Acquired Cystic Kidney Disease 

Updated: Mar 13, 2020
Author: Manish Suneja, MD, FASN, FACP; Chief Editor: Vecihi Batuman, MD, FASN 

Overview

Practice Essentials

Cystic kidney disease is a term that represents a wide spectrum of diseases that may be hereditary, developmental, or acquired; these diseases share the feature of renal cysts.[1] These cysts can occur in the cortex, the corticomedullary junction, and/or the medulla, depending on the underlying disease process. Acquired cysts can be simple or part of acquired cystic kidney disease (ACKD), also called acquired renal cystic disease (ARCD).

Acquired cystic kidney disease is characterized by the development of numerous fluid-filled cysts in the kidneys in individuals who have no history of hereditary cystic disease. These cysts are often bilateral and are usually less than 0.5 cm in diameter but can be as large as 2-3 cm. This condition often occurs in advanced chronic kidney disease (CKD), and the cysts can antedate the clinical recognition of end-stage renal failure. In its early stages, acquired cystic kidney disease does not produce symptoms and is usually discovered incidentally in the course of abdominal imaging procedures.

 

Pathophysiology

Acquired cystic kidney disease (ACKD) was previously thought to be a consequence of hemodialysis. Studies have shown that, although the association of dialysis and ACKD is indisputable, it is the uremic state that promotes the development of ACKD. The development of ACKD does not appear to be associated with any particular type of kidney disorder. Dialysis prolongs the patient's survival to allow more time for acquired renal cystic disease to occur.

The exact mechanism is not known. The postulates are as follows:

  • Tubule block: The development of cysts results from tubular obstruction due to oxalate crystals, fibrosis, or micropolyps; and tubular fluid accumulation due to glomerular filtrate and tubular fluid excretion.
  • Compensatory growth: The profound loss of renal tissue in end-stage kidney disease promotes tubular cell hypertrophy and hyperplasia. Hypertrophy and hyperplasia, together with transepithelial secretion of fluid by the tubular epithelium, result in the development of cysts. Many factors may influence the process, but most important among them are growth factors and activation of oncogenes.
  • Ischemia [2] : Kidney atrophy is a recognized consequence of ischemia that may be caused either by primary renal arterial occlusion or by the secondary arterial occlusions that develop after dialysis is begun. Parenchymal acidosis may result from chronic progressive occlusion and, if sustained just short of causing cell death, might result in renal cyst formation.

Research into the cystic fluid and epithelium suggests that the cysts arise from proliferation of renal tubules.[3, 4] Cystic fluid derives from the ultrafiltrate, transepithelial solute, and fluid secretion, and resembles plasma in its composition.[3] Additionally, microdissection studies have shown that most cysts present a low cuboidal or columnar epithelium, while some of the cells that line cysts show an apical brush border configuration, suggesting that they stem from proximal tubules.[5]

Progressive destruction of the renal parenchyma triggers several mitogenic signals (eg, azotemic products, altered concentration of sodium and potassium, activation of the renin-angiotensin-system, inflammation, local growth factors), ultimately leading to hypertrophy and hyperplasia of renal tubules.[3, 6] In addition, restricted tubular fluid flow and net fluid secretion contribute to cyst formation.[3] Over a period of time, the activation of  proto-oncogenes combined with additional risk factors may result in malignant transformation.[3, 7, 8]  The image below illustrates the proposed pathophysiology of the progression of acquired cystic kidney disease to renal malignancy.

 

Proposed pathophysiology for cyst formation and ma Proposed pathophysiology for cyst formation and malignant transformation. Proposed pathophysiology for cyst formation and malignant transformation in acquired cystic kidney disease. RAAS: Renin-angiotensin-aldosterone system.

Epidemiology

Frequency

United States

The rates of occurrence of acquired cystic kidney disease are 7-22% in the predialysis population, 44% within 3 years after beginning dialysis, 79% more than 3 years after beginning dialysis, and 90% longer than 10 years after beginning dialysis. The rate of progression appears to slow after 10-15 years of dialysis.

