Traditionally, chronic kidney disease (CKD) has been regarded as a progressive, irreversible condition, with treatment goals limited to slowing its progression to end-stage renal disease. However, the emergence of a series of novel therapies in recent years has fundamentally changed this pessimistic narrative. Sodium-glucose cotransporter 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, glucagon-like peptide-1 receptor agonists, and targeted immunotherapies for IgA nephropathy have been clinically proven to enable sustained stabilization of glomerular filtration rate and normalization of albuminuria. This marks a shift in the therapeutic goal of CKD from “slowing progression” to “achieving remission.”
Recently, Navdeep Tangri et al. published a review that systematically elaborates on this paradigm shift, defines the concept and feasibility of CKD remission, and outlines practical pathways in diabetic kidney disease and glomerular diseases, aiming to drive innovation in clinical thinking within nephrology.
CKD is highly prevalent worldwide and has long been considered a chronic, progressive disorder. Patients and clinicians widely view persistent decline in renal function as inevitable, so the acceptable therapeutic objective has been merely to slow CKD progression and delay the onset of renal failure requiring dialysis or kidney transplantation.
Nevertheless, with deeper understanding of kidney diseases and the development and widespread use of novel therapies that preserve renal function, this perspective has undergone a fundamental transformation. Beginning with renin-angiotensin system inhibitors, followed by agents such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) for diabetic kidney disease, and extending to B-cell targeted and complement-targeted therapies for IgA nephropathy (IgAN), modern treatment regimens now hold the potential to fully halt CKD progression.
The era of combination therapy has arrived, particularly in diabetic kidney disease. Triple or quadruple therapy adding nonsteroidal mineralocorticoid receptor antagonists (ns-MRA) and glucagon-like peptide-1 receptor agonists (GLP-1RA) to renin-angiotensin-aldosterone system inhibitors (RAASi) and SGLT2i has enabled patients with clinically significant albuminuria (e.g., urinary albumin-creatinine ratio [UACR] > 100 mg/mmol) to achieve over 50% reduction in albuminuria, restore UACR to near-normal levels, and maintain stable estimated glomerular filtration rate (eGFR).
Accordingly, the therapeutic outlook for CKD has fundamentally shifted from “slowing inevitable renal function loss” to “maintaining stable eGFR and renal function,” thereby reaching a state definable as “CKD remission.”
Dedicated trials in diabetic and non-diabetic CKD patients show that SGLT2i significantly slow the chronic rate of eGFR decline. For example, in the CREDENCE trial, on background RAASi therapy, the annual eGFR slope was -1.85 ml/(min·1.73 m²) in the canagliflozin group versus -4.52 ml/(min·1.73 m²) in the placebo group. The DAPA-CKD trial reported an annual chronic eGFR slope of -1.58 ml/(min·1.73 m²) with dapagliflozin versus -3.84 ml/(min·1.73 m²) with RAASi alone.
Recent combination therapy using ns-MRA and GLP-1RA on top of RAASi and SGLT2i further slowed eGFR decline and albuminuria in these populations. Pooled clinical trial data (including the FLOW trial) indicate that combined SGLT2i and GLP-1RA improves eGFR decline more than either agent alone, achieving a chronic annual eGFR slope of -1.3 to -1.5 ml/(min·1.73 m²).
Furthermore, recently published data from the CONFIDENCE trial show that most patients receiving combined SGLT2i and ns-MRA achieved over 50% albuminuria reduction. For patients with type 2 diabetes — the leading cause of CKD and renal failure worldwide — these findings suggest that remission is possible and achievable, and may substantially reduce the renal and cardiovascular disease burden. The therapeutic target should therefore be to markedly reduce albuminuria and slow the annual eGFR decline to approximately 1 ml/(min·1.73 m²).
In contrast, for patients with progressive glomerular diseases such as IgA nephropathy, historical treatment focused on slowing progression rather than achieving remission. Novel therapies for these conditions demand another shift in mindset: from merely slowing progression to targeting complete remission.
Indeed, data from multiple clinical trials of B-cell targeted therapies for IgA nephropathy show that treated patients achieve an annual eGFR decline slope consistently around 1 ml/(min·1.73 m²) or lower, compared with 2–3 ml/(min·1.73 m²) per year previously attainable with optimal supportive care and therapies targeting non-immune mechanisms of renal injury.
For patients with IgA nephropathy — the most common glomerular disease globally — these findings reinforce the need to pursue remission as a goal through therapies targeting underlying immune biology, combined with foundational CKD treatments such as RAASi and SGLT2i, plus achievement of blood pressure targets, to sustain lifelong renal health. Similar to diabetic kidney disease, combination therapy appears most likely to achieve disease remission in IgA nephropathy.
In summary, the time has come to transform the nephrology narrative. CKD should no longer be viewed as an inevitably progressive and irreversible condition. With novel therapies, especially in combination, CKD remission is both realistic and achievable for many patients. The nephrology community must now shift its focus from “slowing CKD progression” to embracing this unprecedented opportunity to “preserve kidney health.”