Autosomal dominant polycystic kidney disease: risk and progression after the 2025 KDIGO guideline

In February 2025, KDIGO published its guideline on autosomal dominant polycystic kidney disease (ADPKD), which the executive summary describes as the first KDIGO guideline on this subject ^[1][2].

What changed in 2025?

The KDIGO executive summary endorses the Mayo Imaging Classification (MIC) to predict kidney function decline and the timing of kidney failure, with prognostic validity limited to typical (class 1) imaging and to PKD1 or PKD2 variants ^[2]. The MIC sorts height-adjusted total kidney volume for age into five subclasses, 1A to 1E, that indicate accelerating decline ^[2].

Who is at risk of rapid progression?

The Mayo Clinic cohort reported in 2015 included 590 patients; 538 had typical imaging and could be subclassified ^[3]. In the Mayo Clinic cohort, the frequency of kidney failure at 10 years rose from 2.4% in subclass 1A to 66.9% in subclass 1E; in a younger external validation cohort of the same 2015 report it rose from 2.2% in subclass 1C to 22.3% in 1E ^[3]. The executive summary acknowledges that its definition of rapid-progression risk rests largely on clinical consensus, with MRI-based MIC as the primary method ^[2]. It lists these alternative or supporting markers:

• Ultrasound volume by the ellipsoid formula, which KDIGO accepts when MRI and CT are unavailable or contraindicated ^[2].
• Historical eGFR decline of 3 mL/min/1.73 m² per year or more over 3 to 5 years, as KDIGO defines it ^[2].
• Predicting Renal Outcome in PKD score above 6, as KDIGO defines it ^[2].

The executive summary also notes that gene and variant type are associated with severity: PKD1 variants with more severe disease than PKD2, and truncating PKD1 variants more than nontruncating ones; male sex is a possible prognostic factor of more severe disease ^[2].

What does the evidence show for slowing decline?

The executive summary endorses a vasopressin V2-receptor antagonist for adults with an eGFR of 25 mL/min/1.73 m² or more who are at risk of rapidly progressive disease ^[2]. A 2024 Cochrane review (57 studies, 8,016 participants) rated the pooled eGFR difference across three trials of the class (2,758 participants) as moderate-certainty evidence, mean difference 1.26 mL/min/1.73 m² (95% CI 0.73 to 1.78), and found insufficient evidence on kidney failure and death ^[4]. In a 2012 trial, discontinuation was 23% on active drug versus 14% on placebo ^[5]. In a 2017 trial of 1,370 adults in which only patients who tolerated an 8-week run-in were randomized, alanine aminotransferase rose above 3 times the upper limit of normal in 5.6% on active drug versus 1.2% on placebo ^[6].

In a 2014 trial of 558 hypertensive patients aged 15 to 49 with eGFR above 60, annual kidney volume growth was 5.6% with a low target of 95/60 to 110/75 mm Hg versus 6.6% with a standard target (difference -1.00 percentage points, 95% CI -1.67 to -0.33), with no overall change in eGFR ^[4][7]. The KDIGO executive summary sets a home target of 110/75 mm Hg or lower, if tolerated, for people aged 18 to 49 with CKD G1 to G2 and blood pressure above 130/85 mm Hg ^[2].

Where is the evidence uncertain?

The 2024 Cochrane review judged data on mTOR inhibitors, statins, metformin and increased water intake as sparse and inconclusive ^[4]. The executive summary also advises against using sodium-glucose cotransporter-2 inhibitors to slow eGFR decline, and notes that no validated model yet identifies children at risk of rapid progression ^[2].

At the point of care: what to check

• Imaging pattern: typical versus atypical, and MIC subclass, as KDIGO defines them ^[2].
• Genotype, where known, since KDIGO limits the MIC to PKD1 or PKD2 variants ^[2].
• Age and CKD stage, which set the KDIGO home blood pressure target ^[2].
• Liver enzymes, since the 2017 trial found elevations above 3 times the upper limit of normal more often on the V2-receptor antagonist than on placebo ^[6].