Kidney transplant recipients

The prevalence of acquired cystic kidney disease is lower in kidney transplant recipients than in patients on dialysis. In a cohort of 561 kidney transplant recipients, the prevalence of acquired cystic kidney disease was 23%, whereas in patients with end-stage renal disease, the prevalence may vary from 30-90%.[9] However, renal cell carcinoma develops more often in transplant recipients with acquired cystic kidney disease than in those without (19% vs. 0.5%).[9]

Mortality/Morbidity

Acquired cystic kidney disease gives rise to many significant complications, the most serious of which is the development of renal cell neoplasms, ranging from adenoma to metastatic renal cell carcinoma. Other complications include the following:

  • Cystic hemorrhage [10]
  • Cyst infection, abscess formation, and/or sepsis
  • Erythrocytosis
  • Calcification in or around cysts

Malignant transformation

The incidence of renal cell carcinoma (RCC) is 0.18% per year in patients with acquired cystic kidney disease, compared with 0.005% in the general population.[11] Most patients are asymptomatic, but about 15% of patients present with hematuria and flank pain; patients with metastasis may present with lumbar pain. Risk factors include the following:

  • Male sex (male-to-female ratio is 7:1)
  • Long duration of dialysis (8-10 years, although cysts can occur before then)
  • Black race
  • Severe acquired cystic kidney disease with marked organomegaly

Renal cancers from acquired renal cystic disease are multicentric in at least 50% of cases and bilateral in about 10% of cases. They are predominantly of the clear cell or papillary subtype.[9] The International Society of Urological Pathology Vancouver Classification of Renal Neoplasia recognizes acquired cystic disease–associated RCC as a distinct entity within the classification system.[12]

Cystic hemorrhage

Hemorrhage is sometimes associated with hematuria. Bleeding may evolve into cyst rupture, with subsequent retroperitoneal or perinephric hemorrhage (Wunderlich syndrome). Rarely, bleeding can be severe enough to cause hypovolemic shock.

Race-, Sex-, and Age-related Demographics

Acquired cystic kidney disease is relatively more common in blacks. Although only 25% of patients on dialysis in the United States are black, blacks account for 53% of cases of acquired cystic kidney disease.

Acquired cystic kidney disease occurs more frequently in men than in women. Acquired cystic kidney disease–associated RCC is found predominantly in men; the male-to-female ratio is 7:1, compared with 2:1 in the general population.

Acquired cystic kidney disease occurs with equal frequency in children and adults.[13] RCC occurs approximately 20 years earlier in people with acquired cystic kidney disease than in the general population. In children, acquired cystic kidney disease–associated RCC is rare.

 

Presentation

History

Acquired cystic kidney disease has been described in nearly every type of kidney disease that causes progressive renal insufficiency, with the exception of hereditary cystic disorders. The incidence and the number and size of cysts correlate with the number of years the patient is on dialysis.

In the early stages, acquired cystic kidney disease does not produce symptoms; it is usually discovered incidentally in the course of abdominal imaging procedures. Patients with more advanced disease may present with signs and symptoms due to cyst hemorrhage or infection, or distant metastasis from a malignant renal neoplasm.

Hemorrhagic cysts can occur in up to 50% of patients with acquired cystic kidney disease, and may present as flank pain and gross hematuria.[10] Rarely, patients may also develop spontaneous retroperitoneal hemorrhage, resulting in hemorrhagic shock, which may be fatal.[14, 15]

Physical

Acquired cystic kidney disease is usually bilateral. The kidneys are rarely palpable but may become palpable after a bleed. See the table below.

