Baseline Patient Demographic and Clinical Characteristics
A total of 23,235 patients met the sample selection criteria and were included in the analysis. Of these, 18,409 (79%) patients were classified into the normoalbuminuria group, 3863 (17%) into the microalbuminuria group, and 963 (4%) into the macroalbuminuria group (Fig. 1). Baseline demographics such as age, sex, and residential region were different between the three groups (Table 1); patients with microalbuminuria or macroalbuminuria were slightly older (mean age [SD] = 54.9 [10.2] and 56 [10.3] years, respectively) and had more men (60% and 63%) than patients within the normoalbuminuria group (mean age [SD] = 54.3 [9.6] years, 53% male).
Table 1 Patient baseline and clinical characteristics
Patients with more severe nephropathy displayed exacerbated clinical characteristics and higher HRU and costs at baseline. The time from the first observed type 2 diabetes diagnosis in the database to the index date differed between groups, with the macroalbuminuria group having the longest time since diagnosis (mean [SD] = 44.0 [30.5] months), followed by the microalbuminuria (40.5 [27.9] months) and normoalbuminuria (37.8 [26.6] months; p < 0.05 all comparisons) groups (Table 1). A significantly higher comorbidity burden was also observed in patients with microalbuminuria (CCI [SD] = 1.9 [1.4]) and macroalbuminuria (2.5 [1.7]) compared with the normoalbuminuria group (1.6 [1.1]; all p < 0.05). With the exception of outpatient services, where 99% of patients in each group had at least one visit, patients with diabetic nephropathy experienced significantly higher rates of all-cause HRU during the baseline period compared to those with normoalbuminuria (p < 0.05 all comparisons), as well as higher all-cause healthcare costs (p < 0.05, all comparisons) (Table 1).
Nephropathy-Related Treatment Use and Disease Progression During the Follow-up Period
During the 6 months following the index date, nephropathy-related treatments were used by 68% with normal urine albumin levels, 81% of patients with microalbuminuria, and 88% of patients with macroalbuminuria (Table S1). ACE inhibitors were the most commonly used treatment for nephropathy (32%, 41%, and 43% for the normoalbuminuria, microalbuminuria, and macroalbuminuria groups, respectively). Both ACE inhibitors and ARBs were used by 3% of patients with microalbuminuria and 6% of patients with macroalbuminuria.
During the follow-up period, patients with microalbuminuria or macroalbuminuria had a significantly greater risk of progression to a more severe disease stage compared to patients in the normoalbuminuria group (HRs [CI] = 1.31 [1.08, 1.60] and 1.44 [1.21, 1.72], respectively; both p < 0.05) (Fig. 2a). Specifically, the 5-year disease progression rates were 15%, 19%, and 31% for the normoalbuminuria, microalbuminuria, and macroalbuminuria groups, respectively. Patients with microalbuminuria and macroalbuminuria were at significantly higher risk of receiving dialysis/hemodialysis compared to patients with normoalbuminuria (HRs [CI] = 4.23 [2.45, 7.30] and 40.14 [25.33, 63.60], respectively; both p < 0.001) (Fig. 2b). The 5-year dialysis rates were 0.3% among patients with normal albumin levels, 2% among those with microalbuminuria, and 18% among those with macroalbuminuria.
Annual All-Cause and Nephropathy-Related HRU During the Follow-up Period
The annual frequency of all-cause healthcare visits rose significantly with the increasing severity of the patient’s nephropathy, a trend that was consistent across inpatient, outpatient, ER, and other medical services visits (p < 0.05 in all pairwise adjusted IRR comparisons) (Table 2). The microalbuminuria group experienced significantly higher utilization rates of each type of all-cause medical service in comparison with the normoalbuminuria group, particularly inpatient admissions (adjusted IRR [CI] = 1.51 [1.37, 1.65]; p < 0.05 all adjusted IRR comparisons) (Table 2). Furthermore, the macroalbuminuria group experienced particularly heightened average annual incidence rates of all-cause inpatient admissions in comparison with the microalbuminuria and normoalbuminuria groups (adjusted IRRs [CI] of 1.78 [1.50, 2.09] and 2.70 [2.34, 3.16], respectively; both p < 0.05). A similar trend was observed in healthcare visits related to nephropathy, with an increased magnitude of difference between groups. In comparison with the normoalbuminuria group, the microalbuminuria group had significantly higher incidence rates of nephropathy-related inpatient (adjusted IRR [CI] = 2.94 [2.21, 3.88]), ER (4.70 [3.09, 7.76]), outpatient (3.77 [3.16, 4.48]), and other medical service visits (6.26 [2.43, 19.46], all p < 0.05) (Table 2). Additionally, in comparison with both the microalbuminuria and normoalbuminuria groups, patients with macroalbuminuria had significantly higher incidence rates of nephropathy-related inpatient (adjusted IRRs [CI] = 5.24 [3.91, 7.09] and 16.53 [12.14, 21.87], respectively), ER (4.03 [2.49, 6.46] and 18.96 [11.79, 29.88]), outpatient (4.83 [3.51, 6.30] and 18.25 [13.36, 24.86]), and other medical services visits (8.54 [3.87, 19.92] and 50.20 [16.45, 174.00]; all p < 0.05) during the follow-up period, after adjusting for baseline patient demographics (Table 2). For both all-cause and nephropathy-related HRU, the differences in adjusted annual HRU rates between the albuminuria and normoalbuminuria groups increased with disease severity, with the macroalbuminuria group exhibiting the highest HRU in all cases.
Table 2 Comparison of health resource utilization during the follow-up period
Annual All-Cause and Nephropathy-Related Healthcare Costs During the Follow-up Period
Patients with microalbuminuria or macroalbuminuria had significantly higher annual all-cause healthcare costs (2016 US dollars) compared to those in the normoalbuminuria group (mean [SD], normoalbuminuria = $12,353 [20,082], microalbuminuria = $15,893 [29,874], macroalbuminuria = $25,424 [47,844]), with adjusted cost differences of $3580 and $12,830 per year, respectively (p < 0.05, all comparisons) (Table 3). The microalbuminuria group had higher costs than those of the normoalbuminuria group (p < 0.05, all comparisons), and the macroalbuminuria group had significantly higher adjusted all-cause healthcare costs than either the normoalbuminuria or microalbuminuria groups in all categories (with the exception of ER visits in comparison with the microalbuminuria group) (Table 3). Inpatient admissions costs accounted for 45–51% of the adjusted cost differences between groups, followed by outpatient (20–24%) and pharmaceutical costs (10–15%). A similar trend was observed in adjusted nephropathy-related costs (Table 3). Compared to patients in the normoalbuminuria group, patients with microalbuminuria and macroalbuminuria incurred higher total nephropathy-related adjusted healthcare costs, with increases of $362 and $3716, respectively. The nephropathy-related total annual healthcare costs among patients with macroalbuminuria were $4427, driven by high inpatient (mean [SD] = $2048 [10,765]) and outpatient ($1526 [11,515]) medical costs.
Table 3 Comparison of all-cause and diabetic nephrology-related annual healthcare costs during the follow-up period