Kidney-Renal Dysgenesis & Cystic Disease Of The Kidneys - 114

Front 1

VHL is inherited in what percentage of patients? What chromosome is it?

Back 1

70% but they think it is even higher since now finding mosaics. Chromosome 3

Front 2

Name the gene abnormalities for tuberous sclerosis and ADPCKD. What chromosomes are they located on?

Back 2

TS: TSC1 (chromosome 2) and TSC2 (chromosome 16)

ADPCKD: PKD1 (chromosome 16), PKD2 (chromosome 4), PKD3 (?)

Front 3

What is the name given to infants born with bilateral renal agenesis?

Back 3

Potter’s Syndrome (hypertelorism, inner canthal folds, recessive chins), immature lungs and pneumothorax

Front 4

What percent of patients with unilateral renal agenesis have accompanying urologic abnormalities? Name the three most common associations.

Back 4

48% (same % associated with MCDKs)

Primary VUR (28%)

Obstructive megaureter (11%)

UPJ obstruction (3%)

Front 5

What is the hallmark of renal dysplasia on histology?

Back 5

“Primitive duct” (duct encircled by a collar of fibromuscular cells)

Front 6

T/F: Hypodysplasia occurring in conjunction with ectopic ureteral orifices correlates with the degree of ectopia.

Back 6

True- hypodysplasia most often occurs in conjunction with ectopic UOs

Front 7

What is Ask-Upmark kidney? When is it diagnosed, what is its etiology, and how is it treated?

Back 7

Usually diagnosed in adolescence (>10yo). It is segmental hypoplasia believed to be secondary to infection (even though there are some dysplastic areas). Patients have malignant HTN, headaches, hypertensive encephalopathy, retinopathy & proteinuria if bilateral. Tx unilateral with partial/total nephrectomy. Otherwise, anti-hypertensives.

A - adolescence dx, also known as
S - segmental renal hypoplasia, scarring, splitting HA
K - kidney out is tx. or partial

U - up together to remember reflux of urine
P - up together, also P for pounding HA
M - mark together to remember scarring, malignant HTN
A -
R - retinopathy
K - kidney out

Front 8

Hypodysplasia is divided into 4 categories. Name them.

Back 8

Normal versus Abnormal UO

Ureterocele

Urethral Obstrution

Prune-Belly Syndrome

Front 9

What kind of UO ectopia is associated with reflux? What is associated with ureterocele?

Back 9

Lateral: reflux

Medial: ureterocele

Front 10

What is the difference between the terms multicystic and polycystic?

Back 10

Multicystic refers to a dysplastic entity whereas polycystic refers to multiple entities, all of which are non-dysplastic and all with nephrons throughout the kidney

Front 11

What is the gene, chromosome, and protein product associated with ARPKD?

Back 11

PKHD1 gene on chromosome 6 which codes for fibrocystin (aka polyductin)

Front 12

In a child with ARPKD, what other organ system will be involved? How does age at presentation correlate with severity of disease of this system?

Back 12

Congenital hepatic fibrosis. Younger patient at presentation with ARPKD, the milder the liver disease. The younger the patient with liver disease, the milder the renal cystic disease.

Front 13

You are looking at an ultrasound in Sutherland’s clinic for a patient with suspected ARPKD. What clues will you use to lend support to a diagnosis?

Back 13

Look at echogenicity between liver and kidney. At birth, kidneys should have an equal or slightly increased echogenicity compared to liver, and hypoechogenic areas demonstrate renal pyramids. In ARPKD, very enlarged, homogenously hyperechogenic kidneys compared to liver because there is return of sound waves from enormous number of interfaces created by tightly compacted dilated collecting ducts.

Front 14

How does the particular genetic mutation in ADPKD help determine progression of disease, severity, and other associations?

Back 14

Those with polycystin 1 (PKD1) usually has faster disease progression and earlier age of onset of clinical symptoms. Median age of death or onset of renal failure is lower in PKD1 than PKD2. Also, more severe disease is noted when inherited by mother (genomic imprinting).

Front 15

List 5 other manifestations of ADPKD other than renal cysts.

