To the Editor:
Kidney disease is a major public health problem and is associated with substantial morbidity and mortality.1 It is known that the racial/ethnic minorities like people who are Hispanic or Black/African American experience greater rates of chronic kidney disease (CKD) and are 2-4 times more likely to develop kidney failure requiring dialysis as compared to their White counterparts.2 Sex also seems to play a major role in the development and progression of kidney disease.3 Women are more likely to develop kidney disease; however, they have lesser requirements for dialysis as compared to men.3 Given the importance of racial and sex disparity in kidney disease, we reviewed clinical trials (2000-2021) related to kidney disease and further determined the racial/ethnic and sex composition. We hypothesize that race/ethnic minority groups and females are underrepresented in clinical trials that were conducted in United States.
We used data from completed clinical trials from January 1, 2000-December 1, 2021 that were registered and reported on www.ClinicalTrials.gov. We used the terms acute kidney injury, CKD, kidney failure receiving replacement therapy, hemodialysis, peritoneal dialysis, glomerulonephritis, polycystic kidney disease, and kidney transplantation to identify clinical trials. We limited our analysis to adult clinical trials that were conducted in the United States and published in the English language. Two authors (ZA, KA) independently reviewed and verified these studies. We collected baseline demographics including age, sex, and race/ethnicity (self-reported) of the trials’ participants from www.ClinicalTrials.gov or publications arising from those clinical trials when found. We included the following categories of race: White/Non-Hispanic White, Black or African American, Asian, American Indian or Alaska Native, Native Hawaiian or Pacific Islander, and Mixed. We also added a category of others/unknown to include individuals that did not fall into any of the mentioned racial groups. Ethnicity data included Hispanic or Latino. Descriptive data was reported as mean (standard deviation) or as relative (%) frequency using SPSS software version 26 (IBM Corp).
From January 1, 2000 to December 1, 2021, 2,577 studies were reported in www.ClinicalTrials.gov. Of these, 2,166 studies were clinical trials, and 24.6% (n=532) were complete with race/ethnicity and sex data reported and included in the analysis (Fig S1). The reported studies included acute kidney injury 3.9% (n=21), CKD 31.4% (n=167), glomerulonephritis 6.2% (n=33), dialysis (hemodialysis, peritoneal dialysis) 35.2% (n=187), and kidney transplantation 23.3% (n=124) trials, respectively (Table 1).
Table 1.
Characteristics of Registered Kidney Disease Clinical Trials in ClinicalTrial.gov, 2000-2021
| Variable | All | AKI | CKD | GN | Dialysis | Kidney transplant |
|---|---|---|---|---|---|---|
| Clinical trials | 532 | 21 | 167 | 33 | 187 | 124 |
| Total participants | 214,702 | 47,664 | 51,953 | 2,520 | 89,637 | 22,928 |
| Age, y, mean (SD) | 55 (9) | 62 (9) | 61 (8) | 38 (10) | 56 (6) | 51 (6%) |
| Sex, n (%) | ||||||
| Male | 124,431 (58%) | 28,010 (59%) | 31,630 (61%) | 588 (23%) | 50,470 (56%) | 13,733 (60%) |
| Female | 90,271 (42%) | 19,654 (41%) | 20,323 (39%) | 1932 (77%) | 39,167 (44%) | 9,195 (40%) |
| Race/ethnicity, n (%) | ||||||
| White | 116,625 (54%) | 35,357 (74%) | 29,780 (57%) | 941 (37%) | 37,788 (42%) | 12,759 (56%) |
| Black/African American | 54,373 (25%) | 5,367 (11%) | 9,247 (18%) | 294 (12%) | 34,714 (39%) | 4,751 (21%) |
| Hispanic | 14,628 (7%) | 856 (2%) | 1,153 (2%) | 425 (17%) | 9,608 (11%) | 2,586 (11%) |
| Asian | 10,362 (5%) | 350 (0.7%) | 5,563 (11%) | 618 (25%) | 2,923 (3%) | 908 (4%) |
| Native American Indian | 1,304 (0.6%) | 63 (0.1%) | 542 (1%) | 25 (1%) | 619 (0.7%) | 55 (0.2%) |
| Native Hawaii/Pacific Islander | 391 (0.2%) | 62 (0.1%) | 79 (0.2%) | 2 (0.1%) | 214 (0.2%) | 34 (0.2%) |
| Others | 17,019 (8%) | 5,609 (12%) | 5,589 (11%) | 215 (9%) | 3,771 (4%) | 1835 (8%) |
| Funding, n (%)a | ||||||
| NIH | 63 (12%) | 2 (10%) | 23 (14%) | 6 (18%) | 20 (11%) | 12 (10%) |
| Industry | 316 (59%) | 9 (43%) | 97 (58%) | 24 (73%) | 112 (60%) | 74 (60%) |
| University | 246 (46%) | 11 (52%) | 75 (45%) | 10 (30%) | 76 (41%) | 74 (60%) |
| VA | 17 (3%) | 2 (10%) | 12 (7%) | 0 (0%) | 2 (1%) | 1 (1%) |
| Others | 43 (8%) | 2 (10%) | 14 (8%) | 2 (6%) | 17 (9%) | 8 (7%) |
| Trial type, n (%)b | ||||||