Table 1. Comparison of Findings in Acquired Cystic Kidney Disease Versus Autosomal Dominant Polycystic Kidney Disease (Open Table in a new window)

Findings

ACKD

ADPKD

Kidney size

Usually not increased; may be decreased because of the advanced renal disease

Increased

Location of cysts

Cortex and medulla

Cortex and medulla

Corticomedullary differentiation*

Possible

Not possible

Normal parenchyma between cysts*

Yes

No

Extrarenal cysts (eg, liver, pancreas)

No

Yes

Positive family history

No

Yes

*On ultrasonography

Causes

The severity and the duration of azotemia appear to be the critical factors in determining the extent of cyst development.

The causes of multiple renal cysts include the following:

  • Autosomal dominant polycystic kidney disease
  • Autosomal recessive polycystic kidney disease
  • Multicystic renal dysplasia
  • Acquired renal cystic disease
  • Simple renal cysts
  • Medullary sponge kidney
  • Familial juvenile nephronophthisis
  • Medullary cystic disease
  • Von Hippel-Lindau syndrome
  • Tuberous sclerosis complex
  • Glomerulocystic kidney disease
 

DDx

Diagnostic Considerations

When more than one renal cyst is found, consider some of the causes of cystic disorders of the kidney (see the Table 1 in Presentation: Physical).

Acquired cystic kidney disease is strictly confined to the kidneys, in contrast to other hereditary cystic disorders, such as autosomal dominant polycystic kidney disease (ADPKD).

Consider malignant transformation. The Bosniak classification, which divides renal cystic masses into five categories based on imaging characteristics on contrast-enhanced computed tomography, predicts the risk of malignancy and can help guide management decisions[9, 16] ; see Table 2, below.

Table 2: Bosniak Renal Cyst Classification [17, 18] (Open Table in a new window)

Stage

Morphology

Characteristics

Percentage Malignant

Management Recommendations

Bosniak I

Simple cyst with fluid attenuation

No calcifications or septa; hairline-thin wall

~0%

No further workup needed

Bosniak II

Minimally complex cyst; diameter ≤3 cm; uniform hyperattenuation

A few hairline-thin (< 1 mm) septa or thin calcifications; wall shows minimal regular thickening

~0%

No further workup needed

Bosniak IIF

Complexity intermediate between Bosniak II and III

Increased number of septa, minimally thickened with nodular or thick calcifications; contrast may produce perceptible but not measurable enhancement of septa or wall

~5%

Ultrasound/CT follow-up

Bosniak  III

Complex cyst; enhanced septations or wall

Thick, nodular, irregular calcification; septa show thick, irregular, measurable enhancement with contrast

~55%

Partial nephrectomy or radiofrequency ablation in elderly or poor surgical candidates

Bosniak IV

Cystic mass; enhanced soft tissue and cyst

Thick, nodular, irregular calcification; enhanced nodule in septa and wall

~100%

Partial or total nephrectomy

Differential Diagnoses

 

Workup

Approach Considerations

Initial imaging studies include ultrasonography of the kidneys. The distinctive features of acquired cystic kidney disease (ACKD) are renal size (not usually increased) and normal parenchyma distinguishable between cysts (see Table 1 in Presentation: Physical). See the image below.

Acquired cystic kidney disease. Patient with end-s Acquired cystic kidney disease. Patient with end-stage renal disease (ESRD) on maintenance hemodialysis presented with macrohematuria. Ultrasonogram showing numerous cysts in the right kidney and previous cysts in the left kidney.

Detecting ACKD in end-stage renal disease (ESRD) with ultrasonography may be difficult because of the complexity of the cysts and the increased echogenicity of the kidneys in ESRD. Differentiating ACKD from autosomal dominant polycystic kidney disease (ADPKD) may occasionally be difficult.

Sonography is used more often than computed tomography (CT) as the initial screening method. Sonography is better than CT scanning to differentiate a hemorrhagic cyst because almost all hemorrhagic cysts appear isodense or slightly hyperdense on CT scanning. However, clot formation in the cystic cavity appears as an echoic mass by sonography, and dynamic CT scanning is required for differentiation of clot formation from renal cancer.

