Who cares if its protein or albumin in the urine?

Drs. Young, Blaine and Ambruso discuss albuminuria and proteinuria, specifically how to measure and interpret values, and what that means for our patients.

Sophia Ambruso DO @Sophia_Kidney, Sarah Young MD @kidneycritic, Judy Blaine MD, Parisa Mortaji, MD

Transcript

Sophie: Ok, let’s have some fun! Today we’re going to discuss what albuminuria and proteinuria mean to us as nephrologists, how to measure and interpret them and why you all should care to. You’ll have to wait for future Kidney Essential podcasts to get into the fascinating proteinuric diseases.

Let’s start with a case….

Your primary care colleague consults you for a 45 YO woman with poorly controlled type I diabetes mellitus complicated by diabetic neuropathy and retinopathy and hypertension with previous stable “microalbuminuria” that has progressed to 800mg/g of albuminuria and 1600mg/g of proteinuria. She has 2++ protein detected on dipstick, and no red blood cells, white blood cells or casts identified on microscopy. The patient’s serum creatinine has risen from 0.6mg/dL to 1.1 mg/dL over the last 2 years.

Sophie: So, based on what we know about this patient, what is our greatest suspicion for her cause of albuminuria and CKD?

Sarah: given she is 45 and has several complications of her type 1 DM including known retinopathy and neuropathy, diabetic nephropathy is by far the leading suspect . This is further supported by there being no wbc or rbc casts to suggest other GN’s which typically present with hematuria/rbc casts

Judy: It is also mentioned that her DM is poorly controlled and we know poor glucose control is an independent risk factor for albuminuria and dibetic kidney disease

Sophie: Since you’re so confident that this is diabetic nephropathy, would you do anything else to work-up this patient?

Judy: Diabetic nephropathy is often a clinical diagnosis and this patient checks a number of those boxes. However, I’d probably check an age appropriate serologic work-up to r/o other reversible causes of proteinuria like HCV, HBV, SPEP, UPEP, SFLC etc.

Sophie: Great! I agree! I chose a diabetic nephropathy case because I wanted to keep this case simple as we are focusing on albuminuria and not the many glomerular causes of albuminuria! However, since we will be doing diabetic kidney disease podcast at a later time, we’re not going to elaborate much more here.

Sophie: Let’s get back to her proteinuria. Sarah, what is 1600mg/g?

Sarah: That measurement is an protein to creatinine ratio.we use the ratio of protein to creatinine to help account for it being a random urine. the actual protein value could be high or low depending on the urine volume

Sophie: Is that the gold standard measurement for proteinuria?

Sarah: No, the gold standard is a 24-hour urine collection. However, 24-hour collections are cumbersome and often done incorrectly. An protein to creatinine ratio from a spot urine collection will sufficiently estimate a 24-hour urine collection most of the time. We also assess the adequacy of the 24 hour urine by referencing creatinine excretion (10-15mg/kg for women and 15-20mg/kg)

Sophie: Judy, Sarah just discussed how protein in urine, why do we care about albumin? Isn’t just another protein?

Judy: marker of podocyte injury vs immunoglobulins are marker of immune dysfunction, tamm horsfall protein, etc.

Sophie: How do we measure albumin on spot urine to estimate a 24-hour albuminuria collection?

Judy: discuss steady state creatinine excretion, assumption of 1g creatinine excretion per day and how ACR represents grams albumin per grams of creatinine.

Sophie: Why don’t we do a ratio calculation with a 24-hour collection?

Judy:  magic

Sophie: Sarah, you also mentioned that we collect a 24-hour creatinine when checking a 24-hour albumin, why is that?

Sarah: as Judy stated, the kidney maintains a steady state of creatinine excretion. Therefore we can anticipate what a person’s 24-hour creatinine excretion should be based on their size, etc. Therefore, if their urine creatinine is above or below the anticipated value, it helps us determine if the it was an under or over collection.

Sophie: ok, just to summarize, we can use PCR to estimate a 24-hour protein collection and an ACR to estimate a 24-hour albumin collection. However, we DO NOT use ratio calculation with a 24-hour urine collection. However, we SHOULD STILL measure creatinine in a  24 -hour urine as it will tell us if we have an adequate collection.

Judy/Sarah: correct!

Sophie: In the consult, the term ‘microalbuminuria’ is used. Are those small albumin particles?

Judy: no, because albuminuria was considered an early sign of classical diabetic nephropathy, the term microalbuminuria was adopted in reference to persistently elevated levels of albuminuria often undetectable on dipstick.

Sophie: Do you either of use the term microalbuminuria?

Sarah: term continues to be widely utilized among many, microalbuminuria is an outdated term . it just refers to mg of albuminuria as opposed to gramsThe more updated  term is , moderately increased albuminuria’, has been adopted to replace microalbuminuria.

Sophie: So how much albuminuria is ‘moderately increased’?

Sarah: 30-300mg/g on albumin creatinine ratio OR 30-300mg/day on 24-hour urine albumin collection. That translates to 150-500mg/g on PCR or 150-500mg/g on 24-hour urine protein collection.

Sophie:Good to know! So that we don’t bore everyone by reciting the different categories of albuminuria, is there a good resource where learners can find this information?

Judy: sure , refer to KDIGO. JUdy to discuss CV risk etc with albuminuria.

Sophie:Great, thanks! One of the most common questions I receive from trainees is; “how do albuminuria values compare to proteinuria values and can either be used?

Sarah: Either can be used although once you are following one you should probably stick to that value when trending response to therapy. I am moving to albumin as much as possible because i need that value when i calculate patients risk for needing dialysis in the next 2-5 years using the KFRE equation

Sophie: When is the albumin to creatinine ratio not reliable?

Sarah; there are some diseases in which the protein in the urine may not be albumin and so the protein could rise but the albumin could be normal and you would miss the disease causing the protein in the urine. In this case the albumin and total protein are not tracking together so  there is a discrepancy in the measurements

Sophie: What if your institution doesn’t have the capability of checking a urine albumin, can this still be detected?

Judy: All institutions have a urinary dipstick, which only detects albumin. So, if the dipstick is negative for albuminuria but proteinuric measurements are high, this should raise suspicion for a paraproteinemic process.

Sophie: Excellent! Ok, back to the patient, this patient has 800mg/g of albuminuria and 1600mg/g of proteinuria, how much is that?

Sarah: This patient has a lot of albuminuria & proteinuria, not nephrotic range, 

Sophia: For this patient with diabetic nephropathy, when would you recommend nephrology consultation?

Sarah: Any degree of albuminuria and CKD III

Let’s pretend the patient does not have diabetic nephropathy, when would you recommend nephrology consultation?

Judy: freestyle

What is your cutoff ACR or PCR to biopsy a patient?

Sarah: depends on what underlying dz. I take care of sle- and i bx at 500mg

Judy: freestyle

learning Points:

1. Spot albumin to creatinine ratio or protein to creatinine ratio provides a good estimate of 24-hour urinary albumin or protein, respectively
2. Generally, albuminuria and proteinuria values can be used as long as you are consistent and know the range of each
3. When there is a discrepancy between high proteinuria levels and undetectable albuminuria values, through direct measurements or dipstick, a paraproteinemia may be present