West Visayas State University – College of Medicine – Batch 2020

Block XIX
Module 4 Cystic Diseases of the Kidney
Lecture 3
03/ 21/ 19
Dr. Agnes Villaflor

TOPIC OUTLINE III. Medullary Cystic Disease

I. Introduction A. Medullary Sponge Kidney
II. Simple Cysts B. Medullary Cystic Kidney Disease/ Juvenile
III. Autosomal Dominant Polycystic Kidney Disease
IV. Adult Recessive Polycystic Kidney Disease
(Familial) Nephronopthisis
V. Acquired Cystic Disease IV. Dialysis associated Cystic Disease
VI. Medullary Sponge Kidney V. Simple Renal Cysts
VII. Medullary Cystic Kidney Disease/Juvenile (Familial) Can be single or multiple
Nephronopthisis
VIII. Tuberous Sclerosis Smooth border, 1-2 cysts, non-enhancing, no
IX. Von-Hippel Lindau Disease calcifications
Supplementary Notes VI. Parenchymal Renal Cysts
Review Questions
VII. Cystic Change with Obstruction (Potter IV) or
References
Appendices Perihilar Renal Cyst
VIII. Acquired Renal Cystic Disease
LECTURER BOOK REFERENCE OLD TRANS A complication of prolonged renal failure,
especially among patients who are on
prolonged dialytic therapy
I. INTRODUCTION IX. Alport’s Syndrome
X. Renal Pharmacotosis
A. Tuberous Sclerosis (TSc)
B. Von-Hippel Lindau Disease

NON-GENETIC
DEVELOPMENTAL ACQUIRED
• Medullary Sponge • Simple Cysts
Kidney • Hypokalemia-related
• Renal Cystic CKD-related
Dysplasia • Renal
• Lymphangiomatosis
• Solitary Multilocular Cysts
Figure 1. Different morphologic appearances of kidney cysts. In simple
cysts, the size of the kidney is normal with 1-3 cysts found over the
cortex. Dysplastic is likely to be malignant. GENETIC
AUTOSOMAL AUTOSOMAL X-LINKED
Hydronephrotic kidneys (there is obstruction distally, DOMINANT RECESSIVE
pressure goes up; ureters are dilated and even the • ADPKD • ARPKD • Orofacial
pelvis) can be misinterpreted as cysts. • Von Hippel- • Juvenile Digital
Lindau Nephronophthisis Syndrome
A. CLASSIFICATION • Tuberous Type 1
I. Cystic Renal Dysplasia (Potter II) Sclerosis quite rare
II. Polycystic Kidney Disease • Medullary
Cystic Disease
Dominant polycystic (goes beyond the kidney
border)
A. Autosomal Dominant Polycystic Kidney II. SIMPLE CYSTS
• Solitary or multiple, fluid filled
Disease (ADPKD) (Potter III)
• Cysts develop from any part of nephron, usually
without hepatic fibrosis but there are other
cortical
organ aneurysm present (berry aneurysm)
• Basically harmless
adult
• Incidental finding on U/S or IVU
B. Autosomal Recessive Polycystic Kidney
Incidence:
Disease (ARPKD) (Potter I)
─ 2%: patients < 50yo
the classic infantile polycystic
─ 11%: patients 50-70yo
commonly accompanies congenital hepatic
─ >20%: elderly patients
fibrosis

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MD 3 Aklan, Australia, Alimodian
• Usually not loculated and tend to bulge out from renal
surface
• May grow to considerable size (>10cm)
• Occasionally require percutaneous drainage; because
of persistent loin pain
In the event that it enlarges, it can require
percutaneous drainage UTZ guided aspiration of the
fluid, but fluid accumulation can recur.
It’s best to unroof the cyst or use sclerosing agent
space would be obliterated; no more space for fluid
accumulation)
Most common cause of anxiety
• Most common incidental finding at autopsy Figure 3. Pathophysiology of cyst formation
• Often develop after small kidney infarcts (Arterial
Nephrosclerosis) Ordinarily when you age, cysts can develop because
tubular walls weaken.
III. AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY
DISEASE (ADPKD)
• Incidence: 1:1000
• Genes:
PKD 1 gene (86%): chromosome 16
PKD 2 gene (10%): chromosome 4
• AD, yet some sporadic cases are commonly seen
• Pathophysiology:
Early ↑ of plasma ADH, to compensate for ↓
concentrating ability → hypertension and renal
insufficiency
Cysts development induce renal ischemia → +
Figure 4. Timeline of cyst burden and kidney function
RAS → hypertension
↑ angiogenesis (fragile vessels across cyst walls) A. TIMELINE OF THE DISEASE
→ rupture → pain ± hematuria • Change in GFR and kidney function.
• Cysts develop from all segments of nephron (including • Next is cyst development and enlargement.
Bowman’s capsule), during the teenage years, • At age of 15, no appearance of cysts. Kidneys look
presentation is at the 4th or 5th decades normal, although it is already affected.
• At age of 30, there is now hyperfiltration. The cysts are
Diagnostic Criteria for ADPKD now starting to form.
2 cysts (unilateral or < 30 years old • At age of 45, cysts continue to increase in size.
bilateral)
• 4th to 5th decade, there is now end stage renal
2 cysts in each kidney 30-59 years old
4 cysts in each kidney > 60 years old disease (ESRD).
The kidneys tend to be really large. Almost all parts
are filled of cysts.

