Genetic basis - PLN is associated with mutations in KIRREL2 and NPHS1 genes, both important in kidney filtration function. KIRREL2 encodes a protein essential for filtering molecules in kidney glomeruli; NPHS1 encodes nephrin, involved in the filtration barrier. Mutation variants in these genes impair glomerular filtration, allowing loss of proteins into the urine. The genetics of PLN is complex and polygenic, with multiple gene variants and environmental factors influencing disease expression. PLN shows incomplete penetrance, meaning not all genetically predisposed dogs exhibit clinical disease.

Pathophysiology - Dysfunction of glomerular filtration barrier causes excessive protein loss in urine, especially albumin, leading to proteinuria. Protein loss causes hypoalbuminemia, edema (fluid retention in tissues), hypercholesterolemia, and progressive kidney damage. Chronic proteinuria leads to gradual decline in kidney function, progressing to kidney failure

Complications - Clinical signs usually appear in middle-aged to older dogs and may be subtle initially. Signs include vomiting, diarrhea, weight loss, increased thirst and urination, swelling (edema), abdominal fluid accumulation (ascites), and lethargy. Secondary complications include hypertension, thrombosis (clotting disorders), and kidney failure. The disease often leads to poor prognosis with euthanasia in advanced stages.

Why This Matters to Breeders and Vets - Breeders need awareness of the genetic risk to prevent producing affected puppies and improve breed health. Vets play a critical role in early diagnosis and management to slow disease progression and improve quality of life. Understanding the genetics supports responsible breeding and helps in counseling owners on disease risk and prognosis. Early identification enables interventions before severe kidney damage occurs.