| Patient Education |
|
Click here for patient education.
|
|
You are in: eMedicine Specialties >
Nephrology > Cystic Diseases of the Kidney
Acquired Cystic Kidney Disease
Article Last Updated: Aug 30, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Dwarakanathan Ranganathan, MD, FRCP, FRACP, Senior Lecturer, Graduate Medical School, Department of Renal Medicine, University of Queensland; Senior Consultant Nephrologist, Royal Brisbane and Women's Hospital, Australia
Dwarakanathan Ranganathan is a member of the following medical societies: American Society of Nephrology and Transplantation Society
Editors: James W Lohr, MD, Fellowship Program Director, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Buffalo; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; George R Aronoff, MD, Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine; Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine; Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Author and Editor Disclosure
Synonyms and related keywords:
ACKD, renal cystic disease, renal cysts, kidney cysts, acquired renal cystic disease, ARCD, renal cell carcinoma
Background
Renal cystic 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. These cysts can occur in the cortex, 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). ARCD is characterized by the development of numerous fluid-filled cysts in the kidneys in individuals who have no history of hereditary cystic disease. ARCD is a bilateral condition. It can antedate the clinical recognition of end-stage renal failure. In the early stages, ARCD does not produce symptoms and is usually discovered inadvertently in the course of abdominal imaging procedures.
Pathophysiology
ARCD was thought to be a consequence of hemodialysis (HD). Recent studies have shown that, although the association of dialysis and ARCD is indisputable, it is the uremic state that promotes the development of ARCD. Dialysis prolongs the patient's survival to allow more time for ARCD to occur.
The exact mechanism is not known. The postulates are as follows:
- Tubule block: The development of cysts is due to tubular abnormalities; 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: 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.
Frequency
United States
The rates of occurrence of ARCD 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.
Mortality/Morbidity
ARCD 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. The incidence of renal cell carcinoma is 0.18% per year in patients with ARCD compared to 0.005% in the general population.
Race
ARCD is relatively more common in blacks. Blacks account for 53% of cases of ARCD; however, in the United States, only 25% of patients on dialysis are black.
Sex
ARCD occurs more frequently in men than in women. ARCD-associated renal cell carcinoma is found predominantly in men; the male-to-female ratio is 7:1 compared with 2:1 in the general population.
Age
ARCD occurs with equal frequency in adults and children. Renal cell carcinoma occurs approximately 20 years earlier in people with ARCD than in the general population. In children, ARCD-associated renal cell carcinoma is rare.
History
ARCD has been described in nearly every type of renal disease that causes progressive renal insufficiency, with the exception of hereditary cystic disorders. The incidence, the number, and the size correlate to the number of years the patient is on dialysis. ARCD is reversible 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. Occasionally, the disease manifests with severe retroperitoneal or intrarenal hemorrhage, with or without hematuria, flank pain, renal colic, cyst infection, erythrocytosis, or distant metastasis from a malignant renal neoplasm. Renal cell carcinoma is the most serious complication of ARCD. Cysts do not develop in other organs, in contrast to autosomal dominant polycystic kidney disease (ADPKD).
Physical
ARCD is usually bilateral. The kidneys are rarely palpable but may become palpable after a bleed.
Comparison of Findings in ARCD Versus ADPKD
| Findings |
ARCD |
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.
Causes of multiple renal cysts include the following:
- ADPKD
- Autosomal recessive polycystic kidney disease
- Multicystic renal dysplasia
- ARCD
- Simple renal cysts
- Medullary sponge kidney
- Familial juvenile nephronophthisis/medullary cystic disease
Polycystic Kidney Disease
Renal Cell Carcinoma
Other Problems to be Considered
When more than one renal cyst is found, consider some of the causes of cystic disorders of the kidney (see the Table in Physical). ARCD is strictly confined to the kidneys, in contrast to other hereditary cystic disorders, such as ADPKD. Consider malignant transformation.
Imaging Studies
- Ultrasonography
- Initial imaging studies include ultrasonography of the kidneys. Detecting ARCD in end-stage renal disease (ESRD) may be difficult using ultrasonography because of the complexity of the cysts and the increased echogenicity of the kidneys in ESRD. Differentiating between ARCD and ADPKD may occasionally be difficult, and the distinctive features of ARCD are renal size (not usually increased) and the normal parenchyma distinguishable between cysts (see the Table in Physical).
- Sonography is used more often than CT scanning 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.
- CT scanning with contrast
- Early enhancement with contrast is superior to ultrasonography for detecting renal cancer. 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.
- Although CT scanning is useful to clinically diagnose ARCD, acquired cysts in patients before dialysis may be difficult to diagnose because these cysts are usually small.
- Gadolinium-enhanced magnetic resonance imaging (MRI): MRI is useful in patients who cannot tolerate CT scanning with contrast.
Other Tests
- No other test is specific to aid in the diagnosis of ARCD, and patients require investigations related to renal failure.
Procedures
- Fine-needle aspiration of equivocal lesions to rule out malignancy is required.