B. CLINICAL FEATURES
• Asymptomatic (1/3)
• Abdominal/Loin pain or mass
• Hypertension
• UTI
• Renal Calculi (10%)
• Macroscopic Hematuria
microscopic or gross which is usually painless if there
is no concomitant infection or stone formation
• Not all patients (1/3), develop ESRD → onset of
chronic renal failure varies widely: 25-60 years old
Figure 2. In diagnosing ADPKD, family history should be elicited.
Siblings and the next generations should be informed of the possibility
of being affected.

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 Recurrent episodes of infection (pyelonephritis or Trimethoprim
renal abscess) – this is due to the presence of fluid in Clindamycin
the cysts Vancomycin
Presentation comes during the 4th or 5th decade of Clotrimazole
life
PAINFUL CYSTS
RENAL MANIFESTATIONS • Cyst fluid aspiration/drainage (U/S guided)
• Hypertension (60-100%) • Cyst de-roofing: Excision of outer wall (Fiber optic-
• Kidney Failure (50% by age 50) guided/open surgery)
• Gross Hematuria (50%) • Ethanol-induced sclerosis
• Infection (common)
• Nephrolithiasis (20-25%) ENLARGED KIDNEY
• Pain • Avoid tight corsets
• Cyst Rupture and Torsion • Avoid wearing belts and seatbelts
• Functional Renal Disease • Avoid playing contact sports

EXTRARENAL MANIFESTATIONS IV. ADULT RECESSIVE POLYCYSTIC KIDNEY

• Polycystic Liver Disease DISEASE
• Intracranial Aneurysms • AR, chromosome 6
only renal disease that has aneurysms • Genes:
• Valvular Heart Disease MVP Fibrocystin
Ployductib
C. COMMON ASSOCIATIONS • Cysts develop form distal convoluted tubules and
• Liver cysts (70%), hepatic fibrosis (rare) collecting ducts.
• Pancreatic cysts (10%) • Incidence: 1:20,000
• Berry Aneurysms (>20% in (+) F.H., 5% in (-) F.H.), 1:10,000 births
4% risk of rupture if size >10mm, do: MRA every 3 • ESRD usually develops early in childhood; sometimes
years it may be delayed to 20 years of age or rarely, it may
• MV or AI (aortic insufficiency) never occur
• Anemia of Chronic Renal Failure or Polycythemia due • Poor prognosis
to ↑erythropoietin activity • Genetic counseling
• Diverticular disease
• Increase incidence of malignancy A. CLINICAL FEATURES
UTZ is also the best screening tool. Start screening • Oligohydramnios
at age 25-30. • Large echogenic kidneys
If you have identified the family history of the patient, • Pulmonary hypoplasia (major cause of death in the 1st
presence of such is already a diagnostic criteria for year of life)
ADPKD. • Hematuria
• Pyuria
D. TREATMENT • Systemic hypertension
• No strategies to prevent formation and progression of • Hepatic fibrosis in all cases, progressing to portal
cysts hypertension
• The aim is: • Bilateral abdominal masses in infancy
Monitoring and treating complications • Polyuria
Providing appropriate counseling • Enuresis
Do not insert catheter. It will lead to infection. • Hyponatremia
• Hyperchloremic metabolic acidosis
HYPERTENSION
• Goal is ≤125/75 mmHg Compared to ADPKD, ARPKD has Hepatic Fibrosis
• ACE inhibitors in all cases, that’s why if they would live, they could
• Angiotensin II receptor blockers develop portal hypertension.

UTI
• Lipophilic antibiotics with cyst penetrating ability:
Ciprofloxacin

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 • Black race
• Chronic hypokalemia

B. IMAGING
• Renal U/S, CT, MRI:
Demonstration of cysts in kidneys which are not
enlarged
Suspicious cyst findings for RCC:
─ Septa formation
Figure 4. Genetic predisposition of ARPKD. ─ Solid material
─ Contrast enhancement
In a 50-60 y/o patient presenting with a very big cyst,
we might suspect it as polycystic kidney disease but
also check onset of ESRD and the time of the
dialysis because it might be an acquired disease.
Usually there is no further workup done to patients
on dialysis, unless they have residual urine,
hematuria or sudden pain. That’s when we consider
the possibility of acquired cystic disease
complicating into a possible lesion that can turn into
Figure 5. Cortical cysts form in collecting duct.
RCC.

• Secondary to ESRD as well as prolonged dialysis

(9months -7 years)
• Kidneys are generally small but may be normal or
enlarged
• Common in cortex
• Neoplastic changes are common
• You see this in patients who underwent dialysis for
many years.
• The origin is usually in the CORTEX
Figure 6. ARPKD on ultrasound (right).

B. TREATMENT
No specific therapy
Appropriate neonatal intensive care
BP control, dialysis, and kidney transplantation
increases survival into adulthood.

