Cystic and Congenital Diseases of the Kidney Flashcards
Congenital Disorders of the Kidney: Unilateral agenesis
(Bilateral agenesis still birth:
Rare (one in 1,000 liver births) but important to R/O if a procedure (renal biopsy or nephrectomy is being considered. Often hypertrophy present in kidney that is present. > risk hypertension
Congenital Disorders of the Kidney: Ectopic kidney
(most common anatomic site- pelvis):
Kidney not present at usual paravertebral (T10-L2) retroperitoneal site, but present somewhere along normal path of ureter from kidney to bladder.
Congenital Disorders of the Kidney: Horseshoe Kidney
(usually fusion of lower poles (90%):
Prevalence: 1 in 500 – 1000 autopsies
Congenital Disorders of the Kidney: Hypoplasia
(shows no scars and has reduced numbers of renal lobes):
May be unilateral or bilateral and usually observed in low birth weight infants
Non-hereditary Cysts (Acquired): simple
Simple cysts (~20%):
Single or multiple usually involving cortex
Usually 1 to 5 cm
No clinical significance (can cause pain)
Acquired cysts:
Associated with prolonged dialysis
Numerous cortical and medullary cysts (1-4 cm)
Increased risk of renal cell carcinoma (1-4% of dialysis patients)
Multicystic renal dysplasia:
Sporadic disorder mainly in children (unilateral or bilateral)
Many nephrons are immature with undifferentiated mesenchyme
Associated with lower urinary track anomalies (obstruction)
This condition must be distinguished * from autosomal recessive polycystic kidney disease (ARPKD) because it occurs only sporadically and not with a defined inheritance pattern.
- It is more common than ARPKD. The cysts of multicystic renal dysplasia are larger and more variably sized than those of ARPKD. Often multicystic renal dysplasia is unilateral
Most common palpable abdominal mass in the newborn
Unilateral Multicystic Renal Dysplasia - Non-familial Congenital
Most common congenital renal cystic disease.
Caused by failure of the ureteric bud to reach renal blastema during embryologic development and stimulate formation of the renal cortex and associated development of the Nephron. 90% cases have an absent ureter (agenesis) or ureteropelvic obstruction
Renal dysplasia is the leading cause of end-stage renal disease in children.
Pathologic findings:
Extensive multiple variable-sized cysts with intervening undifferentiated mesenchyme (often cartilage formation)
No development of glomeruli
Otherwise normal development with no increased incidence of associated congenital abnormalities
Diagnostic features of renal dysplasia
. Kidney parenchyma is disorganized, tubules are primitive, and there is metaplastic cartilage. There is also hydronephrosis with dilated pelvis and calyces
Metaplastic cartilage is a unique feature of renal dysplasia. Significant inflammation is present as well
Autosomal Dominant Polycystic Kidney Disease (Adult presentation
Hereditary disorder characterized by multiple bilateral expanding cysts that destroy renal parenchyma and cause renal failure (4th-5th decade)
Most common inherited kidney disease (5-10% dialysis pts)
Systemic disease
Mutations in genes PKD1 (less frequent in PKD2) expressed by tubular epithelial cells
Thought to modulate intracellular levels of calcium and primary cilium-centrosome zone complex
Autosomal Dominant Polycystic Kidney Disease presenting symptoms
Presenting symptoms: Moderate to severe renal insufficiency Hypertension Flank pain secondary to hemorrhage into cysts Polyuria Metabolic acidosis Proteinuria
Extra-renal manifestations
Increased incidence of mitral valve prolapse
Hepatic cysts (40 to 75%) and pancreatic cysts (10%)
Intracranial berry aneurysms (10%)
Often survive for many years with azotemia slowly progressing to uremia
Autosomal Dominant Polycystic Kidney
Insidious onset presenting in 4th, 5th or 6th decade because of renal insufficiency (hypertension, azotemia)
PKD2 (Polycystin 2) patients have less aggressive (later onset, less severe) clinical course than PKD1 (Polycystin 1) patients.
