Renal sinus. Parenchyma. Renal calyces. Nephron. Glomerulus.*

These are some of the terms used to describe the anatomy of a kidney. After my first year of high school in 2020, I took a medical terminology course at my hometown’s local community college and heard these terms for the first time. My favorite lesson was the relatively small subsection about the kidneys within the unit on the urinary system. I came away from that summer with a passion for nephrology. My family members’ subsequential kidney disease incidence has only magnified my interest; learning more about nephrology has become a priority for me.

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), chronic kidney disease (CKD) is estimated to affect more than 1 in 7 American adults (37 million) and cost billions of dollars in Medicare spending in 2020. Due to the heavy disease burden and cost associated with CKD alone, the U.S. clearly needs to prioritize quality nephrology research. However, in recent decades, the federal government has not done so.

Federal expenditures on kidney research remain low relative to the annual Medicare spending on kidney disease treatment and are “substantially lower compared to [spending on research on] other chronic diseases” according to a statement by the National Kidney Foundation (NKF) Research Roundtable Work Group in 2022. Additionally, inadequate kidney research in recent decades has, according to a 2019 Kidney Diseases review article, yielded “no tangible progress in clinical practice.” The NKF statement corroborates this scathing indictment, as the researchers and kidney disease patients in the group agreed that decades-long insufficient support for nephrology research “has delayed the development and implementation of new therapies to prevent kidney disease and its progression.” 

So, not only is there a lack of investment in nephrology research, but currently funded research is not advancing clinical practices as much as biomedical research has in other specialties. Perhaps this ineffectiveness is due to the insufficient number of randomized controlled trials (RCTs) in nephrology. 

From 2001 to 2015, nephrology and rheumatology had the lowest number of RCTs published in PubMed articles compared to other medical specialties. This trend is concerning, as RCTs are considered the “gold standard” for determining interventions’ effectiveness due to their random assignment of treatments. When physicians can only use observational studies or low-quality RCTs to inform clinical practice, potentially harmful or ineffective treatments can be mistakenly implemented, resulting in unnecessary costs in patient outcomes and expenditures on such treatments. One such example occurred with epoetins. Targeting unnecessarily high hemoglobin concentrations with epoetins in CKD patients due to insufficient research prior to its widespread implementation resulted in presumed overspending on the treatment and increased mortality. To avoid a repeat of such issues, researchers must conduct more RCTs in nephrology. 

Since relying on low-quality RCTs can lead to the prevalent use of inadequate treatments, it is concerning that American Journal of Kidney Diseases researchers indicated that both the “quality and quantity” of nephrology RCTs “[were] suboptimal and that the reporting of results from these RCTs [was] of low quality” as recently as in 2014. However, experts have published suggestions for how to rectify this issue. This year, Journal of Nephrology researchers recommended that nephrology research journals should require “reporting guidelines and clinical trial registration” from the authors they publish more strictly to ensure that these RCTs are quality. 

While the shortage of RCTs is a widespread anxiety amongst nephrologists, I must acknowledge that some researchers feel that RCTs are not the only way to gather dependable evidence that a treatment is effective. In a 2012 article in Advances in Chronic Kidney Disease, the authors agreed that the lack of RCTs is limiting treatments, particularly those which target “clinical outcomes such as morbidity or mortality” due to insufficient long-term RCT evidence. They emphasized, however, that while RCTs “hold many advantages over observational studies,” it is an unreasonable expectation that all of the “myriads of potential interventions” in nephrology could be tested with RCTs. They suggested, instead, certain “methods whereby observational studies can become acceptable tools for causal inferences,” despite such inferences usually only being possible with RCTs. I acknowledge their point that nephrologists cannot wait for RCTs to be conducted for every single treatment, though I cannot speak to the statistical validity of their proposed method. I would still argue, however, that RCTs must become far more common in nephrology research in the near future.

In conclusion, the federal government needs to invest more in nephrology research.  Once such federal funding is obtained through the NIDDK, it should be directed towards high-quality RCTs in order for researchers to make conclusions about causation between treatments and patient outcomes. The treatments found to be effective must then be implemented into clinical practice in a timely manner.

*Here’s a link if you want to learn more!