Back 15

Berry aneurysms (causing SAH)
Hepatic cysts and othere cysts of pineal gland, pancreas, spleen
Colonic diverticulosis
Mitral valve prolapse
Hypertrophied pyloric stenosis

A - aneurysms
D - diverticulosis
P - ancreas & pineal and liver cysts, pyloric stenosis
K - kidney cysts
D - defects in heart valve

Front 16

T/F: Epo is decreased in patients with ADPKD with ESRD.

Back 16

False. Epo is actually usually high in these patients due to increased renal mass.

Front 17

Is ADPKD associated with increased risk of RCC?

Back 17

No. It appears that this is not the case.

Front 18

How does gender help predict symptoms and prognosis in ADPKD?

Back 18

Men have more renal involvement than women manifesting with HTN and renal insufficiency whereas women more likely to have more severe cystic involvement of the liver as well as cyst and parenchymal infections of kidney.

Front 19

What are the three types of juvenile nephronopthisis and how are they inherited? How is the inheritance pattern of medullary cystic disease different? Which of the two are more common?

Back 19

JN is AR and three types include juvenile (NPH1 gene), adolescent (NPH2), and infertile (NPH3). Medullary cystic disease is inherited in an AD pattern (MCKD1 and 2). JN is much more common than MCD- responsible for 10-20% of renal failure in children

Front 20

What disorders are juvenile nephronopthisis associated with? What is Senior-Loken syndrome?

Back 20

Retinitis pigmentosa, skeletal abnormalities, hepatic fibrosis, Bardet-Biedl syndrome (obesity, MR, hypogonadism, RP, polydactyly). Senior-Loken is JN + retinitis pigmentosa (aka retinal-retinal syndrome)

Front 21

T/F: HTN is one of the earliest signs of juvenile nephronophthisis.

Back 21

False- HTN is not associated with this since it is a salt-losing nephropathy. Most common symptoms of both JN and MCD are polydipsia & polyuria

Front 22

You have a patient referred to you for medullary cystic disease. The parents bring an ultrasound. In what location of the kidney will you look for cysts?

Back 22

Corticomedullary junction

Front 23

Naina tells Dan about a baby she delivered with an enormous placenta. Besides being excellent dinner conversation, is this a clue to a urologic condition?Which type of CN does this baby probably have and why?

Back 23

Why yes it is- congenital nephrosis is usually discovered because of a huge placenta accounting for >25% of birth weight.

Finnish type because the other less common type (diffuse mesangial sclerosis) does not usually present with an enlarged placenta

Front 24

What is the triad of symptoms indicative of tuberous sclerosis complex? What renal abnormalities are associated?

Back 24

Triad: Epilepsy, Mental retardation, Adenoma Sebaceum

Renal: Angiomyolipoma (40-80%), renal cysts (20%), RCC (2%)

Front 25

What chromosomes are associated with TSC? What other disease do you think of if a TSC patient also has several large cysts and how is this related to TSC?

Back 25

TSC1 (chromosome 9) and TSC2 (chromosome 16)- AD inheritance

If multiple cysts, think of concurrent mutations of TSC2 and PKD1 (ADPKD) because genes are adjacent on chromosome 16

Front 26

What are clinical manifestations of VHL Disease? What chromosome/gene?

Back 26

Cerebellar and retinal hemangioblastomas

Cysts of pancreas, kidney, epididymis (epididymal cystadenoma)

Pheo (10-12%)

Clear cell RCC (50%)

Chromosome 3 – VHL gene

Front 27

What is the most common type of renal cystic disease?

Back 27

Multicystic dysplasia. Also, it is one of the most common causes of an abdominal mass in a newborn

Front 28

In Bukowski’s clinic, a one-month old child is referred with a renal ultrasound. He is otherwise healthy. The left kidney has several cysts whereas the right appears to be normal.

What are the top two diagnoses on your differential?

Back 28

MCDK

Hydronephrosis

Front 29

How can you distinguish between MCDK and hydronephrosis by RUS?

