A. Progressive Hereditary Nephritis

1. Persistent hematuria with nephritis, chronic renal failure
2. Most common form is Alport's Syndrome
3. Many other forms exist, however

B. Alport's Syndrome [1]

1. Genetics
   1. X-Linked Disease in ~85% of cases
   2. Abnormal alpha-5 Type IV collagen gene (COL4A5 gene) on chromsome Xq26-48
   3. In female carriers, varaible penetrance
   4. 15% of cases autosomal mutations in COL4A3 or COL4A4 genes, chromosome 2q35-37
   5. All of these mutations cause post-translational defects in Colagen IV protein
   6. This leads to abnormal glomerular basement membrane (GBM)
   7. Different mutations have different ages of onset
2. Classical Components
   1. Microscopic hematuria by age 6 - usual presenting sign
   2. Proteinuria <2gm / day
   3. Progressive renal failure due to segmental glomerular sclerosis
   4. Hearing loss, bilateral sensorineural
   5. Retinopathy and lens abnormalities
3. Kidney biopsy shows thin basement membranes
4. Treatment
   1. Early renal failure treated conservatively with antihypertensives
   2. Angiotensin converting enzyme (ACE) inhibitors are generally preferred
   3. ACE inhibitors reduce proteinuria and slow progression
   4. Dialysis patients are candidates for renal transplantion
   5. Lens abnormalities can be treated with lens implants as in cataract surgery

C. Familial Juvenile Nephrolithiasis

1. Polyuria, Polydipsia, Azotemia
2. Anemia, Growth failure
3. Progressive renal failure
4. Related to medullary cystic kidney

D. Sickle Cell Nephropathy

1. Hematuria, proteinuria
2. Nephrotic syndrome
3. Chronic renal failure (CRF)
4. Inreased incidence of urinary tract infections (upper and lower tract)
5. Hyposthenuria
6. Pathology:
   1. Membranoproliferative Glomerulonephritis
   2. Focal and Segmental Glomerulosclerosis
7. Renal Artery and Renal Vein Thrombosis

E. Polycystic Kidney Disease (PKD)

1. Types
   1. Autosomal Dominant - (adult onset)
   2. Autosomal Recessive form - onset in childhood
2. Progressive cystic enlargement from birth onward
3. Renal Failure
   1. Appears to be age dependent (4th-5th decades)
   2. Usually begins ~10 years after hypertension starts
4. Often associated with bony abnormalities

References

1. Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. 2003. NEJM. 348(25):2543