Frailty Predicts an Increased Risk of End-Stage Renal Disease with Risk Competition by Mortality among 165,461 Diabetic Kidney Disease Patients

Abstract

To examine the effect of frailty on diabetic kidney disease patients' risk of progression to end-stage renal disease (ESRD), mortality, and adverse episodes, as whether frailty modifies their risk of developing ESRD and other adverse outcomes remains unclear. We identified 165,461 DKD patients from the Longitudinal Cohort of Diabetes Patients in Taiwan (n=840,000) between 2004 and 2010, classifying them into those without frailty or with 1, 2 and ≥3 frailty components based on a modified version of FRAIL scale. Using Cox proportional hazard regression analysis, we examined the long-term risk of developing ESRD along with their risk of mortality, supplemented by a competing risk analysis against mortality. Among all participants, 66.2% (n=109,586), 27.2% (n=44,986), 5.9% (n=9,799), and 0.7% (n=1090) patients did not have or had 1, 2, and ≥3 frailty components, respectively. After a 4.1-year follow-up, 4.2% patients developed ESRD and 18.5% died. Cox proportional hazard modeling revealed that patients with 1, 2, and ≥3 frailty components had increased risks of developing ESRD (for 1, 2, and ≥3 components, hazard ratio [HR] 1.13, 1.18, and 1.2, respectively) and mortality (HR 1.25, 1.41, and 1.34, respectively), with. 9% and 16% risk elevations for ESRD and mortality per component increase. Competing risk analysis showed that frailty-induced ESRD risk was attenuated partially by mortality in those with moderate frailty. The receipt of palliative care did not attenuate this risk. Frailty increased the risk of ESRD based on a dose-response relationship among DKD patients with risk competition by mortality.

Frailty predicts a higher risk of incident urolithiasis in 525 368 patients with diabetes mellitus: a population-based study

“…Our study benefited from the diabetic cohort used, the LCDP, that encompassed a representative, nationwide sampling of patients with DM, and the results generated from the analysis of this cohort are enhanced by its comprehensive data documentation and longitudinal nature 7 8 31. Furthermore, the modified FRAIL scale used in this study has been validated before in this database7 8 and other cohorts,32 33 and the code combinations for identifying urolithiasis were also derived from studies using administrative database to uncover cases of urolithiasis. However, several limitations should be noted; frailty was not ascertained using interview results, and extrapolation of our findings to the individual level should proceed cautiously.…”

“…We selected patients with DM from the Longitudinal Cohort of Diabetes Patients (LCDP), a well-maintained cohort of patients with diabetes derived from an annual random selection of 120 000 patients with at least one diagnosis of diabetes from the National Health Insurance Database in Taiwan, between 2004 and 2010 7 8. This led to an initial cohort size of 840 000 during the study period.…”

“…This led to an initial cohort size of 840 000 during the study period. We further restricted the diagnostic criterion for DM to a minimum of three outpatient diagnoses of diabetes (International Classification of Disease 9th version—Clinical Modification (ICD-9-CM) code 250.x) or at least one inpatient diagnosis, a validated approach for increasing the specificity of DM diagnosis 7 8. The exclusion criteria consisted of pediatric cases (age≤20 years), those with missing data, with any codes of the outcome prior to the diagnosis of DM, and those with insufficient length of follow-up (at least 1 year after the date of DM diagnosis, no later than December 31, 2010).…”

“…We further adapted the FRAIL scale by incorporating combinations of diagnostic code groups for each of its five items, as published previously 7. This approach has been repeatedly validated, and scoring results based on this modified FRAIL scale exhibited excellent correlations with patient-level outcomes 7 8. Patients with any code from the diagnostic groupings during the years preceding the index date were deemed to exhibit positivity for that specific FRAIL item.…”

“…Patients with DM are at a higher risk of exhibiting frailty, a degenerative trait characterized by a higher vulnerability to endogenous or environmental injuries, regardless of their age, likely due to the combinatorial effects of hyperglycemia-induced premature cellular senescence, chronic inflammation, and oxidative stress 6. Accumulating evidence indicates that frailty in patients with diabetes causes adverse outcomes ranging from effects on mortality and functional independence, to musculoskeletal degeneration, an increased risk of cardiovascular events, and renal failure 7 8. None of the existing studies has examined whether frailty may influence the probability of urolithiasis in patients with DM.…”