On CT scanning, early enhancement with contrast is superior to ultrasonography for detecting renal cancer.[19] CT scanning is the best imaging technique to establish a diagnosis of cancer. The presence of a small renal cell carcinoma may be suspected if a CT scan shows a mass with contrast enhancement.[20, 21]

Although CT scanning is useful for the clinical diagnosis of ACKD, acquired cysts in patients who have not undergone dialysis may be difficult to diagnose because these cysts are usually small. See the images below.

Acquired cystic kidney disease. A 39-year-old man Acquired cystic kidney disease. A 39-year-old man on dialysis for longer than 10 years with acquired cystic kidney disease. CT scan showed a mass in the lower pole of the right kidney. Fine-needle aspiration cytology (FNAC) of the lesion showed renal cell carcinoma. The patient underwent nephrectomy.
Acquired cystic kidney disease. A 66-year-old man Acquired cystic kidney disease. A 66-year-old man with acquired cystic kidney disease had a mass in the lower pole of the right kidney. CT-guided biopsy proved the mass to be renal cell carcinoma. This patient also had type II dissection of the aorta.

The use of iodinated contrast media in the workup of renal cysts In kidney transplant recipients may be an issue, due to the increased risk of contrast-induced nephropathy.[22] However, gadolinium-enhanced MRI should be avoided in patients with stage 4 or 5 chronic kidney disease, due to the risk of nephrogenic systemic fibrosis (NSF).[23] In a pilot study comparing ultrasound with non-enhanced MRI in kidney transplant patients with ACKD, MRI showed higher sensitivity for detection of renal cell carcinoma and suspicious lesions.[24] Therefore, non–contrast-enhanced MRI seems to be a reasonable alternative for further assessment of a renal lesion, especially when there are limitations to the use of either iodinated or gadolinium-based contrast media.

No other test is specific to aid in the diagnosis of ACKD. However, patients require investigations related to renal failure.

In patients with equivocal lesions, fine-needle aspiration is required to rule out malignancy. If renal malignancy is diagnosed, then other investigations, including chest radiography, are required to rule out distant metastasis.

Histologic Findings

Grossly, the cysts are usually smaller than 0.5 cm in maximal dimension but may attain sizes of 2-4 cm. They occur in both the renal cortex and the medulla.

Many cysts contain a single layer of cuboidal epithelial cells; however, many kidneys also contain atypical cysts characterized by a multilayered epithelial lining. There appears to be a histologic continuum from cysts lined with single-layered epithelia, to those with multilayered epithelia, to renal adenoma and carcinoma. Most acquired cysts originate from the proximal tubule. Oxalate crystal deposition is predominant in the cyst walls and the renal interstitium in acquired renal cystic disease.

 

Treatment

Medical Care

Bleeding episodes (mild) with flank pain are treated with analgesics (eg, acetaminophen, codeine, morphine) with careful dosing consideration related to underlying kidney dysfunction. Avoid aspirin and meperidine. Avoid heparin during hemodialysis. Patients whose bleeding does not resolve spontaneously should undergo renal embolization or nephrectomy, in particular if the cyst is more than 3 cm in diameter.[25]

Surgical Care

See the list below:

  • Severe bleeding episodes are treated with embolization or nephrectomy.

  • If carcinoma is suspected (from CT scan findings; cysts > 3 cm in diameter and cysts < 3 cm but with complications), then consider nephrectomy.

  • Prophylactic contralateral nephrectomy is controversial; bilateral nephrectomy may be considered in those patients likely to receive kidney transplantation.

Long-Term Monitoring

Although patients with end-stage renal disease (ESRD) and acquired cystic kidney disease (ACKD) are at increased risk for renal cell carcinoma (RCC), routine screening for RCC is not recommended for most of these patients, given the relatively low incidence of RCC in the setting of ACKD and the low expected patient survival with ESRD. However, screening may be advisable and required for patients on transplant waiting lists.[26] The screening schedule varies based on individual provider preferences and can range from yearly to once every 5 years.

