretion of >300 mg is a contraindication to donation . US transplant centers survey in 2007 concluded that the most common exclusion criterion for kidney donors was 300 mg/day proteinuria, but almost as many centres were using a protein excretion of 150 mg/day as a cut-off.
although the significance of moderately increased albuminuria has not been fully evaluated in living kidney donors, elevated albumin excretion would currently considered at least a relative contraindication to donation, with risk factors for ESRD may be taken into account. Severely increased proteinuria (ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day, or protein excretion >500 mg/day) constitute an absolute contraindication to donation.
Albumin excretion >30 mg/day (ACR >3 mg/mmol) is associated with an increased risk for complications of CKD. A meta-analysis by the CKD Prognosis Consortium demonstrated associations of an ACR >3 mg/mmol or reagent strip +1 protein with a subsequent risk of all-cause and cardiovascular mortality, kidney failure, acute kidney injury, and CKD progression in the general population and in populations with increased risk for CVD.
Orthostatic proteinuria should not be considered as a contraindication to donation. Orthostatic proteinuria appears benign , but a confident diagnosis requires an ACR on a spot urine sample voided immediately after waking
Many studies examining the renal or cardiovascular outcome for living kidney donors who have donated despite pre-existing low level proteinuria.
In many donors there is a modest increase in urine protein excretion after nephrectomy, the majority of whom have no evidence of accelerated GFR loss over time .
In one study, five donors with low-grade proteinuria (mean 210 mg in a 24 hr urine collection) were more likely to have significant proteinuria 20 years or more after donation (>800 mg/day), although without significant loss of kidney function .A review of 1,519 living kidney donors in Japan identified eight who developed ESRD .Of these, only two had pre-donation proteinuria, both of whom developed cardiovascular disease, hypertension and ESRD 6 and 16 years after donation.
A recent US study among 4,650 living donors found that by 7 years post-donation, after adjustment for age and sex, greater proportions of black compared with white donors had chronic kidney disease (12.6% vs 5.6%), proteinuria (5.7% vs 2.6%) or nephrotic syndrome (1.3% vs 0.1%), suggesting the need for more stringent risk stratification among black donors .
Reference:
BTS guidelines in 2018 .
1-What is your management?
1-First , I will do albumin creatinine ratio or protein creatinine ratio in a spot urine sample to reassess the proteinura .
2- ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day represent absolute contraindications to donation. (C2)
2-Substantiate your answer
The gold standard for measurement of protein excretion is a 24-hour urine collection, but this is cumbersome for patients and often collected inaccurately.
Hence the urine albumin /creatinine ratio (ACR) or protein /creatinine ratio (PCR) in a spot urine sample are now the preferred methods as both correlate well with 24-hour urinary protein excretion and overcome inaccuracies related to incomplete urine collection.
Both(ACR and PCR ) are supported by (KDIGO) ( as appropriate methods to aid in the diagnosis of chronic kidney disease.
ACR is preferred by both KDIGO and the National Institute for Health and Care Excellence (NICE) as it has greater sensitivity than PCR for low levels of proteinuria .
Reference ;
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
Our patient is an athletic 29 year old with mild protienurea.
Donor proteinuria should be measured as albuminuria,not total urine protein.
Initial evaluation of donor albuminuria (screening should be performed using urine albumin-to-creatinine ratio (ACR)
in a random (untimed) urine specimen.
Donor albuminuria should be confirmed using:
Albumin excretion rate (AER, mg/day [mg/d]) in a timed
urine specimen.
Repeat ACR if AER cannot be obtained
Urine AER less than 30 mg/d should be considered an acceptable level for donation
The decision to approve donor candidates with AER 30 to 100 mg/d should be individualized based on demographic and health profile in relation to the transplant
program’s acceptable risk donation threshold.
Donor candidates with urine AER greater than 100 mg/d should not donate.
In general protienurea especially albumin urea is considered as evidence of kidney injury.
Chronic albuminurea for more than sex month is evidence of ckd .
Albuminurea also rise the risk of cv events .
So this patient need to be re-evaluated by using the right method of assessment.
If protienurea is confirmed,the patient may need :
Kidney biobsy
Immunological test to rollout systemic diseae could cause protienurea especially famillial disease .
Split urin collection to roll out exertional proteinurea .
I will not accept this donor .
Reference :
1_Matsushita K, van der Velde M, Astor BC, et al. Association of estimated
glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.
Lancet. 2010;375:2073–2081.
2_Mandelbrot DA, Pavlakis M, Danovitch GM, et al. The medical evaluation
of living kidney donors: a survey of US transplant centers. Am J Transplant. 2007;7:2333–2343.
KDOQO guidelines.
BTS guidelines.
· A proteinuria >300mg/day rules out donation.
· The microalbuminuria value is not clearly defined for donation: a microalbuminuria >30mg/day is a relative contraindication.
· Donation is normally advised against when donors have extreme values of proteinuria (150-300mg/day) or microalbuminuria (30-300mg/day). However, each case can be evaluated individually, taking into account other factors such as age, obesity, HBP or glucose metabolism abnormalities. This donor though he is an athlete, (probably has ? functional proteinuria) but I will exclude him.
