Ask and It Shall Be Given

There is a truism in medicine, commonly invoked on teaching rounds, that goes something like “90% of all diagnoses can be made based only on what a patient tells you.” This aphorism has room for minor variations—sometimes the percentage dips to 80%, sometimes the physical examination is given token credit—but the underlying message remains consistent and unwavering. The patients will tell you what is wrong with them if you just pay attention to what they are saying. In academic hospitals, teaching physicians throw around this old saw to encourage old-fashioned doctoring skills and make students less reliant on the relatively modern luxuries of laboratory tests and imaging studies that can be ordered with a click of a mouse. Increasingly, the emphasis on listening to patients has spread beyond the clinic and hospital space and into the realm of clinical trials. Calls to recommend interventions on the basis of outcomes that are “patient important” and not just “clinically relevant” have been endorsed by researchers, advocacy groups, and regulators, including nephrologists (1,2). The Food and Drug Administration has incorporated consideration of such patient-centered outcomes into its drug approval process and submitted guidance for identifying these outcomes (3).

Nephrologists who treat glomerular diseases may recognize the distinction between “conventional” study outcomes and patient-important outcomes. Although we typically evaluate therapies on the basis of their effects on proteinuria and eGFR in trials, our lived experience in clinic involves accompanying patients as they suffer through debilitating edema, toxic medication effects, and the dreaded fear of dialysis. More comprehensive measures of the patient experience are thus essential both for evaluating the full effect of interventions and for identifying priorities that may have been neglected to provide optimal patient-centered care. Although efforts have been made to define such measures consistently in hemodialysis and kidney transplant, glomerular disease has been lagging in comparison (4–6).

In this issue of CJASN, Carter et al. (7) relay the findings of their study as part of the Standardized Outcomes in Nephrology–Glomerular Disease (SONG-GD) initiative to identify and prioritize outcomes of interest to patients with glomerular diseases (n=101) and their caregivers (n=33). Citing a dearth of data on patient-centered outcomes in glomerular diseases, these investigators led 16 2-hour focus groups in Australia, Hong Kong, the United Kingdom, and the United States using a moderated, structured discussion to help participants generate both outcomes of interest as well as a prioritized ranking of these outcomes. As the authors state, the data that emerged from these focus groups are intended to “guide the selection of outcomes for research in glomerular disease and strengthen the patient-centered evidence base for decision making” (7).

These are lofty goals that likely cannot be achieved by a study of this size with just over 100 patients, but there are still many important lessons that emerge from their findings. First, patients and physicians seem to agree on the most important outcomes when studying glomerular diseases because the top three ranked outcomes for patients—kidney function, mortality, and need for dialysis or transplant—align with the “hard outcomes” that nephrologists and regulatory agencies have demanded from well designed clinical trials of glomerular diseases. Second, life participation (i.e., the ability to do meaningful activities in life) and fatigue are under-recognized outcomes of major significance to patients with glomerular disease and their caregivers, regardless of stage of kidney disease. These outcomes have often been considered the exclusive terrain of late-stage kidney disease or ESKD, but clearly, they play a role much earlier in the disease course. Third, proteinuria was not highly prioritized by any subgroup of patients or caregivers, even though proteinuria is a staple assessment of patients with glomerular disease both in trials and in routine practice. This finding suggests that clinicians are not adequately educating patients on the important role of proteinuria in disease management, specifically the link between proteinuria and risk for future declines in kidney function. Fourth, the patients in these study groups who represent nine different glomerular diseases showed remarkable consistency in identifying certain patient-reported outcomes (PROs) that may not be routinely measured in glomerular disease studies. In addition to life participation and fatigue, anxiety and effect on family were also consistently highly ranked by all participants. If the SONG-GD initiative does guide the selection of PROs for glomerular disease research, these four factors are the logical place to start.