V. ACQUIRED CYSTIC DISEASE

• Found in the rudimentary kidneys of patients with
ESRD, especially the scarred kidneys
• Cysts usually develop from proximal convoluted
tubules/distal convoluted tubules
• Incidence
>5%→ at onset of RRT (renal replacement
treatment)
>80%→ after 10 years of dialysis
• Asymptomatic Figure 7. Acquired Cystic Renal Disease. Cysts are small initially,
• Cyst hemorrhage: flank pain, anemia, hematuria enlarge and multiply in time; can mimic ADPCKD. Neoplasms –
definite increased risk w/ CRF, esp dialysis; often indolent (papillary
• Malignant change (RCC), with an annual incidence of RCC). Kidneys – small, atrophic, hyperechoic.
1%, less often to be metastatic, but with high 5-year
mortality rate VI. MEDULLARY SPONGE KIDNEY
• Sporadic
A. RISK FACTORS • Benign course
• Duration of ESRD less likely to progress to ESRD
• Male gender
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• Cysts develop from medullary to papillary convoluted VII. MEDULLARY CYSTIC KIDNEY DISEASE/
ducts JUVENILE (FAMILIAL) NEPHRONOPHTHISIS
• The ectatic CDs may calcify→ Classical • They are two different terms used for 2 similar
Nephrocalcinosis (50%) diseases; which differ only in their age of onset and
• Upper UTI and renal calculi may be present mode of inheritance
• Microscopic hematuria • Cysts occur in medullary distal convoluted tubules
• Hypercalciuria • Patients have:
defect in parathyroid hormone Tubulointerstitial nephritis
exposure of the kidney to calcium predisposes it to Salt-wasting
develop stones Progressive chronic renal failure
serum Calcium levels increase FN MCKD
AR AD, uncommon
± hyperparathyroidism
ESRD in childhood or before 20 ESRD in 3rd and 4th
Small cysts develop within the dilated collecting years of age (15%) decade
tubules of the renal medulla giving the kidney a Extrarenal Manifestations: • Not associated with
sponge like appearance; the cortex is not involved • Retinitis pigmentosa (10-15%) extrarenal
Gold standard Diagnosis with: IVP – classic • Cerebellar ataxia manifestations
“Paint-brush” appearance • Liver fibrosis • Hypertension is
• Nocturnal enuresis present

A. CLINICAL FEATURES
• Hematuria
• Recurrent UTIs
• Nephrolithiasis
• May show decreased urinary concentrating ability (due
to tubule damage)

B. TREATMENT
• No known therapy
• Increase fluids to prevent stone formation
• Treatment directed toward complications Figure 7. Multicystic dysplastic kidneys (MCDK). Multiple parenchymal
cysts of varying size. Cysts do not communicate. Absence of
(pyelonephritis, renal calculi) identifiable cortical parenchyma. Absence of central sinus structures.
• Only small percentage of pts develop complications,
overall prognosis is good VIII. TUBEROUS SCLEROSIS
• AD, chromosome 9 or 16
• Multiple Hamartomas: skin, CNS, eyes, kidneys and
heart
• Incidence: 1: 10,000
• Clinical Findings:
Intracranial tumors/calcifications:
─ Epilepsy: 80%
─ MR: 50%
• Renal cysts/RCC (5%)
• Skin Lesions:
Shagreen patches
Ash-leaf spots
Figure 6. Brushline in the medullary area.
Adenoma sebaceum (angiofibroma)
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 A. CLINICAL FEATURES VHL is localized to the primary cilia and is necessary
• Renal cysts and angiomyolipomas for the formation of primary cilia
• Renal cell carcinoma (bilateral) Prevalence: 1:30,000
• Cortical tuber • VHL1:
• Retinal hamartoma Retinal Angioma
• Glioma Spinal/Cerebellar hemangioblastoma
• Astrocytoma Pancreatic and renal cysts
• Facial angiofibroma Renal Cell CA
• Ungual fibroma • VHL2:
• Shagreen patch AS IN vhl1 + Pheochromocytoma
• Cardiac rhabdomyoma Risk for renal cell CA
• Pulmonary lymphangioleiomyoma
• Thyroid adenoma SUPPLEMENTARY NOTES (FROM UPCLASS)
A. SIMPLE CYSTS
• This is the most common cause of renal evaluation. It
means that; they had an UTZ, they saw a cyst, got
afraid and went for an opinion. They want to know if
this will transform to a malignancy; or will this cause
renal failure.
• Extremely common as age advances
• Incompletely understood pathogenesis
• Commonly associated with scarred kidney
• As one ages, the kidney function drops. As the nephron
ages their functions decrease,
• It is an incidental finding with normal creatinine and
urinalysis. But some can actually have proteinuria and
hematuria but also incidental.
• Asymptomatic with normal renal function
• Maybe solitary/multiple/unilateral/bilateral or unilaterally
IX. VON-HIPPEL LINDAU DISEASE unilocular, round to oval of varying sizes
• AD, chromosome 3 • Arises as dilated tubules or collecting ducts
• Cysts in kidneys are pre-malignant (>50%); bilateral • UTS: Thin, translucent fibrous wall containing clear or
nephrectomy is often necessary amber colored serous fluid
• Spino-cerebellar hemangioblastoma • Your fear is for it to rupture. That’s all
• Retinal angiomas
• Pancreatic cysts, islet cell tumors PREVALENCE
• Pheochromocytoma • Most common cystic abnormality encountered in
human kidneys
• May be solitary or multiple and are filled with fluid that
is chemically similar to an ultrafiltrate of plasma
• Very rare in children, but the frequency increases with
age

PATHOGENESIS
• Tubular obstruction and ischemia might play a role
• Microdissection studies revealed that diverticula of
distal convoluted and collecting tubules are common
after age 20 years and increase in number with age
• Cysts are thought to derive from progressive dilation
and detachment of these diverticula.

