ADPKD: Malnutrition and Sarcopenia Beyond Kidney Function

Introduction

A recent review published in the International Journal of Molecular Sciences by Brambilla Pisoni et al. examines the prevalence and underlying mechanisms of malnutrition and sarcopenia in adult patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). This study is significant because it challenges conventional understandings of nutritional status in ADPKD, particularly in individuals with relatively preserved kidney function, highlighting the impact of organomegaly.

The Study in Detail

The review, titled "The Hidden Iceberg of ADPKD: Early Organomegaly-Driven Malnutrition and Sarcopenia Beyond Preserved eGFR," was authored by Brambilla Pisoni M. and colleagues from institutions including IRCCS San Raffaele Scientific Institute in Milan, Italy. It was published in Int J Mol Sci. 2026 Feb 9;27(4):1667.

ADPKD is a common monogenic kidney disease characterized by progressive cystic enlargement of the kidneys and potential extrarenal involvement. The authors note that ADPKD patients often present with a distinctive "body phenotype" featuring central adiposity and significant abdominal distension due to enlarged kidneys and liver (organomegaly). The review synthesizes current evidence, emphasizing that traditional anthropometric measures like Body Mass Index (BMI) are often inadequate for assessing nutritional status in these patients because they fail to differentiate between nutritional tissues (muscle, subcutaneous fat) and non-nutritional mass (cyst fluid, fibrotic tissue, expanded extracellular water).

Key findings summarized in the review include:

• Prevalence of Malnutrition: Cross-sectional studies using the modified Subjective Global Assessment (SGA) indicate that approximately one-third of ambulatory ADPKD patients are at risk of or already experiencing malnutrition.
• Role of Organomegaly: Height-adjusted total kidney and liver volume (htTKLV) was identified as the strongest clinical predictor of malnutrition, with estimated Glomerular Filtration Rate (eGFR) playing a secondary role.
• Body Composition Alterations: Bioelectrical impedance analysis (BIA) reveals a disease-specific body composition phenotype in ADPKD, characterized by increased total and extracellular body water (especially in the trunk), a reduced phase angle, and decreased lean mass. These changes are consistent with early malnutrition and sarcopenia and are present even when kidney function is relatively preserved. Matched analyses further distinguish these alterations in ADPKD from those observed in non-ADPKD chronic kidney disease (CKD).
• Impact on Kidney Function: Prospective data suggest that baseline SGA-defined nutritional status independently predicts short-term eGFR decline in typical ADPKD, implying that malnutrition may modify renal disease progression rather than merely being a consequence of advanced disease.
• Sarcopenic Obesity: Narrative syntheses highlight that higher BMI, waist circumference, and visceral fat are associated with larger total kidney volume, faster eGFR loss, and greater symptom burden, raising concerns about a sarcopenic obesity phenotype where excess fat and cystic mass coexist with low muscle mass.

The authors propose a pathophysiological model where organomegaly-driven mechanical effects (such as early satiety and gastrointestinal discomfort), systemic inflammation, insulin resistance, and cyst-related metabolic reprogramming converge to produce "hidden malnutrition," often masked by apparent overweight.

Assessment

This review provides a comprehensive overview of the complex interplay between ADPKD, organomegaly, and nutritional status. Its strength lies in synthesizing evidence that challenges the conventional reliance on BMI and eGFR as primary indicators of health in ADPKD patients. By highlighting the limitations of these measures and emphasizing the role of htTKLV and specific body composition changes, the review offers a more nuanced understanding of the disease's impact on patient well-being.

A key insight is the concept of "hidden malnutrition" and sarcopenic obesity, which underscores that patients may appear overweight or obese due to increased cyst volume and fat, while simultaneously experiencing muscle wasting and nutrient deficiencies. The finding that malnutrition can independently predict eGFR decline suggests a potential bidirectional relationship, where nutritional status influences disease progression, rather than being solely a result of it.

While the review effectively consolidates existing knowledge, it is important to note that it is a synthesis of current evidence rather than a new primary research study. Therefore, the conclusions are based on the collective strength and limitations of the studies reviewed. The call for prospective studies to test individualized nutritional strategies is a crucial next step, as current evidence primarily focuses on observational and cross-sectional data.

Practical Relevance

The findings have significant practical implications for the clinical management of ADPKD patients. They strongly advocate for a paradigm shift in how nutritional status is assessed and managed:

• Enhanced Nutritional Screening: Routine nutritional screening using tools like the Subjective Global Assessment (SGA) or Patient-Generated Subjective Global Assessment (PG-SGA) should be integrated into standard ADPKD care.
• Advanced Body Composition Assessment: Bioelectrical impedance analysis (BIA) should be considered for a more accurate assessment of body composition, particularly in patients with severe organomegaly or symptomatic polycystic liver disease. This can help distinguish between nutritional tissues and non-nutritional mass.
• Early Intervention: Recognizing that malnutrition and sarcopenia can occur even with preserved kidney function, early nutritional interventions are crucial. These interventions should focus on muscle preservation and addressing specific nutrient deficiencies.
• Personalized Nutritional Strategies: Future research should focus on developing and testing individualized, muscle-preserving nutritional strategies tailored to the unique metabolic and mechanical challenges faced by ADPKD patients.

For individuals living with ADPKD, these insights emphasize the importance of discussing nutritional concerns with their healthcare providers, even if their eGFR is stable or they appear to be of normal weight. A comprehensive nutritional assessment may reveal underlying issues that could impact disease progression and overall quality of life.

Conclusion

The review by Brambilla Pisoni et al. illuminates the often-overlooked aspects of malnutrition and sarcopenia in ADPKD patients, particularly those with significant organomegaly. It highlights that conventional assessment methods are insufficient and advocates for specialized nutritional and body composition evaluations. Integrating these assessments into routine care and developing targeted nutritional interventions are critical steps toward improving outcomes for individuals with ADPKD.