Back 29

MCDK shows a haphazard arrangement of various sized cysts with no visible communication

Hydronephrosis shows organized arrangement of larger cyst (representing renal pelvis) and surrounding calyces, they also connect

Front 30

What is(are) your next study(ies) and why?

Back 30

DMSA scan to assess for function of the left kidney (MCDK has no function whereas hydronephrotic kidneys usually have some function)

VCUG (rule out VUR in contralateral kidney- occurs in 18-43% of these patients). Also, UPJ obstruction occurs in contralateral kidney in 3-12%

Front 31

Should you have this patient follow-up? Would you recommend prophylactic nephrectomy?

Back 31

Follow-up should be made at least in first 5 years of life- for the possibility of tumor and hypertension but it is controversial as to how often (some suggesting every 3 months for 8 years)

Nephrectomy is not warranted even though there is a slight increased risk of Wilms’ tumor (4-fold) compared to general population. Sutherland uses increasing size as an indication for surgery.

Front 32

When is a benign multilocular cyst usually diagnosed? How is it diagnosed?

Back 32

Usually before age 4 (more in males) or after 30 (more in females)

The only way to determine diagnosis of multilocular cystic lesion on imaging is by surgical excision (whether in a child or adult)

Front 33

A 1yo child is referred with an ultrasound. The radiologist describes this as a possible multilocular cystic lesion.

Name four lesions which are considered in the differential of a multilocular cystic lesion in a child’s kidney. Is there an equivalent spectrum in adults?Is the cystic component a good or bad prognostic indicator?Can these lesions on the spectrum convert to one another?

Back 33

Benign multilocular cyst, multilocular cystic partially differentiated Wilms’ tumor, Multilocular cyst with nodules of Wilms’ tumor, Cystic Wilms’

Yes- benign multilocular cyst, multilocular cystic RCC, multilocular cyst with nodules of RCC(?), and cystic RCC

Improved prognosis

No- neither in adults nor children.

Front 34

List the CT criteria for a simple cyst (which is similar to that of U/S).

Back 34

Sharp, thin, distinct, smooth walls and margins

Spherical or ovoid shaped

Homogeneous content

Front 35

What is the typical density (in HU) of a simple cyst? What if it is hyperdense (20-90 HU)?

Back 35

Should be -10 to +20 HU

Hyperdense is still likely benign IF no enhancement with IV contrast and other criteria for benign cyst is met on CT plus evaluation for size (must be <3cm) and location (at least ¼ of cyst’s circumference extends beyond renal contour so that smoothness of a good portion of cyst can be evaluated)

Front 36

What are the three remaining indications for cyst puncture?

Back 36

Suspected infection

Low-level echoes on ultrasound but classic cyst findings on CT

Indeterminate findings on imaging with a poor surgical candidate

Front 37

Describe the Bosniak Classification system.

Back 37

Category I: typical benign cyst

Category II: benign cystic lesions minimally complicated (septations, small calcifications, infection or high density) and do not require surgery

Category IIF:These cysts might contain more hairline thin septa. Minimal enhancement of a hairline thin septum or wall can be seen and there might be minimal thickening of the septa or wall. The cyst might contain calcification that might be nodular and thick but there is no contrast enhancement. There are no enhancing soft-tissue elements. Totally intrarenal non-enhancing high-attenuation renal lesions of ≥3 cm are also included in this category. These lesions are generally well marginated

Category III: complicated lesions with more extensive calcification, thick wall which is irregular, increased septation (multilocular cystic lesion), chronic infection with thickened wall. These lesions are indeterminate cystic masses that have thickened irregular walls or septa in which enhancement can be seen.

Category IV: cystic malignant tumors, requires nephrectomy. These lesions are clearly malignant cystic lesions that contain enhancing soft-tissue components.

Front 38

A patient comes to clinic with history of renal colic, recurrent UTI, and an episode of gross hematuria which has since resolved. He comes with an IVU from his primary care physician. On review, it appears that the kidneys are enlarged, and papillae resemble a bouquet of flowers. What is the diagnosis and what other radiographic findings might you look for?

Back 38

Medullary sponge kidney- dilatation of the distal portion of the collecting ducts with numerous associated cysts and diverticula.