Figure 9. Tumors in Von-Hippel Lindau disease.

PATHOLOGY
Inherited cancer syndrome with renal manifestations • Lined by a single layer of epithelial cells
Autosomal dominant condition caused by mutations • Filled with a clear, serous fluid
in the VHL tumor suppressor gene

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• Grow slowly, but huge cysts, up to 30 cm in diameter,
have been described
• The inner surface of these cysts is glistening and
usually smooth
• The cysts are often cortical and distort the renal
contour, but they may be deep cortical or apparently
medullary in origin
• They do not communicate with the renal pelvis.
• The walls typically are thin and transparent but may
become thickened, fibrotic, and even calcified, possibly
from earlier hemorrhage or infection.
TREATMENT
• Treatment of simple renal cyst is indicated only if it is
symptomatic or causing obstruction.
• Intermediate-sized cysts can be aspirated
percutaneously, and a sclerosing agent can be instilled
into the cavity in an attempt to prevent recurrence.
• Cysts more than 500 mL in volume are usually drained
surgically.
• Hypertension has sometimes disappeared after
successful aspiration of the cyst fluid or surgical
removal of the cyst.
B. AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY
DISEASE
• Without hepatic fibrosis but there are other organ
aneurysm present (berry aneurysm)
• Adult (there is an autosomal recessive type found in
infants and children)
• Due to renal replacement therapy and dialysis
• Characterized by progressive formation of epithelial-
lined cysts in the kidney.
• Cellular defects of ADPKD:
Increased cell proliferation and fluid secretion
Decreased cell differentiation
Abnormal extracellular matrix
• Worldwide, 1:1000 in general population
• Accounting for 6% of patients in dialysis and transplant
program
This is one condition where you do not get the
native kidneys when you transplant. Normally, you
add one more kidney and usually the transplanted
kidney is in the iliac fossa and the native kidneys
remain. You only remove the native kidney if the
ADPKD is so large, or if there are stones or
something in the native kidney that will pose high
risk complications after the transplant. For
example, there are stones or staghorn that can be
a source of recurrent infection on the post-
transplanted kidney
Usually undergo nephrectomy. They don’t have
severe anemia during CKD stage. Thus, they have
higher hemoglobin levels compared to other
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GN/diabetic patients who develop CKD3 – 4 or
ESRD stage.
• Abnormal gene on short arm of chromosome 16
• i.e. 16p13.3 (PKD-1), 4q12-22 (PKD-2), 3rd locus
found
• Present in 3rd-5th decade
Very important is the identification of family history,
although not all children will develop the disease
but screening can start at the second decade
because at the third decade, cysts may start to
form.
─ Dull loin pain, flank masses, azotemia, positive
family history, hypertension, hematuria, colic
etc.
• Progressive renal failure→ anemia (later stage) and
↓GFR, ↑Ur and Cr
Associated cysts in liver of biliary type, in pancreas
(10%), spleen, thyroid and seminal vesicle
• Vascular anomalies including Berry aneurysms (33%),
aortic aneurysm, aortic root dilatation and mitral valve
prolapse.
• All these actually means that there is a defect in
COLLAGEN
Most severe forms early in life
Less severe forms present later (always bilateral,
congenital hepatic fibrosis)
• The most common complication is recurrent infection
because there is urine stasis. Second, there is rupture
of the cyst thus there is gross hematuria. And third
because of urinary stasis, you can have stone
formation.
• So it’s INFECTION, HEMORRHAGE & LITHIASIS.
• So patients will present with either colic, or recurrent
infection.
• Early identification is important because you can
actually retard or avoid complications. Because with
complications, progression to renal failure is fast. So
avoid stone formation and episodic UTIs.
EPIDEMIOLOGY
• Most common life-threatening MONOGENIC
DISEASE, affecting 12 million people worldwide.
• Incidence: 1:400 to 1:1000
• Current number affected: 400,000
• Approximately 1800 started on HD each year
• Racial distribution
GENETICS
• Caused by mutations in PKD1 and PKD2, which,
respectively, code for polycystin-1 (PC1) and
Polycystin-2 (PC2).
• PKD 1 – 85-90%
• PKD 2 – 10-15%
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• PKD1 gene is on 16p and codes for polycystin 1. It has • Enlarged kidneys can each reach a fourfold increase in
3 homologous copies and hence mutations are difficult length and weigh up to 20 times the normal weight.
to identify • Many patients are asymptomatic until the 4th-5th
• PKD2 gene is located on 4p and codes for polycystin 2 decade of life and are diagnosed by incidental
• Polycystin – iron channel regulation discoveries of hypertension or abdominal masses
• Back or flank pain is a frequent symptom in ~60% of
Protein Products of PKD Gene patients which may result from renal cyst infection,
POLYCYSTIN -1 POLYCYSTIN-2 hemorrhage, or nephrolithiasis.
Broad tissue Broad tissue expression • Gross hematuria from cyst rupture occurs in ~40% of
expression (immunolocalization): patients and most of them will have recurrent episodes.
(immunolocalization): • Kidney (all nephron • Proteinuria is usually a minor feature.
• Kidney (lateral segments) • Cyst from dilated tubule with weakened wall and
membrane of the • Heart contains filtrate or formed urine
tubular cells) • Ovary
• Brain • Testes Renal Manifestations:
• Heart • Vacular smooth • GROSS HEMATURIA
• Bone muscle Seen in up to 50 % of patients
• Muscle • Small intestine Flank pain
Cyst hemorrhage may occur in the absence of
Large 11- Calcium-permeable
gross hematuria
transmembrane six-transmembrane
Cyst rupture can cause retroperitoneal bleeding
protein that protein that
• CYST INFECTION
functions like a G structurally belongs
UTI
protein-coupled to the transient
Pyelonephritis
receptor. receptor potential
Perinephric abscess
Expression is high (TRP) cation channel
Exposure due to retroperitoneal rupture
in development and family
Cyst infection is the SECOND most common