Aggressive (earlier onset, more severe) clinical course seen in:
African-Americans (correlates with associated sickle cell trait)
Males greater than females
Presence of hypertension
Increased incidence nephrolithiasis and urinary tract infection.
Autosomal Recessive Polycystic Kidney Disease (Childhood presentation)
(Oligohydramnios, pulmonary hypoplasia, characteristic facies and deformity of the spine and limbs)
Hereditary disorder characterized by cystic dilation of collecting ducts, biliary ductal ectasia and hepatic fibrosis.
Much less common than adult polycystic kidney disease
Mutations in genes PKHD1 (transmembrane protein expressed by renal tubular and biliary duct epithelial cells)
Thought to disrupt normal function of primary cilium
Historically, this disease was known as Potter cystic kidney type I
Primary organ systems affected are kidney and hepatobiliary track
Bilateral renal involvement with massively enlarged kidneys with up to 90% of collecting ducts are involved
Congenital hepatic fibrosis progress to portal hypertension
Clinical diagnosis increasingly relies on imaging and genetic testing instead of histopathologic analysis
Autosomal Recessive Polycystic Kidney Disease (Outcome)
Patients who survive the first month >80% survive beyond 15 years of age
Systemic hypertension develops in approximately 75%
Congenital hepatic fibrosis and portal hypertension develop in 44%
Improved management of renal insufficiency and end-stage renal disease has resulted in a greater number of patients developing portal hypertension
Cysts are SMALL and uniformly distributed so that the disease is usually symmetrical in appearance, involving both kidneys
Renal cysts are cylindrical, arising predominantly in * collecting ducts and distal tubules *.
Nephronophthisis
Autosomal recessive genetically heterogeneous renal disease with mutations in proteins involved in the function of primary cilia, basal body and centrosomes ESRD
Reduced urinary concentrating ability with polyuria and polydipsia
Salt wasting precedes decline in glomerular filtration rate
Three clinical variants have been described based upon the median age of onset of end-stage renal disease
Infantile − 1 year of age
Juvenile − 13 years of age
Adolescent − 19 years of age
Diagnosis of juvenile nephronophthisis:
Polyuria due to decrease concentrating ability and normal urinalysis
Progressive chronic kidney disease with normal blood pressure
Ultrasound shows normal or slightly decreased sized kidneys with increased echogenicity
Confirm with genetic test (NPHP1 20-40% cases)
* If NPHP1 negative –>
- Renal biopsy - chronic tubulointerstitial changes with thickened tubular basement membrane
Robbins: Morphology of Nephronophthisis
In Nephronopthisis, the kidneys are small, have contracted granular surfaces, and show cysts in the medulla, most prominently at the corticomedullary junction. Small cysts are also seen in the cortex. The cysts are lined by flattened or cuboidal epithelium and are usually surrounded by either inflammatory cells or fibrous tissue. In the cortex there is widespread atrophy and thickening of the tubular basement membranes, together with interstitial fibrosis. In general, glomerular structure is preserved.
Medullary Cystic Kidney Disease
Autosomal dominant
Much rarer than nephronophthisis
Histopathologically indistinguishable from nephronophthisis
Genetics distinct from nephronophthisis NPHP mutations. (Responsible genes MCKD1, MCKD2)
Clinically medullary cystic disease is distinguished from nephronophthisis by:
Autosomal dominant
Later age of onset
Progression to end-stage renal disease in 3rd-4th decade
No growth retardation
No associated extra renal manifestations
Medullary Sponge Kidney
Relatively common and characterized by dilated medullary and papillary collecting ducts
Less than 5% of cases are familial
Associated with nephrolithiasis, hematuria, infection
Asymptomatic unless complicated by nephrolithiasis, hematuria or infection (4th - 5th decade)
Probably developmental defect in the medullary pyramids (other congenital defects ie. Marfan’s syndrome, Ehlers-Danlos)
Tuberous Sclerosis Complex
Autosomal dominant syndrome with hamartomas developing in multiple organ systems including kidneys, brain, heart, lungs and skin
57% of tuberous sclerosis complex patients have kidney involvement (angiomyolipoma (85%), cysts (45%) and malignant neoplasms (4%)
Clinical Diagnostic Criteria for Tuberous Sclerosis Complex
2 major features or 1 major feature and 2 minor features indicate definite tuberous sclerosis complex
Major criteria (11 different criteria): Facial angiofibroma Nontraumatic ungal or periungal fibroma Retinal nodular hamartomas **Renal angiomyolipoma
Minor criteria (9 different criteria) Multiple random dental pits Gastrointestinal hamartomatous polyps Bone cysts Renal cysts
Angiomyolipoma
Sporadic angiomyolipomasare usually solitaryand more frequentlyfound in middle-aged women.
