CYSTIC KIDNEY

DISEASES

By:Dr./ SAHAR H. MOSTAFA

ELMATARIA TEACHING HOSPITALCAIRO-EGYPT

DECEMBER, 2016

LIST OF ABBREVIATIONS ADPKD: autosomal

dominant polycystic kidney disease

ARPKD: autosomal recessive polycystic kidney disease

C.D.: collecting duct CKD: cystic kidney disease CRF: chronic renal failure DCT: distal convoluted

tubule ESRD: end-stage renal

disease FN: familial

nephronophthisis GBM: glomerular basement

membrane

GN: glomerulonephritis IN: interstitial nephritis MCKD: medullary cystic

kidney disease MSK: medullary sponge

kidney NS: nephrotic syndrome PCT: proximal convoluted

tubule RCC: renal cell carcinoma RRT: renal replacement

therapy TSc: tuberous sclerosis UTI: urinary tract infection VHL: Von Hippel-Lindau

CYSTIC KIDNEY DISEASES

OVERVIEW: Simple cysts Autosomal dominant polycystic

kidney(ADPKD) Autosomal recessive polycystic

kidney(ARPKD) Acquired cystic kidney disease(ACKD) Alport’s syndrome Medullary sponge kidney(MSK) Medullary cystic kidney disease(MCKD) Renal phacomatosis:Tuberous sclerosis(TSc)

and Von Hippel-Lindau disease(VHL)

SIMPLE CYSTS Solitary or multiple, fluid-filled Cysts develop from any part of nephron, usually

cortical Incidental finding on U/S or IVU Incidence:

o 2%patients < 50 Ys oldo 11%patients 50-70 Ys oldo >20%elderly patients

Usually not loculated and tend to bulge out from renal surface

May grow to considerable size(>10cm) Usually harmless Occasionally require percutaneous drainage;

because of persistent loin pain

ADPKD Incidence: 1: 1000 Genes:

o PKD 1 gene(86%): on chromosome 16o PKD 2 gene(10%): on chromosome 4

AD, yet some sporadic cases are commonly seen Pathophysiology:

o Early ↑ of Plasma ADH, to compensate for ↓ concentrating ability hypertension and renal insufficiency

o Cysts development induce renal ischemia and + RAS hypertension

o ↑ Angiogenesis(fragile vessels across cyst walls) rupture Pain ±hematuria

ADPKD Cysts develop from all segments of

nephron(including Bowman’s capsule), during the teenage Ys, presentation is in 4th or 5th decades

Diagnostic Criteria for ADPKD

2 Cysts (unilateral/or/ bilateral)

< 30 Ys old

2 Cysts(in each kidney) 30-59 Ys old

4 Cysts(in each kidney) > 60 Ys old

ADPKD Clinical Features:

o Asymptomatic(~1/3)o Abdominal/Loin Pain or Masso Hypertensiono UTIo Renal calculi(10%)o Macroscopic hematuriao Not all patients(~1/3), develop ESRD onset of CRF varies

widely:25-60 Ys Common Associations:

o Liver cysts(70%), hepatic fibrosis(rare)o Pancreatic Cysts(10%)o Berry Aneurysms(>20% in +ve F.H., 5% in –ve F.H.), 4% risk

of rupture if size >10mm, do: MRA every 3 Yso MVP, or A.I.o Anemia of CRF/or Polycythemia due to ↑ erythropoeitin

activityo Diverticular disease

Increase incidence of malignancy

TREATMENT OF ADPKDNo strategies to prevent formation and progression of

cysts; the aim is instead at: monitoring for & treating complications, as well as providing appropriate couselling

Treatment of hypertension(to ≤ 125/75mmHg): ACE-Is, ARBs Treatment of UTI: Lipophilic Antibiotics with cyst-penetrating

ability(ciprofloxacin, trimethoprim, clindamycin, vancomycin, clotrimazole)

Treatment of painful cyst:o Cyst fluid aspiration/drainage(U/S-guided)o Cyst de-roofing: Excision of outer

wall(Fibreoptic-guided/open surgery)o Ethanol-induced sclerosis

Treatment of enlarged kidney:o Avoid tight corsetso Avoid wearing belts and seat beltso Avoid playing contact sports

