Nephropathy and albuminuria: the gateway to cardiovascular risk. Use of RAAS inhibitors and nephroprotective drugs

Abstract

Chronic kidney disease (CKD) in people with type 1 diabetes (T1D) should be regarded as part of the cardiorenal continuum rather than solely a microvascular complication. Screening is based on the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), beginning five years after diagnosis, with confirmation of any abnormal finding. CKD presentation is heterogeneous, as eGFR may decline before the onset of albuminuria. However, the FinnDiane Study showed that non-albuminuric CKD accounted for only 2% of cases, whereas the combination of albuminuria and an eGFR <60 mL/min/1.73 m² identified individuals at the highest risk of cardiovascular events and mortality. Regression of albuminuria was associated with lower renal and cardiovascular risk. Nevertheless, 63% of individuals with T1D and CKD failed to simultaneously achieve blood pressure, cholesterol, and HbA1c targets [1].

Albuminuria is now recognized not only as a marker of kidney damage but also as a marker of vascular risk and a therapeutic target. Blockade of the renin–angiotensin–aldosterone system (RAAS) remains the foundation of kidney-protective therapy. In patients with CKD, an angiotensin-converting enzyme inhibitor (ACE inhibitor) or an angiotensin receptor blocker (ARB) should be initiated in the presence of hypertension or a UACR ≥30 mg/g, titrated to the maximum tolerated dose, with reassessment of blood pressure, serum creatinine, and potassium within 2–4 weeks [2].

Beyond RAAS blockade, kidney-protective therapies in T1D continue to evolve, although the evidence remains limited. In a real-world study, sodium-glucose cotransporter-2 (SGLT2) inhibitors were associated with better preservation of eGFR and lower rates of heart failure, CKD progression, and hospitalization than glucagon-like peptide-1 receptor agonists (GLP-1 RAs), albeit at the expense of an increased risk of diabetic ketoacidosis and urinary tract infections, emphasizing the need for careful patient selection, patient education, and glucose and ketone monitoring [3]. Recent evidence also supports the use of GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists as adjunctive therapy in T1D, demonstrating benefits in glycemic control, body weight, and cardiovascular risk factors, with emerging evidence suggesting potential reductions in major adverse cardiovascular events (MACE) and advanced kidney disease [4]. In the FINE-ONE randomized, double-blind, placebo-controlled trial, 242 adults with T1D, CKD, a UACR of 200–5000 mg/g, and background RAAS inhibitor therapy received finerenone for six months, resulting in a 25% reduction in UACR compared with placebo [5].

Overall, contemporary management of diabetic kidney disease in T1D integrates three complementary therapeutic goals: reducing cardiovascular risk, lowering albuminuria, and slowing the decline in kidney function.