IVU is actually more sensitive than CT for mild cases of MSK. Features include bilaterally enlarged kidneys sometimes with calcification, elongated papillary tubules which fill with contrast, and papillary contrast blush and persistent medullary opacification with papillae resembling bouquet of flowers, bunches of grapes, or bristles on a brush (discrete linear stripes).

Front 39

What electrolyte abnormality is often present with medullary sponge kidney and how is this helpful in treatment?

Back 39

Hypercalcemia is present in 33-50% of patients (for different reasons- renal calcium leak, increased calcium absorption or increased PTH)

Thiazides are a helpful adjunct in treatment, even if hypercalciuria is not present. Second line medical management is inorganic phosphates.

Front 40

T/F: Acquired renal cystic disease occurs more often in hemodialysis patients than those undergoing peritoneal dialysis.

Back 40

False- They occur at nearly the same rate. Also, it has been discovered that ARCD also occurs in CKD patients not yet on dialysis.

Front 41

Why do we care about acquired renal cystic disease?

Back 41

They may produce symptoms (loin pain, hematuria) and also predispose to RCC. 80% of those with ESRD who develop RCC have ARCD. They also have RCC at an earlier age (3rd to 4th decades)

Front 42

List three ways that RCC in ESRD is different biologically than classic RCC.

Back 42

Males are affected more frequently than females (7:1 compared to 2:1)

Age at occurrence is 5 years less than classic form

Incidence of RCC in ESRD is 3-6 times that of classic form, up to 10x in blacks

Front 43

An ESRD patient is referred to Dr. Wallen for hematuria. You find out that he has been on hemodialysis for 4 years. Local cystoscopy shows no obvious lesions. What will you do next and how do you plan to follow him?

Back 43

This is controversial, but aggressive plans would recommend starting with a renal ultrasound and CT after 3 years of dialysis. Then every 6 months, get a repeat CT and ultrasound if ARCD is diagnosed. However, in the US, we are less conservative, and use ultrasound only. Screening with CT only if known ARCD, male gender, and prolonged dialysis.

Front 44

What are the differences between calyceal diverticulum, pyelogenic cyst and pyelocal calyceal diverticulum?

Back 44

Calyceal diverticulum is a lesion that communicates with a calyx or infundibulum. Pyelogenic cyst is a lesion that communicates with the renal pelvis. Pyelocal calyceal diverticulum describes both entities.

Front 45

How does PKD1 and the PKD2 gene play a role in normal development of the kidney?

Back 45

Polycystin-1 is a long-chain glycoprotein produced by the ADPKD gene PKD1 on chromosome 16. Polycystin-2 is produced by the PKD2 gene on chromosome 4. These two genes seem to play a role, along with the signaling gene WNT4, in normal tubulogenesis in the developing metanephrenic kidney. When either the PKD1 or the PKD2 gene is abnormal, cystic kidneys can develop

Front 46

What is Knudson's two hit theory of gene mutation causing disease?

Back 46

Each gene within a cell is one of a set of two; each is called an allele. One defective allele may be the carrier for the defect. Its normal allele is referred to as the "wild type." In Knudson's (1991) two-hit theory, the first hit in an inherited mutation is found in all cells of an individual (i.e., a germline mutation). The second hit occurs when the wild-type allele spontaneously mutates within a specific organ, although it may be a different mutation than in the primarily affected allele

Front 47

How do patients with Von-Hippel Lindau disease show a good real world example of the two hit theory of Knudson's genetic theory of certain disease formation?