low in the adult. Expression is
cause of death for patients with ADPKD. (The
relatively constant
major or PRIMARY cause of mortality:
PC1 & PC2
Cardiovascular complications)
Found on the primary cilium (a hair-like
An infected cyst and acute pyelonephritis are the
structure present on the apical membrane of a
most common renal infections often due to gram-
cell)
negative bacteria, associated with fever and flank
They bind to each other via their respective C-
pain, with or without bacteremia.
terminal tails to form a receptor-channel
• NEPHROLITHIASIS
complex and regulate each other’s function
Due to urine stasis
PC1/2 protein complex serves as a
Seen in up to 25 % of all ADPKD patients
mechanosensor or chemical sensor and
Stones contain uric acid and calcium oxalate
regulates calcium and G-protein signaling
Factors responsible for nephrolithogenesis include
May also directly regulate the cell cycle, actin
decreased urinary NH4, decreased urinary pH, and
cytoskeleton, planar cell polarity (PCP), and cell
decreased urinary acetate
migration.
Distal acidification defects, abnormal ammonium
transport, low urine pH, and hypocitraturia may be
CLINICAL FEATURES
important in the pathogenesis of renal stones in
• Chronic flank pain
ADPKD.
• Acute pain indicates:
• RENAL FUNCTION IMPAIRMENT
Infection (pyelonephritis-pyocyst)
Renal concentration defect
Urinary tract obstruction
Decreased renal blood flow
Sudden hemorrhage into cysts
Acidification defect (decreased NH3)
• Hematuria
Increase in Renal Angiotensin activity and matrix
• Impaired renal concentrating ability
synthesis
• Nephrolithiasis in 15-20%
• ESRD IN ADPKD
• Hypertension in 75% adults
16, 298 patients were treated for ADPKD (5% of all
• Progressive bilateral formation of renal cysts
ESRD)
• Hundreds to thousands of cysts are usually present in
2, 144 patients entered ESRD
the kidneys of most patients in the fifth decade.
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 50 % of all ADPKD patients enter ESRD by age
60
Total cost of RRT for ADPKD patients
exceeded $1 billion
Extra-renal Manifestations:
• POLYCYSTIC LIVER DISEASE (PLD)
Diagnosis: >4 cysts in the liver
May occur independent of PKD
Biliary Hamartomas, Biliary Fibroadenomas,
Dilatation of Intra/Extra hepatic ducts
Liver cysts increase with estrogen exposure
Cysts may cause abdominal distention, dyspnea,
obstructive jaundice, and ascites due to IVC
compression
Cysts in the pancreas and liver.
• INTRACEREBRAL ANEURYSM (ICA)
Overall incidence 8% of all ADPKD patients
Familial clustering (22% of those with familial
history of ICA)
Majority are asymptomatic
20-50% of patients may experience “warning
headaches” preceding the index episode of
subarachnoid hemorrhage due to ruptured ICA.
Yearly rupture rate is 0.5% for aneurysms <5 mm
and 4 % for aneurysms >10mm
1/3 of all patients with a ruptured aneurysm are not
hypertensive at the time of rupture
Screening: MRA with gadolinium is highly sensitive
and does not impose risk of contrast nephropathy.
─ Can detect cysts as small as 2-3mm
Indications for ICA screening:
─ Family history (ICA/SAH)
─ Prior aneurysmal rupture
─ Before high risk surgery ( must)
─ High risk occupation
• Anxiety on part of the patient
• VALVULAR HEART DISEASE
Mitral Valve Prolapse 25% (books says 30%)
MR, TR, Tricuspid valve prolapse, AI
Histopathology: MYXOID DEGENERATION
Screening: if clinically indicated
RISK FACTORS
• Hypertension – risk factor for both cardiovascular and
kidney disease progression
• Gross Hematuria
• UTI
• Multiparity
• Male Sex
• Black race
• Diagnosed of ADPKD before age 30
• Onset of hematuria before age 30
• Dyslipidemia
• DD ACE polymorphism
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• Sickle cell disease
PATHOLOGIC FEATURES
• Bilaterally enlarged kidneys (up to 4000g)
• Diffuse cystic (1-2% cystic nephrons) change with
uninvolved intervening parenchyma
• Varying sized, numerous to innumerable generally
spherical unilocular cysts, distributed in cortex and
medulla obscuring normal reniform shape and
corticomedullary junction, containing yellowish to turbid
to brown to back fluid
• Distorted pelvi-calyceal system
Unlike in ARPKD wherein it is not distorted
• Cysts arising from any part of nephron or collecting
duct
The transformation to neoplasm is rare. If you look
at it, there is variation in the size.
DIAGNOSIS
• ULTRASOUND
Often used for pre-symptomatic screening of at-
risk subjects and evaluation of potential living-
related kidney donors from ADPKD families.
Diagnostic UTZ criteria based on age:
─ 15-29y.o: 2 cysts in one or both kidney
─ 30-59y.o: 2 cysts in each kidney
─ >60y.o: 4 cysts each kidney
• GENETIC
PKD2 100% mutations detectable
PKD1 75 to 80% mutations detectable
Genetic Screening:
─ Who should be screened: Equivocal sonogram
in a young adult who is a potential renal
transplant donor
─ Issues: Psychological burden, Insurance and
employment risk
• PRE-SYMPTOMATIC
pre-symptomatic screening of at-risk subjects
• DIAGNOSTIC CRITERIA using ULTRASOUND
Age 15-29 ------- 2 cysts in one or both kidneys
Age 30-59 ------- 2 cysts in each kidney
Age >60 --------- 4 cysts in each kidney
Extra-Renal Symptoms
• Cysts in : Liver, spleen, pancreas, ovaries
• Intracranial aneurism
• Colonic diverticular disease
• Mitral valve prolapse
Factors Affecting Progression to End Stage Renal
Failure:
• Hypertension
• Recurrent Hematuria
• UTI (men)
• Massive Liver cystic disease (mostly women)
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• More than pregnancies
• Age at symptomatic diagnosis
• Sickle Cell Trait
MANAGEMENT
• For Flank Pain
Analgesics
Avoid NSAIDS (due to depletion of protective
prostaglandins)
Risk of narcotic dependence
Cyst decompression, aspiration, ethanol, sclerosis
(to obliterate potential space for fluid deposition),
and laparoscopic fenestration
• Cyst hemorrhage
Self-limited
Segmental Artery embolization ( severe)
• Cyst Infection
Bactrim
Quinolones
Cloramphenicol
Treatment often requires 4-6 weeks
• Nephrolithiasis
Extracorporeal shock wave lithotripsy ( if allowable
for size)
Potassium citrate or Bacitra for prevention of
nephrolithiasis if needed (Give antibiotics for
possible infections)
• Hypertension
ACE Inhibitors and ARB are preferred
