Hospital admissions for severe infections in people with chronic kidney disease in relation to renal disease severity and diabetes status

Abstract

Summary Background Immunosuppressive agents are being investigated for the treatment of chronic kidney disease (CKD) but may increase risk of infection. This was a retrospective observational study intended to evaluate the risk of hospitalized infection in patients with CKD, by estimated glomerular filtration rate (eGFR) and proteinuria status, aiming to identify the most appropriate disease stage for immunosuppressive intervention. Methods Routine UK primary‐care and linked secondary‐care data were extracted from the Clinical Practice Research Datalink. Patients with a record of CKD were identified and grouped into type 2, type 1 and nondiabetes cohorts. Time‐dependent, Cox proportional hazard models were used to determine the likelihood of hospitalized infection. Results We identified 97 839 patients with a record of CKD, of these 11 719 (12%) had type 2 diabetes. In these latter patients, the adjusted hazard ratios (aHR) were 1.00 (95% CI: 0.80‐1.25), 1.00, 1.03 (95% CI: 0.92‐1.15), 1.36 (95% CI: 0.20‐1.54), 1.82 (95% CI: 1.54‐2.15) and 2.41 (95% CI: 1.60‐3.63) at eGFR stages G1, G2 (reference), G3a, G3b, G4 and G5, respectively; and 1.00, 1.45 (95% CI: 1.29‐1.63) and 1.91 (95% CI: 1.67‐2.20) at proteinuria stages A1 (reference), A2 and A3, respectively. All aHRs (except G1 and G3a) were significant, with similar patterns observed within the non‐DM and overall cohorts. Conclusions eGFR and degree of albuminuria were independent markers of hospitalized infection in both patients with and without diabetes. The same patterns of hazard ratios of eGFR and proteinuria were seen in CKD patients regardless of diabetes status, with the risk of each outcome increasing with a decreasing eGFR and increasing proteinuria. Infection risk increased significantly from eGFR stage G3b and proteinuria stage A2 in type 2 diabetes. Treating type 2 DM patients with CKD at eGFR stages G1‐G3a with immunosuppressive therapy may therefore provide a favourable risk‐benefit ratio (G1‐G3a in type 2 diabetes; G1‐G2 in nondiabetes and overall cohorts) although the degree of proteinuria needs to be considered.

Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy

“…The clinical diagnosis of DKD is based on the measurement of the estimated glomerular filtration rate (eGFR) and the albuminuria/proteinuria, along with clinical observations, including diabetes duration and the presence of diabetic retinopathy [5,6]. The major threats presented by DKD are risks of mortality, cardiovascular disease, end-stage renal disease, and infections, and a common risk factor for these DKD-related complications is proteinuria [7][8][9]. A better understanding of the mechanisms underlying proteinuria in DKD may help to develop novel treatment strategies for this aspect of DKD.…”