| Phase 1 | 49 (17%) | 0 (0%) | 13 (13%) | 5 (16%) | 24 (24%) | 7 (18%) |
| Phase 1/2 | 26 (9%) | 0 (0%) | 4 (4%) | 2 (7%) | 6 (6%) | 14 (35%) |
| Phase 2 | 104 (35%) | 15 (80%) | 36 (35%) | 17 (55%) | 35 (34%) | 1 (2%) |
| Phase 2/3 | 18 (6%) | 4 (20%) | 5 (5%) | 1 (3%) | 6 (6%) | 2 (5%) |
| Phase 3 | 98 (33%) | 0 (0%) | 45 (43%) | 6 (19%) | 31 (30%) | 16 (40%) |
Abbreviations: AKI, acute kidney injury; CKD, chronic kidney disease; GN, glomerulonephritis; NIH, National Institutes of Health; SD, standard deviation; VA, Veterans Affairs.
Categories of study funding are not mutually exclusive.
237 studies have unknown phase.
The total participants census in all trials was 214,702 with 58% males (n=124,431) and 42% females (n=90,271). The mean (standard deviation) age of participants was 55 (9) years. Overall, for kidney disease trials, the representation of White participants was highest (54%, n=116,625) followed by Black/African American participants (25%, n=54,373). Hispanic, Asian, and American Indian/Native Hawaiian/Pacific Islander patients accounted for only 7% (n=14,628), 5% (n=10,362), and 0.8% (n=1,695) of trial participants, respectively. Race/ethnicity and sex participation percentages in kidney disease clinical trials remained unchanged in the last 20 years (Fig S2). Interestingly, race/ethnicity participation varied by trial type (Table 1). In dialysis trials, Black/African American patients have approximately equal representation as White patients (39% [n=34,714] vs 42% [n=37,788], respectively). However, in CKD and acute kidney injury trials, Black/African American patients remain underrepresented compared with their expected proportion based on US Renal Data System data (Fig 1). Hispanic patients were also underrepresented in CKD and dialysis trials relative to their expected proportion (Fig 1). In CKD trials, females were underrepresented (39%, n=20,323) as compared to males (61%, n=31,630), whereas in glomerulonephritis trials, females (77%, n=1,932) were predominantly included as compared to males (23%, n=588) (Table 1). This finding of overrepresentation of females in glomerulonephritis trials can be explained as 30% of trials included in our analysis were for lupus nephritis, which is more common among female patients. Race and sex enrollment nearly matched their expected proportion in kidney transplant trials (Fig 1).
Figure 1.
Comparison of kidney disease burden in US adults vs trial enrollment stratified by (A) race and (B) sex. AKI, acute kidney injury; CKD, chronic kidney disease; USRDS, US Renal Data System.
Our study findings showed that race/ethnic minorities remained consistently underrepresented in US-based kidney disease clinical trials in proportion to kidney disease burden in these groups. Females were underrepresented in CKD trials. Overall, this is concerning as clinical trials will not be generalizable if they are not tested in diverse racial and ethnicity and sex groups. Our study has some limitations. We included limited studies before 2007, owing to lack of a mandate on clinical trials demographics submission to www.ClinicalTrials.gov before 2007. Also, only half of completed studies reported both race and sex. More studies are needed to better understand the barriers of minority and female patient participation including lack of trust and poor access to clinical trials. In the future, clinical investigators should focus on balancing the racial and sex representation in kidney disease clinical trials enrollment to eliminate these disparities.
Article Information
Authors’ Contributions
Research idea and study design: ZA, KA, AK, RM; data acquisition, analysis, or interpretation of data: ZA, KA, AW, VG, TC, AK, RM. Supervision/mentorship: RM, AK. AK and RM contributed equally to this work. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
Support
This work was supported by grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) K23 (DK132680-01) (to Dr Malhotra).
Financial Disclosure
The authors declare that they have no relevant financial interests.
Peer Review
Received May 12, 2022. Evaluated by 1 external peer reviewer, with direct editorial input from the Statistical Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form November 2, 2022.
Footnotes
Figure S1: Flow chart of study
Figure S2: Race/ethnic and gender representation trends in kidney disease clinical trials
Supplementary Material
Fig S1-S2.
References:
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Fig S1-S2.