The findings in the study by Carter et al. (7) complement and expand on the existing literature on patient-centered outcomes in glomerular disease. A useful contrast can be made with a recent report on health-related quality of life (HRQoL) in nearly 1600 adult and pediatric patients with glomerular disease from the Cure Glomerulonephropathy (CureGN) study in which we both participate (8). That study attempted to identify clinical variables associated with HRQoL measured by items from the National Institutes of Health–sponsored Patient-Reported Outcomes Measurement Informative System (http://www.nihpromis.org), including measures of physical and mental health, mobility, anxiety, fatigue, and sleep impairment. It is reassuring that the domains of HRQoL selected by the CureGN investigators for measurement were largely confirmed by Carter et al. (7) as being important to patients, particularly fatigue and anxiety. In the CureGN study, we found that patient-reported edema consistently had the strongest and most robust association with each measured domain of HRQoL, with effect beyond typical measures of disease state, including eGFR. Interestingly, Carter et al. (7) did not find fluid retention to be a highly ranked priority overall. This may reflect the broader variety of diagnoses in the population studied by Carter et al. (7) because fluid retention seemed to be more important among their predominantly proteinuric subgroup. Alternately, although the symptom of edema per se may not be a high priority for many patients, it may nevertheless be a surrogate (and perhaps even a mediator) of associated symptoms with higher priority, such as fatigue. Likewise, other studies have shown that proteinuria and disease duration are associated with HRQoL in glomerular disease, despite not being explicitly high priorities in the work by Carter et al. (7,9,10). These contrasts highlight the complex interplay between subjective and objective disease measures, experienced quality of life, and patient priorities. They also illustrate the point that not all patient-important outcomes are patient reported (e.g., kidney function) and that, conversely, not all measurable PROs are patient important. Studies like the one by Carter et al. (7) will help to focus on those that are.

There are important limitations to the report from Carter et al. (7) that must be considered before adopting their findings across a wide spectrum of patients. Beyond the small sample size, the study only included patients aged 18 years old and older, and it was composed mostly (75%) of patients aged 40–79 years old. Therefore, we should not presume that the PROs of import elicited in these focus groups necessarily translate to pediatric and young adult patients. On the basis of the locale of the focus groups, representation of black (4%) and Hispanic (17%) patients was much lower than in the United States disease population, particularly given that two of the four leading diseases enrolled were lupus nephritis and FSGS. In addition, participants were selected by their nephrologists (“purposive sampling”), which may have introduced a degree of selection bias toward those healthy enough to participate in a 2-hour focus group or as reflected in more than half of the patients identifying as unemployed or retired, toward those with the kind of flexible schedule that many patients with glomerular disease do not have.

Beyond identifying important PROs for glomerular disease studies, the focus groups in the SONG-GD initiative also aimed to explore reasons for the identification and prioritization of such outcomes. Their qualitative findings are grouped into three themes—constraining day-to-day existence, impaired agency and control over health, and threats to future health and family—and then, they are further subdivided into an additional four to five subthemes (e.g., “altered appearance eroding self-confidence”). These subthemes could easily be incorporated into a patient report form or other questionnaire to inform a glomerular disease study, but of equal import, these qualitative findings have the ability to immediately affect routine care of patients with glomerular disease. Clinicians caring for patients with glomerular diseases could, for example, ask their patients if they are feeling a “demoralizing loss of freedom” and “uncertainty from unpredictable hazards” (two of the subthemes delineated in this study) just as they might ask about edema or gross hematuria.

In his memoir The Lost Art of Healing: Practicing Compassion in Medicine, cardiologist Bernard Lown (11) (best known for developing the direct current defibrillator) recalls the simple advice that he received from a Siberian physician: “Every time a doctor sees a patient, the patient should feel better as a result” (11). Lown (11) spends most of his book trying to convince his readers that physician-patient dialogue has, is, and always will be the only reliable way to ensure such a positive medical outcome. “I know of few remedies more powerful than a carefully chosen word,” writes Lown (11). “Patients crave caring, which is dispensed largely with words” (11). Active listening and empathetic dialogue with patients with glomerular disease about what is most important to them will not only enhance our ability to perform clinical trials in this space but also, improve the chances of patients feeling better, regardless of disease course.

Disclosures

Dr. Bomback and Dr. Canetta have nothing to disclose.

Funding

None.