Blood pressure control to a target of 140/90 mmHg
is recommended
Maintaining a target systolic BP to 110 mmHg in
patients with moderate or advance disease may
increase the risk of renal disease progression by
reducing renal blood flow.
• CKD
Dietary protein restriction
Control of dyslipidemia (statins)
Control of acidosis
Prevention of hyperphosphatemia
Management of Hypertension
─ Give phosphate binder to manage phosphate
levels
• More than half of ADPKD patients eventually require
peritoneal dialysis, hemodialysis, or kidney
transplantation.
• Peritoneal dialysis may not be suitable for patients with
massively enlarged polycystic kidneys due to small
intraabdominal space for efficient peritoneal exchange
of fluid and solutes and increased chance of abdominal
hernia and back pain.
• Patient with very large polycystic kidneys and recurrent
renal cyst infection may require pre-transplant
nephrectomy or bilateral nephrectomy to accommodate
the allograft and reduce the pain.
CCetC
Block XIX: Cystic Diseases of the Kidney
MD 3
C. AUTOSOMAL RECESSIVE
POLYCYSTIC KIDNEY DISEASE
• The classic infantile polycystic
• There is an accompanying congenital hepatic fibrosis
• Childhood
• 1:30,000
• Autosomal recessive pattern
• Bilateral
• In utero - poor renal function and failure to form
significant amounts of fetal urine
• Oligohydramnios + pulmonary hypoplasia. Thus
newborns do not have sufficient lung capacity to
survive
• Mutation in a single gene, PHKD1, is responsible for all
the clinical presentations of ARPKD.
• ARPKD
• Rare, 1:6-14, 000 live births
• Abnormal gene located on chromosome 6p21
• May be still born or neonatal death due to pulmonary
insufficiency
Seldom do they survive because there is
progressive renal failure
If they do survive the neonates will have urine
concentrating defects, anemia and hypertension
• 1 in 4 chance, neither parent shows signs
• Progressive renal failure
• Low specific gravity, mild proteinuria, urine
concentrating defect, anemia, hypertension → CCF
• Bilaterally symmetrical enlargement of kidneys (gross
appearance)
• Smooth surface with innumerable 1-2mm cysts
• Diffuse fusiform dilatation of the collecting ducts
(histology)
• Kidneys appear Enlarged but normally shaped pelvi-
calyceal system
• Normal reniform shape complete with fetal lobation and
normal sized (undilated) ureter
• Normal glomeruli and tubules
• Normal interstitium and no dysplasia
• Congenital hepatic fibrosis is almost always present
• Normal numbers of nephrons, no interstitial fibrosis and
no dysplasia.
• INCIDENCE OF ARPKD:
1: 20, 000
30 % affected neonates die
Genetic locus : 6p
Those who survive at birth have poor prognosis or
severely impaired
CLINICAL FEATURES
• Generally diagnosed in utero or within the neonatal
period.
• Large echogenic kidneys
• Oligohydramnios& Pulmonary hypoplasia
• Caused by reduced fetal urine production
10 of 14
• Hematuria • Exhibits reduced kidney concentrating ability
• Pyuria • Increased frequency of UTI
• Systemic Hypertension • 0.5 to 1% of all IVP (Intravenous Pyelography)
• Progressive renal insufficiency • Male and female affected equally
• Liver manifestations associated with periportal fibrosis • Dilatation in collecting ducts
(Congenital Hepatic Failure & Caroli’s disease) • In 70% bilateral renal involvement
• Portal Hypertension • It presents in 3rd or 4th decade with:
• Renal and liver pathology inversely related Kidney stone
• Oligohydramnios infection
• Potter’s facies hematuria
• Respiratory distress- pulmonary hypoplasia • Gold standard Diagnosis with: IVP (brush border IVP
structures)
DIAGNOSIS • Renal function is normally preserved
• Ultrasonography • Relatively common and benign, present at birth and not
Reveals large echogenic kidneys with poor usually diagnosed until age 40-60
corticomedullary differentiation. • Characterized by widening and cystic dilatation of distal
Diagnosis can be made in utero after 24 wks AOG collecting tubules
in severe cases. • 70% bilateral, maybe affecting all papillae
Absence of renal cysts in either parent helps • Infection and calculi occasionally seen as result of
distinguish ARPKD from ADPKD in older patients. urinary stasis in the tubules
• Clinical, laboratory, or radiographic evidence of hepatic
fibrosis CLINICAL FEATURES
• Hepatic pathology demonstrating characteristic ductal • Hematuria
plate abnormalities • Recurrent UTIs
• Family history of affected siblings or parental • Nephrolithiasis
consanguinity is helpful. • may show decreased urinary concentrating ability (due
to tubule damage)
TREATMENT
• No specific therapy TREATMENT
• Appropriate neonatal intensive care • No known therapy
• BP control, dialysis, and kidney transplantation • Increase fluids to prevent stone formation
increases survival into adulthood. • Treatment directed toward complications
(pyelonephritis, renal calculi)
D. MEDULLARY SPONGE KIDNEY • Only small percentage of pts develop complications,
• Idiopathic overall prognosis is good
• Very common (1:200)
• Normal renal functions E. MEDULLARY CYSTIC DISEASE
• Dilated distal portions of collecting ducts • Uncommon
• Superficially resemble cysts: • Both autosomal dominant and recessive way of
Urinary stones within the cysts ( common) inheritance occur
Superimposed infection (pyelonephritis) • Medullary Cystic Kidney Disease (MCKD)
─ Recurrent hematuria MCKD Type I
─ Concentrating defects MCKD Type II
─ Hyperparathyroidism • A rare, familial disease that may become symptomatic
• Chronic back pain during adolescence
Manage symptomatically • Manifested by many small cysts scattered through the
Good prognosis renal medulla
• Caused by a developmental malformation and cystic • Patients may present with pallor, polyuria, and lethargy
dilatation of the renal collecting ducts. d/t electrolyte loss
• Variable sized medullary cysts • May later develop HTN
• Benign
• Associated with an increased frequency of calcium PATHOGENESIS AND PATHOLOGY
phosphate and calcium oxalate kidney stones • Small kidneys
• Altered flow characteristics in the kidney tubules may • Cysts at the corticomeduallry junctions and in the
lead to the development of a nidus for stone formation medulla (unlike in PKD which is in the cortex)

