Latest Research on CKD Reversal
Current State of CKD Reversal Evidence
True reversal of established chronic kidney disease remains largely unachievable with current therapies, though recent evidence demonstrates that disease-modifying medications can slow or potentially halt progression, and in rare cases, structural improvements have been documented. 1
The concept of CKD reversal must be distinguished from slowing progression. The 2023 KDIGO guidelines define "chronic kidney disease-modifying treatment" as interventions that have a positive effect on kidney disease trajectory (i.e., slow or reverse kidney damage and functional decline) and reduce risk of kidney failure—notably, the emphasis remains on slowing rather than reversing damage. 1
Evidence for Structural Reversal
Acute Kidney Disease vs. Chronic Kidney Disease
The strongest evidence for actual reversal exists in the acute kidney disease (AKD) phase rather than established CKD:
Complete reversal of kidney injury within 48-72 hours of AKI onset is associated with better outcomes than longer durations, but this represents prevention of CKD development rather than reversal of established disease. 1
Persistent AKI that continues beyond 48 hours frequently becomes AKD, which exists on a continuum toward CKD, making early intervention critical. 1
Glomerulosclerosis Reversal Research
Limited evidence suggests structural reversal may be possible in specific contexts:
Mechanisms for potential glomerulosclerosis reversal include matrix remodeling, capillary reorganization, and podocyte reconstitution, though current therapy with renin-angiotensin system inhibition alone is insufficient to initiate and maintain long-term regression of glomerular structural injury. 2
Animal studies demonstrate that healthy bone marrow cell infusion can increase glomerular capillary density and reduce sclerosis in established CKD, though translation to human therapy remains experimental. 3
Disease-Modifying Medications: The Current Standard
SGLT2 Inhibitors as First-Line Therapy
SGLT2 inhibitors represent the most significant advancement in slowing CKD progression and should be first-line therapy for most CKD patients regardless of diabetes status. 4, 5
These agents substantially reduce the risk for kidney failure and cardiovascular complications in patients already treated with adequate doses of renin-angiotensin system inhibitors. 6, 7
SGLT2 inhibitors are particularly beneficial for patients with eGFR 30-60 mL/min/1.73 m² and/or albuminuria (especially UACR >300 mg/g). 5
The glycemic benefits diminish when eGFR is <45 mL/min/1.73 m², but renal and cardiovascular benefits persist. 5
Renin-Angiotensin System Blockade
RAS inhibitors (ACE inhibitors or ARBs like losartan) remain essential for patients with CKD and albuminuria to slow progression, though they do not reverse established disease. 4, 8
Maximum tolerated doses should be used, particularly in patients with hypertension and albuminuria. 4
Monitor serum creatinine and potassium within 2-4 weeks after initiation; continue therapy unless creatinine rises by more than 30%. 8
Avoid combination therapy with multiple RAS inhibitors (ACE inhibitor + ARB + direct renin inhibitor) due to increased adverse effects without additional benefit. 8
Combination Therapy Approach
In high-risk patients with elevated UACR, combining SGLT2 inhibitors with RAS inhibitors produces additive benefits in reducing kidney failure risk, though dedicated randomized controlled trial data for all combinations remain limited. 1
The absolute benefit of SGLT2 inhibitors on top of RAS blockade is larger in those with higher baseline UACR. 1
Parallel initiation of medications with different mechanisms is now recommended rather than incremental escalation schemes. 1
Lifestyle Modifications That Slow Progression
Specific lifestyle interventions demonstrate measurable effects on slowing CKD progression:
Protein intake should be maintained at 0.8 g/kg body weight per day; avoid high protein intake (>1.3 g/kg/day) which accelerates kidney function decline. 4, 9
Dietary sodium restriction to <2,300 mg/day controls blood pressure and reduces cardiovascular risk. 4, 9
Plant-based diets, adherence to the alternate Mediterranean diet, and Alternative Healthy Eating Index-2010 slow CKD progression. 9
Regular walking and weight loss demonstrate beneficial effects on disease trajectory. 9
Blood Pressure Targets
Target systolic blood pressure <120 mmHg to reduce risk of CKD progression, with even more stringent control (<130/80 mmHg) recommended for patients with albuminuria. 4, 9
Critical Gaps in Reversal Research
The 2023 KDIGO conference identified that 37% of CKD recommendations remain ungraded due to insufficient evidence, with only 10% graded "A" for quality. 1
Major research needs include:
Defining exactly which interventions can initiate true structural reversal beyond slowing progression. 1
Understanding the relationship between acute kidney injury and CKD progression, and whether this relationship can be positively influenced. 1
Developing multipronged strategies including novel anti-inflammatory and antifibrotic molecules to potentiate regression of glomerulosclerosis. 2
Establishing optimal timing and combinations of disease-modifying medications. 1
Clinical Bottom Line
Current evidence supports aggressive use of SGLT2 inhibitors combined with RAS blockade, strict blood pressure control, and lifestyle modifications to slow or halt CKD progression in most patients, but true reversal of established kidney damage remains an aspirational goal rather than an achievable outcome with existing therapies. 1, 4 The focus should be on early intervention during the AKI-to-AKD transition phase when complete reversal remains possible, and on maximizing disease-modifying medications to prevent progression to kidney failure. 1, 4