Significance of patient and transplant factors in development of kidney dysfunction in patients with cGvHD

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potentially curative therapy for hematologic malignancies¹; however, use of allo-HSCT can lead to long term complications, such as chronic graft-versus-host disease (cGvHD) and kidney dysfunction, both of which can cause significant morbidity.¹

Kidney dysfunction can present as acute kidney injury, which causes a drop from baseline in the estimated glomerular filtration rate (eGFR), and chronic kidney disease (CKD), which is a persistent drop in eGFR over 3 months or more.¹ Individuals who have undergone allo-HSCT and develop CKD are at a higher risk of death compared with those individuals with normal eGFR. In addition, cGvHD is a risk factor for development of CKD.

Here, we summarize key findings from a study investigating the incidence of kidney dysfunction in patients with cGvHD and assessing the impact of kidney dysfunction on overall survival.¹

Study design¹

• Overall, 365 patients were included for analysis in the Clinical and Biological Factors Determining Outcomes in Chronic Graft-Versus-Host Disease (NCT00092235) study.
  • Patients received multi-disciplinary evaluation for 1 week
  • eGFR was calculated using patient age, sex, and serum creatinine
  • Univariate and multivariate analysis was performed to investigate which factors were associated with kidney dysfunction

Results¹

Patient and cGvHD characteristics at enrollment are shown in Table 1. The majority of patients were white and had received a human leukocyte antigen matched transplant.

Table 1. Baseline patient and cGvHD characteristics*

cGvHD, chronic graft-versus-host disease; HLA, human leukocyte antigen; NIH, National Institutes of Health. *Adapted from Beshensky, et al.1
Characteristic, % unless otherwise stated	All patients (N = 365)
Median age (range), years	49 (18.1–75)
Sex
Male	44
Female	56
Race
Non-Hispanic White	88
Non-Hispanic Black	4
Hispanic other	4
Hispanic White	2
Asian	1
Non-Hispanic other	<1
HLA match
Matched	84
Mismatched	13
Unknown	2
Conditioning regimen
Myeloablative	55
Non-myeloablative	44
Unknown	1
Median time from transplant to cGvHD diagnosis (range), months	7.8 (0.6–260.7)
NIH Global Score
Mild	2
Moderate	25
Severe	73
Prior lines of systemic therapy
0–2	27
3–5	54
6–8	16
9–10	2
Unknown	<1

In this study, kidney dysfunction was defined as eGFR of <60 ml/min/1.73 m², with moderate-severe kidney dysfunction defined as eGFR <45 ml/min/1.73 m². For the study population, the median eGFR was 96.4 ml/min/ 1.73 m², with kidney dysfunction occurring in 18% of patients and moderate-severe kidney dysfunction occurring in 8% of patients.

Univariate analysis

Univariate analysis revealed that increasing patient age was strongly associated with kidney dysfunction. Associations between other patient and transplant factors with kidney dysfunction is shown in Figure 1.

CNI, calcineurin inhibitor; GvHD, graft-versus-host disease; HLA, human leukocyte antigen.
*Adapted from Beshensky, et al.¹

Other factors which were found to be associated with kidney dysfunction were:

• No/mild cGvHD involvement of joints/fascia (p = 0.009), mouth (p = 0.037), and skin (p = 0.03); these were more frequently moderate-severe in patients without kidney dysfunction.
• Presence of (p = 0.049) and/or increase in severity of proteinuria (p = 0.023) and increasing blood urea nitrogen (p < 0.0001).
• Presence of non-active GvHD (p = 0.04).

The average National Institutes of Health cGvHD organ score was lower in patients with kidney dysfunction (p = 0.0048). No association was found with diabetes (as measured by use of diabetes medication).

Overall survival

Median overall survival was found to be significantly lower in patients with moderate-severe kidney dysfunction versus those without, as shown in Figure 2. However, there were no significant differences in overall survival between patients with or without kidney dysfunction. 

 *Data from Beshensky, et al.¹

Conclusion 

This study revealed that approximately one fifth of patients with cGvHD had kidney dysfunction, with around half experiencing moderate-severe dysfunction; overall survival was significantly reduced in these patients. Certain factors, such as age and prior treatments, may have prognostic value for the development of kidney dysfunction in patient with cGvHD.

This study is limited by its cross-sectional design and measurement of eGFR at only a single time point. In addition, there were no control patients without cGvHD at a similar time point posttransplant. Therefore, additional multicenter, longitudinal studies are needed to fully determine the relationship between cGvHD, allo-HSCT, and kidney dysfunction.