Ciliopathies
ADPKD ARPKD Nephronophthisis Medullary Cystic Kidney Disease Tu
Inheritance Autosomal dominant Autosomal recessive Autosomal recessive Autosomal dominant Au
Type 1 2 --- Juvenile Infantile Adolescent *a.k.a A.D. tubulointerstitial kidney disease*
Mutation PKD1 [85%] PKD2 [15%] PKHD1 NPHP1 NPHP2 NPHP3 MCKD1 & MCKD2 TS
Protein Polycystin 1: Polycystin 2: Fibrocystin (polyductin) Nephrocystin (inversin) MUC1 & Uromodulin Ham
affected cell cycle Ca channel
regulator
Age of 30-50 years old Neonatal ESRD at ESRD at ESRD at 19 20-40 y.o.
diagnosis - T. 2. → slower progression (30% die at this age) 13 y.o. 1 y.o. y.o.
Pathogenesis - Must have second hit→ only Fibrocystin in: Nephrocystin binds to adhesion Same pathogenesis as other Hamar
develops in 1-2% of cells ● Renal epithelium → proteins & is involved in development ciliopathies. inhibits
- Cilium protein dysfunction same as ADPKD of tubule geometry - Uromodulin additionally regulates growth
● Membrane protein ● Bile ducts → hepatic uric acid → Gout → Ham
displacement fibrosis (obligatory comple
● No cell cycle regulation involvement) fibroma
→ Epithelium over reproduction
and cyst formation
Clinical - Bilateral renal cysts → - Bilateral renal cysts → - Shrunken kidneys - Shrunken kidneys - Rena
Features enlargement enlargement - Renal cysts - Renal cysts ●
● Different sizes ● Equally sized ● At the corticomedullary border ● At the corticomedullary
● Any part of nephron can - Obligatory liver involvement ● In DCT & collecting duct border ●
be affected - Portal fibrosis ● Compression can cause ● In DCT & collecting duct - ↑risk
- Polyuria, hematuria - Portal hypertension → Fanconi Syndrome ● Compression can cause ●
- Prone to UTIs & stones splenomegaly, umbilical & - Salt wasting & polyuria Fanconi Syndrome ●
- Hypertension esophageal varices - Growth retardation - Polyuria & polydipsia - Cardi
- Associated cysts - Hypertension → ESRD - Progressive renal insufficiency → - Growth retardation - Hama
● Liver - In-utero renal impairment → ● ESRD - Progressive renal insufficiency → - Ungu
● Pancreas Potter sequence: ● Anemia ● ESRD - Shag
● Spleen 1. Oliguria → - Biliary duct enlargement & hepatic ● Anemia - Assoc
● Lung oligohydramnios portal fibrosis - Biliary duct enlargement & hepatic ●
- ECM abnormalities cause: 2. ↓liquid in lungs → - Senior-Loken Syndrome: Juvenile + portal fibrosis
● Berry aneurysms in pulmonary hyperplasia retinitis pigmentosa - MCKD2→ w/ gout
Willis circle 3. ↓uterine space → - Extrarenal malformations: situs - Class
● Coronary artery retrognathia & clubbed feet inversus (associated w/ infantile) ●
ADPKD ARPKD Nephronophthisis Medullary Cystic Kidney Disease Tu
Inheritance Autosomal dominant Autosomal recessive Autosomal recessive Autosomal dominant Au
Type 1 2 --- Juvenile Infantile Adolescent *a.k.a A.D. tubulointerstitial kidney disease*
Mutation PKD1 [85%] PKD2 [15%] PKHD1 NPHP1 NPHP2 NPHP3 MCKD1 & MCKD2 TS
Protein Polycystin 1: Polycystin 2: Fibrocystin (polyductin) Nephrocystin (inversin) MUC1 & Uromodulin Ham
affected cell cycle Ca channel
regulator
Age of 30-50 years old Neonatal ESRD at ESRD at ESRD at 19 20-40 y.o.
diagnosis - T. 2. → slower progression (30% die at this age) 13 y.o. 1 y.o. y.o.
Pathogenesis - Must have second hit→ only Fibrocystin in: Nephrocystin binds to adhesion Same pathogenesis as other Hamar
develops in 1-2% of cells ● Renal epithelium → proteins & is involved in development ciliopathies. inhibits
- Cilium protein dysfunction same as ADPKD of tubule geometry - Uromodulin additionally regulates growth
● Membrane protein ● Bile ducts → hepatic uric acid → Gout → Ham
displacement fibrosis (obligatory comple
● No cell cycle regulation involvement) fibroma
→ Epithelium over reproduction
and cyst formation
Clinical - Bilateral renal cysts → - Bilateral renal cysts → - Shrunken kidneys - Shrunken kidneys - Rena
Features enlargement enlargement - Renal cysts - Renal cysts ●
● Different sizes ● Equally sized ● At the corticomedullary border ● At the corticomedullary
● Any part of nephron can - Obligatory liver involvement ● In DCT & collecting duct border ●
be affected - Portal fibrosis ● Compression can cause ● In DCT & collecting duct - ↑risk
- Polyuria, hematuria - Portal hypertension → Fanconi Syndrome ● Compression can cause ●
- Prone to UTIs & stones splenomegaly, umbilical & - Salt wasting & polyuria Fanconi Syndrome ●
- Hypertension esophageal varices - Growth retardation - Polyuria & polydipsia - Cardi
- Associated cysts - Hypertension → ESRD - Progressive renal insufficiency → - Growth retardation - Hama
● Liver - In-utero renal impairment → ● ESRD - Progressive renal insufficiency → - Ungu
● Pancreas Potter sequence: ● Anemia ● ESRD - Shag
● Spleen 1. Oliguria → - Biliary duct enlargement & hepatic ● Anemia - Assoc
● Lung oligohydramnios portal fibrosis - Biliary duct enlargement & hepatic ●
- ECM abnormalities cause: 2. ↓liquid in lungs → - Senior-Loken Syndrome: Juvenile + portal fibrosis
● Berry aneurysms in pulmonary hyperplasia retinitis pigmentosa - MCKD2→ w/ gout
Willis circle 3. ↓uterine space → - Extrarenal malformations: situs - Class
● Coronary artery retrognathia & clubbed feet inversus (associated w/ infantile) ●
