Prologue
After reading this week’s #NephJC article, I immediately offered to provide commentary on it for several reasons which I will discuss. I will close with my recommendations on how to implement this study into clinical practice.
The aim of this study is a worthy one. It supports the early detection of kidney diseases and is aligned with one of the three aims of the Advancing American Kidney Health Initiative. The purpose of this study was to develop equations to convert urine protein:creatinine ratio (PCR) and dipstick protein to albumin creatinine ratio (ACR) and to evaluate its use in screening, categorizing, and risk-stratifying patients with CKD. This study sought to solve a problem in kidney health, the lack of routine testing for albumin especially in primary care medicine. The investigators should be commended in their desire to find an alternative to albumin testing which is more costly than urine protein testing. I had a recent event that illustrates the nature of the problem.
After attending a patient kidney disease support meeting, I had a participant send me a follow up question about the Kidney Failure Risk Equation (KFRE) calculator. The eGFR for this person was 30, and she was becoming anxious as her kidney function was declining. I sensed her fear because I felt the same loss of control when my kidneys were failing. She was feeling helpless facing an uncertain future. She was unable to complete the calculator because her nephrologist had not tested her ACR.
Study
The measurement of albuminuria is considered the gold standard of quantifying proteinuria. Some providers and researchers quantify urinary protein by using a total protein assay or dipstick. This method is motivated by lower cost, tradition, among other reasons. Some tools physicians use to qualify risk are based upon albumin and not protein. This study was initiated to address this gap. The size and collaborative nature of this study is quite impressive. Nearly a million participants were in this study. The source of the participants were 12 research studies and 21 clinical cohorts globally. While data sharing remains a challenge for the general research community, this collaborative study follows the Surrogate Endpoint Workgroup as a great example of teamwork and working towards the greater good. I encourage the nephrology community to share their collaborative outputs with the Critical Path Institute (CPI). The CPI is a catalyst in the development of new approaches to advance medical innovation and regulatory science. The organization has had difficulty with other research communities sharing their data. The nephrology community deserves recognition for their leadership.
Speaking from the US perspective, there is one limitation of the study. Less than 5% of the study participants were Black. Considering that 35% of the people on dialysis in the United States are African American, it underscores the importance of prioritizing enrollment of African Americans into kidney disease clinical trials especially early intervention trials
Results
The investigators were able to prove that a PCR conversion equation could predict ACR values. First, the sensitivity, specificity, and positive and negative predictive values of the predicted ACR in detecting an ACR of 30 or greater varied by cohort but were similar between the crude and adjusted values. Thus, supporting the role of predicted ACR in screening for CKD. Second, the kidney failure risk estimate calculated by 2-year 4-variable KFRE demonstrated agreement especially in the OLDW cohorts. In these cohorts, the sensitivity and specificity were 96% and 99% respectively
Discussion
As someone who advocates for kidney health, I am grateful that the NIDDK sponsored this study to advance early detection of kidney diseases. It is motivating to see the community work together. I want to recognize the willingness of the global nephrology community to collaborate for the common good. While this may not be the stated objective, the study results may serve as a catalyst for primary care physicians to test routinely for proteinuria.
Against the backdrop of this important study exists the willingness and ability of PCPs to treat proteinuria or make an early referral to a nephrology. Allow me to share two examples from my professional experience. At a patient advisory board for Fabry disease patients, a young African American man shared his difficulty in having his PCP intervene on his proteinuria. On several appointments the physician dismissed the proteinuria by saying it was caused by the patient’s weightlifting. The young man eventually made a self-referral to a nephrologist who diagnosed his Fabry disease.
My other example involves a different rare genetic kidney disease patient. While working on a project involving FSGS, I attended a NephCure patient meeting where another young African American man shared his frustration by his primary physician’s refusal to intervene on his proteinuria. In this situation, the patient reported that his PCP said the proteinuria was caused by the patient’s drug use. The patient responded by stating that he had never used illicit drugs. Like the other example, this man self-referred to a nephrologist who diagnosed him with FSGS and treated his proteinuria. While both of these individuals were able to advocate for themselves, this does not happen all of the time.
Recommendations:
To ensure that the PCR conversion equation becomes a component of routine PCP screening, I have made three recommendations:
1) Nephrology Training of PCPs: Earlier this year, I attended a regional National Kidney Foundation meeting where PCPs were provided educational training on treating kidney diseases. The meeting was well attended with over 50 PCPs. The meeting was successful based upon the leadership of a local community nephrologist. He conceived the training, and had an active role ensuring the meeting was well attended. At a minimum, PCPs should be trained on recognizing common kidney diseases, the value of reducing proteinuria, and the importance of making early referrals to a nephrologist.
2) Dissemination of Kidney Failure Risk Equation (KFRE) calculator:
The KRFE calculator promotes kidney health and patient activation. However, it is not clear how often this tool is used in clinical practice, and much less among people living with kidney diseases. If there is a national plan to put the PCR equation calculator into practice, then there is a need to educate PCPs and nephrologists on its clinical utility. In a parallel path, there is a need to educate kidney disease patients on its value and activate its use in their self-management. One approach is to calculate the KRFE in the EMR automatically.
3) Value Proposition of Early Detection and Intervention of Kidney Disease: As the US kidney care system transfers to kidney health, there is a need for both PCPs and Nephrologists to consistently communicate the value of maintaining native kidneys. Studies have shown that people living on dialysis are not routinely educated on the health risks on dialysis nor are they educated on their expected life expectancy. Speaking from my own transplant journey the long-term health risks of my transplant medications were not fully disclosed, and only accumulate over time.