Histologic Findings
Grossly, the cysts are usually smaller than 0.5 cm in maximal dimension but may attain sizes of 2-4 cm. They affect 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 renal interstitium in ARCD.
Staging
If renal malignancy is diagnosed, then other investigations, including chest radiography, are required to rule out distant metastasis.
Medical Care
Bleeding episodes (mild) with flank pain are treated with analgesics (eg, morphine, codeine, acetaminophen). Avoid aspirin, meperidine, and propoxyphene. Avoid heparin during HD.
Surgical Care
- Severe bleeding episodes are treated by embolization or nephrectomy.
- If carcinoma is suspected (from CT scan findings), then consider nephrectomy (cysts > 3 cm in diameter and cysts <3 cm but with complications).
- Prophylactic contralateral nephrectomy is controversial; bilateral nephrectomy may be considered in those patients likely to receive kidney transplantation.
Consultations
If carcinoma is suspected in ARCD, consult a urologist.
Diet
No specific dietary intervention is required.
Activity
During a bleeding episode, bed rest is required.
No specific drugs are indicated in the management of ARCD, except analgesics for the treatment of pain. Drugs for underlying disease are required.
Drug Category: Analgesics
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.
| Drug Name | Acetaminophen (Tylenol, Aspirin Free Anacin, Feverall) |
|---|
| Description | 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. |
|---|
| Adult Dose | 325-650 mg PO/PR q4-6h or 1000 mg tid/qid; not to exceed 4 g/d |
|---|
| Pediatric Dose | <12 years: 10-15 mg/kg/dose PO q4-6h prn; not to exceed 2.6 g/d
>12 years: 325-650 mg PO q4h; not to exceed 4 g/d |
|---|
| Contraindications | Documented hypersensitivity; known G-6-PD deficiency |
|---|
| Interactions | Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity |
|---|
| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
|---|
| Precautions | Hepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; contained in many OTC products and combined use with these products may result in toxicity due to cumulative doses exceeding recommended maximum dose |
|---|
| Drug Name | Codeine |
|---|
| Description | Indicated for moderate to severe pain. Binds to opiate receptors in CNS, causing inhibition of ascending pain pathways, altering perception and response to pain. |
|---|
| Adult Dose | 10-60 mg/dose PO/IM/SC q4-6h prn; not to exceed 360 mg/d |
|---|
| Pediatric Dose | 0.5 mg/kg/dose PO/IM/SC q4-6h prn; not to exceed 60 mg/dose |
|---|
| Contraindications | Documented hypersensitivity; high altitude cerebral edema (HACE) diagnosis; elevated intracranial pressure (ICP) |
|---|
| Interactions | Toxicity increases with concurrent administration of tricyclic antidepressants, MAO inhibitors, neuromuscular blockers, CNS depressants, phenothiazines, and narcotic analgesics |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
|---|
| Precautions | Use to treat cough in HACE diagnosed patients only if absolutely necessary; may depress hypoxic ventilatory rate and respiratory drive during sleep |
|---|
| Drug Name | Morphine (MS Contin, MSIR, Oramorph, Duramorph) |
|---|
| Description | 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. |
|---|
| Adult Dose | Starting dose: 0.1 mg/kg IV/IM/SC
Maintenance dose: 5-20 mg/70 kg IV/IM/SC q4h
Relatively hypovolemic patients: Start with 2 mg IV/IM/SC; reassess hemodynamic effects of dose |
|---|
| Pediatric Dose | Infants and children: 0.1-0.2 mg/kg dose IV/IM/SC q2-4h prn; not to exceed 15 mg/dose; may initiate at 0.05 mg/kg/dose |
|---|
| Contraindications | Documented hypersensitivity; hypotension; potentially compromised airway where establishing rapid airway control would be difficult |
|---|
| Interactions | Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic antidepressants, MAO inhibitors, and other CNS depressants may potentiate adverse effects of morphine |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
|---|
| Precautions | Caution in hypotension, respiratory depression, nausea, emesis, constipation, urinary retention, atrial flutter, and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate |
|---|
Further Inpatient Care
- Patients admitted with cyst bleeding need further investigation for malignancy.
Further Outpatient Care
- 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.
Complications
- Malignant transformation
- The risk of renal cell carcinoma is increased 40 fold in patients with ARCD as compared to the general population. Most patients are asymptomatic, but about 15% of patients manifest with pain, hemorrhage, and metastasis (lumbar pain). Risk factors include male sex (male-to-female ratio is 7:1), long duration of dialysis, black race, and severe ARCD with marked organomegaly.
- Renal cancers from ARCD are multicentric in at least 50% of cases and bilateral in about 10%; they are predominantly of the papillary subtype.
- 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. Calcification can occur in or around cysts.
- Cyst infection, abscess formation, and/or sepsis
- Erythrocytosis
Prognosis
- ARCD 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. Death is usually associated with metastasis and accounts for 2% of the deaths in renal transplant patients.
Patient Education
Medical/Legal Pitfalls
- Malignancy should not be overlooked in patients with ARCD.
Special Concerns
- Screening of native kidneys in transplant recipients may be performed when they are referred for ultrasonographic evaluation of the renal allograft.