Gentil Govantes MA, Pereira Palomo P. Assessing and selecting a living kidney donor. Nefrologia. 2010 Jan 1;30:47-59.
A 29 year old athletic male, excellent kidney function offered a kidney form his father with excellent match, and no DSA, whom has no hematuria but proteinuria of 300 mg/day by 24 hour urine collection.
What is your management?
This is a 24 hour urine collection for protein could be affected by:
Complete history and physical examination to be done evaluating, general health , if any febrile illness, if there anemia, if any sternous activity lastly, any trauma ,. etc
So will review his urinalysis again if there is infection , hematuria and if there is any albuminuria by diptick, then will ask for Albumin creatinine ratio spot urine,ACR is preferred by both KDIGO and the National Institute for Health and Care Excellence (NICE) as it has greater sensitivity than PCR for low levels of proteinuria , and it is evident that an ACR >3 mg/mmol or reagent strip +1 protein increase risk of all-cause and cardiovascular mortality, kidney failure, acute kidney injury, and CKD progression in the general population and in populations with increased risk for CVD
If ACR is < 3 performed early out of bed morning sample then i’ll proceed with him as adonor.
Substantiate your answer
References:
[1] BTS -Andrews PA, Burnapp L. British Transplantation Society / Renal Association UK Guidelines for Living Donor Kidney Transplantation 2018: Summary of Updated Guidance. Transplantation. 2018 Jul;102(7):e307. doi: 10.1097/TP.0000000000002253. PMID: 29688993; PMCID: PMC7228639.
[2] Lentine KL, Kasiske BL, Levey AS, Adams PL, Alberú J, Bakr MA, Gallon L, Garvey CA, Guleria S, Li PK, Segev DL, Taler SJ, Tanabe K, Wright L, Zeier MG, Cheung M, Garg AX. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017 Aug;101(8S Suppl 1):S1-S109. doi: 10.1097/TP.0000000000001769. PMID: 28742762; PMCID: PMC5540357.
This apparently healthy potential kidney donor has proteinuria pf 300mg/day, and he is athletic.
Almost all guidelines exclude donor with proteinuria >250-300mg/day. But we need to make sure this is measured properly. Adequate collection over exactly 24hours is important and it can be done by educating the donor how to do it to avoid under or over collection. Alternatively, we can measure 24hours urine creatinine to assess proper collection, not to forget, this donor is athletic, and it is known that proteinuria increases with exercise, notably heavy one. So, repeating the measurement after holding exercise for few days may solve this issue.
Prevalence of proteinuria during exercise ranges from 18% up to 100% depending on type of exercise and its intensity. A higher incidence of proteinuria has been observed in some sports requiring great exercise intensity and it is certainly related to muscular work intensity and would decrease after prolonged training
References:
Renal alterations during exercise
Guido Bellinghieri 1, Vincenzo Savica, Domenico Santoro
Summary: 29-year-old male offered kidney to his father who is 61 years old with excellent kidney functions but has mild proteinuria in 24 hours 300mg/day.
The likely step to this interesting case is that the patient must be interrogated and investigated. History of any family persons with kidney disease or early kidney disease. Ask about history of consuming high protein food like protein shakes, trauma to abdomen but this may accompany with hematuria. Also, strenuous activity like exercise may see proteinuria, fever, heart failure, UTI, etc. Once these aspects have been evaluated, the patient must be investigated to see what more detail that can be obtained and arrive to a diagnosis.
Investigations must be indicated to find the possible causes, like:
1) Urinalysis, urine dipstick and urine culture
2) The 24 hours’ urine collection for protein must be repeated in two weeks to one-month period.
3) An albumin creatinine ration must be done to know if it is definitely albuminuria from proteinuria. If the albuminuria is greater than 30 mg/dl the patient has albuminuria and as such there may be some glomerulopathy. This may warrant renal biopsy with other specific studies like autoimmune disease.
4) Having albuminuria is not a good idea for someone to donate their kidney as there is possibility of worsening kidney functions.
Now based on KDIGO guidelines and kidney transplant:
1) albumin is a better marker to measure than proteinuria and as such should be performed on all possible donors.
2) The confirmation test is the albumin creatinine ratio and perform an albumin excretion rate (AER)
3) If one encounters that the albumin is less than 30 mg /day, then it is safe for patient to donate the kidney
4) If albumin is greater than 100mg /day, then donors should refrain from doing such.
As it relates with BTS the potential donor protein must be quantified but performing ACR on a spot urine. An albumin protein can be performed however there is contraindication depending on what level of albumin or protein is excreted. If the ACR is greater than 30 mg/mmol and the total PCR id greater than 50 mg/mmol then there should be no donation. If the excretion of albumin is greater than 300 mg /day and the protein is greater than 500 mg/day, then donation is not possible.
The reasons for such are that there are already kidney damages and if the patient donate one of his kidneys there will be worsening of kidney function.
KDIGO guidelines 2017
BTS guideline 2018