CCetC
Block XIX: Cystic Diseases of the Kidney 11 of 14
MD 3
• The glomeruli are hyalinized, tubular basement Corticomedullary cysts
membrane is irregular, tubules vary in appearance Progressive CKD leading to renal failure
from atrophic to tortuous, interstitium reveals fibrosis Proteinuria is absent or mild
and mononuclear cell infiltrates (suspected to be end- Urine sediment is not active
stage of another tubulointerstitial disease) • Divided into:
Infantile form
CLINICAL MANIFESTATIONS ─ Caused by NPHP2 mutations
• Early adolescence polyuria, polydipsia, enuresis, defect ─ Associated with end-stage kidney failure in
in urinary concentrating ability, growth retardation, and early childhood
anemia • Juvenile form
• Adolescent form
TREATMENT Develops end-stage renal failure in early adulthood
• No specific therapy exists • The multiple genes and gene products (nephrocystins)
• Symptomatic and electrolyte imbalance correction that are responsible for NPHP are expressed in cilia,
• No current medical therapy to prevent progression to basal bodies, and the centromeres of kidney tubule
ESRD cells.
• Adequate water and salt replacement essential to • No specific clinical test that define NPHP
replenish renal losses • No specific therapies. Therapy is aimed at treating
• Renal transplantation if there is progression signs of these diseases as well as the systemic
abnormalities seen with all CKDs.
Differentiation of MCKD Types I & II • Chronic dialysis or kidney transplantation is eventually
MCKD Type I: required for NPHP-affected individuals.
• Mutations in the mucin 1 gene MUC1.
• Do not have elevated uric acid levels F. TUBEROUS SCLEROSIS
• Clinically exhibits slowly progressive CKD in adulthood • Rare Autosomal Dominant syndrome
• Minimal amounts of increased urine protein • Prevalence: 1: 10,000
• Occasional renal cysts on UTZ.
• Genetic Loci: TSC1 9q encoding hamartin; TSC2 16p
• Kidney histology shows tubulointerstitial fibrosis &
adjacent to PKD1 locus encoding tuberin
tubular atrophy
• Gene product in Tuberin (GTPase)
MCKD Type II:
• Mutations in the UMOD gene, which encodes the • Clinical Features:
protein uromodulin (Tamm-Horsfall protein). Renal cysts
• Also known as Uromodulin-associated kidney disease Angiolipomas
(UAKD), along with other UMOD-related diseases. ─ Multiple & bilateral
• Kidney cysts are not common features ─ Usually benign
• Should be suspected clinically in patients with a family ─ Might bleed
history of late-onset kidney disease, benign urine ─ Surgical removal if >4cm in diameter
sediments, absence of significant proteinuria, and ─ Increased risk of Renal Cell CA
hyperuricemia. ─ Cortical tuber
─ Retinal hamartoma
LABS ─ Glioma
• Urine analysis (UA) shows inability to concentrate urine ─ Astrocytoma
• CBC to confirm anemia ─ Facial angiofibroma
• Chemical panel to check phosphate, sodium, BUN, ─ Ungual fibroma
creatinine levels ─ Shagreen Patch
─ Cardiac rhabdomyoma
RADIOLOGY ─ Pulmonary lymphangioleiomyoma
• Ultrasound and CT Scan to diagnose ─ Thyroid Adenoma
─ Retinal hematoma
NEPHRONOPHTHISIS • Mechanistically, the TSC1 & TSC2 gene products
• Autosomal recessive disorders tuberin and hamartin interact physically. This protein
• Quite rare but the most common inherited childhood complex is localized to the base of the cilia and inhibits
form of kidney failure requiring kidney replacement intracellular signaling processes mediated by mTOR,
therapy (dialysis) leading to abnormal growth in a number of tissues.
• Disorders of ciliary function
• The various forms of NPHP’s features:
Tubulointerstitial fibrosis
CCetC
Block XIX: Cystic Diseases of the Kidney 12 of 14
MD 3
 REVIEW QUESTIONS 4. This has a classic paint-brush appearance in IVP.
1. Acquired Cystic Disease has a tendency to a. Alport’s Syndrome
undergo malignant change and develop into b. Medullary Sponge Kidney
Renal Cell Carcinoma. The following are c. Tuberous Sclerosis
suspicious cyst findings in U/S that suggest RCC d. Medullary Cystic Kidney Disease
except: 5. Which of the following statements is true
a. Contrast enhancement a. Tuberous sclerosis is characterized by skin
b. Septa formation lesions namely ash-leaf spots, shagreen
c. Atrophy patches, confetti lesions and angiofibroma.
d. Solid Material b. Von Hippel Lindau Syndrome is an autosomal
2. Which of the following is NOT true about simple dominant disease that commonly involves
cysts. chromosome 9 and 6.
a. It is the most common cause of anxiety. c. Juvenile (Familial) Nephronophthisis affects the
b. It is usually an incidental finding. proximal convoluted tubules.
c. It develops in the distal convoluted tubules. d. All of the above
d. It is basically harmless.
3. TM, 29, went for OPD consult due to gross
hematuria accompanied with abdominal and loin Answers: CCDBA
pain. Upon PE, he was noted to be hypertensive.
Diagnosis of ADPKD was made. As the clinical REFERENCES
clerk on duty, what would be part of your • Upclass notes
treatment plan? • Doc’s lecture
a. Cyst fluid aspiration/drainage (U/S guided) to
address the painful cysts
b. Advise TM to avoid contact sports to prevent
rupture of cyst
c. Lipophilic antibiotics
d. AOTA
e. A & B only