Back 47

For example, the typical somatic cells in the kidney and all other cells of a patient with VHL disease typically are heterozygous for the VHL gene located on chromosome 3; that is, the mutant VHL allele is inherited and its mate is the normal wild-type allele. However, the configuration of wild-type VHL makes it prone to spontaneous mutation. If the wild-type allele develops a defect within the cells of a specific organ, those cells no longer are able to produce normal pVHL with its suppressor properties. That organ then has the propensity to develop a tumor. In kidney cells of individuals with VHL disease, for example, heterozygosity is lost when the wild-type allele mutates, and there is a propensity to develop a clear cell renal cell carcinoma. To determine whether cysts lined with epithelial cells are predisposed to renal cell carcinoma (RCC), Lubensky and coworkers (1996) studied partial nephrectomy specimens of two patients with familial VHL disease with RCC who underwent renal-sparing surgery. The makeup of 26 cysts was studied with microdissection techniques. Each cyst was found to be lined with a single layer of clear epithelial cells. Twenty-five of the 26 cysts had a mutation of the wild-type allele; in only one case was the usual heterozygosity of the disease maintained. This finding supports the two-hit theory. Once the heterozygosity for VHL is lost in a specific organ, in this case the kidney, the cyst can progress into a tumor. However, the progression to RCC in VHL disease typically is slow.

Front 48

What can lead to renal agenesis, in general? How common is bilateral renal agenesis?

Back 48

Renal agenesis, or absent kidney development, can occur secondary to a defect of the wolffian duct, ureteric bud, or metanephric blastema. Bilateral agenesis occurs in 1 of every 4000 births and has a male predominance

Front 49

What is Mayer-Rokitansky-Küster-Hauser syndrome?

Back 49

group of associated findings that include unilateral renal agenesis or renal ectopia, ipsilateral müllerian defects, and vaginal agenesis.

A woman with this condition is hormonally normal; that is, she will enter puberty with development of secondary sexual characteristics including thelarche (****) and adrenarche (pubic hair). Her chromosome constellation will be 46,XX. Ovaries are intact and ovulation usually occurs. Typically, the vagina is shortened and intercourse may in some cases be difficult and painful. Medical examination supported by gynecologic ultrasonography demonstrates a complete or partial absence of the cervix, uterus, and vagina.
If there is no uterus, women with MRKH cannot carry a pregnancy. However, it is possible for these women to have genetic offspring by in vitro fertilisation (IVF) and surrogacy. Uterine transplantation is currently not a treatment that can be offered as the technology is still in its infancy.
Women with MRKH typically discover the condition when, during puberty years, the menstrual cycle does not start (primary amenorrhea). Some women find out earlier through surgeries for other conditions, such as a hernia.

Front 50

What is different about renal dysplasia and hypoplasia and are the two unique or do they ever occur at the same time in the same patient?

Back 50

Although dysplasia is always accompanied by a decreased number of nephrons (i.e., hypoplasia), the converse is not true; hypoplasia may occur in isolation. When both conditions are present, the term hypodysplasia is preferred

Front 51

What is this a picture of?

Back 51

Medullary sponge Kidney.

Medullary sponge kidney (MSK) is a birth defect of the tubules—tiny tubes inside the kidneys. In a normal kidney, urine flows through these tubules as it is being formed. In MSK, tiny sacs called cysts form in the medulla—the inner part of the kidney—creating a sponge-like appearance. The cysts keep urine from flowing freely through the tubules.

Front 52

Is multicystic dysplastic kidney an inherited disorder?

Back 52

*No, it is congenital but not inherited.

Front 53

Why is tuberous sclerosis known as tuberous sclerosis?

Back 53

he name, composed of the Latin tuber (swelling) and the Greek skleros (hard), refers to the pathological finding of thick, firm and pale gyri, called "tubers," in the brains of patients postmortem. These tubers were first described by Désiré-Magloire Bourneville in 1880; the cortical manifestations may sometimes still be known by the eponym Bourneville's disease.

Front 54

What is this picture illustrating an example of a clinical finding in?

Back 54

Tuberous sclerosis, these are the adenoma sebacum.

Remember mnemonic zits, fits, and nitwits.

Front 55

Why is tuberous sclerosis known as tuberous sclerosis

Back 55

he name, composed of the Latin tuber (swelling) and the Greek skleros (hard), refers to the pathological finding of thick, firm and pale gyri, called "tubers," in the brains of patients postmortem. These tubers were first described by Désiré-Magloire Bourneville in 1880; the cortical manifestations may sometimes still be known by the eponym Bourneville's disease.

These show some of those "tubers."