Schwarz et al studied RCC in renal transplant recipients with ACKD and recommended the following screening and management protocol, incorporating the Bosniak renal cyst classification system (see DDx)[27, 9] :

  1. All recipients: Yearly ultrasound screening of the native kidneys.

  2. ACKD and Bosniak category I or II cysts (benign simple cysts): Twice yearly ultrasound screening, computed tomography (CT) scan if progression is evident

  3. ACKD and Bosniak category IIF (F for follow-up) cysts (moderately complex cysts): Quarterly ultrasound screening and yearly CT or magnetic resonance imaging scan; nephrectomy if progression is evident, even if the condition does not reach Bosniak category III or IV

  4. ACKD and Bosniak category III (“indeterminate” cystic masses) or IV (clearly malignant cystic masses): Nephrectomy

 

 

 

 

Medication

Medication Summary

No specific drugs are indicated in the management of acquired cystic kidney disease, except analgesics for the treatment of pain. Drugs for underlying disease are required.

Analgesics

Class Summary

These agents act at the central nervous system (CNS) mu receptors and are the criterion standards for the treatment of pain resulting from kidney disease. They are inexpensive and proven effective. Disadvantages include sedation, respiratory depression, smooth muscle spasm, and the potential for abuse and addiction.

A review of opioid equivalents and conversions may be found in the following reference article:

 http://emedicine.medscape.com/article/2138678-overview

 

Acetaminophen (Tylenol, Aspirin Free Anacin, Feverall, Acephen, Cetafen Extra, FeverAll, Little Fevers, Mapap, Non-Aspirin Pain Reliever, Nortemp Children's, Ofimev, Pain Eze, Pharbetol, Q-Pap, Silapap, Triamininc, Valorin)

Drug of choice (DOC) for pain in patients with documented hypersensitivity to aspirin or NSAIDs, with upper GI disease, or who are taking oral anticoagulants.

Effective in relieving mild to moderate acute pain; however, has no peripheral anti-inflammatory effects. May be preferred in elderly patients because of fewer GI and renal adverse effects.

Codeine

Indicated for moderate to severe pain. Binds to opiate receptors in CNS, causing inhibition of ascending pain pathways, altering perception and response to pain.

Morphine (MS Contin, Duramorph, Avinza, Astramorph, Depodur, Infumorph, Kadian, MorphaBond, Arymo ER)

DOC for analgesia because of reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various IV doses are used; commonly titrated until desired effect obtained.

For chronic severe pain unremitting to alternative therapy, oral immediate–release and extended-release morphine sulfate may be warranted. Arymo ER is a morphine sulfate abuse-deterrent formulation.

 

Follow-up

Further Outpatient Care

See the list below:

  • If the cyst is less than 3 cm in diameter and no bleeding has occurred, follow up with imaging studies.

  • If tumor enlargement is present with associated persistent hematuria, consider surgery if the patient's status permits.

Prognosis

Acquired cystic kidney disease reverses in some patients after successful renal transplantation. Some native kidneys continue to develop cysts after transplantation, and in these patients, renal function conceivably remains significantly compromised, thereby maintaining the cystogenic state. Cyclosporine use has been associated with a greater prevalence of post-transplant ACKD than in the  pre-cyclosoporine era.[28]

Cysts do not develop in other organs, in contrast to autosomal dominant polycystic kidney disease (ADPKD).

Acquired cystic kidney disease can be progressive if the patient is on dialysis for an extended period; malignant transformation may also occur. The 5-year survival rates after diagnosis of malignancy are comparable to those observed in renal cell carcinoma in the general population. Renal cell carcinoma in patients with ESRD is associated with more favorable histologic features and prognosis.[29]  Death is usually associated with metastasis and accounts for 2% of the deaths in renal transplant patients.