- Routine screening for ARCD in patients on dialysis is controversial; the controversy is based partly on the cost of such programs and mainly on the lack of data on the effect of screening on the patients' outcome, including survival.
| Media file 1:
Acquired cystic kidney disease. Patient with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) presented with macrohematuria. Ultrasonogram showing numerous cysts in the right kidney and previous cysts in the left kidney. |
 |  View Full Size Image | |
Media type: Image
|
| Media file 2:
Acquired cystic kidney disease. A 39-year-old man on dialysis for longer than 10 years with acquired renal cystic disease (ARCD). 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. |
 | View Full Size Image | |
Media type: Image
|
| Media file 3:
Acquired cystic kidney disease. A 66-year-old man with acquired renal cystic disease (ARCD) 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. |
 | View Full Size Image | |
Media type: Image
|
- Cohen EP, Elliott WC. The role of ischemia in acquired cystic kidney disease. Am J Kidney Dis. Jan 1990;15(1):55-60. [Medline].
- Dunnill MS, Millard PR, Oliver D. Acquired cystic disease of the kidneys: a hazard of long-term intermittent maintenance haemodialysis. J Clin Pathol. Sep 1977;30(9):868-77. [Medline].
- Dwarakanathan S. Acquired renal cystic disease. Nephrology. 2003;8:A62-A63.
- Fleming S, O''Donnell M. Surgical pathology of renal epithelial neoplasms: recent advances and current status. Histopathology. Mar 2000;36(3):195-202. [Medline].
- Grantham JJ. Acquired cystic kidney disease. Kidney Int. Jul 1991;40(1):143-52. [Medline].
- Gulanikar AC, Daily PP, Kilambi NK, et al. Prospective pretransplant ultrasound screening in 206 patients for acquired renal cysts and renal cell carcinoma. Transplantation. Dec 27 1998;66(12):1669-72. [Medline].
- Hayakawa M, Nakajima F, Tsuji A, et al. Cytokine levels in cystic renal masses associated with renal cell carcinoma. J Urol. May 1998;159(5):1459-64. [Medline].
- Ishikawa I, Saito Y, Asaka M, et al. Twenty-year follow-up of acquired renal cystic disease. Clin Nephrol. Mar 2003;59(3):153-9. [Medline].
- Ishikawa I. Hemorrhage versus cancer in acquired cystic disease. Semin Dial. Jan-Feb 2000;13(1):56.
- Kyushu Pediatric Nephrology Study Group. Acquired cystic kidney disease in children undergoing continuous ambulatory peritoneal dialysis. Am J Kidney Dis. Aug 1999;34(2):242-6. [Medline].
- Levine E, Slusher SL, Grantham JJ, Wetzel LH. Natural history of acquired renal cystic disease in dialysis patients: a prospective longitudinal CT study. AJR Am J Roentgenol. Mar 1991;156(3):501-6. [Medline].
- Levine E. Acquired cystic kidney disease. Radiol Clin North Am. Sep 1996;34(5):947-64. [Medline].
- Liu JS, Ishikawa I, Horiguchi T. Incidence of acquired renal cysts in biopsy specimens. Nephron. Feb 2000;84(2):142-7. [Medline].
- Moskowitz DW, Bonar SL, Liu W, et al. Epidermal growth factor precursor is present in a variety of human renal cyst fluids. J Urol. Mar 1995;153(3 Pt 1):578-83. [Medline].
- Nahm AM, Ritz E. Acquired renal cysts. Nephrol Dial Transplant. Jul 2001;16(7):1506-8. [Medline].
- Rubenstein I, Zanier J, Moraes E, et al. Renal cell carcinoma in patients with acquired renal cystic disease. Br J Urol. 1997;80:118-9.
- Stewart JH, Buccianti G, Agodoa L, et al. Cancers of the kidney and urinary tract in patients on dialysis for end-stage renal disease: analysis of data from the United States, Europe, and Australia and New Zealand. J Am Soc Nephrol. Jan 2003;14(1):197-207. [Medline].
- Takebayashi S, Hidai H, Chiba T, et al. Using helical CT to evaluate renal cell carcinoma in patients undergoing hemodialysis: value of early enhanced images. AJR Am J Roentgenol. Feb 1999;172(2):429-33. [Medline].
- Todd TD, Dhurandhar B, Mody D, et al. Fine-needle aspiration of cystic lesions of the kidney. Morphologic spectrum and diagnostic problems in 41 cases. Am J Clin Pathol. Mar 1999;111(3):317-28. [Medline].
- Truong LD, Krishnan B, Cao JT, et al. Renal neoplasm in acquired cystic kidney disease. Am J Kidney Dis. Jul 1995;26(1):1-12. [Medline].
- Vaseemuddin M, Kraus MA. Quiz page. Acquired kidney disease (ACKD) with associated bilateral renal cell carcinoma. Am J Kidney Dis. Oct 2005;46(4):A48, e47-9. [Medline].
Acquired Cystic Kidney Disease excerpt Article Last Updated: Aug 30, 2006
|