ARPKD AR, chromosome 6 Genes:

o Fibrocystino Polyductin

Cysts develop from DCT and CDs Incidence: 1: 10,000 births ESRD usually develops early in childhood;

sometimes it may be delayed to 20 Ys of age or rarely, may never occur

Poor prognosis Genetic counseling

ARPKD Clinical presentation:

Bilateral abdominal masses in infancy Polyurea Enuresis Hyponatremia Hyperchloremic metabolic acidosis Hepatic fibrosis in all cases, progressing to

portal hypertension Hypertension Pulmonary hypoplasia(major cause of death in

1st year of life)

ARPKDSagittal sonogram: multiple microcysts in left kidney, not communicating with each other

ACKD In the rudimentary kidneys of patients with ESRD,

especially the scarred kidneys Cysts usually develop from PCT/DCT Incidence:

o >5% At onset of RRTo >80% After 10 Ys of dialysis

Asymptomatic Cyst hemorrhage: Flank pain, anemia, hematuria Risk Factors:

o Duration of ESRDo Male gendero Black raceo Chronic hypokalemia

ACKD Malignant change(RCC), with an annual

incidence of 1%, less often to be metastatic, but with high 5-year mortality rate

Renal U/S, CT, MRI: Demonstration of cysts in Kidneys which are

not enlarged Suspicious cyst findings for RCC:

Septa formation Solid material Contrast enhancement

ACKD

ALPORT’S SYNDROME Incidence: 1: 5000 X-Linked, dominant Absence of alpha-5 chain of type IV

collagen Abnormal GBM(basket-weave appearance) Absent Good-Pasture Ag in GBM;

predisposition to anti-GBM GN after transplantation(graft failure)

ALPORT’S SYNDROME Deafness(sensorineural, bilateral) Microscopic hematuria, proteinuria NS(30%) CRF, in all affected males(not in female

carriers) Ocular abnormalities in 40%(Lenticonus,

retinal flecks, cataract Macro thrombocytopenia Leiomyomata(rare) D.D. with benign familial hematuria(thin

membrane nephropathy)

MSK Sporadic Benign course: less likely to progress to ESRD Cysts develop from medullary and papillary CDs The ectatic C.Ds may calcify Classical

Nephrocalcinosis(50%) Upper UTI and renal calculi may be present Microscopic hematuria and hypercalciuria ± Hyperparathyroidism

MEDULLARY SPONGE KIDNEY

JUVENILE(FAMILIAL) NEPHRONOPHTHISIS(FN)/MEDULLARY CYSTIC KIDNEY DISEASE(MCKD) They are 2 different terms used for 2 similar

diseases; which differ only in their age of onset and mode of inheritance

Cysts occur in medullary DCT Patients have:

Tubulo-IN Salt-wasting Progressive CRF

FN MCKDAR AD, uncommon

ESRD in childhood or before 20 Ys of age(15%)

ESRD in 3rd,4th decade

Extrarenal manifestations:a. Retinitis

pigmentosa(10-15%)b. Cerebellar ataxiac. Liver fibrosisd. Nocturnal Eneuresis

NOT associated with extrarenal manifestationsHypertension is present

TUBEROUS SCLEROSIS(EPILOIA) 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:

o Shagreen patcheso Ash-leaf spotso Adenoma Sebaceum(angiofibromas)

TUBEROUS SCLEROSIS- SKIN LESIONSa: Ash-leaf maculeb: Adenoma Sebaceumc: Peri-ungual fibromad: Shagreen patches

VON HIPPEL-LINDAU SYNDROME(VHL) AD, chromosome 3 Cysts in kidneys are pre-

malignant(>50%); bilateral nephrectomy is often necessary

Spino-cerebellar hemangioblastoma Retinal angiomas Pancreatic cysts, islet cell tumors Pheochromocytoma

VON HIPPEL-LINDAU SYNDROME(VHL)Left: Multiple renal tumors and cystsRight: Cut surface of the same kidney

SELF-ASSESSMENT QUESTIONS

A 55-Y-old man undergoes IVP, as part of work-up of HTN. A 3-cm solitary radiolucent mass is noted in the left kidney; the study otherwise is normal. The man complains of no symptoms referable to the urinary tract and examination of urinary sediment is within normal limits.

Which of the following studies should be performed next?a. Repeat IVP in 6-Monthsb. Early-morning urine collections for cytology (3

samples)c. Selective renal arteriographyd. Renal U/Se. CT scanning with contrast enhancement of the

left kidney

A 55-Y-old man undergoes IVP, as part of work-up of HTN. A 3-cm solitary radiolucent mass is noted in the left kidney; the study otherwise is normal. The man complains of no symptoms referable to the urinary tract and examination of urinary sediment is within normal limits.