APPENDIX

CCetC
Block XIX: Cystic Diseases of the Kidney 13 of 14
MD 3
 FEATURE SIMPLE CYST ADPKD ARPKD ACKD MCD MSK
Inheritance pattern none Autosomal Autosomal None Often present, None
dominant recessive variable pattern
Incidence/prevalence Common, 1/200 to Rare 40% in Rare Common
increasing w/ age 1/1000 dialysis
patients
Age of onset Adult Usually Neonates, Older adults Adolescents, Adults
adults children young adults
Presenting symptom Incidental finding, Pain, Abdominal Hematuria Polyuria, Incidental,
hematuria hematuria, mass, renal polydipsia, UTI,
infection, failure. enuresis, renal hematuria,
family Failure to failure, failure renal calculi,
screening thrive to thrive
Hematuria Occurs Common Occurs Occurs Rare Common
Recurrent infection Rare Common Occurs No Rare Common
Renal calculi No Common No No No common
Hypertension Rare Common Common Present from Rare No
underlying
disease
Method of diagnosis Ultrasound Ultrasound, Ultrasound CT Scan Non reliable Excretory
gene linkage urogram
analysis
Renal size Normal Normal to Large Small to Small Normal
very large initially normal,
occasionally
large

CCetC
Block XIX: Acute Kidney Injury 14 of 14
MD 3