From the Guidelines
Membranous nephropathy is not associated with inflammation, and its pathophysiological relationship with Polycystic Kidney Disease (PKD) is distinct, with PKD being linked to genetic mutations, specifically PKD1 and PKD2 genes for autosomal dominant PKD and PKHD1 for autosomal recessive PKD. The pathophysiology of membranous nephropathy (MN) involves immune complex deposition in the glomerular basement membrane, leading to thickening of the membrane without significant inflammatory cell infiltration, as noted in the KDIGO 2021 clinical practice guideline for the management of glomerular diseases 1. This is in contrast to other glomerular diseases that show prominent inflammatory features. The immune deposits in MN consist primarily of IgG and complement components that form along the epithelial side of the basement membrane, creating a characteristic "spike and dome" appearance on electron microscopy. On the other hand, Polycystic Kidney Disease (PKD) is a genetic disorder, with the majority of cases being associated with mutations in the PKD1 and PKD2 genes for autosomal dominant PKD, as discussed in the KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD) 1. While PKD does have a chromosomal basis, membranous nephropathy can be either primary (idiopathic) or secondary to conditions like lupus, hepatitis B, or certain medications. Key points to consider in the relationship between MN and PKD include:
- The distinct pathophysiological mechanisms underlying each disease, with MN involving immune complex deposition and PKD involving genetic mutations affecting cyst formation and kidney function.
- The lack of a direct inflammatory link between MN and PKD, as MN is characterized by its lack of significant inflammatory cell infiltration.
- The importance of genetic testing in diagnosing and managing PKD, as well as the potential for secondary causes of MN that may influence its treatment and prognosis. Given the most recent and highest quality evidence from the KDIGO 2025 guideline for ADPKD 1, the pathophysiological relationship between MN and PKD is best described as distinct, with PKD being linked to genetic mutations and MN being characterized by immune complex deposition without significant inflammation.
From the Research
Pathophysiological Relationship between Membranous Nephropathy (MN) and Polycystic Kidney Disease (PKD)
The pathophysiological relationship between MN and PKD is complex and not fully understood. However, some studies suggest that:
- MN is an autoimmune disease characterized by the formation of immune complexes in the glomerulus, leading to nephrotic syndrome and kidney failure 2, 3
- PKD is a genetic disorder caused by mutations in the PKD1 and PKD2 genes, leading to the formation of cysts in the kidneys and eventual kidney failure 4
- There is evidence to suggest that MN and PKD can co-exist in some cases, although this is rare 5
- The relationship between MN and PKD may be linked to immune and inflammatory mechanisms, with some studies suggesting that immune-related genes and cytokines may play a role in the progression of MN 6
Association with Inflammation
Some studies suggest that MN is associated with inflammation, with immune complexes and cytokines playing a role in the disease progression 2, 3, 6. However, the exact mechanisms by which inflammation contributes to MN are not fully understood.
Association with Systemic Abnormalities
There is evidence to suggest that MN and PKD can be associated with systemic abnormalities such as diabetes and hypertension, although the exact relationship between these conditions is not fully understood.
Key Findings
- MN is an autoimmune disease characterized by the formation of immune complexes in the glomerulus 2, 3
- PKD is a genetic disorder caused by mutations in the PKD1 and PKD2 genes 4
- MN and PKD can co-exist in some cases, although this is rare 5
- Immune-related genes and cytokines may play a role in the progression of MN 6
- Inflammation may contribute to the progression of MN 2, 3, 6