Which of the following studies should be performed next?a. Repeat IVP in 6-Monthsb. Early-morning urine collections for cytology

(3 samples)c. Selective renal arteriographyd. Renal U/S {to differentiate simple cyst

from RCC}e. CT scanning with contrast enhancement of

the left kidney

A 49-Y-old woman with known PKD and serum creatinine of 3.0 mg/dl, comes to the ER because of abdominal and flank pain. She passed blood-tinged urine the day before. Examination revealed a BP of 180/105, pulse of 92 bpm and a T o of 38 o C. Large bilateral upper quadrant masses are palpated; the right is somewhat tender. Bowel sounds are normal. Plain film of abdomen reveals large upper quadrant masses bilaterally. A few areas in the upper pole of the right kidney have complex echoes and no solid masses are seen.

Urine analysis shows 1+ protein, RBCs > 100/HPFWhich of the following is the most likely cause of the

patient’s condition?a. Renal infarctionb. UTIc. Renal cell carcinoma(RCC)d. Hemorrhage into a renal cyste. Arteriovenous(AV) malformations

A 49-Y-old woman with known PKD and serum creatinine of 3.0 mg/dl, comes to the ER because of abdominal and flank pain. She passed blood-tinged urine the day before. Examination revealed a BP of 180/105, pulse of 92 bpm and a T o of 38 o C. Large bilateral upper quadrant masses are palpated; the right is somewhat tender. Bowel sounds are normal. Plain film of abdomen reveals large upper quadrant masses bilaterally. A few areas in the upper pole of the right kidney have complex echoes and no solid masses are seen.

Urine analysis shows 1+ protein, RBCs > 100/HPFWhich of the following is the most likely cause of the

patient’s condition?a. Renal infarctionb. UTIc. Renal cell carcinoma(RCC)d. Hemorrhage into a renal cyst {pain+echoes+RBCs}e. Arteriovenous(AV) malformations

A 47-Y-old man has an excretory urogram for investigation of microscopic hematuria, discovered on a routine urine analysis. He is apparently healthy and entirely without complaints. Kidneys are of normal size, with calcification and collection of dye in dilated medullary structures. Some E-, BUN, creatinine, Ca+, P- and uric acid are normal. Creatinine clearance is 103 ml/min. Urine analysis reveals rare RBCs and no protein.

Which of the following is/are true of this patient?

a. There is significant chance that symptomatic renal stones will develop

b. There is significant chance that he has hypercalciuriac. He is likely to have impaired urine concentrating abilityd. His condition is likely to progress to chronic ESRDe. His children have a 50% chance of experiencing the same

condition

A 47-Y-old man has an excretory urogram for investigation of microscopic hematuria, discovered on a routine urine analysis. He is apparently healthy and entirely without complaints. Kidneys are of normal size, with calcification and collection of dye in dilated medullary structures. Some E-, BUN, creatinine, Ca+, P- and uric acid are normal. Creatinine clearance is 103 ml/min. Urine analysis reveals rare RBCs and no protein

All of the following is true of this patient, except:

a. There is significant chance that symptomatic renal stones will develop

b. There is significant chance that he has hypercalciuriac. He is likely to have impaired urine concentrating abilityd. His condition is less likely to progress to chronic ESRDe. His children have a 50% chance of experiencing the same

condition {MSK is a congenital, not hereditary}

A 60-Y-old man with ESRD from chronic GN, presents with acute onset of gross hematuria and mild flank pain. He has been on dialysis for 4 Ys and his course has otherwise been uneventful. He was afebrile and the hematuria resolved without intervention.

Which of the following is most appropriate now?a. Renal U/Sb. CTc. Angiographyd. IVPe. None of the above

A 60-Y-old man with ESRD from chronic GN, presents with acute onset of gross hematuria and mild flank pain. He has been on dialysis for 4 Ys and his course has otherwise been uneventful. He was afebrile and the hematuria resolved without intervention.

Which of the following is most appropriate now?a. Renal U/Sb. CT {ACKD has 10% incidence of malignancy, CT

will be useful in diagnosis and also for staging}c. Angiographyd. IVPe. None of the above