1. INHERITED RENAL DISORDERS

2. AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Prevalence: 1:300 to 1:1000
90% of cases are inherited, 10% are sporadic
Only1 to 5% nephrons developed cysts
Cysts are in medulla and cortex
ADPKD causes symptoms in third or fourth decade
50% of patients developing ESRD by age 60

3. RENAL Symptoms of ADPKD
Chronic flank pain
Acute pain indicates:
infection (pyelonephritis- pyocyst)
urinary tract obstruction
sudden hemorrhage into cysts
Hematuria
Impaired renal concentrating ability
Nephrolitiasis in 15%to 20%
Hypertension in 75% adults

4. Diagnostic Criteria- Ultrasound
Age ………..2 cysts in one or both kidneys
Age 30 to 59 …….2 cysts in each kidney
Age >60 ………….4 cysts in each kidney

10. EXTRARENAL SYMPTOMS CYSTS in: Liver Spleen Pancreas Ovaries
Intracranial aneurism
Colonic diverticular disease
Mitral valve prolapse

11. Factors affecting progression to End Stage Renal Failure
Hypertension
Recurrent Haematuria
UTI (in men)
Massive Liver cystic Disease (mostly women)
More than 3 pregnancies
Age at symptomatic diagnosis
Sickle Cell Trait

12. Autosomal recessive (infantile) polycystic kidney disease
Infants, adolescents, young adults
1 in 20,000 affected
1 in 10,000 in Finland
Up to 50% livebirths die within hours of birth
Those that survive neonatal period – 50% alive at 10 yo

13. Most severe forms early in life
Less severe forms present later
Always bilateral
Always congenital hepatic fibrosis
AR – 1 in 4 chance – neither parent shows signs
Ch. 6 identified in all forms

14. Clinical features Renal and liver pathology inversely related
Oligohydramnios
Potter’s facies
Respiratory distress –pulmonary hypoplasia

16. Histopathology Retain fetal lobulation Subcapsular cysts
Radial cortical cysts – dilated tubules

17. Evaluation Liver biopsy if necessary Detailed family history
In utero US
Oligohydramnios, enlarged kidneys
IVP
Medullary streaking (Sunburst pattern) – due to dilated collecting tubules
Dense nephrogram
US – microcysts
Liver biopsy if necessary
Detailed family history
Genetic counselling

18. MEDULARY SPONGE KIDNEY
0.5 to 1% of all IVP
Male and female affected equally
Dilatation in collecting ducts
In 70% bilateral renal involvement
It presents in third or fourth decade with:
kidney stone
infection
hematuria
Diagnosis with: IVP
Renal function is normally preserved

19. Relatively common and benign, present at birth and not usually dx’d until age 40-60
Characterized by widening and cystic dilatation of distal collecting tubules
70% bilateral, maybe affecting all papillae
Infection and calculi occasionally seen as result of urinary stasis in the tubules

20. Pts present with:
Hematuria
Recurrent UTIs
Nephrolithiasis
UA may show decreased urinary concentrating ability (due to tubule damage)

22. Treatment
No known therapy
Increase fluids to prevent stone formation
Treatment directed toward complications
Pyelonephritis
Renal calculi
Only small percentage of pts develop complications…overall prognosis is good

24. Medullary Cystic Disease
A rare, familial dz that may become symptomatic during adolescence
Manifested by many small cysts scattered through the renal medulla
Pts may present with pallor, polyuria, and lethargy
May later develop HTN

25. Labs Rad UA shows inability to concentrate urine CBC to confirm anemia
Chem panel to check phosphate, sodium, BUN, creatinine levels
Rad
US and CT scan to dx

26. Tx No current medical therapy to prevent progression to ESRD
Adequate water and salt replacement essential to replenish renal losses
Renal transplantation

28. Liddle syndrome Rare autosomal dominant disorder Presented with:
hypertension
hypokalemia
metabolic alkalosis
Renin and aldostrone are suppressed
Caused by activating mutations in amiloride-sensetive sodium channel

30. Bartter’s syndrome
Bartter’s syndrome is usually diagnosed in childhood, sometimes associated with growth and mental retardation. The defect is impaired NaCl reabsorption in the loop of Henle. Findings are similar to administration of a loop acting diuretic:
Salt loss leading to volume depletion and activation of the renin-angiotensin system
Increased urinary calcium

31. Bartter’s syndrome Presented with: normal blood pressure hypokalemia
metabolic alkalosis
Renin and aldostrone are activated
Caused by mutation in frusomide sensitive channel
Weakness, muscle cramp, polyuria

33. 3 or 4 types of Bartter’s have been identified:
Defects in the luminal Na-K-Cl transporter
Defects in the luminal potassium channel
Defects in the basolateral chloride channel

34. Gitelman’s syndrome
Like Bartter’s an autosomal recessive disorder, but not usually diagnosed early in life.
Findings mimic administration of a thiazide diuretic: the defect is in the Na-Cl transporter.
Patients may complain of polyuria, cramps.
They do not have hypercalciuria, but typically have low serum magnesium levels.

35. Diagnosis is made by history as well as lab findings
Diagnosis is made by history as well as lab findings. Lab findings are indistinguishable from thiazide use:
Hypokalemia, hypomagnesemia, increased renin and aldosterone levels, decreased urinary calcium.
Genetic screening?

37. Gitelman’s syndrome: treatment
Potassium
Magnesium
Aldactone or amiloride
ACEI’s
NSAIDS of no benefit
Continues to require very large doses of KCl, and is on amiloride.
Magnesium levels have consistently been low or low normal.

39. RENAL TUBULAR ACIDOSIS
Disorder of renal acidification out of proportion to the reduction in GFR
Hyperchloremic metabolic acidosis with normal serum anion gap
There are multiple forms of RTA

41. ALPORT SYNDROME The most common inherited nephritis X-linked
Defect in the gene for the a5 chain of type IV collagen (major component of GBM)
EM: fragmentation and lamellation in GBM
Deafness in 30 to 50%
Ocular lesion in 15 to 30%

42. Thin segment
Thick segment
Note the abnormal appearance of the glomerular basement membrane (GBM) typical of Alport's syndrome, including irregular contours, areas of thinning, and marked thickening and splitting with inclusion of electron-dense granules in electron-lucent areas

43. BLADDER CANCER
Cancers occurred 90% in bladder, 8% in pelvic, 2% in ureter & urethra
Male/female=4/1
Withes/ blacks=2/1
Risk factors are: smoking
aniline dyes
drugs
radiation
infection
Symptoms: gross hematuria, irritative symptoms
Diagnosis: urine cytology, CT scan, IVP

44. RENAL CELL CARCINOMA 90% Kidney cancer Male/Female=2/1
Incidence peaks between the ages of 50 to 70
Risk factors: smoking
obesity
acquired cyst in ESRD
tuberous sclerosis
VHL

45. SYMPTOMS: Hematuria
abdominal pain
abdominal mass
fever
Weight loss
anemia
varicocele