They are oftenasymptomaticand are
usually discovered on imaging studies performed for unrelated conditions. Some cases present withmassive retroperitoneal hemorrhagewhich may be fatal.
Angiomyolipomas occurring in the setting of tuberous sclerosis are frequently bilateral, multiple, occur at younger age, and affect both genders.
The Bosniak classification system of renal cystic masses
divides renal cystic masses into five categories based on imaging characteristics on contrast-enhanced CT. It is helpful in predicting a risk of malignancy and suggesting either follow up or treatment.
Nephrolithiasis
Formation and retention of solid phase inorganic and organic concretions in the urinary track- stone formation
Most important determinant of stone formation is increased urine concentration of stones constituents exceed solubility Low urine volume (uric acid stones) Metabolic disorder Urine pH (uric acid stones) Presence of bacteria
Types of Kidney Stones
Calcium stones (Calcium oxalate > Calcium phosphate)
Uric acid stones (uric acid de novo synthesis and tissue catabolism; purine metabolism)
Struvite stones (NH4MgPO4-carbonate-apatitie; associated with urea ammonium splitting infectious organisms
Cystine stones (Uncommon)
Urinary Risk Factors for Stone Formation: Calcium, Uric, Struvite
Calcium stones:
Hypercalciuria with or without hypercalcemia
Increased uric acid (crystal nucleation within collecting ducts)
Over absorption of oxalate in patients with enteric diseases such as Crohn’s colitis
Uric acid stones:
Hyperuricosuria
Low urine pH
Low urine volume
Struvite stones:
More frequent in women (urinary track infection)
Urinary stasis (older age)
Urea splitting organisms (Proteus mirabilis)
Imaging of stones
Diagnosis generally made via imaging Helical CT is modality of choice High sensitivity No need for contrast Able to visualize uric acid stones Can detect stones as small as 1mm If stone passed – may see evidence Perinephric stranding or hydronephrosis
Clinical Manifestations of stones
Acute Renal Colic (Flank Pain) - Movement of stone from renal pelvis to ureter - Sudden onset of unilateral flank pain - Generally quite severe -Pain waxes and wanes, rarely goes away ----May radiate to different spots -----Associated with Nausea/vomiting Blood in urine Obstruction
Risk Factors for stones
Dietary Factors - Animal protein Raises urine Ca and uric acid excretion, lowers urine citrate - High sodium or sucrose Increases urine calcium excretion - Calcium and potassium DECREASE risk
Fluid intake
- Risk increases as urine volume falls
Uric acid stones
Urinary pH key to supersaturation Treat by increasing urinary pH (goal: 6-7) Alkali rich foods Oral bicarbonate Allopurinol if alkalinization fails Not visible on plain radiographs
Struvite stones
Infectious or triple-phosphate stones
Only form when upper urinary tract infected with urease producing bacteria
Proteus mirabilis, Klebsiella pneumoniae
Hydrolysis of urea by urease results in pH>8
Struvite (MgNH4PO4-H2O) forms – staghorn calculus
Require urologic intervention for removal
Antibiotics slow but don’t remove infection
Cystine Stones
Uncommon autosomal recessive disorder
Defective proximal tubule reabsorbtion of filtered dibasic amino acids
Stones are visible on plain radiographs – often as staghorn calculi or multiple bilateral stones
Treat by increasing urinary volume and/or increasing pH.
